Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice4754ENYukiomiEguchiDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversitySoichiroUshioDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKeiichiIrieDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityYutaYamashitaDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityMiyuEguchiDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTakafumiNakanoDepartment of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKenichiMishimaDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityOriginal Article10.18926/AMO/70072Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1757-47491812026Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae9ENSushmitaKunduDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsSourinAluDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsAbhishekSinghDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsAnimeshGopeDivision of General Medicine, ICMR- National Institute for Research in Bacterial InfectionsRanjan KumarNandyDivision of Bacteriology, ICMR- National Institute for Research in Bacterial InfectionsAsish K.MukhopadhyayDivision of Bacteriology, ICMR- National Institute for Research in Bacterial InfectionsShin-ichiMiyoshiDivision of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNabendu SekharChatterjeeDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsSushmitaBhattacharyaDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsBackground Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.<br>
Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09–0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.<br>
Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322025Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 StudyENKayokoTaoDepartment of Pediatrics, National Cancer Center HospitalTakakoYoshiokaDepartment of Pathology, National Center for Child Health and DevelopmentMihoKatoDepartment of Childhood Cancer Data Management, National Center for Child Health and DevelopmentKazuyukiKomatsuDepartment of Pediatrics, Hamamatsu University School of MedicineShinichiTsujimotoDepartment of Pediatrics, Yokohama City UniversityKenichiSakamotoDepartment of Pediatrics, Shinshu University School of MedicineKazukiTanimuraDepartment of Pediatrics, National Cancer Center HospitalMinakoSugiyamaDepartment of Pediatrics, National Cancer Center HospitalMasahiroSekiguchiDepartment of Pediatrics, The University of TokyoYoshikoNakanoDepartment of Pediatrics, The University of TokyoYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushiYatabeDepartment of Diagnostic Pathology, National Cancer Center HospitalAkihikoYoshidaDepartment of Diagnostic Pathology, National Cancer Center HospitalHajimeOkitaDepartment of Pathology, Keio University School of MedicineJunkoHiratoDepartment of Pathology, Public Tomioka General HospitalKenichiKohashiDepartment of Pathology, Graduate School of Medicine, Osaka Metropolitan UniversityYukichiTanakaDepartment of Pathology, Kanagawa Children's Medical CenterShinjiKohsakaDivision of Cellular Signaling, National Cancer Center Research InstituteTakashiKuboDepartment of Clinical Genomics, National Cancer Center Research InstituteKunikoSunamiDepartment of Laboratory Medicine, National Cancer Center HospitalMakotoHirataDepartment of Genetic Medicine and Services, National Cancer Center HospitalShuichiTsutsumiGenome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of TokyoHiroyukiAburataniGenome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of TokyoKatsuyoshiKohDepartment of Hematology and Oncology, Saitama Children's Medical CenterMasahiroHirayamaDepartment of Pediatrics, Mie University Graduate School of MedicineShuheiKarakawaDepartment of Pediatrics, Hiroshima University HospitalYukayoTerashitaDepartment of Pediatrics, Hokkaido University HospitalHiroyukiFujisakiDepartment of Pediatric Hematology and Oncology, Osaka City General HospitalTakeshiYagiOkinawa Prefectural Nanbu Medical Center & Children's Medical CenterAkihiroYonedaDepartment of Pediatric Surgery, National Center for Child Health and DevelopmentShinjiMochizukiDepartment of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health SecurityHiroyukiShichinoDepartment of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health SecurityTatsuyaSuzukiDepartment of Hematology, National Cancer Center HospitalTetsuyaTakimotoDepartment of Childhood Cancer Data Management, National Center for Child Health and DevelopmentKoichiIchimuraDepartment of Pathology, Kyorin University Faculty of MedicineChitoseOgawaDepartment of Pediatrics, National Cancer Center HospitalKimikazuMatsumotoChildren's Cancer Center National Center for Child Health and DevelopmentHitoshiIchikawaDepartment of Clinical Genomics, National Cancer Center Research InstituteMotohiroKatoDepartment of Pediatrics, The University of TokyoTo develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1479-58762312025Tumor marker–guided precision BNCT for CA19-9–positive cancers: a new paradigm in molecularly targeted chemoradiation therapy1387ENNoriyukiKanehiraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiTajimaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTatsunoriOsoneDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesTakuyaFujimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriSakuraiInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityNatsukoKondoInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityNarikazuNagahisaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruKameiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTaigaFujitaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAkiraMoriharaGraduate School of Environmental, Life Science, Okayama UniversityYutakaTakaguchiFaculty of Sustainable Design, Department of Material Design and Engineering, University of ToyamaMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityTakeshiTakaradaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMinoruSuzukiInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiMichiueNeutron Therapy Research Center, Okayama UniversityBackground: Boron neutron capture therapy (BNCT) is a molecularly targeted chemoradiation modality that relies on boron delivery agents such as p-borophenylalanine (BPA), which require LAT1 (L-type amino acid transporter 1) for tumor uptake. However, the limited efficacy of BPA in LAT1-low tumors restricts its therapeutic scope. To address this limitation, we developed a tumor marker–guided BNCT strategy targeting cancers overexpressing the clinically validated glycan biomarker CA19-9.<br>
Methods: We conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) datasets to identify LAT1-low cancers with high CA19-9 expression. These analyses revealed elevated expression of fucosyltransferase 3 (FUT3), which underlies CA19-9 biosynthesis, in pancreatic, biliary, and ovarian malignancies. Based on this, we synthesized a novel boron compound, fucose-BSH, designed to selectively accumulate in CA19-9–positive tumors. We evaluated its physicochemical properties, pharmacokinetics, biodistribution, and antitumor efficacy in cell lines and xenograft models, comparing its performance to that of BPA.<br>
Results: Fucose-BSH demonstrated significantly greater boron uptake in CA19-9–positive cell lines (AsPC-1, Panc 04.03, HuCCT-1, HSKTC, OVISE) compared to CA19-9–negative PANC-1. In HuCCT-1 xenografts, boron accumulation reached 36.2 ppm with a tumor/normal tissue ratio of 2.1, outperforming BPA. Upon neutron irradiation, fucose-BSH–mediated BNCT achieved > 80% tumor growth inhibition. Notably, fucose-BSH retained therapeutic efficacy in LAT1-deficient models where BPA was ineffective, confirming LAT1-independent targeting.<br>
Conclusions: This study establishes a novel precision BNCT approach by leveraging CA19-9 as a tumor-selective glycan marker for boron delivery. Fucose-BSH offers a promising platform for expanding BNCT to previously inaccessible LAT1-low malignancies, including pancreatic, biliary, and ovarian cancers. These findings provide a clinically actionable strategy for tumor marker–driven chemoradiation and lay the foundation for translational application in BNCT. This strategy has the potential to support companion diagnostic development and precision stratification in ongoing and future BNCT clinical trials.<br>
Translational Relevance: Malignancies with elevated CA19-9 expression, such as pancreatic, biliary, and ovarian cancers, are associated with poor prognosis and limited response to current therapies. This study presents a tumor marker–guided strategy for boron neutron capture therapy (BNCT) by leveraging CA19-9 glycan biology to enable selective tumor targeting via fucose-BSH, a novel boron compound. Through transcriptomic data mining and preclinical validation, fucose-BSH demonstrated LAT1-independent boron delivery, potent BNCT-mediated cytotoxicity, and tumor-specific accumulation in CA19-9–positive models. These findings support a precision chemoradiation approach that addresses a critical gap in BNCT applicability, offering a clinically actionable pathway for patient stratification and therapeutic development in CA19-9–expressing cancers.No potential conflict of interest relevant to this article was reported.Informa UK LimitedActa Medica Okayama1949-09761712025Asiatic acid, a novel ciprofloxacin adjuvant inhibits Shigella flexneri infection2586329ENPriyankaMaitraDivision of Biochemistry, ICMR-National Institute for Research in Bacterial InfectionsSamhatiBhuktaDivision of Biochemistry, ICMR-National Institute for Research in Bacterial InfectionsAnimeshGopeDivision of Clinical Medicine, ICMR-National Institute for Research in Bacterial InfectionsPratanuKayetDivision of Bioinformatics, ICMR-National Institute for Research in Bacterial InfectionsSurajitBasakDivision of Bioinformatics, ICMR-National Institute for Research in Bacterial InfectionsShin-IchiMiyoshiDivision of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiKitaharaCollaborative Research Center of Okayama University for Infectious Diseases in India, ICMR-National Institute for Research in Bacterial InfectionsShantaDuttaDepartment of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsSushmitaBhattacharyaDivision of Biochemistry, ICMR-National Institute for Research in Bacterial InfectionsBacterial infection caused by intracellular pathogens such as Shigella flexneri is a rapidly increasing global health concern that requires urgent and necessary action. The dearth of licensed vaccines against shigellosis and the decline in susceptibility to conventional antibiotics has encouraged the development of new antibiotic principles and drugs. The treatment options are decreasing faster than the discovery rate of new antibacterial agents. Combinatorial approach of antibiotics with non-antibiotic adjuvants is a promising aspect to treat resistant bacterial infections. Asiatic acid, a membrane-disrupting triterpenoid with wide antimicrobial and immunomodulatory properties, can potentiate antibiotics, but the exact mechanisms remain broadly unexplored. Therefore, in this study, we screened the interaction of asiatic acid with several antibiotics. The results showed synergistic interactions of asiatic acid with antibiotics against susceptible and multidrug-resistant S. flexneri clinical isolates. Particularly important was the interaction of asiatic acid with the quinolone antibiotics ciprofloxacin and nalidixic acid. A detailed study showed that combined treatment of asiatic acid with ciprofloxacin inhibited S. flexneri biofilm formation and resistance development. An increase in membrane disruption and depolarization upon co-treatment was evident by surface electron and confocal microscopy. In addition, asiatic acid and ciprofloxacin synergism was identified to inhibit efflux activity and intracellular bacterial viability. However, asiatic acid showed no synergistic toxicity with ciprofloxacin towards mammalian cells. The antibacterial activity was further verified in a S. flexneri infected mice model. Therapeutic benefits were evident with reduced bacterial burden, recovery from intestinal tissue damage and increase in mice survivability. The results showed that this combination can target the bacterial membrane, efflux pump proteins and biofilm formation, thereby preventing resistance development. The combination treatment offers a proof of concept in targeting essential bacterial activities and might be developed into a novel and efficient treatment alternative against S. flexneri.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Inhibition of Air-Exposure Stress–Induced Autolysis in Clostridium perfringens by Zn2+345352ENNozomuMatsunagaDepartment of Life Science, Faculty of Science, Okayama University of ScienceSeiraEgusaDepartment of Life Science, Faculty of Science, Okayama University of ScienceRiyoAonoDepartment of Medical Technology, Kagawa Prefectural University of Health SciencesEijiTamaiDepartment of Infectious Disease, College of Pharmaceutical Science, Matsuyama UniversityYasuoHitusmotoDepartment of Life Science, Faculty of Science, Okayama University of ScienceSeiichiKatayamaDepartment of Life Science, Faculty of Science, Okayama University of ScienceOriginal Article10.18926/AMO/69435Clostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006726192025Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic9347ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroOkumuraDepartment of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of MedicineSeiyaKatoDivision of Pathology, Saiseikai Fukuoka General HospitalKenjiOnoueDepartment of Cardiovascular Medicine, Nara Medical UniversityToruKuboDepartment of Cardiology and Geriatrics, Kochi Medical School, Kochi UniversityHidemichiKouzuDepartment of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of MedicineToshiyukiYanoDepartment of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of MedicineTakayukiInomataDepartment of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental SciencesHypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin–actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0753-33221882025Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study118137ENYoshikaSakamotoDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesTakahiroNiimuraDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesMitsuhiroGodaDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesNanamiTomochikaDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesWakanaMurakawaDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesFukaAizawaDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesKentaYagiDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesHirofumiHamanoDepartment of Pharmacy, Okayama University HospitalYukiIzawa-IshizawaDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalKeisukeIshizawaDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical SciencesSunitinib (SUN), a drug used to treat advanced renal cell carcinoma and other cancers, causes cardiotoxicity. This study aimed to identify a potential drug candidate to counteract SUN-induced cardiotoxicity. We analysed real-world data from adverse event report databases of existing clinically approved drugs to identify potential candidates. Through in silico analyses and in vitro experiments, the mechanisms of action were determined. The study identified calcitriol (CTL), an active form of vitamin D, as a promising candidate against SUN-induced cardiotoxicity. In H9c2 cells, SUN decreased cell viability significantly, whereas CTL mitigated this effect significantly. The SUN-treated group exhibited increased autophagy in H9c2 cells, which was reduced significantly in the CTL group. Bioinformatics analysis using Ingenuity Pathway Analysis revealed the mechanistic target of rapamycin (mTOR) as a common factor between autophagy and CTL. Notably, rapamycin, an mTOR inhibitor, nullified the effects of CTL on cell viability and autophagy. Furthermore, SUN treatment led to significant reductions in cardiomyocyte diameters and increases in their widths, changes that were inhibited by CTL. SUN also induced morphological changes in surviving H9c2 cells, causing them to adopt a rounded shape, whereas CTL improved their morphology to resemble the elongated shape of the control group. In conclusion, the findings of the present study suggest that CTL has the potential to prevent SUN-induced cardiomyocyte damage through autophagy, particularly via mTOR-mediated pathways. The findings indicate that CTL could serve as an effective prophylactic agent against SUN-induced cardiotoxicity, offering a promising avenue for further research and potential clinical applications.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0163-21162025Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting Inflammasome-Associated ActivationENMikakoIshiguroDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAkinobuTakakiDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSakikoHiraokaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJyunkiToyosawaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYukiAoyamaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShokoIgawaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasushiYamasakiDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHideakiKinugasaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground Nonsteroidal anti-inflammatory drugs (NSAID), which are commonly used to manage pain and inflammation, often cause gastrointestinal injuries, including small intestinal damage. Berberine (BBR) is a traditional Chinese medicine that protects against these injuries. However, the mechanism of action is not fully understood.<br>
Aims This study aimed to evaluate the protective effects of BBR against NSAID-induced intestinal injury and elucidate the underlying molecular mechanisms.<br>
Methods We evaluated the effects of BBR on NSAID-induced intestinal injury using a combination of mouse models and human gut organoids. Mice were treated with indomethacin with or without BBR to induce small intestinal injury. Human gut organoids were exposed to NSAID, with or without BBR, to assess their direct epithelial effects. Histological analyses, cytokine measurements, and Western blotting were performed to evaluate intestinal damage, tight junction integrity, and inflammasome-associated activation.<br>
Results In NSAID-treated mice, BBR markedly reduced ulcers and adhesions and preserved ileal Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1) levels. BBR inhibited both NOD-like receptor family pyrin domain-containing 6 and NOD-like receptor family caspase recruitment domain–containing protein 4 inflammasome activation, reducing Caspase-1 maturation and downstream interleukin-1β and tumor necrosis factor-α release. In human gut organoids, BBR demonstrated comparable protective effects by directly mitigating NSAID-induced epithelial barrier disruption caused by Claudin-1 and Occludin downregulation, although it did not restore ZO-1 expression.<br>
Conclusions BBR effectively prevented NSAID-induced small intestinal injury by maintaining tight junction integrity and inhibiting inflammasome-associated activation, indicating its potential as a therapeutic agent against such damage.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0753-33221862025(+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet118030ENHarukaAoki-SaitoDepartment of Allergy and Respiratory Medicine, Gunma University Graduate School of MedicineHirokiMandaiDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceTakashiNakakuraDepartment of Anatomy, Teikyo University School of MedicineTsutomuSasakiDivision of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto UniversityTadahiroKitamuraMetabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma UniversityKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakeshiHisadaGunma University Graduate School of Health SciencesShuichiOkadaDepartment of Diabetes, Soleiyu Asahi ClinicSeijiSugaDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityMasanobuYamadaDepartment of Medicine and Molecular Science, Gunma University Graduate School of MedicineTsugumichiSaitoDepartment of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei UniversityObjective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.<br>
Methods: Male C57BL/6 J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180 mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.<br>
Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-γ (PPARγ). This effect was synergistic with that of a PPARγ agonist.<br>
Conclusion: This study demonstrated that (+)-terrein effectively induces PPARγ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7932025Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells157166ENOmer FarukHatipogluDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityTakashiNishinakaDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityKursat OguzYaykasliDepartment of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenShujiMoriDepartment of Pharmacology, School of Pharmacy, Shujitsu UniversityMasahiroWatanabeDepartment of Pharmacology, School of Pharmacy, Shujitsu UniversityTakaoToyomuraDepartment of Pharmacology, School of Pharmacy, Shujitsu UniversityMasahiroNishiboriDepartment of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityHideoTakahashiDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityHidenoriWakeDepartment of Pharmacology, Faculty of Medicine, Kindai UniversityOriginal Article10.18926/AMO/68723Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1880-65467522025Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells100016ENYutaroAsakaDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshioMasumotoDivision of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori UniversityAtsuhitoUnedaDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesVanessa D.ChinUMass Chan Medical School, UMass Memorial Medical CenterYusukeOtaniDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolTirsoPenaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolHaruyoshiKatayamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakutoItanoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTeruhikoAndoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRongshengHuangDepartment of Trauma Orthopedics, The Second Hospital of Dalian Medical UniversityAtsushiFujimuraDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesGlioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells' changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through alpha 1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high alpha 1Dadrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama1662-5102192025Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus1551700ENHaoWenDepartment of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNagisaSadaDepartment of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTsuyoshiInoueDepartment of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe ketogenic diet increases ketone bodies (beta-hydroxybutyrate and acetoacetate) in the brain, and ameliorates epileptic seizures in vivo. However, ketone bodies exert weak or no effects on electrical activity in rodent hippocampal slices. Especially, it remains unclear what kinds of conditions are required to strengthen the actions of ketone bodies in hippocampal slices. In the present study, we examined the effects of acetoacetate on hippocampal pyramidal cells in normal slices and epileptiform slices of mice. By using patch-clamp recordings from CA1 pyramidal cells, we first confirmed that acetoacetate did not change the membrane potentials and intrinsic properties of pyramidal cells in normal slices. However, we found that acetoacetate weakened spontaneous epileptiform bursts in pyramidal cells of epileptiform slices, which were acutely induced by applying convulsants to normal slices. Interestingly, acetoacetate did not change the frequency of the epileptiform bursts, but attenuated individual epileptiform bursts. We finally examined the effects of acetoacetate on excitatory synaptic barrages during epileptiform activity, and found that acetoacetate weakened epileptiform bursts by reducing synchronous synaptic inputs. These results show that acetoacetate attenuated neuronal bursts in epileptiform slices, but did not affect neuronal activity in normal slices, which leads to seizure-selective actions of ketone bodies.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1383-57691062025The antimalarial activity of transdermal N-89 mediated by inhibiting ERC gene expression in P. Berghei-infected mice103026ENHiroakiMatsumoriDivision of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThi QuyenDinhDivision of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShin-ichiMiyoshiResearch Center for Intestinal Health Science, Okayama UniversityMasayukiMoritaDepartment of Anatomy, Kawasaki Medical SchoolHye-SookKimDivision of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThrough studies of new antimalarial drugs, we identified 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) as a potential drug candidate. Here, we analyzed the antimalarial action of a transdermal formulation (td) of N-89, designed for easy use by children, using Plasmodium berghei-infected mice as a model for malaria patients. The td N-89 or artemisinin (ART) formulation was transdermally administered to P. berghei-infected mice with 0.2–0.4 % parasitemia, twice daily for four days, at an effective dose of 90 % for malaria. Parasitemia was decreased in td N-89 and td ART groups during the drug treatment; then, three of the eight mice in td N-89 group were completely cured without relapse. Additionally, abnormal trophozoites in td N-89 group were observed 8 h after administration and increased up to 24 h. To study the change in endoplasmic reticulum-resident calcium-binding protein (ERC) gene expression with td N-89, we investigated the gene expression of P. berghei ERC (PbERC) after td N-89 treatment. PbERC gene expression was increased time-dependently in control group, and was statistically decreased at 4 and 8 h and then increased similar to that of control group at 12 h in td ART group. In contrast, the expression in td N-89 group was almost steady starting from 0 h. We also studied parasite egress-related genes expression after td N-89 treatment, plasmepsin X, subtilisin-like protease 1 and merozoite surface protein 1, were suppressed at 12 h compared to control group. These results suggest that N-89 affects function of endoplasmic reticulum via regulating gene suppression and subsequently parasite growth is inhibited.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2049-41731332025Long-Term Follow-Up of a Patient With SPG11198200ENYosukeOsakadaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTaijunYunokiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikaMatsuokaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeFukuiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiichiroTsunodaDepartment of Neurology, Tsuyama Chuo HospitalKentaroDeguchiDepartment of Neurology, Okayama City HospitalRyutaMoriharaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruYamashitaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiIshiuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityWe present a case of a male patient with disease-causing variants in SPG11, a causative gene for autosomal recessive spastic paraplegia with a thin corpus callosum (ARHSP-TCC), as well as juvenile amyotrophic lateral sclerosis (ALS5) and Charcot–Marie–Tooth disease (CMT2X). A neurological examination at age 18 revealed dysarthria, muscle weakness in bilateral lower extremities, hyperreflexia in patellar reflex, hyporeflexia in Achilles reflex with an extensor plantar reflex, and intellectual disability. Magnetic resonance imaging revealed a thin corpus callosum and ears of the lynx sign. At the age of 26, weakness and muscle atrophy progressed. While no sensory disturbances were noted, there was a mild decrease in sensory nerve action potentials of the sural nerve over the 8 years between 18 and 26. Clinicians should be aware that SPG11 belongs to the same spectrum of disorders as ALS5 and CMT2X and presents various phenotypes depending on the stage of the disease.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2071-105016232024Assessing CO2 Reduction Effects Through Decarbonization Scenarios in the Residential and Transportation Sectors: Challenges and Solutions for Japan's Hilly and Mountainous Areas10342ENXiyueHaoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityChuyueYanDepartment of Socio-Environmental Energy Science, Graduate School of Energy Science, Kyoto UniversityDaisukeNarumiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDepopulation, aging, and regional decline are becoming increasingly serious issues in Japan's hilly and mountainous areas. Focusing on mitigating environmental damage and envisioning a sustainable future for these regions, this study examines the potential for reducing CO2 emissions in the residential and transportation sectors by 2050. Bottom-up simulations were used to estimate CO2 emissions. Subsequently, six decarbonization scenarios were formulated, considering various measures from the perspectives of population distribution and technological progress. Based on these scenarios, this study analyzes changes in future population, energy consumption, and CO2 emissions by 2050. The results of this study show the following. (1) Depopulation and aging problems in these regions are expected to become more severe in the future. It is necessary to take action to promote sustainable regional development. (2) Pursuing decarbonization has a positive impact on enhancing regional sustainability; however, maintaining the intensity of measures at the current level could lead to a reduction of only 40% in CO2 emissions per capita by 2050 compared with 2020. (3) Scenarios that strengthen decarbonization measures could achieve a reduction of over 95% by 2050, indicating that carbon neutrality is attainable. However, this will require implementing measures at a higher intensity, especially in the transportation sector.No potential conflict of interest relevant to this article was reported.Institute of Electrical and Electronics Engineers (IEEE)Acta Medica Okayama2169-3536122024Aromug: A Mug-Type Olfactory Interface to Enhance the Sweetness Perception of Beverages7836678378ENDaikiMayumiGraduate School of Science and Technology, Nara Institute of Science and TechnologyYugoNakamuraFaculty of Information Science and Electrical Engineering, Kyushu UniversityYukiMatsudaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityShinyaMisakiGraduate School of Science and Technology, Nara Institute of Science and TechnologyKeiichiYasumotoGraduate School of Science and Technology, Nara Institute of Science and TechnologySugary beverages are a significant contributor to sugar consumption, and their excessive consumption is associated with increased risks of elevated blood glucose levels and diabetes. Many individuals have a strong preference for sugary beverages and often find beverages with lower sugar content to be less satisfying. Attempts to switch to less sugary options are frequently short-lived, leading to a return to higher-sugar beverages. Recognizing that 75 – 95% of taste perception is influenced by scent, we investigated a scent-based approach to reduce sugar intake while preserving the perception of sweetness. This study introduces an olfactory interface in the form of a mug named “Aromug,” designed to emit a sweet scent in sync with the drinking action. Aromug incorporates motion sensing and scent presentation functions to enhance the perceived sweetness of a beverage, thereby encouraging a gradual reduction in sugar intake. Our experiments, involving 33 participants, demonstrated that the combined scents of sugar-free coffee and chocolate increased the perception of sweetness (p =1.641×10−2 ). The study also found that the simultaneous presentation of scent and visual cues improved taste satisfaction and sweetness perception. Additionally, we observed variations in sweetness preference related to age and frequency of coffee consumption. It was particularly observed that people in their 20s and those who frequently drink coffee tend to perceive the taste of beverages as sweeter. This suggests a potential for Aromug to customize the scent experience based on individual preferences, offering a novel way to encourage healthier beverage choices.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1574-69683712024Regulatory role of VvsB protein on serine protease activity of VvsA in Vibrio vulnificusfnae053ENTomokaKawaseGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAnusuyaDebnathDepartment of Biotechnology, Brainware UniversityKeinosukeOkamotoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground:Vibrio vulnificus NCIMB2137, a Gram-negative, metalloprotease negative estuarine strain was isolated from a diseased eel. A 45 kDa chymotrypsin-like alkaline serine protease known as VvsA has been recently reported as one of the major virulence factor responsible for the pathogenesis of this strain. The vvsA gene along with a downstream gene vvsB, whose function is still unknown constitute an operon designated as vvsAB. Objective: This study examines the contribution of VvsB to the functionality of VvsA. Method: In this study, VvsB was individually expressed using Rapid Translation System (RTS system), followed by an analysis of its role in regulating the serine protease activity of VvsA. Result: The proteolytic activity of VvsA increased upon the addition of purified VvsB to the culture supernatant of V. vulnificus. However, the attempts of protein expression using an E. coli system revealed a noteworthy observation that protein expression from the vvsA gene exhibited higher protease activity compared to that from the vvsAB gene within the cytoplasmic fraction. These findings suggest an intricate interplay between VvsB and VvsA, where VvsB potentially interacts with VvsA inside the bacterium and suppress the proteolytic activity. While outside the bacterial milieu, VvsB appears to stimulate the activation of inactive VvsA. Conclusion: The findings suggest that Vibrio vulnificus regulates VvsA activity through the action of VvsB, both intracellularly and extracellularly, to ensure its survival.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7832024Effect of Lipopolysaccharide on the Duration of Zolpidem-Induced Loss of Righting Reflex in Mice227235ENYudaiWadaDepartment of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroUshioDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshitoZamamiDepartment of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/67197Zolpidem, a non-benzodiazepine hypnotic, is primarily used to treat insomnia. In a previous study, pior treatment with non-benzodiazepine receptor agonists was associated with inflammation. The present study aimed to clarify the association between the effects of zolpidem and inflammation in mice treated with lipopolysaccharide (LPS), a known model of inflammation. We assessed the zolpidem-induced loss of righting reflex (LORR) duration 24 h after LPS treatment in mice. Additionally, the expressions of γ-aminobutyric acid (GABA)A receptor subunit and K+-Cl− cotransporter isoform 2 (KCC2) mRNA in the hippocampus and frontal cortex were examined in LPS-treated mice. Pretreatment with LPS was associated with significantly prolonged duration of zolpidem-induced LORR compared to control mice. This effect was significantly attenuated by administering bicuculline, a GABAA receptor antagonist, or flumazenil, a benzodiazepine receptor antagonist, in LPS-treated mice. Compared to controls, LPS-treated mice showed no significant change in the expression of GABAA receptor subunits in the hippocampus or frontal cortex. Bumetanide, an Na+-K+-2Cl− cotransporter isoform 1 blocker, attenuated the extended duration of zolpidem-induced LORR observed in LPS-treated mice. LPS significantly decreased Kcc2 mRNA expression in the hippocampus and the frontal cortex. These findings suggest that inflammation increases zolpidem-induced LORR, possibly through a reduction in KCC2 expression.No potential conflict of interest relevant to this article was reported.岡山大学教師教育開発センターActa Medica Okayama2186-1323142024現行いじめアンケートの妥当性と課題 ―教師の「いじめの深刻さ認識」を指標として―207221ENSenaMIYAGAWAGraduate School of Education，Okayama University (Master Degree Course)TazukoAOKIFaculty of Education，Okayama University10.18926/CTED/66782 いじめ早期発見を目的としたアンケートが全国で実施されているが，いじめの認知件数は減少していない。そこで，全国14都道府県のいじめアンケートを集計し，内容を分析した。加えて，このいじめアンケートが「いじめに該当する」としている行為に着目し，いじめ行為に対する，教師の「いじめに対する深刻さの認識」を調査した。その際，宮川・青木（2023）が示した「いじめの深刻度」に関する知見を用いた。分析の結果，教師は「やり返せる行為」よりも，「やり返せない行為」をより深刻と捉えていることがわかった。つまり，教師は「深刻と捉えられるべきいじめ行為」を深刻だと捉えており，現行いじめアンケートが「いじめに該当する」としている行為は妥当であると考えた。このことは，現行いじめアンケートでは早期発見が難しいことを示唆している。よって，早期発見と言うよりは，未然防止につながる新しいアンケートの開発の必要性について考察した。No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1368-83751422023EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma106433ENKokiUmemoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriEguchiDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyaNakamuraDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuoOgawaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKunihiroYoshidaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidekaKanemotoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiSatoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiRyumonDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokazuYutoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaokiKataseDepartment of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki UniversityTatsuoOkuiDepartment of Oral and Maxillofacial Surgery, Shimane University Faculty of MedicineHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjectives: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance.<br>
Materials and methods: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS).<br>
Results: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner.<br>
Conclusion: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama2504-284X82023Sustainable development goals in teacher education: comparing syllabi in a Japanese and a Slovenian university1215500ENKhalifatullohFiel'ardhGraduate School of Education, Okayama UniversityGregorTorkarFaculty of Education, University of LjubljanaHanaRožmanFaculty of Education, University of LjubljanaHirokiFujiiGraduate School of Education, Okayama UniversityIntroduction: This research aims to explore the integration of Sustainable Development Goals (SDGs) within teacher education programs, focusing on the Faculty of Education at Okayama University, Japan and the University of Ljubljana, Slovenia.<br>
Methods: We employed a qualitative content analysis of the syllabi (n = 2,079 from Okayama University; n = 504 from University of Ljubljana) and combined it with insights from semi-structured interviews.<br>
Results: The analysis illuminated a strong emphasis on Quality Education (SDG 4) in both institutions. However, certain SDGs, like Climate Action (SDG 13), were less represented, marking potential areas for enhancement. Differences were also identified in the distribution of SDGs-related content between compulsory and elective courses, indicating institutional priorities. Interview reflections emphasized the pivotal role of educators in realizing SDGs and highlighted the necessity of collaboration to achieve these global objectives.<br>
Discussion: The insights from interviews and syllabi content analysis underscore the urgency to bridge the identified gaps in SDG coverage. Disparities in emphasis between the two Education for Sustainable Development (ESD)-committed universities were noted, suggesting the importance of fostering strategy exchange and partnerships across institutions.<br>
Conclusion: Enhancing the alignment of teacher education programs with SDGs requires collective efforts. By addressing the gaps and promoting effective collaboration, these programs can achieve greater relevance and efficacy in promoting the SDGs.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1472-69392412023Radiation in an emergency situation: attempting to respect the patient's beliefs as reported by a minor80ENTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYasuhiroKoideDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiTsukaharaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground Each individual's unique health-related beliefs can greatly impact the patient-clinician relationship. When there is a conflict between the patient's preferences and recommended medical care, it can create a serious ethical dilemma, especially in an emergency setting, and dramatically alter this important relationship.<br>
Case presentation A 56-year-old man, who remained comatose after out-of-hospital cardiac arrest, was rushed to our hospital. The patient was scheduled for emergency coronary angiography when his adolescent daughter reported that she and her father held sincere beliefs against radiation exposure. We were concerned that she did not fully understand the potential consequences if her father did not receive the recommended treatment. A physician provided her with in depth information regarding the risks and benefits of the treatment. While we did not want to disregard her statement, we opted to save the patient's life due to concerns about the validity of her report.<br>
Conclusions Variations in beliefs regarding medical care force clinicians to incorporate patient beliefs into medical practice. However, an emergency may require a completely different approach. When faced with a patient in a life-threatening condition and unconscious, we should take action to prioritize saving their life, unless we are highly certain about the validity of their advance directives.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia395405ENMarkoPavlovicUniversity Hospital Center Mostar, University of MostarDraganBabicUniversity Hospital Center Mostar, University of MostarPejanaRastovicUniversity Hospital Center Mostar, University of MostarJuricaArapovicUniversity Hospital Center Mostar, University of MostarMarkoMartinacHealth Care Center Mostar, University of MostarSanjaJakovacUniversity Hospital Center Mostar, University of MostarRomanaBarbaricUniversity Hospital Center Mostar, University of MostarOriginal Article10.18926/AMO/65750We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=−0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=−0.258, t=−2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=−0.247, p=0.019) and antipsychotic treatment duration (ρ=−0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan387394ENTakahiroKataokaDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesHiroshiHabuDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyumiTanakaDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesShotaNaoeDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesKaitoMurakamiDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesYukiFujimotoDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesRyoheiYukimineDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesSoshiTakaoDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumihiroMitsunobuDepartment of Longevity and Social Medicine (Geriatrics), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiYorifujiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiyonoriYamaokaDepartment of Radiological Technology, Okayama University Graduate School of Health SciencesOriginal Article10.18926/AMO/65749No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis.No potential conflict of interest relevant to this article was reported.Japan Atherosclerosis SocietyActa Medica Okayama1340-347830122023Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)19271949ENToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatokoNaoeMedical Affairs Department, Mochida Pharmaceutical Co., Ltd.HiroyukiWakabayashiMedical Affairs Department, Mochida Pharmaceutical Co., Ltd.TakashiYanoMedical Affairs Department, Mochida Pharmaceutical Co., Ltd.TakuyaMoriClinical Research Department, Mochida Pharmaceutical Co., Ltd.ShingoKandaClinical Development Planning and Management Department, Mochida Pharmaceutical Co., Ltd.MakotoAritaLaboratory for Metabolomics, RIKEN Center for Integrative Medical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119.<br>
Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated.<br>
Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted.<br>
Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Changes in TRPV1 Receptor, CGRP, and BDNF Expression in Rat Dorsal Root Ganglion with Resiniferatoxin-Induced Neuropathic Pain: Modulation by Pulsed Radiofrequency Applied to the Sciatic Nerve359364ENTomohiroKoshidaDepartment of Anesthesiology and Pain Clinic, Faculty of Medicine, University of MiyazakiToyoakiMarutaDepartment of Anesthesiology and Pain Clinic, Faculty of Medicine, University of MiyazakiNobuhikoTanakaTanaka homecare clinicKotaroHidakaDepartment of Anesthesiology and Pain Clinic, Faculty of Medicine, University of MiyazakiMioKurogiDepartment of Anesthesiology and Pain Clinic, Faculty of Medicine, University of MiyazakiTakayukiNemotoDepartment of Pharmacology, Faculty of Medicine, Fukuoka UniversityToshihikoYanagitaDepartment of Clinical Pharmacology, School of Nursing, Faculty of Medicine, University of MiyazakiRyuTakeyaDepartment of Pharmacology, Faculty of Medicine, University of MiyazakiIsaoTsuneyoshiDepartment of Anesthesiology and Pain Clinic, Faculty of Medicine, University of MiyazakiOriginal Article10.18926/AMO/65741Pulsed radiofrequency (PRF) is a safe method of treating neuropathic pain by generating intermittent electric fields at the needle tip. Resiniferatoxin (RTX) is an ultrapotent agonist of transient receptor potential vanilloid subtype-1 (TRPV1) receptors. We investigated the mechanism of PRF using a rat model of RTX-induced neuropathic pain. After administering RTX intraperitoneally, PRF was applied to the right sciatic nerve. We observed the changes in TRPV1, calcitonin gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) in the dorsal root ganglia by western blotting. Expressions of TRPV1 and CGRP were significantly lower in the contralateral (RTX-treated, PRF-untreated) tissue than in control rats (p<0.0001 and p<0.0001, respectively) and the ipsilateral tissues (p<0.0001 and p<0.0001, respectively). BDNF levels were significantly higher in the contralateral tissues than in the control rats (p<0.0001) and the ipsilateral tissues (p<0.0001). These results suggest that, while TRPV1 and CGRP are decreased by RTX-induced neuronal damage, increased BDNF levels result in pain development. PRF may promote recovery from neuronal damage with concomitant restoration of TRPV1 and CGRP, and exert its analgesic effect by reversing BDNF increase. Further research is required to understand the role of TRPV1 and CGRP restoration in improving mechanical allodynia.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1059-13111072023Comprehensive study of metabolic changes induced by a ketogenic diet therapy using GC/MS- and LC/MS-based metabolomics5259ENMariAkiyamaDepartment of Child Neurology, Okayama University HospitalTomoyukiAkiyamaDepartment of Paediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeSaigusaTohoku Medical Megabank Organization, Tohoku UniversityEijiHishinumaTohoku Medical Megabank Organization, Tohoku UniversityNaomiMatsukawaTohoku Medical Megabank Organization, Tohoku UniversityTakashiShibataDepartment of Child Neurology, Okayama University HospitalHirokiTsuchiyaDepartment of Child Neurology, Okayama University HospitalAtsushiMoriDepartment of Neurology, Shiga Medical Centre for ChildrenYujiFujiiDepartment of Paediatrics, Hiroshima City Funairi Citizens HospitalYukikoMogamiDepartment of Paediatric Neurology, Osaka Women's and Children's HospitalChihoTokorodaniDepartment of Paediatrics, Kochi Health Sciences CentreKozueKuwaharaDepartment of Paediatrics, Ehime Prefectural Central Hospital,YurikaNumata-UematsuDepartment of Paediatrics, Tohoku University School of MedicineKenjiInoueDepartment of Neurology, Shiga Medical Centre for ChildrenKatsuhiroKobayashiDepartment of Paediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjective: The ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a subset of patients with drug-resistant epilepsy, although the mechanisms of the KD have not been fully elucidated. The aims of this observational study were to investigate comprehensive short-term metabolic changes induced by the KD and to explore candidate metabolites or pathways for potential new therapeutic targets.<br>
Methods: Subjects included patients with intractable epilepsy who had undergone the KD therapy (the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil). Plasma and urine samples were obtained before and at 2–4 weeks after initiation of the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS).<br>
Results: Samples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively. The KD increased ketone bodies, various fatty acids, lipids, and their conjugates. In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA, including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric acid and lactic acid, were elevated.<br>
Conclusions: The metabolites that were significantly changed after the initiation of the KD and related metabolites may be candidates for further studies for neuronal actions to develop new anti-seizure medications.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama2234-943X132023LOXL1 and LOXL4 are novel target genes of the Zn2+-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells1142886ENDaisukeHirabayashiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-ichiYamamotoDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroMaruyamaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYouyiChenDepartment of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical UniversityNi Luh Gede YoniKomalasariDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiMurataDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaGoharaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFanJiangDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJinZhouMedical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of TechnologyI. Made WinarsaRumaFaculty of Medicine, Udayana UniversityI. WayanSumardikaFaculty of Medicine, Udayana UniversityAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolFutoshiKuribayashiDepartment of Biochemistry, Kawasaki Medical SchoolShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: EMT has been proposed to be a crucial early event in cancer metastasis. EMT is rigidly regulated by the action of several EMT-core transcription factors, particularly ZEB1. We previously revealed an unusual role of ZEB1 in the S100A8/A9-mediated metastasis in breast cancer cells that expressed ZEB1 at a significant level and showed that the ZEB1 was activated on the MCAM-downstream pathway upon S100A8/A9 binding. ZEB1 is well known to require Zn2+ for its activation based on the presence of several Zn-finger motifs in the transcription factor. However, how Zn2+-binding works on the pleiotropic role of ZEB1 through cancer progression has not been fully elucidated. <br>
Methods: We established the engineered cells, MDA-MB-231 MutZEB1 (MDA-MutZEB1), that stably express MutZEB1 (Delta Zn). The cells were then evaluated in vitro for their invasion activities. Finally, an RNA-Seq analysis was performed to compare the gene alteration profiles of the established cells comprehensively. <br>
Results: MDA-MutZEB1 showed a significant loss of the EMT, ultimately stalling the invasion. Inclusive analysis of the transcription changes after the expression of MutZEB1 (Delta Zn) in MDA-MB-231 cells revealed the significant downregulation of LOX family genes, which are known to play a critical role in cancer metastasis. We found that LOXL1 and LOXL4 remarkably enhanced cancer invasiveness among the LOX family genes with altered expression. <br>
Conclusions: These findings indicate that ZEB1 potentiates Zn2+-mediated transcription of plural EMT-relevant factors, including LOXL1 and LOXL4, whose upregulation plays a critical role in the invasive dissemination of breast cancer cells.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1472-68312312023Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review90ENXiaotingChenDepartment of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ZulemaAriasDepartment of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University KazuhiroOmoriDepartment of Periodontics and Endodontics, Okayama University HospitalTadashiYamamotoDepartment of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiShinoda-ItoDepartment of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7662022Graphene Oxide-based Endodontic Sealer: An in Vitro Study715721ENMohammed Zahedul Islam NizamiDepartment of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMelahatGorduysusDepartment of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiShinoda-ItoDepartment of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiYamamotoDepartment of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYutaNishinaResearch Core for Interdisciplinary Sciences, Okayama UniversityShogoTakashibaResearch Core for Interdisciplinary Sciences, Okayama UniversityZulemaAriasDepartment of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOriginal Article10.18926/AMO/64122The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231802022Re-examining the Educational Significance of Learning Bodily Movement: An Approach Using the Concept of“ Affordance”6167ENToruTakahashiFaculty of Education, Okayama University10.18926/bgeou/63924This study aims to re-examine the educational significance of learning bodily movement. To realize this goal while considering the related discussions in the previous studies, a potential cue from the concept of affordance developed by Gibson is taken into account. Understanding bodily movement from a perspective related to the concept of affordance generates a notion that learning movement will serve as a proof of using affordances in the environment, which will eventually lead to more options in life in the sense of expanding the possibilities for action. Furthermore, the sense of expanding the possibilities for action is human development, which is something that lasts a lifetime. Simply put, learning movement in itself constitutes a foundation for enriching life and living better, and this further can be recognized as possessing educational significance.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7622022Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells203215ENTomoyaMasudaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuuriHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiIedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoUrataOncolys BioPharma Inc.ShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/63425The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression.No potential conflict of interest relevant to this article was reported.ELSEVIERActa Medica Okayama2215-016182021Production of TRPM4 knockout cell line using rat cardiomyocyte H9c2101404ENChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakazuMaedaDepartment of Medicine, Okayama UniversityJianChenDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesThe method presented in this article are related to the research article entitled as "Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress" [1]. TRPM4, a non-selective monovalent cation channel, is not only involved in the generation of the action potential in cardiomyocytes, but also thought to be a key molecule in the development of the ischemia-reperfusion injury of the brain and the heart [2-5]. However, existing pharmacological inhibitors for the TRPM4 channel have problems of non-specificity [6]. This article describes methods used for targeted genomic deletion in the rat cardiomyocyte H9c2 using the CRISPR-Cas9 genome editing system in order to suppress TRPM4 protein expression. Confocal microscopy, flow cytometry, Sanger sequencing, and western blotting are performed to confirm vector transfection and the subsequent knockout of the TRPM4 protein. These data provide information on the comprehensive analyses for knocking out the rat TRPM4 channel using CRISPR/Cas9. The analyses include confocal microscopy, flow cytometry, Sanger sequencing, and western blotting. This dataset will benefit biological and medical researchers studying the function of TRPM4-expressing cells including neurons, cardiomyocytes, and vascular endothelial cells. It is also useful to study the involvement of the TRPM4 channel in pathological processes such as cardiac arrhythmia and ischemia-reperfusion injury. The dataset can be used to guide the experiment of knocking out the TRPM4 gene and its subsequent application to the study of disease process caused by the gene. No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7552021Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease549556ENNamiIsookaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/62767Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells.No potential conflict of interest relevant to this article was reported.Sage Publications LtdActa Medica Okayama1179-5476142021Urinary Retention as the Presenting Clinical Manifestation of Unstable Thoracic Spinal Fracture with Diffuse Idiopathic Skeletal Hyperostosis13ENHisashiHamaguchiDepartment of Emergency Medicine, Kasaoka Daiichi HospitalTetsuyaYumotoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroMaeDepartment of Emergency Medicine, Kasaoka Daiichi HospitalAyumuTakeshitaDepartment of Orthopedic Surgery, Kasaoka Daiichi HospitalMinaeAoyamaDepartment of Orthopedic Surgery, Fukuyama City HospitalKeiyaYamanaDepartment of Orthopedic Surgery, Fukuyama City HospitalAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPatients with diffuse idiopathic skeletal hyperostosis (DISH) are at high risk for unstable vertebral fracture, which can be frequently missed. An 80-year-old man with pre-existing muscle lower limb weakness due to frailty was referred from another hospital, presenting with progressive urinary retention and its related symptoms, which had been treated as a urinary tract infection at previous hospital. One week prior to our visit, he had fallen. On arrival, he appeared lethargic and unable to follow commands. He denied any back pain. Computed tomography identified a T10 fracture and dislocation associated with DISH. Although immediate surgical fixation was performed, the patient did not recover from the neurological deficits. Diagnostic delay of DISH-associated vertebral fracture can occur due to both patients' and clinicians' delayed action. We believe this case report can help clinicians recognize this potentially devastating condition.No potential conflict of interest relevant to this article was reported.National Library of MedicineActa Medica Okayama2470-3524712021Photoelectric dye-based retinal prosthesis (OUReP) as a novel type of artificial retinaENToshihikoMatsuoOphthalmology, Okayama University HospitalTetsuyaUchidaolymer Materials Science, Okayama University Graduate School of Natural Science and Technology,We have developed the world's first novel type of artificial retina, OUReP (Okayama University Retinal Prosthesis), in which a photoelectric dye that converts light energy into electric potential is covalently bonded to the surface of a polyethylene thin film as an insulator. The receptor that absorbs light and the output device that generates displacement current to stimulate nearby neurons are integrated in a sheet of thin film. It has become possible to measure the surface potential of the artificial retina OUReP using a Kelvin probe that measures the surface potential of semiconductors. When light is turned on and off to the artificial retina OUReP, the surface potential changes rapidly. As the light intensity is increased, the potential change on the surface of the artificial retina becomes larger. As for safety, the artificial retina OUReP was not toxic in all tests for biological evaluation of medical devices. As for efficacy, the artificial retina OUReP was implanted under the retina by vitreous surgery in monkey eyes which had chemically-induced macular degeneration with photoreceptor cell loss. Over the next 6 months, retinal detachment did not occur during the course, and the artificial retina was in contact with the retinal tissue. The amplitude of the visual evoked potential attenuated by macular degeneration recovered 1 month after implantation of the artificial retina, and the recovery of amplitude was maintained until 6 months after the implantation. By using multielectrode array-mounted dish recording system, it has been proved that action potential spikes are induced when the artificial retina is placed on degenerative retinal tissue of retinal dystrophic rats or mice and exposed to light, which is used as an index of the effectiveness of the artificial retina. We have established manufacturing and quality control of the device in a clean room facility, proved the safety and efficacy, and are preparing for first-in-human investigator-initiated clinical trials.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7452020Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients381389ENKoichiroYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaHanayamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKouHasegawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMiyoshiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokoOgawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikakoObikaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiItoshimaDepartment of Laboratory Medicine, Okayama University HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/60797To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (≥ 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=−0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-291X53132020High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4422430ENYumiSakamotoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTatsuoOkuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceToshiyukiYonedaDepartment of Cellular and Molecular Biochemistry, Osaka University Graduate School of DentistryShojiRyumonDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTomoyaNakamuraDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiKunisadaDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasanoriMasuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKishoOnoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKyoichiObataDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTsuyoshiShimoDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoAkiraSasakiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceBone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7442020Immobility-reducing Effects of Ketamine during the Forced Swim Test on 5-HT1A Receptor Activity in the Medial Prefrontal Cortex in an Intractable Depression Model301306ENKeiTakahashiDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroUshioDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/60368Ketamine has been clinically proven to ameliorate depression, including treatment-resistant depression. The detailed mechanism of action of ketamine in treatment-resistant depression remains unclear. We examined the effects of ketamine on the immobility times of adrenocorticotropic hormone (ACTH)-treated rats during the forced swim test, and we explored the mechanism by which ketamine acts in this model. We investigated the neuroanatomical site of action by microinjecting ketamine into the medial prefrontal cortex of rats. A significant reduction of the rats’ immobility during the forced swim test was observed after the intraperitoneal injection of ketamine in both saline- and ACTH-treated rats. The microinjection of ketamine into the medial prefrontal cortex also decreased immobility during the forced swim test in both saline- and ACTH-treated rats. The immobility-decreasing effect of intraperitoneally injected ketamine was blocked by administering WAY100635, a 5-HT1A receptor antagonist, into the medial prefrontal cortex. These findings contribute to the evidence that ketamine can be useful against treatment-resistant depressive conditions. The immobility-reducing effects of ketamine might be mediated by 5-HT1A receptor activity in the medial prefrontal cortex.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7432020Stem Cell Therapy in Heart Disease: Limitations and Future Possibilities185190ENToshikazuSanoDepartment of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San FranciscoShutaIshigamiDepartment of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San FranciscoTatsuoItoDepartment of Hygiene, Kawasaki Medical UniversityShunjiSanoDepartment of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San FranciscoReview10.18926/AMO/59948Heart diseases are one of the major causes of morbidity and mortality worldwide. Despite major advances in drug and interventional therapies, surgical procedures, and organ transplantation, further research into new therapeutic options is still necessary. Stem cell therapy has emerged as one option for the treatment of a variety of heart diseases. Although a large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach, the results obtained from these clinical studies are inconsistent, and stem cell-based improvements of heart performance and cardiac remodeling were found to be quite limited. Since the precise mechanisms underlying the therapeutic actions of stem cells are still under debate, researchers have developed a variety of strategies to improve and boost the potency of stem cells in repair. In this review, we summarize both the current therapeutic strategies using stem cells and future directions for enhancing stem cell potency.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1567-5769832020The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1106429ENSakiNakagawaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOmoriDepartment of Periodontics and Endodontics, Okayama University HospitalMasaakiNakayamaDepartment of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Medical Technology, School of Health Science, Gifu University of Medical ScienceSatoshiYamamotoDepartment of Periodontics and Endodontics, Okayama University HospitalHiroyaKobayashiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitHidefumiSakoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyosukeSakaidaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiYoshimuraivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySatokiIshiiDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySoichiroIbaragiDepartment of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKimitoHiraiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeYamashiroDepartment of Periodontics and Endodontics, Okayama University HospitalTadashiYamamotoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1420-304924132019Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities2495ENMaram HusseinZahraDivision of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityTarek A. R.SalemDepartment of Biochemistry, College of Medicine, Qassim UniversityBishoyEl-AaragDivision of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityNermeenYosriDepartment of Chemistry, Faculty of Science, Menoufia UniversitySamahEL-GhlbanBiochemistry Division, Chemistry Department, Faculty of Science, Menoufia UniversityKholoudZakiDepartment of Chemistry, Faculty of Science, Menoufia UniversityAmel H.MareiDepartment of Chemistry, Faculty of Science, Menoufia UniversityAidaAbd El-WahedDepartment of Chemistry, Faculty of Science, Menoufia UniversityAamerSaeedDepartment of Chemistry, Quaid-i-Azam UniversityAlfiKhatibDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University MalaysiaMohamed F.AlAjmiPharmacognosy Group, College of Pharmacy, King Saud UniversityAbdulrahman M.ShathiliAl-Rayan Research and Innovation Center, Al-Rayan CollegesJianboXiaoInstitute of Chinese Medical Sciences, University of MacauShaden A. M.KhalifaClinical Research Centre, Karolinska University HospitalHesham R.El-SeediDepartment of Chemistry, Faculty of Science, Menoufia UniversityBACKGROUND/AIM:Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers.<br/>
METHODS:The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.<br/>
RESULTS:A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.<br/>
CONCLUSION:Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7352019The Role of High Mobility Group Box-1 in Epileptogenesis383386ENLiFuDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroNishiboriDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/57367 High mobility group box-1 (HMGB1) is a non-histone, DNA-binding nuclear protein belonging to the family of damage-associated molecular patterns (DAMPs). HMGB1 has been reported to play an important role during epileptogenesis although the mechanisms of its actions are still not clear. Many hypotheses have been suggested especially about the relationship between HMGB1 and inflammation responses and blood-brain barrier disruption during epileptogenesis. In this review, we will mainly discuss the role of HMGB1 in epileptogenesis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama222541102019Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actionsEN Mohamed E.AbouelelaDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Mohamed A.A.OrabiDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Reda A.AbdelhamidDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Mohamed S.AbdelkaderDepartment of Pharmacognosy, Faculty of Pharmacy, Sohag University Hafez R.MadkorDepartment of Biochemistry, Faculty of Pharmacy, Al-Azhar University Faten M.M.DarwishDepartment of Pharmacognosy, Faculty of Pharmacy, Assiut University TsutomuHatanoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bakheet E.M.ElsadekDepartment of Biochemistry, Faculty of Pharmacy, Al-Azhar University Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TaxonomyFunctional Disorder, Traditional Medicine, Herbal Medicine.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7342019Dynamic Reorganization of Microtubule and Glioma Invasion285297ENYoshihiroOtaniDepartment of Neurosurgery, The University of Texas Health Science Center at HoustonTomotsuguIchikawaDepartment of Neurosurgery, Kagawa Prefectural Central HospitalKazuhikoKurozumiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/56930 Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion.No potential conflict of interest relevant to this article was reported.Mary Ann LiebertActa Medica Okayama193733412519-202019A reporter system evaluates tumorigenesis, metastasis, β-catenin/MMP regulation, and druggability14131425ENChiharuSogawaDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriEguchiDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukaOkushaDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazumiOhyamaDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoharuIizukaResearch program for undergraduate students, Okayama University Dental SchoolRyuKawasakiResearch program for undergraduate students, Okayama University Dental SchoolYusakuHamadaResearch program for undergraduate students, Okayama University Dental SchoolMasaharuTakigawaAdvanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNorioSogawaDepartment of Dental Pharmacology, Matsumoto Dental UniversityKuniakiOkamotoDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKen-ichiKozaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cancer invasion, metastasis, and therapy resistance are the crucial phenomena in cancer malignancy. The high-expression of matrix metalloproteinase 9 (MMP9) is a biomarker as well as a causal factor of cancer invasiveness and metastatic activity. However, a regulatory mechanism underlying MMP9 expression in cancer is not clarified yet. Additionally, a new strategy for anti-cancer drug discovery is becoming an important clue. In the present study, we aimed (i) to develop a novel reporter system evaluating tumorigenesis, invasiveness, metastasis, and druggability with a combination of three-dimensional (3D) tumoroid model and Mmp9 promoter and (ii) to examine pharmacological actions of anti-cancer medications using this reporter system. High expression and genetic amplification of MMP9 were found in colon cancer cases. We found that proximal promoter sequences of MMP9 in murine and human contained conserved binding sites for transcription factors β-catenin/TCF/LEF, glucocorticoid receptor (GR), and NF-κB. The murine Mmp9 promoter (-569 to +19) was markedly activated in metastatic colon cancer cells and additionally activated by tumoroid formation and by β-catenin signaling stimulator lithium chloride (LiCl). The Mmp9 promoter-driven fluorescent reporter cells enabled the monitoring of activities of MMP9/gelatinase, tumorigenesis, invasion, and metastasis in allogeneic/syngenic transplantation experiments. We also demonstrated pharmacological actions as follows. ids Dexamethasone and hydrocortisone, steroidal medications binding to GR, inhibited the Mmp9 promoter but did not inhibit tumorigenesis. On the other hand, an antimetabolite 5-fluorouracil, a golden standard for colon cancer chemotherapy, inhibited tumoroid formation but did not inhibit Mmp9 promoter activity. Notably, anti-malaria medication artesunate inhibited both tumorigenesis and the Mmp9 promoter in vitro, potentially through inhibition of β-catenin/TCF/LEF signaling. Thus, this novel reporter system enabled monitoring tumorigenesis, invasiveness, metastasis, key regulatory signalings such as β-catenin/MMP9 axis, and druggability.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7312019Histidine-rich Glycoprotein Could Be an Early Predictor of Vasospasm after Aneurysmal Subarachnoid Hemorrhage2939ENAtsushiMatsumotoDepartment of Neurological Surgery, Kagawa University Faculty of MedicineTakehiroNakamuraDepartment of Medical Technology, Kagawa Prefectural University of Health SciencesAyaShinomiyaDepartment of Neurological Surgery, Kagawa University Faculty of MedicineKenyaKawakitaEmergency Medical Center, Kagawa University HospitalMasahikoKawanishiDepartment of Neurological Surgery, Kagawa University Faculty of MedicineKeisukeMiyakeDepartment of Neurological Surgery, Kagawa University Faculty of MedicineYasuhiroKurodaEmergency Medical Center, Kagawa University HospitalRichard F.KeepDepartment of Neurosurgery, University of MichiganTakashiTamiyaDepartment of Neurological Surgery, Kagawa University Faculty of MedicineOriginal Article10.18926/AMO/56456 Cerebral vasospasm (CVS) is a major contributor to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. We measured histidine-rich glycoprotein (HRG), a new biomarker of aSAH, in cerebrospinal fluid (CSF) to investigate whether HRG might be an early predictor of CVS. A total of seven controls and 14 aSAH patients (8 males, 6 females aged 53.4±15.4 years) were enrolled, and serial CSF and serum samples were taken. We allocated these samples to three phases (T1-T3) and measured HRG, interleukin (IL)-6, fibrinopeptide A (FpA), and 8-hydroxy-2’-deoxyguanosine (8OHdG) in the CSF, and the HRG in serum. We also examined the release of HRG in rat blood incubated in artificial CSF. In contrast to the other biomarkers examined, the change in the CSF HRG concentration was significantly different between the nonspasm and spasm groups (p<0.01). The rat blood/CSF model revealed a time course similar to that of the human CSF samples in the non-spasm group. HRG thus appears to have the potential to become an early predictor of CVS. In addition, the interaction of HRG with IL-6, FpA, and 8OHdG may form the pathology of CVS.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7262018Difference between the Right and Left Phrenic Nerve Conduction Times, Latency, and Amplitude563566ENYoshimiKatayamaDepartment of Rehabilitation Medicine, Okayama University HospitalMasuoSendaDepartment of Rehabilitation Medicine, Okayama University HospitalDaisukeKanedaDepartment of Rehabilitation Medicine, Okayama University HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/56373 We studied phrenic nerve conduction times in 90 phrenic nerves of 45 normal subjects. The phrenic nerve was stimulated at the posterior border of the sternomastoid muscle in the supraclavicular fossa, just above the clavicle, with bipolar surface electrodes. For recording, positive and negative electrodes were placed on the xiphoid process and at the eighth intercostal bone-cartilage transition, respectively. We studied both the right and left sides to determine whether there was any difference between the two sides. The mean onset latency (± SD) of the right compound muscle action potentials (CMAPs) (5.99±0.39 msec) was significantly shorter than that of the left CMAPs (6.45±0.50 msec). The mean peak latency was significantly shorter in the right CMAPs (10.22±1.33 msec) than the left CMAPs (12.48±2.02 msec). The mean (± SD) amplitude was significantly lower in the left CMAPs (0.42±0.11 mV) than the right CMAPs (0.49±0.10 mV). The difference between the length of the nerve on the right and left sides might have affected the difference in latency between the two sides.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014てんかん治療ガイドラインについて5558ENNobutoshiMorimotoKojiAbeNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014糖尿病の腎臓においてcholecystokininはマクロファージに対する抗炎症作用を介した新規の保護効果を発揮する16ENSatoshiMiyamotoKenichiShikataKyokoMiyasakaShinichiOkadaMotofumiSasakiRyoKoderaDaishoHirotaNobuoKajitaniTetsuharuTakatsukaHitomiKataoka UsuiShingoNishishitaChikageHoriguchi SatoAkihiroFunakoshiHisakazuNishimoriHaruhito AdamUchidaDaisukeOgawaHirofumiMakinoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812412012ニガウリ抽出物の血糖降下作用に関する文献的考察1526ENMitsumasaMankuraYasukoNodaAkitaneMoriDiabetes mellitus (DM) represents a global health and economical problem. Many patients with DM in Asia, South America, India and East Africa have traditionally used the water extract of unripe fruits of Momordica charantia (bitter melon) as some form of complementary and alternative medicine. Studies of laboratory animals have shown the beneficial blood-glucose lowering and anti-diabetic effects of this remedy. Some oral components that bring lower blood glucose level have been isolated : charantin (sterol glycosides), charantin (polypeptide) and cucurbine-type triterpenes. Part of their actions are related to AMP-activated kinase and repression of the oxidative stress that is increased in DM. Most clinical reports are not fully convincing due to the lack of randomized control studies. The present article reviews the pharmacological and clinical effects of bitter melon with special emphasis on the anti-diabetic effects, and some effects that would require caution in the context of human trials.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812412012ランビエ絞輪周囲のECMによるdiffusion barrier形成と跳躍伝導における役割14ENYokoBekkuYoshifumiNinomiyaToshitakaOohashiNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558333721921ELECTRIC CHARGES OF THE RED BLOOD CORPUSCLES134ENK.KosakaM.Seki1. It is stated that the erythrocytes show a different cataphoresis in the same solution according to the species of the animals and the erythrocytes of the same animal in two different solutions. 2. The erythrocytes of the rabbit possess in 0,9% NaCl solution a positive charge unlike those of the other animals, while they are charged in the isotonic sugar solution most negatively charged. 3. The cataphoresis of the erythrocytes was observed under the microscope not only in the NaCl solution but in many other salt solutions. 4. The statement follows how the cataphoretic phenomena which the erythrocytes show in the isotonic solution of NaCl or cane-sugar are modified by the addition of several reagents. 5. A test is made showing the change of pH of different solutions after the addition of the erythrocytes. 6. It is demonstrated that some Cl-ions in solutions of NaCl or KCl are taken by the erythrocytes which in turn give off some HCO3-ions. 7. Of all the animals the efficiency of the erythrocytes to raise pH of some salt solutions, especially of acid salt solutions is the greatest in the rabbit and the least in the dog as far as they were examined. 8. On the other hand the erythrocytes of the rabbit have a weaker efficacy to neutralize an alkaline solution than those of the dog, guinea-pig or goat. 9. While the erythrocytes absorb some Cl-ions in an acid salt solution, they release these in an alkaline salt solution. 10. The strong efficiency of the rabbit erythrocytes to raise pH of some solutions is an important factor, the explanation, perhaps, being that they possess a positive charge in the salt solution unlike those of almost all other animals. Likewise the fact that the erythrocytes of the dog have a strong negative charge in the salt solution seems to bear upon their weak efficacy to neutralize an acid solution. 11. In order to explain the cataphoresis of the erythrocytes in the sugarsolution a hypothesis is offered concerning the permeability of the membrane of the erythrocytes. If the erythrocytes of the rabbit are thrown into a sugar solution which contains no electrolytes, there would occur a condensation of the cell membrane, so that it would hinder the passage of some anions, while the diffusion of cations goes on unaffected. On the other hand the permeability of the erythrocytes of the dog and cat seems to remain almost unchanged in the sugar solution as well as in the salt solution. For this reason the erythrocytes of the rabbit become in the sugar-solution strongly negatively charged, while those of the dog and cat remain weakly negatively charged. 12. Such solutions as 3,0% glycerine, 5,0% d-glucose, 5,0% laevulose, 9,5 % lactose and 2,0% glycocoll have the same effect as that of 9,5% canesugar solution on the cataphoresis of the erythrocytes. 13. The erythrocytes of the rabbit which have a strong power to neutralize an acid solution and are slightly positively charged in 0,9% NaCl solution resist the haemolytic effect of the acid more obstinately than those of other animals. On the contrary the crythrocytes of the goat which show a strong negative potential in 0,9% NaCl solution are most liable to the haemolysis caused by the acid. Generally speaking it seems probable that erythrocytes which are strongly negatively charged in the NaCl solution dissolve in an acid solution more easily than those weakly charged. 14. But in a solution of reserve acidity in which some substance acts as "buffer" the erythrocytes of the rabbit are most liable to haemolysis, while those of the goat and dog show a great resistance at least during the first few hours. 15. The erythrocytes of the dog are most easily dissolved in the alkaline solution. With this special exception, the erythrocytes of the rabbit are most liable to haemolysis and those of the goat and rat show the greatest resistance when they are thrown into the solution. Generally speaking it seems probable, that less negatively charged erythrocytes in the NaCl solution are more liable to the haemolytic effect of the base, the case of the dog being excluded. 16. Those elements which possess lower solution pressures than hydrogen have generally a strong power to dissolve or destroy the erythrocytes, and less negatively charged erythrocytes seem to be more liable to haemolysis in solutions of the copper, mercury, silver, gold or platinum compounds. 17. Those elements which possess higher solution pressures than hydrogen have generally only a weak haemolytic effect or none at all, but the trivalent cations Fe(…) and Al(…) are powerful in causing haemolysis, their effect resembling that of the acid. 18. The haemolytic effect of saponin, natrium oleat and alcohol has no bearing on the electric charge of the erythrocytes and seems to be chiefly concerned with the action to dissolve the lipoid. 19. Likewise the haemolysis caused by hypotonic solutions has no relation to the electric charge of the erythrocytes.20. The resistance of the erythrocytes towards hypotonic NaCl solutions is increased by the effect of the alkali and decreased by that of the acid (HAMBURGER). This change is seen very markedly in the goat erythrocytes which have a strong negative potential, while the positively charged erythrocytes of the rabbit in such cases show very little or no change at all. 21. The haemolytic serum has a power to neutralize the charge of the erythrocytes. This action must be attributed to either the amboceptor or agglutinin, the complement having surely nothing to do with it. An experiment on the goat erythrocytes gave a result, which seems to suggest, that the amboceptor acts upon the erythrocytes more effectually than the agglutinin, as far as the electric charge is concerned.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812332011生活習慣病治療のパラダイムシフト―慢性炎症を標的とした治療戦略―197206ENKenichiShikataNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812312011アンフィファイジンとN-WASPのダイナミックな相互作用は，アクチン重合を制御する111ENHiroshiYamadaSergiPadilla-ParraSun JooParkToshikiItohMathildeChaineauIlariaMonaldiOttavioCremonaFabioBenfenatiPietro DeCamilliMaïtéCoppey-MoisanMarcTramierThierryGalliKohjiTakeiNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558673-41955興奮伝播性と圧効果 第一編 筋肉收縮の伝播性と圧効果に就て（其の一）655666ENG.NagaoBy means of the isolated chamber method after Sugi the propagation of the excitation and by routine method action potential were examined at compressed muscle. Following results are obtained; 1) Muscle contraction evoked by high hydrostatic pressure does not propagate along muscle fiber. 2) When muscle is immersed into solution in which the muscle reacts to pressurestimulation more sensitively but to electric stimulation less sensitively, its contraction does not propagate. 3) In case of the compression contraction no action current appears. 4) Muscle tissue becomes less acid by pressure contraction than by tetanic contraction.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155869101957発育電位時間曲線によるチフス菌代謝の研究 第2編 各基質における酵素促進剤及び阻害剤の電位に及ぼす影響26152630ENKazuoAkitaIn the present part, the influence of various enzyme-activators and -inhibitors on oxidation-reduction potential was studied. The salt solution (pH 7.2) was used as the fundamental culture medium; Salmonella typhi 57 S as the test organism. The results were as follows: 1) In the medium of glucose or pyruvate Mg(++) of the concentration over 10(-4)M accelerated the fall of potential. 2) 10(-2)M KCN inhibited the fall of potential in the media of all the substrates tested, whereas 10(-3)M inhibited it in those of the substrates other than pyruvate, succinate, aspartate and alanine, and 10(-4) M inhibited only in that of lactate. 3) NaF of the concentrations over 10(-3) M inhibited the fall of potential in the media of the substrates other than lactate, acetate and succinate. 10(-1) M NaF, however, showed some inhibition even in that of succinate. 4) NaN(3) of all concentrations inhibited the fall of potential in the media of all the substrates other than lactate, acetate and succinate. However, 10(-1)M in the medium of lactate, 10(-3) M in that of acetate, 10(-2) M in that of succinate inhibited the fall of potential. 5) Monoiodoacetic acid of the concentrations over 10(-3) M inhibited the fall of potential in the medium of lactate, that over 10(-4) M inhibited it in that of succinate. 6) 2, 4-Dinitrophenol of all the concentrations tested inhibited the fall of potential in the media of all the substrates tested. 7) The inhibitive action of these five sorts of inhibitors to the fall of potential resembled their action to the oxygen consumption of Salmonella typhi.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15586921957表面電極筋電図の周波数スペクトルに関する基礎的研究401411ENShuzoOkumuraIn recent years, the clinical application of electromyogram has advanced extremely. But this clinical electromyogram is located principally on the single unit electromyogram by the co-axial needle electrode. Accordingly the author has undertaken a basic study in order to clarify the clinical value of the electromyogram by the skin surface electrode. Then, for a portion of this study, the frequency spectrum of the surface electrode electromyogram had been examined by Fouriers integration analysis. (1) The pattern of the surface electrode electromyogram had been examined by function theory, and explained its meaning of the frequency sqectrum of the surface electrode electromyogram by Fouriers analysis from next stand point. Standing in this point, next theory should be recognized; the electromyogram can not mean the direct record of an action potential of a muscle fiber or a muscle fascicle, and electromyogram includes in it necessarily the variation of charactristics of the electrofield, viz. an organism (expressed as volum conductor), and the charactristics of amplifier and recorder. Those charactristics are expressed by number of coefficients by frequency. (2) The frequency spectrum of the surface electrode electromyogram fluctuates by the method of pick-up, acting state of a muscle, individuarity and etc. (3) At standerd state this frequency spectrum mainly distributes from 10c. (cycle per second) to 600c., and essential parts of this spectrum distributes from 20c. to 70c. (4) The study on the origin of those fluctuation will be explained in the next part.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15587112-21959Verdohemochromeの生成とその性状に関する研究 第1編 Pyridine hemin-Hydrazine-O(2)反応系によるVerdohemochromeの生成に関する分光化学的研究83258336ENShigeoKatamiThe influence to the formation of verdohemochrme was spectrochemically observed on the action of hydrazine sulphate and oxygen to pyridine hemin in various changes of the reacting condition and the formation process of the product with the absorption maximum at 630 mμ was spectrochemically observed on the action of hydrogen peroxide and hydrazine sulphate to pyridine hemin under the airless condition. And the results were as follows. 1. In this reaction system, the influence of pH was great, the formation dosis of verdohemochrome was low on the high pH-value of reaction solution, the reaction was slow and the formation dosis of verdohemochrome was declined on the pH-value around 7.0, and it was decided that the pH-value at 8.5-8.0 was the most suitable. 2. The pyridine concentraticn was the most suitable in 20% of absolute concentration, the reacting process was not good below 20% and the decomposition of verdohemochrome was promoted on the over dosis. 3. There was the correlation between the hemin concentration and hydrazine concentration, the most proper concentration rate was needed and the dosis of hydrazine sulphate was needed in 10 or 25 times' Mol. concentration of hemin dosis. 4. The most proper concentration of hemin was 20mg/dl, when the concentration of hydrazine sulphate was made to be the most proper concentration rate to the hemin concentration. 5. In the reaction using hydrazine sulphate, the shaking of flask at 50°C was necessary and it was more slow in comparison with the reaction using ascorbic acid. 6. The formation of the product with the absorption maximum at 630 mμ was certified in the pyridine hemin-hydrazine-H(2)O(2) reaction system and the absorption maximum was easily shifted to 650mμ on the aeration of oxygen to the above product. 7. In this reaction system, it persevered the absorption of pyridine hemichrome, and the absorption picture of pyridine hemochrome was observed on the progression of the pyridine hemin-hydrazine-H(2)O(2) reaction system under the airless condition. 8. Since the above results, it was understood that the oxydation-reduction potential in the hydrazine reaction system was much different in comparison with that of the 1-ascorbic acid reaction system.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558719-21959心筋に及ぼす高圧の影響 その1 摘出蛙心に対する高圧の影響58495855ENHirosiYasudaWhen high hydrostatic pressure was applied to isolated frog heart, following changes were observed on the cardiac action: 1) At relatively low pressure, heart rate increased, but at moderate high pressure, it decreased. 2) There occurred no change of conduction time, namely P-Q interval. 3) Upon appling pressure, the amplitude of action potential of ventricle muscle, i.e. the height of R wave augumented.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama42004Active link mechanisms for physical man-machine interaction38953900ENJumpeiOchiTatsuyaHashimotoKoichiSuzumoriTakefumiKanda<p><p>In this paper, we propose a new type of haptic interface, named active link mechanism. This device realizes physical man-machine interaction (PMI) between machines and persons. Two prototypes were developed to demonstrate the potential of the active link mechanisms. Developed interface devices are an active tetrahedron and an active icosahedron. Nine-DOF micro spherical joints and pressure control pneumatic cylinders were developed to realize the active tetrahedron, while fifteen-DOF micro spherical joints and intelligent pneumatic cylinders were developed for the active icosahedron. The tetrahedron successfully realizes "virtual touch"; the operators feel actions, forces, and shapes of the virtual objects in PC and also move and deform them. Real time PMI is realized by building the developed devices into MSC.Visual-Nastran4D. MSC.VisuaI-Nastran4D is a mechanism analysis software, which can make motion analysis in real time. The active icosahedron also realized dynamic interaction with virtual objects in PC, showing the potential of the devices as a haptic interface.</p></p>
No potential conflict of interest relevant to this article was reported.Acta Medica Okayama42004Active link mechanisms for physical man-machine interaction38953900ENJ.OchiTatsuyaHashimotoKoichiSuzumoriJ.TanakaTakefumiKanda<p>In this paper, we propose a new type of haptic interface, named active link mechanism. This device realizes physical man-machine interaction (PMI) between machines and persons. Two prototypes were developed to demonstrate the potential of the active link mechanisms. Developed interface devices are an active tetrahedron and an active icosahedron. Nine-DOF micro spherical joints and pressure control pneumatic cylinders were developed to realize the active tetrahedron, while fifteen-DOF micro spherical joints and intelligent pneumatic cylinders were developed for the active icosahedron. The tetrahedron successfully realizes "virtual touch"; the operators feel actions, forces, and shapes of the virtual objects in PC and also move and deform them. Real time PMI is realized by building the developed devices into MSC.Visual-Nastran4D. MSC.VisuaI-Nastran4D is a mechanism analysis software, which can make motion analysis in real time. The active icosahedron also realized dynamic interaction with virtual objects in PC, showing the potential of the devices as a haptic interface. </p>
No potential conflict of interest relevant to this article was reported.The Company of Biologists LimitedActa Medica Okayama0022-094920462001Reproductive behaviour in the male cricket Gryllus bimaculatus DeGEER: II. Neural control of the genitalia11391152ENMikihikoKumashiroMasakiSakaiTo understand the neural mechanisms of reproductive behaviour in the male cricket, we identified motor neurones innervating the muscles in each genital organ by backfilling
with cobalt/nickel and recording their extracellular spike activity from nerve bundles of the terminal abdominal ganglion during tethered copulation and spermatophore formation. During tethered copulation, at least two
motor neurones innervating two ipsilateral muscles were activated during projection of the guiding rod of the phallic dorsal pouch. Only one motor neurone, innervating four ipsilateral muscles of the dorsal pouch, was responsible for
spermatophore extrusion by deforming the dorsal pouch. For spermatophore transfer, three motor neurones, singly innervating three epiphallus muscles, played a major role in opening passages for haemolymph to enter the ventral lobes and median pouch by bending the epiphallus. Two
ventral lobe and 3–5 median pouch motor neurones seemed to play a role in expanding or folding the two membranous structures by relaxing or contracting their muscle fibres. After spermatophore transfer, most of the genital motor
neurones exhibited a rhythmic burst of action potentials causing movement of the phallic complex coupled with strong abdominal contractions. For spermatophore formation, the genital motor neurones began to accelerate
their rhythmic bursts approximately 30 s prior to
subgenital plate opening and then changed their activity to tonic bursting or silence. The results have allowed us to describe the timing of the onset and termination of genital muscle contraction more precisely than before, to examine the neural mechanisms of copulatory motor control and to speculate on the neural organization of the reproductive centre for spermatophore extrusion and protrusion.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama4062004Effects of demethylating agent 5-aza-2 '-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines 597603ENJunMurakamiJun-ichiAsaumiYuuMakiHidetsuguTsujigiwaMasahiroKurodaNoriyukiNagaiYoshinobuYanagiTetsuyoshiInoueShojiKawasakiNoriakiTanakaNagahideMatsubaraKanjiKishi<p>Maspin, which belongs to the serine protease inhibitor (serpin) superfamily, has been proposed as a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis. In the present study, we examined the effects of 5-aza-2'-deoxycytidine (5-aza-dC), a demethylating agent, and FR901228, a histone deacetylase (HDAC) inhibitor, on maspin expression in oral cancer cell tines. The expression levels of maspin mRNA were divided into two groups, which was the maspin tow-expressed and high-expressed cell lines in the 12 oral cancer cell lines. The maspin promoter contained only a few methylated CpG sites in the maspin low-expressed cell lines. Moreover, the methylation status was not altered after 5-aza-dC treatment. However, the transcription of the maspin gene was clearly increased following 5-aza-dC treatment in a number of oral cancer cell tines. These results imply that an action of 5-aza-dC is separate from induction of promoter demethylation. Treatment with FR901228 resulted in a time-dependent stimulation of the re-expression of maspin mRNA as early as 4 h after treatment in the maspin downregulated cells. The re-expression of the maspin gene may contribute to the recuperation of biological functions linked to FR901228 such as an inhibitory effect on tumor angiogenesis and cell invasion. These results indicate that maspin and its target genes may be excellent leads for future studies on the potential benefits of FR901228, a HDAC inhibitor, in cancer therapy.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5351999Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias.233238ENKuiHongKengo FukushimaKusanoHiroshiMoritaYoshihisaFujimotoXianWangHiroshiYamanariTohruOheArticle10.18926/AMO/31636<p>Ischemic preconditioning has been acknowledged as a powerful method of decreasing ischemic injury. However, the antiarrhythmic mechanism of ischemic preconditioning during ischemia is unclear. We studied the effects of ischemic preconditioning on arrhythmias and cardiac electrophysiology during ischemia in Langendorff rat hearts (n = 44). In the non-preconditioned group (PC(-); n = 24), the hearts underwent 5-min zero-flow global ischemia without any prior ischemic preconditioning. In the preconditioned group (PC(+); n = 20), the hearts were preconditioned by three cycles of 3-min zero-flow global ischemia and 5-min reperfusion before undergoing 5-min global ischemia. Ischemic preconditioning reduced the incidence of ischemia-induced arrhythmias (PC(-); 38.9%, PC(+): 8.3%, p < 0.05), shortened monophasic action potential duration (MAPD, P < 0.05), attenuated conduction delay (conduction time; PC(-): 234.2%, PC(+): 173.4%, P < 0.05) and increased the ventricular fibrillation threshold. Although the shortening of MAPD in PC(-) hearts was not influenced by the presence or absence of arrhythmias, conduction time prolongation at 3-min was more obvious in PC(-) hearts with arrhythmia than in PC(-) hearts without arrhythmia (PC(-) with arrhythmia: 220.2%, PC(-) without arrhythmia: 190.7%, P < 0.05). We concluded that ischemic preconditioning could protect the rat hearts from ischemia-induced arrhythmias and postulated that attenuation of conduction delay during ischemia might be an important factor in the antiarrhythmic action of ischemic preconditioning.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X3931985Determination of the onset of beta-methyl-digoxin action by potentiation of the adenosine response in guinea pigs.171177ENTamotsuFukudaYasuhiroKawakamiKatsushiFurunoYasunoriArakiArticle10.18926/AMO/31529<p>The onset of beta-methyl-digoxin action was investigated by the potentiation of the adenosine response in guinea pigs and rats, and compared with that of digoxin and dipyridamole. A number of i.v. infusions of adenosine were given to determine the mean control adenosine response and its 95% confidence limits. After oral administration of the drugs, successive infusions of adenosine were continued until a drug-induced potentiation of the adenosine response was observed. The time of appearance of the potentiated adenosine response was marked as the onset of action of the drugs. The onset of action in guinea pigs was 9 to 12 min for 0.2 to 0.4 mg/kg of beta-methyl-digoxin, 90 to 100 min for 0.2 mg/kg of digoxin and 25 min for 5 mg/kg of dipyridamole. The maximal potentiation was 48.8 to 53.8% at 18 to 21 min for beta-methyl-digoxin, 74.5% at 130 min for digoxin and 74.8% at 80 min for dipyridamole. Adenosine infused i.v. into rats produced heart block, as in guinea pigs. However, in rats, the adenosine response was not potentiated by beta-methyl-digoxin and digoxin. Dipyridamole at a dose as high as 200 mg/kg produced 25.8% potentiation at 36 min after oral administration to rats.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama1221958Effect of histamine releasers and of anti-inflammatory drugs on the egg-white edema of rat's hind paws in relation to skin histamine93111ENShozoIrinoArticle10.18926/AMO/31359<p>1. A method was described for a fairly accurate judgement of the effect of drugs inhibiting the edema in hind paws of a rat caused by local injection of egg white.
2. The degree of inhibition of egg-white edema by single doses of sinomenine, compound 48/80, or dextran was in parallel with histamine reduction in skin and other tissues of the paws (and the skin of abdomen), although prevention of the edema by prolonged treatment with sinomenine was incomplete even when the releasable histamine of the skin was practically exhausted. 3. Sodium salicylate, aminopyrine, butazolidine sodium, cortisone, and guaiazulene were capable of inhibiting egg-white edema without modifying the content of skin histamine. These drugs and a small dose of phenergan potentiated the inhibition by dextran of egg-white edema and inhibited the release of histamine by dextran. These actions lasted for
over 24 hours with the exception of guaiazulene. 4. Irgapyrin and a large dose of phenergan, which possess actions of histamine release and of histamine release inhibition and also antihistaminic action, caused a slight reduction of skin histamine and a comparatively marked inhibition of the edema. 5. In adrenalectomized or hypophysectomized rats, the edema-inhibiting effect of salicylate and aminopyrine decreased but that of cortisone
increased. The effect of guaiazulene remained unchanged. 6. The observations that inhibition of egg-white edema is caused by (a) histamine releasers, (b) histamine-release inhibitor, and (c) drugs exerting both histamine release and inhibition of the release were discussed with the consideration to a relationship between egg-white edema and
skin histamine.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama1341959Excitatory and inhibibitory reflexogenic skin areas for the intercostal respiratory neurons in the dog301313ENTadaakiSumiSatoruKotaniArticle10.18926/AMO/31220<p>1. Effects of various kinds of adequate stimuli such as touching, pinching, heating and cooling to various skin areas as well as repetitive electrical stimulations to a nerve branch innervating the skin areas upon the unitary discharges of the expiratory or the inspiratory muscle units of the intercostal muscles were studied on the spinal dogs. Effects of pinching upon the intercostal nerve action potentials elicited in reflex by single
electrical shock to the adjacent intercostal nerve were also studied. 2. Excitatory skin area for the expiratory discharges roughly exhibits a triangle, one of whose vertex faces the sternum, the side against the vertex corresponds to the apical line of the spine and includes the spot from where the discharges of a muscle unit are led off. The triangular area is surrounded by a belt-shaped zone having no reflex response. All the other wide area is the inhibitory one. 3. Both the excitatory and the inhibitory skin areas for the discharges of the inspiratory muscle unit are exceedingly narrow in contrast to those for the expiratory discharge, having a tendency to be limited to the small localized area involving the spot from where the discharges are led off. In the other extensive area, however, any reflex effect is not provoked.
4. The more intense and noxious the adequate stimuli become, the more prominent the effect come to be. 5. When the repetitive electrical stimuli to the skin nerve innervating the excitatory area are weak in intensity or low in frequency, an increasing discharge of the respiratory muscle unit results, whereas when the stimuli are sufficiently raised in either of the two factors above described, a remarkable inhibition preceded by a momentary acceleration ensues. In the case of stimulation of the skin nerve innervating the inhibitory area, however, the inhibition alone is obtained throughout.
6. Reflex action potentials in the intercostal nerve elicited by single shock stimuli to the adjacent intercostal nerve show a shortening of latency and an increase in size by pinching the excitatory skin area, while the reverse effects to those above described are obtained by pinching the inhibitory one.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4441990Interaction of Sevoflurane, Isoflurane, Enflurane and Halothane with Non-Depolarizing Muscle Relaxants and their Prejunctional Effects at the Neuromuscular Junction209215ENOsamuKobayashiYoshioOhtaFutamiKosakaArticle10.18926/AMO/30427The interaction of four inhalational anesthetics (sevoflurane, isoflurane, enflurane and halothane) with pancuronium and vecuronium and also their prejunctional actions at the neuromuscular junction were quantitatively studied using rat phrenic nerve-hemidiaphragm preparations. To investigate the prejunctional effects of inhalational anesthetics, a train-of-four ratio (T4/T1) and the tetanus ratio (the ratio of the final response to the initial response during tetanus) were evaluated. All four inhalational anesthetics markedly potentiated the neuromuscular blockade of twitch response caused by either pancuronium or vecuronium with halothane and enflurane being the most potent both on a % concentration basis and on a MAC (minimum alveolar concentration) basis. Although none of the four inhalational anesthetics had any effects on the T4/T1 ratio, they produced variable effects on the tetanus ratio. Sevoflurane had little effect on the tetanus ratio, whereas 1 and 2% isoflurane and 1, 2 and 3% enflurane increased the tetanus ratio and 5% halothane and 5% enflurane significantly reduced the tetanus ratio. Halothane and enflurane had the most potent depressant action of the four inhalational anesthetics both on the % concentration basis and on the MAC basis. These results indicate that the main site of action of inhalational anesthetics is a postjunctional site at the neuromuscular junction and that they do not seem to act on prejunctional sites at the concentrations used in clinical situations.No potential conflict of interest relevant to this article was reported.BioMed CentralActa Medica Okayama1465-5411642004Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of actionR291R299ENMikiTsujita-KyutokuTakashiYuriNaoyukiDanbaraHidetoSenzakiYasuhikoKiyozukaNorihisaUeharaHidehoTakadaTakahikoHadaTeruoMiyazawaYutakaOgawaAiroTsubura<p><b>Introduction</b> The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA).<br />
Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21<sup>Cip1/Waf1</sup>, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet.<br />
<b>Results</b> CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G<sub>1</sub> fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G<sub>0</sub>/G<sub>1</sub> arrest, which involved increased expression of p53 and p21<sup>Cip1/Waf1</sup>, and decreased expression of cyclin D<sub>1</sub>. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner.<br />
<b>Conclusion</b> CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.</p>No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558714-21959癲癇痙攣伝導路としての遠淡蒼球線維に関する生理学的研究19691988ENShinichiroFujiiIn this study, the auther has attempt to study electrophysiologically the aspect of pallidofugal fibers which are intermediated by the pallidum to the fibers arising from the motor area as the conduction system of epileptic discharge. Action potentials of motor cortex, basal ganglia, nuclei of the midbrain and spinal cord were recorded during major convulsive or subclinical seizures which are elicited by local administration of metrazol to the motor cortex or the thalamus of dogs. For subcortical recordings, a pair of bipor needle electrodes made of steel wire, mapproximately 200 μ in diameter on tungsten microelectrodes approximately 20 μ in diameter at the tip were used. Both steel and tungsten electrodes insulated by baking enamel except the tip. Spike discharges (duration of each spike is 20-60 msec. amplitude 50-100 μV recorded by abovementioned electrodes) are accounted for the epileptic discharges in this study. The results were as follows: 1) There are two different pathways transmitting the discharges from the motor area to the pallidum, one is direct connection between the motor cortex to the pallidum and the other has some relays the nuclei, thalamus and caudate nucleus, between them. These different pathways are connected separately to two different pallidofugal fiber group at the pallidum. 2) The pallidofugal fiber group, which is connected to the former pathways at the pallidum, are relayed at the contralateral substantia nigra and then terminated to anterior horn cells of the spinal cord. There is a fiber crossing to the other side at the midbrain between the pallidum and substantia nigra. 3) The pallidofugal fiber group connected to the latter at the pallidum does not show crossing to the other side on its course to the homolateral substantia nigra. But the downward fibers from the substantia nigra show a crossing to the other side at the pons and terminate in the contralateral anterior horn cells.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558713-21959Rigidity. Spasticity及びClonusとr-motor fiberとの関係に関する研究14271440ENKokichiFukuMatthews and Ruthworth described selective gamma efferent fiber paralysis by Procaine applied to the peripheral nerve of cat. In our present study, the posterior tibial nerve was injected with 2% procaine at popliteal fossa in the patients who clinically showed either rigidity or spasticity in the calf muscles or ankle clonus. These clinical signs were decreased or abolished after the injection although voluntary contraction of the muscles and the monosynaptic H-reflex response following electrical shocks to the nerve were preserved. Even at this stage of anesthesia, action potentials of the sciatic nerve set up on stimulating the posterior tibial nerve was detected as well as before the injection through a pair of bipolar needle electrodes inserted in the sciatic nerve at the buttocks. These results indicated that procaine solution of the dosis used in the experiments blocks fibers of small diameter including gamma efferent fibers mainly though it is not effective to the alpha motor and group I afferent fibers, and clinical symptoms of hyperactive stretch reflex i. e. rigidity, spascity and clonus may depend on excessive bias on the muscle spindles in the calf muscles through gamma efferent fibers.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155870101958ギラン・バレー症候群を呈する多発性神経根炎の筋電図学的研究 第二篇 Coxsaekie Virus及びPolio Virus接種マウスの筋電図,殊にLaw amplitude NMU Voltage並びにSynchronization Voltageに関する実験的研究36513668ENTadaoYodaWith a view to pursue the mechanism eliciting low amplitude NMU voltage (L.A. NMU V.) and synchronization voltage (S.V.) which have a great significance in the electromyograms of Guillain-Barres syndrome (G.B.S.) and paralytic poliomyelitis and also to find out clues for the etiologic factor of G.B. the author performed the follwing experiments. Namely, inducing disease with the inoculation of agents isolated from infants with Guillain-Barres syndrome, such as coxsackie virus of A group type 2, Okumoto strain, the same type 19 Dohi strain and B group type 1 Saragai strain which mainly induce myositis, into young mice 15 days old, and also infecting polio virus type Ⅰ (Mahoney strain), type Ⅱ (Lansing strain), or type Ⅲ (mouse adapted Leon strain) into mature mice, the author compared the electromyograms from m. bicepus brachii, m. gasfrocnemius, and intercostal muscle of these mice, and obtained the following results. The test materials were 136 muscles from 32 young mice injected with coxackie virus (C. V.) and 191 muscles from 45 mature mice injected with polio virus (P. V.). 1. It has been verified that the electromyograms of normal young and mature mice, generally do not differ greatly from those of human with the exception of contact voltage, proving electromyographic experiments of mice are possible. In measuring the duration and amplitude of 374 and 492 action potentials of normal young mice and mature mice, and in the percentage histograms of each, the average duration has been found to be 4.69 ± 0.36 m. sec. in young mice, while 5.12 ± 0.11 m. sec. in mature mice; and the average amplitude to be 244.5 ± 7.36 μv and 252.3 ± 8.13 μv, respectively. In other words, both the average duration and amplitude are greater in mature mice than those in young ones. 2. L. A. NMU voltage has been recognized in 50 per cent of the mice injected with C. V. A-group strain, in 20 per cent of the mice infected wtih C. V. B-group strain, and in 27.2 per cent of total muscles examined, while on the contrary, in the mice infected with P. V. it has been found only in one mouse out of the twenty-two infected with Lansing strain and in 1.1 per cent of all muscles infected with P. V.. Conversely, synchronization voltage has been recognized in the mice infected with P. V. type Ⅰ, Ⅱ, or Ⅲ in 42.8, 54.5, and 22.2 per cent of respective group, and in 20.9 per cent of entire muscles examined, while S. V. can not at all be recognized in the mice infected with C. V. From these results it has been experimentally proven that L. A. NMU voltage is the abnormal electromyogram appearing mainly in the case of muscular disturbances, while S. V. is that appearing chiefly by lesions of the anterior horn of the spine. 3. The incidence of L. A. NMU V. observed in the young mice infected with Okumoto strain and that of S. voltage observed in the mature mice infected with Lansing strain both show a tendency to increase with the lapse of time. 4. The percentage histograms of the duration and amplitude of 234 action potentials obtained from young mice infected with Okumoto strain show a greater tendency of the shift to left than respective one observed in the normal young mice; their average values (2.8 ± 0.13 m. sec, and 155.1 ± 10.8 μv, respectively) are both smaller than those in normal young mice. And the differences in the average values of duration and amplitude are both statistically significant. 5. The percentage histograms of the duration and amplitude of 278 action potentials obtained from the mature mice infected with Lansing strain show a greater tendency of the shift to right than those of normal mature mice; and their average values (5.24 ± 0.10 m. sec, and 327.2 ± 20.8 μv, respectively) are both greater than those in normal mature mice. However, the difference in the average values of the duration is not statistically significant. 6. The pattern of L. A. NMU V. observed immediately after the crisis in C. V. infected mice often presents relatively interfering pattern, but it turns scanty with the lapse of time. From this fact it is assumed that the pathologic changes in nerve fibers are formed secondly. 7. In contrast to the opinion that the low amplitude NMU voltage appears in neurogenic atrophy as well as in myogenic atrophy, the author has verified that it mainly appears in myogenic atrophy. Furthermore, the author would put an especial emphasis on the fact that in the differentiation of myogenic atrophy and neurogenic atrophy not only numbers of frequenies of discharges but also the fluctuations in the duration should be taken into consideration. 8. From electromyographic findings obtained in the above-mentioned experiments and from those findings in G. B. syndrome reported previously in Part 1, it has been confirmed that Guillain-Barres syndrome is the disease accompanied by pathologic changes in muscles and the anterior horn of the spine.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15587031958癲癇痙攣の興奮伝導機序に関する実験的研究723752ENShuzoOkumuraThe auther has attempt to study the propagating mechanism of the excitement, which can be thought as the origin of the epileptic convulsion. The action potential has been recorded from cerebral cortex, basal ganglia, nucleus of midbrain and muscles of extremities during convulsion, which precipitated by intravenous administration of metrazol (10% solution of Cardiazol) on cats. Needle electrodes (200 enamel insulated steel wire) were used as recording electrodes, and the spike wave (duration 20 to 60 msec. amplitude 50 to 100 μV by abovementioned electrode) was applicated as an indication of the excitement. 1) Motor cortex, caudate and pallidum, thalamus and black substance have demonstrated their important function in the propagating mechanism of the excitement. And motor cortex has been more sensitive than other structures. 2) On the occasion of metrazol convulsion, the spike wave is detected in the first place at cerebral cortex. The spiking at cerebral cortex propagates to basal ganglia with some seconds delay time, and then the spiking propagate also to basal ganglia. Moreover, the spiking at basal ganglia propagate to mid-brain nucleus. The onset of a convulsive movement is earlier than the beginning of the spiking at basal ganglia, and is delayed from the beginning of the spiking at cerebral cortex. The convulsive pattern of muscles change from former clonic convulsion to tonic convulsion in the course of propagation of the spiking to basal ganglia. 3) The auther has presumed that a typical epileptic convulsion, which has clonic-, tonic-and clonic stadium a its components, should have above mentioned propagating mechanism of the excitemnent from electroencephalographical findings.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558744-71962人骨格筋の電気生理学的ならびに組織学的研究 第3編 人骨格筋の活動電位の伝導速度について499507ENTamotsuShinozakiThe conduction velocity of action potential of isolated human skeletal muscle was examined in oxygenated Tyrode's solution. 1. The velocity is distributed mainly between 3 and 4 m/sec, being neither more than 4.5 m/sec, nor less than 2.3 m/sec. 2. In the pectoralis major muscle and the rectus abdominis the conduction velocity does not distribute uniformly, but has two peaks. One peak is between 3 and 3.6 m/sec, and the other is between 3.6 and 4.2 m/sec. 3. When current I is applied intracellulary across the fiber membrane, the membrane potential is changed as much as V in terminal value. Then muscle fibers can be divided into two groups by V/I value and the conduction velocity. In one group V/I is in inverse proportion to the 3 power of the velocity. This means, if resistance of membrane and capacitance of membrane are constant in a group, the conduction velocity is in the proportion to the root of the fiber diameter, which is rational to the cable theory. The difference of two groups may depend upon the difference of capacitance of membrane.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558744-71962人骨格筋の電気生理学的ならびに組織学的研究 第1編 人骨格筋の筋線維膜の電気的常数及び膜電位について477486ENTamotsuShinozakiNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558778-91965液性抵抗因子と癌に関する実験的研究 第3編 血清properdin上昇作用および制癌性を有する薬剤の作用機序に関する実験的研究12231231ENKazutadaMiyakeFor the purpose to elucidate action mechanism of pantothenic acid (PaA) and γ-aminobutyric acid (GABA) that possess the ability to raise the serum properdin level and show anticancer effect when administered to cancer-bearing animals, a series of in vivo and in vitro experiments was carried out and the following results were obtained. 1. PaA, when give to normal mice, accelerates the liver catalase activity, and when it is administered alone or concurrently with anticancer agent to cancer-bearing mice, the catalase activity is enhanced to a still greater extent. 2. PaA, GABA, Orotic acid, Thio-TEPA, and mitomycin C have been found to accelerate the anaerobic glycolysis of Ehrlich carcinoma cells but carzinophilin rather suppresses it. 3. The effect of PaA and GABA on the serum properdin level resembles closely to that of ACTH, but differs from the effect of cortisone in that the high level of the serum properdin is sustained even after the completion of drug administration. 4. GABA, ACTH, and PaA have the ability to prolong the survival time of cancer-bearing mice, but cortisone rather aggravates cancer. 5. From these findings it is concluded that PaA and GABA do not act directly on tumor cells but act on the pituitary body by way of the higher nervous center while on the other hand, these drugs act on the cells of host, especially those of the reticuloendothelial system and liver, thus potentiating anticancer factors including the serum properdin level.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558764-61964細胞内微小電極法による赤筋線維並びに白筋線維の機能分化による興奮伝導速度の差に関する研究 第3編 人腹直筋筋線維の静止電位,活動電位及び興奮伝導速度の時間的変化について187191ENHikozoShimadaUsing the intracellular microelectrode, the relationship between the freshness of muscle fibers and their electrophysiological charactor was studied in the surgecally exstirpated human m. rectus abdnminis, namely, the decrease rate of their conduction velocity, amplitude of action-potential and resting-potential was measured according to the times from the insertion of microelectrode into muscle fibers aud the following results were obtained. 1. The decrease of conduction velocity was not so obvious for 15 minutes, namely, its average decrease rate was about 10% for 15 minutes. 2. The decrease of amplitude of action-potential and resting-potential was prominent for 15 minutes, namely their average decrease rates were about 50% for 15 minutes. It was further assumed that the main cause of these decrease might be attribute to the mechanical injuly of muscle fibers by the insertion of microelectrode into them. 3. No marked difference was observed between the decrease rate of conduction velocity, amplitude of action-potential and resting-potential of the red and that of white muscle fibers.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558761-31964人体脊髄運動ニウロンのH-reflex並に動作様式に関する研究 第1編 人体H-reflexにおける促進及び回復曲線に関する実験的研究ならびに理論的考察4762ENMasayukiKamimuraSerial records of H-reflex of splnal motoneuron were obtained by the recording of action potential of soleus muscle, triggered by conditioning and testing electrical shocks on the posterior tibial nerve. The fascilitation and recovery process of the spinal motoneuron was studied by the serial records of the H-reflex. The clinical material was 30 cases including normal subjects, patients with pyramidal lesion, and patients in acute stage of cerebrel
intervantion. In commonly, the H-reflex triggered by test shock (H) was not observed by the test shock which was given within 3 millisecond (ms') following conditioning shock, but start to appeared at 4ms appeared in peak amplitude (maximal deflection) at 6ms., and disappeared by 9 to 13ms. Later than 9 to 13ms., H-reflex falled in a silent period. However, the detail of the abovementioned characteristics of the H-reflex appeared in some difference, i.e. on the patient with pyramidal lesion H-reflex continued to appear until 18ms. with maximal deflection of 150% of the H-reflex, on the normal subject those were 10ms. and on the patient in acute stadium of cerebral surgical intervention those were 9ms. and 50% . The author intended to describe the complate disappearance of H-reflex within 3ms. following conditioning shock as the first silent period, and presumed that the first silent
period would be the result of combination of refractory period of Group Ia fiber and inhibition of Group Ib fiber. The auther also would suppose the detailed characteristics of the H-reflex at the period of 4 to 10ms. following conditioning shock was caused by the afterhyperexcitability of the motoneuron by the conditioning shock as well as summation of the test shock, but the IPSP of Group Ib efferent impulses and influence of Renshow cell were other important mechanisms. The author intended to call abovementioned brocess the fascillitatry of human H-reflex.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558819-101970γ-amino酪酸誘導物質の痙攣抑制作用に関する電気生理学的ならびに臨床的研究 第Ⅰ編 電気生理学的研究505518ENHiroshiSugataniIt is reported that GABA (γ-amino butyric acid) & GABOB (γ-amino β-hydroxy butyric acid) have an inhibitory action to the central nervous system. Recently, S-GABA (γ-amino β-sulfonyl butyric acid) & P-GABA (γ-amino β-phenyl butyric acid) have been composed from GABOB, and reported that they also have an inhibitory action to the convulsive seizure. In the experiments in dogs, P-GABA, S-GABA & GABOB solutions were applied on the cerebral at rest and after discharge caused by electrical stimulation of motor cortex were recorded to examine the anti-convulsive action of these solutions. In the experiments in cats, cortical evoked potentials caused by electrical stimulation of thalamus were recorded to examine the action of GABOB by mearns of computer technique. Furthermore, the application of GABOB & S-GABA solution on the epileptogenic cortical focus of human epileptic was performed and the corticogram was recorded with reference to spikes and after-discharges to examine the anti-convulsive actions of these solutions. The results are following: 1) Application of S-GABA solution on the cerebral cortex caused low voltage activity and spiking activity in corticogram. 2) P-GABA caused spiking activity, developing to the generalized convulsive seizure pattern. 3) These spiking activity caused by S-GABA and P-GABA was, inhibited by GABOB
solution. 4) S-GABA did not inhibit the after discharge or spiking activity on the epileptogenic cortical focus of human epileptic. GABOB, however, showed a strong inhibitry action to after discharge & spiking activity. 5) Application of GABOB on the cerebral cortex reversed the cortical evoked potentials caused by electrical stimulation of thalamus. From these findings, it is concluded that GABOB has an inhibitory action on the cerebral cortex, but S-GABA & P-GABA have no inhibitory action.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558897-81977生体膜系に対するビスコクラウリン型アルカロイドの作用とその作用機序に関する研究 第1報 細胞膜傷害によるK(+)遊出に対するセファランチンの阻止作用749756ENMasanobuMiyaharaKozoUtsumiKatsumiSagiyamaKanameAonoConcerining the physiological properties possessed by the cell membrane, recently an attention has been called on various problems such as the cell recognition mechanism to begin with, and the mutual relationships among the intercellular communication mechanism, as well as the metabolism adjustment of membrane binding enzymes, aside from the compartmentation of substances. Essentially the physico-chemical properties of the membrane of cancer cell and proliferating cells are important in relation to the treatment of cancer. And attempts are being made to change the cell metabolism by artificially altering the physicochemical properties of the cell membrane. Cepharanthine, one of the biscoclaurin alkaloids, is known from olden days to possess a thanatophidia hemolytic property, but this property seems to bring about the change in the physico-chemical properties of the cell membrane, and it is interesting in the point that this substance may have a membrane modifying property. For these reasons, during the investigation on the actions of alkaloids on the cell membrane many interesting phenomena have been elucidated. This report presents the results recently obtained about the changes in physico-chemical properties of biological membrane by the treatment with cepharanthine. The obtained results were as follows. 1. Cepharanthine inhibits K(+)-release from red blood cells when these cells are treated with snake venom, phospholipase A, lysolecithine, lead acetate and hexane. But the alkaloid does not inhibit K(+)-release induced by ionophores, surface active agents and HVJ. 2. Cepharanthine inhibits the hyperpolalization of membrane potential induced by lead acetate or hexane. 3. Similar inhibitory effect of cholesterol on K(+)-release from the cells by the treatment with lead acetate is observed. 4. From these results it is suggested that the inhibitory action of cepharanthine on K(+)-release from cells is due to the action of decrease in membrane fluidity.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558923-41980軟体動物巨大神経細胞興奮性に対するphenylalanine,tyrosine,tryptophanを含んだoligopeptideの作用に関する研究463482ENAkinoriSakai1.巨大アフリカマイマイ(Achatina fulica Férussac)食道下神経節中に2個の自発発火を有する巨大神経細胞(TAN;tonically autoactive neuroneおよびPON;periodically oscillating neurone)を同定して,その興奮性に対するL-Phe, L-Tyr, L-Trpなどを含んだoligopeptideの作用を検定した.2, TANに対して, 3つのoligopeptideが顕著な抑制作用を呈した.その臨界濃度は, L-Lys-L-Phe-L-Tyrは3×10(-6)～10(-5)kg/l, L-Phe-L-Tyrは3×10(-6)～10(-5)kg/l, L-Phe-L-Trpは10(-5～)3×10(-5)kg/lであった.3.これら3つの抑制性oligopeptideの作用は, TAN神経膜に対する直接の過分極作用であり,そのイオン機構はCl-非依存性であると考えられた.またこれらのoligopeptideは,スパイクの発生およびそのリズム(膜の脱分極時)には影響しなかった.4.そのほかTANに対して, L-Trp-L-Trp, L-Trp-L-Tyr, L-Phe-L-Phe, L-Phe-L-Phe-L-Phe, L-Tyr-L-Tyr, L-Tyr-L-Tyr-L-Tyrが,高濃度(2×10(-4)kg/l)で弱い抑制作用を示した.5.上記物質以外に, L-Phe, L-Tyr, L-Trp, L-His, L-Metなどを含んだ多数のoligopeptideを検定したが,いずれもTANに作用を持たなかった.6. PONに対して, TANと同じ3つのoligopeptideが抑制作用を示した.この臨界濃度はTANの場合より濃く, L-Lys-L-Phe-L-Tyrは5×10(-5)～10(-4)kg/l, L-Phe-L-Tyrは10(-4)～2×10(-4)kg/l, L-Phe-L-Trpは2×10(-4)kg/lであった.この3物質以外では,検定されたoligopeptideはすべて, PONに作用を持たなかった.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558919-101979心臓交感神経刺激による心電図変化(実験的検討)12071234ENHidenoriYoshidaElectrocardiographic changes caused by electrical stimulation of individual cardiac sym-pathetic nerves were observed with Frank's corrected orthogonal lead system and Frank's vetorcardiogram. The effects of drugs on nervous stimulation and the electrocardiographic changes after the resection of the cardiac nerves were investigated in 45 closed chest dogs. The following results were obtained: 1. The amplitude of the Twave decreased in Y lead and increased in Z lead in 20 out of 34 cases in which the right stellate ganglion [R.S.G.(A)] had been stimulated and in all cases in which the right recurrent cardiac nerve (R.Rec.C.N.) and the left ventromedial cervical cardiac nerve (L.V.M.C.N.) had been stimulated. Spatial maximum T vector displaced anteriorly and superiorly. The magnitude of spatial maximum T vector increased in all cases. 2. An increase in the amplitude of T waves in Y lead was seen in all cases in which the left stellate ganglion (L.S.G.), and the left ventrolateral cervical cardiac nerve (L.V.L.C.N.) had been stimulated, and in 14 out of 34 cases in which the right stellate ganglion [R.S.G.(B)] had been stimulated. The spatial maximum T vector was displaced inferiorly. The magnitude of the spatial maximum T vector increased in all cases. 3. The amplitude of the T wave increased in Y lead with simultaneous stimulation of both right and left stellate ganglia. The spatial maximum T vector was displaced inferiorly and the magnitude of the spatial maximum T vector increased in all cases. These electrocardiographic changes were similar to the changes which occurred with single L.S.G. stimulation. 4. Rotation of the T loop in the left saggital plane was clockwise in more than 80 % of cases with R.S.G. stimu-lation. However, rotation of the T loop in left saggital plane was counter clockwise in more than 75-80% of cases with L.S.G. and simultaneous stimulation of both right and left stellate ganglia. These results suggest that right and left cardiac sympathetic nerves innervate different myocardial areas and affect the local myocardial action potentials to cause these electrocardiographic changes. 5. In more than 40% of cases with stimulation of left cardiac sympathetic nerves (L.S.G., L.V.L.C.N.). arrythmias such as A-V dissociation and A-V junc-tional rythm were recognized. In more than 90% of cases with stimulation of right cardiac sympathetic nerves (R.S.G., R.Rec.C.N.), marked increase of sinus rythm occurred. 6. These electrocardiographic changes resulting from nervous stimulation decreased or disappeared after the use of propranolol. These results suggest that these electrocardiographic changes were caused by β -effects of catecholamines. 7. The QT ratio corrected by the formula of Bazett increased in all cases of right and left cardiac sympathetic nervous stimulation. 8. Long term observations after right or left stellate ganglionectomy revealed no significant changes in electrocardiographic patterns and a tendency to decrease in the QT ratio corrected by the formula of Bazett.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15589611-121984脳性麻痺に関する臨床的研究 第1編 Dystonic型およびathetotic型脳性麻痺患者の節電図学的研究11191134ENMasaoMurakamiSeven dystonic and eight athetotic patients with cerebral palsy were clinically diagnosed following the classification of motor symptoms of the American Academy for Cerebral Palsy, and examined with surface electromyography while at rest in the supine position, under mental stress, making voluntary contractions and responding to passive stretch. Involuntary movements of both dystonic and tension athetotic cerebral palsy were characterized by nonreciprocal involuntary muscle activity in agonists and antagonists. There was more tonic involuntary muscle activity in dystonic than in tension athetotic cerebral palsy patients. During involuntary movements in three dystonic patients, muscle action potentials recorded simultaneously in different muscles had a uniform pattern of duration and amplitude. Electromyographical findings under mental stress were almost the same as those at rest in both dystonic and tension athetotic forms, except that the amplitude and duration of muscle activity was larger under mental stress than at rest. When both dystonic and tension athetotic patients were asked to make voluntary contractions, they were unable to do so smoothly, because involuntary movements were induced in agonists and antagonists. Especially in dystonic patients, voluntary efforts induced involuntary movements not only in agonists and antagonists but also in other muscles not concerned with voluntary contraction. In all dystonic patients, the responses to passive stretch were characterized by rigidity or rigidospasticity. In five tension athetotic patients, the stretch reflex was characterized by spasticity, but in three patients the stretch reflex was not seen at all. Therefore, it is assumed that dystonic movements arise from rigidity or rigidospastic hypertonus. In three dystonic patients, the stretch reflex brought about action potentials not only in antagonists of the stretched muscle, but also in other muscles not concerned with passive stretch. These synchronized action potentials were neither of involuntary muscle activity induced by passive stretch nor of paradoxical contraction of Westphal. It is presumed that such action potentials are induced by suprasegmental central mechanisms closely related to the stretch reflex.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558931-21981運動準備電位に関する研究 第1編 健康人および不随意運動症患者における運動準備電位3152ENYoshimiBabaReadiness potentials on voluntary hand movements were recorded from the scalp (C3: left central, C4: right central), premotor cortex, subcortical white matter and VL nucleus of the thalamus. The subjects were 6 healthy right-handed men and 23 patients with involuntary movement disorders. The subjects lay on a bed in a dark room where they performed quick, repetitive voluntary contractions with the left or right fist. The contractions were self-paced at a frequency of about one every 6 sec. Linked mastoid electrodes served as a reference throughout the experiment. The EEG was amplified with Nihonkohden RDU-5 DC amplifiers. Clenching of the fist triggered the pulse-generator which produced an immediate pulse and a one second delayed pulse. An EMG was also recorded. These signals were recorded on magnetic tape. Analysis of the data was acoomplished by playing the tape back. The EEG and EMG activity were summated by Nihonkohden ATAC 501-20 computor. In most subjects, readiness potentials were obtained before the voluntary movements. Readiness potentials were measured as the amplitude of premovement potential (N) and the interval between the beginning of the potential and the initiation of motor action (T). 1. Readiness potentials with negative shift were recorded on the scalp (C4, C3). In 6 right-handed healthy men, the means of T and N were 0.8 sec. and 7.0 μV, respectively, in C4, and 0.8 sec., 8.6 μV in C3 on right-hand movements. Conversely, the means of T and N on left hand movements were 1.0 sec., 9.2 μV in C4, and 1.0 sec., 8.4 μV in C3, respectively. The amplitude (N) in C3 on right-hand movements was significantly higher than in C4 (p<0.05 t-test). 2. Readiness potentials on the scalp were also recorded in 16 patients who had involuntary movement disorders, such as Parkinsonism, torsion dystonia or intention tremors. The means of T and N were 1.3 sec., 7.7 μV in C4 and 1.3 sec., 8.2 μV in C3 on right-hand movements. Conversely, the means of T and N on left-hand movements were 1.2 sec., 8.2 μV in C4 and 1.2 sec., 6.3 μV in C3. The mean T value was longer than the control group (p<0.01, t-test). 3. In Parkinsonian patients, the mean T value of readiness potentials on the central region contralateral to the hand movements was 1.1 sec. in 6 patients without akinesia (stage I, II). Conversely, that in 4 patients with akinesia (stage III) was 1.4 sec., which was longer than the control group (p<0.05 t-test). The length of T rather than the rigidity seemed to correlated with akinesia in patients with Parkinsonism. 4. Simultaneous recordings from the premotor cortex, subcortical white matter (2cm below the cortex) and VL nucleus of the thalamus were done during stereotactic surgery in the nonanesthetic state. Patterns of readiness potentials recorded from the premotor cortex were similar to those recorded from the scalp, but those recorded from the VL nucleus and the white matter were reversed in polarity. According to simultaneous recordings from the cortex and VL nucleus, readiness potential began approximately 0.2 sec. earlier at the cortex than the VL nucleus (p<0.01 t-test). This result is some evidence that the readiness potential initiates from the cortex of the motor area contralateral to the moving hand. 5. Readiness potentials were recorded 2-4 weeks after stereotactic VL thalamotomy. The mean T and N values of readiness potentials were almost the same as those before the surgery. The readiness potential was also recorded in a patient with thalamic syndrome who had a vascular lesion in the right thalamus. The potential showed a normal pattern from the intact side of the scalp, but on the lesion side, no potential could be obtained. These results suggest that the thalamus plays an important role in the origin of the readiness potential of the motor cortex.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558987-81986非脱分極性筋弛緩薬の作用に及ぼす酸-塩基平衡の影響607612ENKazumiOnoThe effect of pH changes on neuromuscular (NM) transmission, both in the presence and in the absence of muscle relaxants (MR), was investigated using phrenic nervehemidiaphragm preparations of rats. The first finding of this study indicated that the primary site of action of pH changes in the absence of MR is muscle itself and not the NM junction. The second finding was that the effect of pH changes on the potency of d-Tc and vecuronium was very different from that of metocurine, pancuronium or alcuronium. The action of d-Tc and vecuronium was potentiated in acidosis and antagonized in alkalosis. In contrast, that of metocurine, pancuronium or alcuronium was antagonized in acidosis and potentiated in alkalosis. The above finding suggests that a difference exists between mono- and bisquaternary MR with regard to the response to pH changes.No potential conflict of interest relevant to this article was reported.岡山大学医学部保健学科Acta Medica Okayama1345-09481612005局所筋機能測定のための筋内挿入型プローブの開発18ENHisaoOkaMotonariEdamatsuShogoWatanabeTomokiKitawaki10.18926/15177臨床においては,筋機能や機能不全を診断するために,表面筋電図や針筋電図,筋生検などが行われている｡しかし,これらの方法では筋機能や筋収縮メカニズムを連続的に測定することは難しい｡本研究では新たに筋内挿入型プローブと測定システムを開発した｡測定プローブは光ファイバと6本の白金細線から構成されている｡光ファイバを用いて筋の局所血流量と筋内圧力を測定し,6個の電極を用いて運動単位活動電位を測定した｡プローブと測定システムの基礎特性を確認した後,麻酔下のラットの排腹筋において,安静時および局所虚血時の活動電位,血流量,筋内圧力を測定した｡また脛骨神経を電気刺激し,活動電位波形から伝播速度を算出したところ,プローブは正常に動作していることが確認できた｡さらに筋小胞体からのカルシウム放出チャネルを抑制するdantroleneを筋注すると,筋内圧力波形は大きく減少したが,活動電位波形はほとんど変化しないことがわかった｡No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155878101966Picrotoxineの白鼠性周期におよぼす影響955961ENHichiroHarada1. It was found that picrotoxine has an effect to arrest the sexual cycle on mature female rats for the period of 8 to 15 days, with the picture of diestrus. During the arrest of the sexual cycle the uterus presented a picture of luteohormone action, and the ovaries showed that of vigorous activity of the lutein body and the growth of ovarian follicles was inhibited and on about the seventh day of the reststadium the ovarian follicles began to develop and the luteinbody under-went retrogressive metamorphosis.
2. When luminal, a brain-stem narcotics, was concurrently used, there could be seen no such effects of picrotoxine just mentioned nor any noteworthy findings of the uterus and ovaries while in the case of concurrent use of urethan the effect of picrotoxine was rather potentiated.
3. The combined use of atropine or yohimbine had practically no influence on the effect of picrotoxine.
4. It seems that picrotoxine attacks the sexual function regulating center in the diencephalon, especially its inhibitory center of the sympathetic nervous system. In this instance, since the duration of the arrest of the sexual cycle and the findings of both organs coincide with those of pseudopregnancy, as reported by Long et al., the excitation of the central nervous system induces the pseudopregnancy phenomenon and the cerebral cortex plays a role of inhibitor and the resultant paralysis enhances the excitation of this centerNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581021-21990一過性虚血後の慢性期ラット脳における生化学的変化に検する研究129141ENHiroshiYoshikawaIn recent years, cases of sequelae of cerebrovascular disease such as vascular dementia due to death of many neurons have been increasing. Such neuronal death following brain ischemia had been considerd to be due to an energy deficiency resulting from an impaired respiratory chain. However, the detection of the delayed neuronal death showed that neuronal death is not caused by mere energy deficiency. Most previous studies on delayed neuronal death focused on the changes in morphology and energy metabolism in the acute to subacutte stage. There are few reports concerning biochemical changes in the chronic stage, especially in neurotransmitter receptors. Transient ischemia for 20 minutes in a rat four-vessel occlusion model was induced, and serial histological and biochemical changes were evaluated until the chronic stage. Destruction of pyramidal cells in the CAI area of the hippocampus was completed by 10 days after cerebral ischemia followed by recirculation of cerebral blood flow. Light microscopy showed no progression after this day. The level of acetylcholine (ACh) was significantly decreased in the hippocampus, striatum, and frontal cortex at the termination of ischemia but recovered to normal 21 days after recirculation of cerebral blood flow. The binding sites of muscarinic ACh receptors (mACh-R) per usit of protein were increased in the hippocampus 21 days after recirculation of blood flow. However, no changes were observed in the total number of mACh-R in the entire hippocampus. Thuse finings suggest no changes in the ACh neuronal system in the chronic stage and no direct association between this ayatem and delayed neuronal death. On the other hand, N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptirs, showed no change in the hippocampus until after 10 days, but decreased to half after 21 days despite no evidence of histological progression of neuronal death. Thus, delayed neuronal death after transient forebrain ischemia appears to be deu to release of glutamate, an excitatory amino acid. Our findingd show the specific death of neurons with NMDA receptors for glutamate.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155810341991ラット脳内 σ 受容体の薬理学的特異性に関する研究―とくに抗精神病薬との抗虚血剤の作用について―281292ENYoshifumiZushiPharmacological specificity of several classes of drugs such as antipsychotics and antiischemic agents was assessed for σ receptors labeled with [(3)H] haloperidol. Specific binding of [(3)H] haloperidol in the presence of 25 nM spiperone was saturable and high affinity )Kd=1.96±1.31 nM, Bmax=2.37±0.27pmol/mg of protein;n=8). Among the 29 antipsychotics tested in inhibition studies, bromperidol and haloperidol were the most potent inhibitors (Ki=0.9nM, 1.0nM, respectively). The conventional antipsychotics moperone, timiperone etc. and the novel promising drugs YM-09151, Y-516, BMY-14802 and remoxipride potently inhibited [(3)H] haloperidol binding with the Ki in the range of low to moderate nanomolar. On the other hand, among the other 27 drugs tested, the antispasmodics eperisone and tolperisone, the antiischemic agents ifenprodil, the Ca(2+) antagonist flunarizine and cinnarizine, and the antitussives carbetapentane, cloperastine and dextromethorphan, were especially potent inhibitors. These results, taken together with the evidence that the antiischemic agents ifenprodil and dextromethorphan antagozine NMDA responses and NMDA receptor complex is a possible site of action for neuroprotective agents, strongly suggest that σ receptors may be potential sites of action for antiischemic as well as antipsychotic drugs, i.e., σ receptors mediate the neuroprotective effects of certain antiischemic agents by affecting the NMDA receptor complex.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581031-21991無麻酔･無拘束下ラットの出血性低血圧モデルにおける内因性 Thyrotropin releasing hormone (TRH) の血圧維持作用ならびにその作用部位に関する実験的研究5363ENMineoMiyazakiA pressor effect of TRH in hemorrhagic hypotensive rats was studied. First, TRH (1mg/kg, 2mg/kg, 5mg/kg), its analogue MK771 (0.2mg/kg) and anti-TRH antibody were given intravenously. The change in the mean arterial blood pressure (MAP) was observed. After administration of TRH, MAP rose dose-dependently, and it also rose after administration of MK771. The anti-TRH antibody significantly suppressed the compensatory and reflective increase of MAP following the hemorrhage. This suggested that the endogenous TRH plays an important role in the maintenance of MAP in the hemorrhagic hypotensive state. Next, the same hypotention models were made using adreno-demedullated rats. TRH or anti-TRH antibody was given intravenously. TRH significantly increased MAP, while the anti-TRH antibody suppressed MAP. This indicates that the pressor effect of TRH is not mediated by the adrenal medulla. The endogenous TRH may play its maintenance role of blood pressure via medulla oblongata.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581045-61992トリプトファン代謝産物のラット脳機能に対する影響の研究471482ENYutakaNishijimaThe effects of tryptophan (Trp) metabolites administered into right cerebroventricle (1μmol) on the electrocorticograms (ECoG) of rats were studied to investigate the roles of Trp metabolites in the brain function. Kynurenine, anthranilic acid, and xanthurenic acid has no effect on ECoG until the end of recording 4 hours after the administration. 3-Hydroxykynurenine had a suppressive effect on the ECoG transitory, and kynurenic acid suppressed ECoG slightly. 3-Hydroxyanthranilic acid which is a metabolite of 3-hydroxykynurenine, induced spike discharges with a long latency (60-230 min after the administration). 3-Hydroxyanthranilic acid is thought to be metabolized to o-aminophenol, quinolinic acid and picolinic acid. Among the 3-hydroxyanthranilic acid metabolites, o-aminophenol induced spike discharges a few min after the administration, and the spike discharges a few min after the administrations, and the spike discharges lasted 60 min. On the other hand, quinolinic acid suppressed ECoG, and picolinic acid had no effect. These electrocorticographic findings suggest that 3- hydroxyanthranilc acid might induce spike discharges after metabolization to o-aminophenol.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581045-61992担癌マウスにおける摘脾と免疫賦活剤の効果425431ENShojiroTakatsukaTo determine the effect of splenectomy on tumor growth, the immunological role of the spleen was studied at various time intervals following subcutaneous implantation of MH-134 hepatoma cells into syngeneic C(3) H/He mice.
Both tumor neutralizing activity and PHA-suppressor cell activity were generated. the former reached a maximum on the 28th day of implantation, and belonged to Lyt-1(+)2(-)T cells. The latter appeared on the 3rd day, decreased once, and increased again. Mainly, this suppres-sive activity was found in Lyt-1(+)2(-)T cells on the 3rd day and in nylon-wool-adherent cells after the 14th day. Splenectomy or sham splenectomy (sham ope) was performed on the 3rd day of implantation. There was no significant difference in tumor growth between the groups. Immunotherapy with lentinan effectively suppressed tumor grouth both in the tumor-bearing mice that had splenectomy and in those that had sham ope, with no significant difference in tumor growth between the two groups. Therefore, the effectiveness of splenectomy on tumor growth might be difficult to evaluate, since these opposite activities are simultaneously induced in the spleen of tumor-bearing mouse.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581043-419921,25-DihydroxyvitaminD(3)によるヒト骨肉腫細胞 MG63 からのinsulin-like growth factor binding protein 3 の産生増加323330ENTadashiMoriwakeSeveral types specific insulin-like growth factor binding proteins (IGFBPs) are produced by peripheral tissue-derived cells and they modulate the functions of insulin-like growth factors. In this study, both the secretion of IGFBP-3 from a human osteosarcoma cell line MG63 and effects of 1, 25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on the production of IGFBP-3 were investigated. The β subunit of IGFBP-3 was detected immunocytochemically in the perinuclear cytoplasm of MG63 cells. Immunoblotting and SDS-PAGE analysis revealed that both 140-150KD MW entire molecules and 40-60KD MW β subinit molecules of IGFBP-3 were present in cell-conditionel media. 1,25-(OH)(2)D(3) stimulated the production of the IGFBP-3 molecule by MG63 cells. The concentration of IGFBP-3 conditioned media began to rise at 24 hours after the addtiton of 10(-9)M of 1,25-(OH)(2)D(3) and reached the peak level at 48 hours. Dose-dependent effects of 1,25-(OH)(2)D(3) were demonstrated. These findings show that MG63 produces IGFBP-3 and that 1,25-(OH)(2)D(3) stimulates the production of this protein. These findings suggest that the synergistic effects of 1,25-(OH)(2)D(3) on the action of IGF-I on osteoblastic cells may be modulated by locally produced IGFBP-3.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155810411-121992Spasticity に対する脊髄硬膜外刺激の作用メカニズムに関する研究11591171ENKoujiMunedaTo investigate the mechanism of the inhibitory effect of dorsal column stimulation (DCS) on the monosynaptic reflex, excitability of the Ia fiber terminal was measured by Wall's method before, during and after epidural spinal cord stimulation. The experiment was performed under general anesthesia on five normal cats and five cats which had undergone hemisection of the lower thoracic cord more than three weeks before the experiment. Bipolar silver-ball electrodes were placed epidurally on the midline of the thoracic cord, caudal to the hemisected site. During and after DCS, increase of the excitability of the Ia fiber terminal was observed in both normal and hemisected cats, suggesting that the presynaptic inhibition at the Ia fiber terminal plays an important role in inhibition of the monosynaptic reflex. Moreover, this excitability change was maintained more than ten minutes after cessation of DCS, compatible with a clinical observation that the inhibitory effect of DCS on spasticity often continues after turning off the stimulating system. However the mechanism of this after-effect is unknown.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581043-41992カイニン酸, キスカル酸およびその拮抗薬投与にともなう脳波および線条体モノアミン代謝産物の変動221234ENMasatsuneYamamotoThe CNS action of kanie acid (KA), quisqualic acid (QA) and 1-(4-chlorobenzoyl)-piperazine-2, 3-dicarboxylic acid (pCB-PzDA) was investigated in male Sprague Dawley rats, and their effects on monoamina metabolite levels in rat striatum were studied using brain dialysis. Intracerebroventricularly injected KA and QA (100nmol) induced spike discharges, and pCB-PzDA (100nmol) suppressed electrocorticograms (ECoG) for 1 hour. pCB-PzDA aggravated KA induced spike discharges and inhibited QA-induced spike discharges. Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels increased transitorily by injection of 100nmol and continuously by injection of 100nmol of KA. KA increased the 5-hydroxyindoleachtic acid (5-HIAA) level 2 hours after the administration dose-dependently. Though 10nmol of QA increased the HVA level slightly, 100nmol of QA increased the DOPAC, HVA and 5-HIAA levels. Though 100nmol of pCB-PzDA increased the DOPAC and HVA levels, it inhibited the increases in DOPAC, HVA and 5-HIAA levels induced by KA. On the other hand,pCB-PzDA inhibited the increases in DOPAC, HVA and 5-HIAA levels induced by QA for 1 hour, after which the DOPAC and HVA levels increased additively. These finding suggest that pCB-PzDA acts not only as a non-NMDA antagonist but also on dopaminergic neurons directly.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155810411-121992気管支喘息の血小板機能に関する研究 第2編 喘息患者血小板の12-HETE 産生能とリンパ球機能に及ぼす影響に関する検討10791086ENKojiSunamiTo clarify the role of platelets in the pathogenesis of bronchial asthma, the production of 12-hydroxyeicosatetraenoic acid(12HETE) from platelets of asthmatics was examined by high performance liquid chromatography(HPLC). The effect of platelets on lymphocyte function was also studied by lymphocyte blastogenesis. The results were as follows : 1) The production of 12HETE from platelets of asthmatics were significantly higher than that of normal subjects(p<0.01). 2) Blastogenesis of lymphocytes was significantly suppressed by addition of platelets(p<0.05). 3) Blastogenesis of lymphocytes was significantly suppressed by addition of more than 12.5ng/ml of 12HETE, 10ng/ml of transforming growth factorβ(TGE-β) or 50ng/ml of serotonin.
These results suggest that platelets play an important role in the pathogenesis of asthmatic responses mediated by activated lymphocytes.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992長期リンパ球混合培養で誘導される抑制性T細胞の免疫学的解析843852ENKatsutoshiTsuboiSuppressor T cells (Ts) may play an important role in the regulation of immunological responses. Ts may play a role in the long-term acceptance of an allogeneic organ graft and the beneficial effects of donor-specific blood transfusions on subsequent transplant survival. The population of Ts induced in mixed lymphocyte culture (MLC) was analyzed, and the mechanism underlying the suppressor activity was examined. The Ts generated in 10-day MLC were found to belong to the OKT8(+) subset and inhibited both mixed lymphocyte reaction (MLR) and cell-mediated lympholysis. These Ts inhibited MLR in an antigen-specific manner, but failed to alter the kinetics of the MLR. Furthermore, these Ts inhibited the production of endogenous interleukin-2 and exerted a suppressive effect only when added early in the culture. In condition, the precise target of Ts generated in 10-day MLC might be the earliest responding T helper clone.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581065-61994間質性肺疾患の病態に関する研究―気管支肺胞洗浄液中サイトカインの検討―641654ENKeisukeSugimotoVarious cytokines are known to participate in the pathogenesis of interstitial pneumonia follewed by lung fibrosis due to the proliferation of fibroblasts and production of collagen fibers. Patients with interstitial pneumonia including idiopathic interstitial pneumonia (IIP) and interstitial pneumonia with collagen vascular disease (IP with CVD) were examined by bronchoalveolar lavage (BAL). Cytokines such as IL-1α, TGF-α, and TGF-β in BAL fluid were measured by enzyme linked immunosorbent assay (ELISA). The concentrations of TGF-α and TGF-β in BAL fluid of patients with IIP and IP with CVD were higher than those of normal control, while IL-1α, in BAL fluid was detected in few patoents. The level of TGF-β in BAL fluid was higher in patients with greater decreases in pulmonary function and overt fibrosis on chest X-ray film, although TGF-α was higher in patients with milder disorders. The concentrations of TGF-α and TGF-β showed positive correlation with soluble IL-2 receptor as well as procollagen type Ⅲ in BAL fluid. These results indicated that cytokines regulationg lung fibrosis play important roles in the pathogenesis of interstitial pneumonia.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581037-81991カイニン酸誘発けいれんにおける細胞外ドパミン量の経時的変化―脳内微小透析法を用いた実験的研究―769778ENMasaruOhnishiTo investigate the role of brain dopaminergic systems in epilepsy, striatal extracellular levels of dopamins (DA) and its metabolites (3,4-dihydroxyphenylacetic acid : DOPAC and homovanillic acid : HVA) were measured during kainate-induced limbic seizures in freely-moving rats, using brain microdialysis. DA and its metabolites were measured by high performance liquid chromatography. Systemic injection of kainate (10mg/㎏, i. p.), which caused stable limbic seizures, significantly decreased the levels of DA and its metabolites. Intrahippocampal injection of kainae (2.5nmol), which also caused limbic seizures, significantly decreased only the DA levels, while DOPAC and HVA levels were unchanged. Similar to the results of the systemic injectjon, intrastriatal perfusion of kainate (10(-2) or 10(-6) M) significantly decreased the levels of DA, DOPAC and HVA in a dose-dependent manner. These findings indicate that, during kainate-induced limbic seizures, DA release was significantly reduced in the striatum. In conclusion, the hypofunction of striatal dopaminergic systems is related to the initiation and progress in epileptic seizures.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581037-81991抗精神病薬によるジストニアの発現機序に関する実験的研究―σ (sigma) sites の関与について―749757ENKazuyaOkumuraRecent findings have suggested that neuroleptics exhibit a strong affinity for not only dopamine receptors, but also the sigma sites. Therefore, some clinical or adverse effects of neuroleptics may be due to their action on the sigma sites. This study showed that intrarubral microinjection of 1,3-di-o-tolylguanidine (DTG) or (＋) -3- (3-hydroxyphenyl) -N-1-propyl) piperidine, sigma ligands, and several neuroleptics such as haloperidol caused dystonic reactions in rats resembling tha acute dystonic reaction in humans. The intensity and duration of the dystonia induced by these drugs showed a correlation with their affinities for the sigma sites. These findings raise the possibility that the acute dystonic reaction, one of the motor side effects of neuroleptics, might be mediated via the sigma sites. On the other hand, BMY 14802, an atypical neuroleptic, never caused dystonia after intrarubral microinjection. Furthermore, BMY 14802 still inhibited the dystonia induced by intrarubral microinjection of DTG. This reduction in DTG-induced dystonia by BMY 14802 may result its direct inhibitory effects against DTG at the sites, because BMY 14802 possesses potent sigma affinty. These findings imply that sigma ligands may be divided into two categories, dystonia-reinforcing and -reducing groups. Application of this theory should lead to the elucidation of the mechanism of neuroleptics-induced dystonia and other motor side effects.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581065-61994虚血心筋の収縮能に与えるATP感受性カリウムチャネルの影響473482ENKouzouMizuoTo determine role of the ATP-sensitive potassium channel (KATP channel) in myocardial function during myocardial ischemia, we evaluated regional myocardial shortening and myocardial blood flow using a constant, low flow perfusion system in open-chest dogs. Coronary blood flow was decreased to halt the control level by constricting the perfusion line with a constant pressure throughout the experiment. Glibenclamide (G), a KATP channel blocker, and pinacidil (P), a KATP channel opener, was infused into the coronary perfusion line after the flow was reduced. When coronary flow was reduced, coronary perfusion pressure was decreased to 55% of the control value, segmental shortening (% SS) of the subendocarial myocardium from 18±2% to 13±2% (mean ± SEM)(P<0.05) and the subendocardial to subepicardial (endo/epi) blood flow ratio measured with colored micrsphers ranged from 1.17±0.04 to 0.82±0.05(p<0.05). The infusion of G caused further reduction of % SS to 3±1% (P<0.001) without significant change in the endo/epi blood flow ratio. Additional infusion of P improved % SS to 11±2%, which did not significanlty differ from the pre-G value. The fingings strongly strongly suggest that KATP channels participate in maintaining myocardial function during ischemia.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581055-61993ラドン水吸入による家兎の副腎髄質カテコラミン分泌作用―組織循環増加作用との関わりについて―419426ENIchioSuzukaTo clarify the relationship between in the increase in subcutaneous tissue perfusion rate (TPR) upon inhalation of radon water and the vasoactive effects of radon, rabbits inhaled nebulized water containing 14,000-18,000 Bq/1 radon (radon group) taken from Ikeda Mineral Spring, Shimane Pref., Japan. Control rabbits inhaled radon water from the same springs which had been kept for over 10 radon half-life periods. TPR was evaluated 15 minutes after the beginning of inhalation by mass spectrometry. After inhalation for 90 minutes, plasma and adrenal glands were removed, and levels of adrenaline and noradrenaline were analyzed by high-performance liquid chromatography (THI mithod). Each group was divided into 4 subgroups according to intravenously injected medication as follows : 1) no medication (without adrenergic blocker), 2) phentolamine (α-blocker), 0.05mg/kg/min, 3) propranolol (non-selective β-blocker), 1mg/kg, and 4) atenolol (selective β1-blocker), 6mg/kg. In the radon group, plasma adrenaline and noradrenaline levels were significantly higher (p<0.01, p<0.05), and adrenaline and noradrenaline levels were significantly lower (p<0.01, P<0.01), than those in the control group. In the no medication and phentolamine subgroups, TPRs in the radon group were significantly higher than those in the control group (p<0.01, P<0.01). In the propranolol and atenolol subgroups, no significant change of TPR was found. It is suggested that catecholamines are secreted from the adrenal glands upon inhalation of radon water and that the β1-action of catecholamines contributes to the increase in tissue perfusion.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581063-419941-β-D-arabinofuranosyl-cytosineの抗腫瘍効果増強に関する研究325334ENNaokiHayashi1-β-D-arabinofuranosyl-cytosine (ara-C) is one of the most effective agents in the chemo-therapy of acute non-lymphocytic leukemia (ANLL). Herein, the effects of uracil(U), deoxyuridine (UdR) and uridine (UR) on the anti-tumor activity of ara-C and on ara-C accumulation in the cells were studied. Growth-inhibition activities of ara-C alone and in combination with U, UdR and UR were determined by the trypan blue method. Cell-killing activities against MOLT-4, HL60, human leukemic progenitors (L-CFU) and human colony forming units (G-CSF) were determined by a colonogenic assay. The growth-inhibition activity of ara-C against MOLT-4 and HL60 was not enhanced by U or UdR. On the other hand, 10(-3)mol UR enhanced the growth-inhibition activity of ara-C against both MOLT-4 and HL60. The 50% inhibition dose (ID50) of ara-C was 6.0×10(-7)mol for MOLT-4 and 4.0×10(-7)mol for MOLT-4 and HL60. On the other hand, in the culture medium containing 10(-3)mol UR ID50 was 3.0×10(-8)mol for MOLT-4 and HL60. Cell-killing acticvity of ara-C was enhanced by 10(-3)mol UR. The 50% lethal dose (LD50) of ara-C for MOLT-4 and HL60 was decreased from 9.0×10(-7)mol to 5.0×10(-8)mol and from 5.0×10(-7)mol to 5.0×10(-8)mol after a 72-hour exposure to 10(-3)mol of UR, respectively. Cell-killing activity of ara-C against L-CFU was enhanced by 10(-3)mol UR in 4 of the 9 ANLL patients. On the other hand, the cell-killing activity of ara-C against G-CSF was enhanced in 2 of the 9 healthy individuals. 10(-8)mol ara-C, UR enhanced the cell-killing activity against L-CFU in 2 of the 9 ANLL patients, but not for G-CSF. Accumlation of (3)H-sra-C in MOLT-4 cells at 12, 24 and 48 hours was significantly increased in culture medium containing 10(-8)mol of (3)H-ara-C and 10(-3)mol of UR. Accumulation of 3H-ara-C in HL60 cells at 24 and 48 hours was also significantly increased. It is noteworthy that the cell-killing activity of ara-C against not only human lymphoid and myeloid leukemic cell lines but also L-CFU was enhanced by the combination with a nucleoside (UR), but not with anti-lrukemic agents. These findings provide some information on the enhancement of the anti-tumor activity and mechanims of resistance of ara-C.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581051-21993慢性経口投与による ACE 阻害剤の虚血心筋保護効果165172ENMinoruNaitohThe protective effect of angiotensin converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion injury was estimated in the isolated working rat heart. Male Wistar rats were divided into four groups and reared for 6 weeks : fed without ACEI (Group A), fed with Captopril 30mg/kg/day (Group B), fed with Captopril 60mg/kg/day (Group C) and fed with Enalapril 20mg/kg/day (Group D). Isolated perfused rat hearts were ischemic for 20min at 37℃ and were reperfused for 30min at 37℃.
Addition of ACEI preserved cardiac output, prevented increase of coronary resistance and release of cardiac enzyme (CPK) in Group B,C,D hearts compared with Group A. These findings suggest that ACEI can protect the myocardium from ischemia and reperfusion injury by pretreatment.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155810611-121994びまん性汎細気管支炎の病態に関する研究―エリスロマイシンの作用機序を中心に―11431157ENShoichiroIrieDPB has been known as a chronic respiratory infection with poor prognosis until introduction of erythromycin (EM) therapy with low-dose and long-term administration. As symptoms and prognosis of DPB were improved enormously under EM therapy, EM therapy on DPB was analyzed to clarify the action and mechanisms. EM in a daily dese of 600 mg was administered to 9 patients with DPB for about 38 months and 7 normal volunteers for 2 months. Most patients with DPB showed the relief of symptoms within 2 months, although the EM concentrations in the blood and sputa were lower than the antibacterial therapeutic level. Immunological examination revealed the decrease in cold agglutinin titer and CD4/CD8 ratio after EM therapy. The neutrophil chemotactic factor (NCF) derived from the mononuclear cell culture of DPB patients was higher than that in the normal control. EM therapy decreased the level of NCF not only in patients with DPB but also in normal volunteers. These findings indicate that the immunological effects of EM play an important role in the treatment of DPB.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581069-101994ラット脳線条体からのモノアミン放出におよぼす δ-Guanidinovaleric acid 及びGABA 受容体作動薬の影響に関する研究9851002ENKazuoIwayaδ-Guanidinovaleric acid (GVA) is an endogenous convulsant and is thought to be a specific GABA antagonist. In the present study, we examined the effects of GVA and GABA agonists, GABA, muscimol and baclofen, on dopamine and serotonin releases in rat striatum using a brain dialysis technique. GVA produced a significant increase in DA released transiently (1mM) and throughout the experiment (10mM) compared with the controls. It also produced a significant increase in 5-HT release in both concentrations throughout the experiment. GABA (10mM) inhibited DA and 5-HT releases induced by GVA. Muscimol (10mM) inhibited DA and 5-HT releases induced by GVA. Especially muscimol was more effective in the inhibition of 5-HT release. Baclofen (10mM) inhibited only DA release induced by GVA. These results suggest that the activation of GABA receptor inhibits the release of DA and 5-HT in the striatum, and that the DAergic system regulates the GABA-B receptor while the 5-HTergic system mainly regulates the GABA-A receptor.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581067-81994小児期における Insulin-like growth factor binding protein-4 (IGFBP-4) の骨成長に及ぼす影響779787ENYoshitakaYamanakaIGFBP-4 is a 24kD protein, originally isolated from the conditioned medium of human bone cells, and has been implicated as a potent inhibitor of IGF action in vitro. To clarify its biological functions in human bone, I measured the serum concentration of IGFBP-4 from patients with endocrinologic disorders, using Western immunoblot. In normal children, IGFBP-4 increased with age. The serum IGFBP-4 levels of patients with GH deficiency and panhypopituitarism were lower than those of normal children. In addition, the serum levels of IGFBP-4 were also significantly lower in children with Turner's syndrome than in the age-matched normal children who were post pubertal. These findings suggest that GH and the sex steroid increase the production of serum IGFBP-4. Then, I examined the influence of GH on the serum level of of IGFBP-4. In the good responders to GH therapy, IGFBP-4 decreased rapidly during the first month, continued to decrease until the third month, and then increased slowly. On the contrary, in the poor responders to GH therapy, the IGFBP-4 level increased until the third month and then remained at a high level. The increased serum IGFBP-4 level may , at least in part, contribute to the low response to GH therapy in the poor responders.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581077-81995改良型神経伝達物質放出測定装置によるE1マウス海馬切片よりの神経伝達物質放出と抗てんかん薬ゾニサミドの影響に関する研究6978ENAtsushiEndoUsing an experimental apparatus for estimating neurotransmitter release from brain slices, which involved an improved type of perfusion chamber and more well-controlled tube lines than the previous one were aspartic acid and γ-aminobutyric acid (GABA) release from hippocampal slices from epileptic E1 mice estimated more exactly and stably. Zonisamide had no effect on the aspartic acid release from hippocampal slices of E1 mice by zonisamide. However, zonisamide accelerated dose dependently GABA release from hippocampal slices of non-stimulated E1 mice, though no such acceleration was observed in stimulated E1 mice, i. e., repeatedly convulsed E1 mice.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581083-61996顆粒球コロニー刺激因子の同種免疫応答に及ぼす影響97105ENSatoshiUeyamaThe administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) increased weight and cellularity of the spleen, leukocyte and granulocyte count of the peripheral blood in a dose- and duration-dependent fashion in mice. When spleen cells as well as serum from mice treated with intraperitoneal injection of 200μg/㎏ of rhG-CSF daily for 7 days were added to an allogeneic mixed lymphocyte reaction (MLR) culture, MLR was significantly suppressed nonspecifically and in a dose-dependent fashion. MLR was also suppressed by adding supernatant of spleen cells using transwells, indicating that suppression was mediated by soluble factor (s) secreted from the spleen cells. The producer cells of the inhibiting factor were found in more mature granulocytes with a high density in the spleen. These results suggested that the proliferated granulocytes induced by G-CSF produced and released factor (s) that suppress allogeneic immune responses.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581093-61997長寿者の居住地の特性と日常生活動作能力 (Activities of Daily Living : ADL)5774ENHidetoshiArakiA study on relationship between the living environment and activities of daily living (ADL) was conducted to all eldery persons of more than 100 years old in 1993. The response was received from 840 males (73.6%) of 100-107 years of ages. Living environment was devided into three areas according to the geographical areas (Hokkaido-Tohoku-Hokuriku-Sanin, Kanto-Tokai-Kinki, and Sanyo-Shikoku-Kyushu), two community types according to an urban or an agricultural or fishing village, and four community sizes according to number of the population. Factors considered to contribute to a high level of ADL were evaluated. The results can be summarized as follows. 1. According to the geographical area, the independence rate (percentage of individuals who were competent for ADL) was significantly higher in Sanyo-Shikoku-Kyushu area than in Kanto-Tokai-Kinki area in all items examined (transferring, feeding, continence and bathing). Regional differences were observed in the state of living, state of medical care, social and cultural activities, and dietary habit since the age of 80 years, watching TV and an interest in health as social and cultural activites were related to high independence rates in areas such as Sanyo. 2. According to the community type, the state of medical care, whether there was a family doctor, social and cultural activities, and dietary habit since tha age of 80 years in agricultural and fishing communities appeared to be favorable for independence rate, but there were not observed significant relations. 3. According to the community size, none of the residents in large cities were independent in eating, continence, or bathing. The independence rate of continence was significantly lower than that in small cities and towns or villages in rural districts, suggesting that large cities are an environment unfavorable for socially independent longevity. The household composition, social and cultural activities, and dietary habit since the age of 80 years were different according to the community size, and reading newspapers of social and cultural activities was related to high independence rates in small cities and towns or villages of rural districts.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581113-81999デイサービス中断の要因 ―女性の場合―5160ENHatsueOkanoTo cope with problems resulting from a rapidly aging society with a low birth rate, effective methods must be established to support home care services through a welfare service system. Characteristics of 40 elderly women living in S City with their familes who had stopped receiving "day service" (discontinued group) were compared with 40 age-matched elderly women selected among those regularly receiving the day service st the same facility. In addition, factors that influenced the women to stop receiving "day service" were studied. A questionnaire consisting of 20 items concerning various activies of daily living (ADL), instrumental ADL(IADL), health states, ecnomical coditions, and reasons for quiting the service was completed by all subjects. The results showed that ADL, IADL and health staes were significantly lower in the discontinued group than those of the control group. About half of the elderly in the dis-continued group quit the services in order to receive medical care at medical institutes. These women were older in age and lower ADL and IADl than those who quit for other reasons. Time needed to care for their husbands and housekeeping, were also reasons for qutiting the day service in the relatively younger group whose ADL snd IADL were well maintitained. Therefore, I concluded that "day service at welfare facilities" may become competitive with medical and health facilities already supporting home care services for the aged. if knowledge increases about social resources to support home care services.No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama038630693942008参入阻止モデルの１つの変遷193200ENKazuhiroOhnishi10.18926/OER/12389The limit pricing model by Bain, Sylos−Labini and Modigliani is a famous theory on entry deterrence. A single incumbent firm or a coordinated cartel competes against a single potential entrant. The limit pricing model assumes that the incumbent firm can continue to produce at its pre−entry output level regardless of the potential entrant’s actions. However, it has been pointed out that the limit pricing model is unrealistic and only an empty threat. That is, it is possible to judge the success of the incumbent firm’s strategic behavior only if the decisions that the incumbent firm made prior to entry cause changes in the post−entry competing environment. Irreversible behavior, such as the installation of machinery and equipment, can be said to be the essence of
competition among firms. The possibility of firms using excess capacity to deter entry has been studied by many
economists. This paper surveys theories of entry deterrence.No potential conflict of interest relevant to this article was reported.岡山大学農学部Acta Medica Okayama0474-02549012001Structural Characterization of ACC Synthase Genes from Melon and Cucumber and their Promoter Activities Determined by GUS Transient Assay2735ENShinjiroShiomiOguraEmiMikihiroYamamotoReinosukeNakamuraYasutakaKuboAkitsuguInabaIn orader to clarify the differences in regulatory mechanism(s) of the expression of 1-aminocyclopropane-1-carboxylate(ACC) synthase(ACS)genes during ripening in climacteric melon fruit and non-climacteric cucumber fruit, two sets of their genomic DNA sequences, including ca. 2kb of the promoter regions were determined, using PCR-based methods. ACS genes from melon (CMe-ACS1,2) were structurally similar to their counterpart from cucumber (CS-ACS1,2) in terms of size and position of exons and introns, restriction map, and sequencd identity of exeons, introns, proximal 5'-flanking promoter regions and splice junction. Southern blot analysis indicated that each ACS gene is present as a single copy. Transient promoter activity was investigated with two constructs of promoter-β-glucuronidase (GUS) fusion, CMe-ACS1:GUS and CS-ACS1:GUS, in mature mesocarp tissue of the two fruits. In melon disks, GUS activities conferred by the promoters of both CS-ACS1 (-2098～+42) and CMe-ACS-1(-2187～+67) were detected, which were decreased by treatment with 1-methylcyclopropene(1-MCP), an ethylene action inhibitor. In cucumber disks, however, only CS-ACS1:GUS was expressed; the activity was decreased with 1-MCP, and it was not affected by propylene. These results suggest that the promoter of CS-ACS1 has a potential to be expressed in the mesocarp tissue of ripening melon fruit, and that the difference in ethylene biosynthesis between melon and cucumber during ripening may be due to the difference in capability of forming trans-acting factor(s), not due to their ACS1 promoter activities.No potential conflict of interest relevant to this article was reported.