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<p>To assess the role of the kidney dopamine system on the diuretic state induced by angiotensin-converting enzyme (ACE) inhibitors, we examined the changes in urinary excretion and plasma level of dopamine, and kidney dopamine receptors in spontaneously hypertensive rats (SHR) treated with cilazapril, an ACE inhibitor. We administered cilazapril 10 mg/kg orally to 13-week-old SHR daily for 21 days (CILAZA group). Systolic blood pressure was significantly decreased in the CILAZA group on Day 6 compared with that in vehicle-treated SHR (control group). The urine volume was three- to fivefold higher in the CILAZA group, and total urinary dopamine secretion was also increased compared with the control group. There was no significant difference in affinity and number of kidney dopamine receptors between the CILAZA and the control groups. In conclusion, the diuretic effect caused by cilazapril is partly mediated by inhibition of the water reabsorption via the increase of dopamine production in the kidney.</p>

The antitumor effects of indomethacin and interleukin 2 (IL-2) were studied in C3H/HeJ mice inoculated with MH134 hepatoma cells. Combined treatment with indomethacin and IL-2 augmented natural killer (NK) cells in mice with MH134-induced peritoneal carcinomatosis, and the survival of the treated mice was significantly longer than the non-treated mice. In animals with subcutaneous MH134 tumors, the combined therapy with indomethacin and IL-2 significantly suppressed tumor growth and induced complete regression of the tumor in three out of five mice. These results suggest that indomethacin and IL-2 therapy could be effective on human gastrointestinal cancer cells as well.

We examined the pharmacokinetics of phenobarbital before and during pregnancy in rats. Animals were divided into four groups: (a) control, (b) pregnant, (c) phenobarbital-treated, and (d) phenobarbital-treated pregnant groups. The increase in body weight of nonpregnant or pregnant rats was not influenced by long-term phenobarbital treatment. Plasma phenobarbital concentrations during the period of long-term phenobarbital treatment with a fixed dosage by body weight were not significantly affected by pregnancy. Furthermore, pregnancy did not affect pharmacokinetic parameters of phenobarbital between 0.25 and 24h after administration. These results suggest that pregnancy does not influence on the pharmacokinetics of long-term phenobarbital treatment at a fixed dosage by body weight.

Eighty-one adult Nigerians with essential hypertension were randomly allocated to receive doxazosin, hydrochlorothiazide/amloride, or amlodipine. In each group, the patients were further classified as obese and non-obese, and total cholesterol as well as high density lipoprotein (HDL) cholesterol was determined before and after the 3-month treatment period. The total cholesterol level was significantly reduced in the non-obese patients, but did not show any significant change in the obese patients after doxazosin therapy, indicating the beneficial effects of doxazosin therapy in non-obese patients. The levels of total cholesterol increased and HDL cholesterol decreased in both the obese and the non-obese patients after hydrochlorothiazide/amloride therapy. Amlodipine treatment did not cause any significant change in the total and HDL cholesterol levels in both the obese and non-obese patients. These findings are worthy of consideration by clinicians and researchers when selecting the most appropriate drug for antihypertensive pharmacotherapy.

Seventy-six patients with ulnar neuropathy at the elbow were divided into 3 classes (Grades I, II, and III) according to their clinical features and the maximal motor nerve conduction velocity (MCV), and the amplitude ratios at the across-elbow segment were retrospectively analyzed. To determine the criteria for abnormality, a control study was conducted on 150 healthy volunteers ranging in age from 20 to 89 years (6 age groups). The normal value for MCV could be set for two age groups: those under 60 and those over 60 years old. The 95% confidence limit was 54m/s for the former and 50m/s for the latter. There was no statistically significant difference in the amplitude ratio among the age groups. The confidence limit was set uniformly at 0.82 (above elbow/below elbow). An abnormality in either MCV or the amplitude ratio was found in 66.7% of Grade I (recent and mild symptoms), 89.7% of Grade II (persistent symptoms), and 100% of Grade III cases (marked intrinsic muscle atrophy). Evaluation using the combination of MCV and the amplitude ratio, considering the age-related normal value, appeared to be useful in establishing a differential diagnosis of ulnar neuropathy at the elbow.

The reduced hepatic blood flow calculated from hepatic scintigram with 198Au colloid was elucidated as the primary responsible factor for postoperative hepatic insufficiency. However 198Au colloid is no longer in use because of the high levels of radiation. Although 99mTc-phytate behaves similarly to 198Au on imaging, there were discrepancies between the hepatic blood flow index (KL) value and the severity of cirrhosis determined by laboratory data or by histology. In the measurement of hepatic blood flow using a radioactive colloid, factors like organ distribution, stability and uniformity of the colloid particles influence the values. In the present study, a 111In colloid was prepared and administered to rats to investigate the usefulness: as much as 95.4 (0.8) [Mean (+/- SD)]% of the colloid accumulated in the liver at pH 6.8. The distribution of particle diameter was within a relatively narrow range with the peak at 0.2 to 0.4 microns. Moreover, the KL values were not affected by condition of the reticuloendothelial system. The values showed a significant correlation with the measurements of the hepatic tissue blood flow obtained by the hydrogen gas clearance method (gamma = 0.83, P < 0.001). Thus, the 111In colloid can be clinically used as a substitute for 198Au colloid in the preoperative examination for estimation of the limit of resection.

The medical records of 16 consecutive patients with Crohn's disease surgically treated in our department from 1978 to 1993 were retrospectively reviewed. The indication for surgery was obstructive symptoms due to Crohn's strictures that were unresponsive to conservative therapy. The types of operations performed were classified into five categories. Nine patients (56.3%) had small bowel resection only, 4 (25.0%) underwent an ileocolonic resection, 1 (6.3%) had a total colectomy, 1 (6.3%) had Mile's operation and 1 (6.3%) had subtotal gastrectomy with gastrojejunostomy and antral mucosectomy. Of these 16 patients, 13 (81.3%) had resection with a single anastomosis and strictureplasty was concomitantly performed in only 2 cases (12.5%). Crohn's disease recurred in 3 patients (18.8%), 1 of whom required a second operation.

In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA) glutamate-receptor-subunit (GluR-1) mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg)-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days) significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01) and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001). These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs.

We administered a biological response modifier Picibanil (OK-432), attenuated Streptococcus pyogenes, via the dorsal vein of the penis after 70% hepatectomy in rats, and clarified the scavenging effect of Picibanil on free radicals generated in the regenerating liver. A group of 5 rats was intravenously administered with 25 KE/kg of OK-432 after hepatectomy, while the control group was given saline after hepatectomy. Serum levels of aspartate aminotransferase and alanine aminotransferase and the value of thiobarbituric acid-reactive substances in serum and hepatic tissue after hepatectomy were serially measured, and these values were significantly lower in Picibanil treated animals than in control animals. Free radical production in the regenerating liver was also measured by electron spin resonance spectrometry, and OK-432 injection significantly reduced free radical production. These results suggested that OK-432 reduced hepatocellular damage in regenerating liver by inhibiting lipid peroxidation.

The incidence of nosocomial infections with methicillin-resistant Staphylococcus aureus is of great concern in Japan and the developed world as a whole. Simple typing techniques like coagulase and phage typing are quick and useful for monitoring and evaluating these organisms. In view of this, the current status of antimicrobial susceptibility in Staphylococcus aureus (S. aureus) isolates in Okinawa typed by coagulase and phage typing was studied. Of 508 isolates, methicillin-resistant S. aureus (MRSA) comprised 54.3% (minimum inhibitory concentration (MIC) > or = 16 micrograms/ml). Coagulase type II and phage group III were the most prevalent, comprising 65.2% and 38%, respectively. These were followed by phage non-typable group and coagulase type III with 36.6% and 12.7%, respectively. Compared to a previous study conducted in 1989, there has been an increase of about 17% in the MRSA isolation rate with a concomitant increase of about 11% in the coagulase type II MRSA isolation rate and a decrease of about 27% in the isolation rate of coagulase type III MRSA. Using a panel of 16 antibiotics, coagulase type II MRSA were resistant to all except Arbekacin and Vancomycin. Arbekacin and Vancomycin were the sole antibiotics to which resistance was not expressed by any of the isolates. With regard to the methicillin-sensitive S. aureus (MSSA), coagulase type III and phase group III were the most prevalent, comprising 25.9% and 32.3%, respectively.

An enzyme-linked immunosorbent assay (ELISA) using biotin-labelled oligo-dT primer and digoxigenin (Dig)-dUTP was designed to measure the reverse transcriptase (RT) activity of human immunodeficiency virus type 1 (HIV-1). The ELISA system involves the selective detection step of a newly synthesized cDNA by two specific bindings, biotin-streptavidin binding and alkaline phosphatase (AP)-conjugated anti-Dig-Dig binding, and the enzymatic amplification step to increase coloring generated by AP. This method was used to measure the activity of RT in the culture supernatants of peripheral leukocytes obtained from four anti-HIV-1-positive persons cocultivated with those from four anti-HIV-1-negative persons. RT activity was detected in all of four anti-HIV-1-positive culture supernatants but not in those cultivated with anti-HIV-1-negative supernatants alone. Thus, our improved ELISA for detection of HIV-1 appears to be sensitive enough and useful for routine laboratory work. This non-radioactive method will also be useful for detecting other retroviruses and for screening of RT inhibitors.

The purpose of this study was to determine the aerobic training intensity from the maximal and submaximal running exercise in 21 untrained adult men. To accomplish this, we evaluated the relationship between physiological (oxygen intake and heart rate) and physical parameters (running speed) of training intensity, and determined the training intensity at the submaximal exercise. Oxygen intake and heart rate were measured by a treadmill test. The maximal oxygen intake (VO2 max), and the aerobic threshold (AerT) and anaerobic threshold (AT) were measured to determine respiratory gas exchange. Running capacity was measured by a 12-min running and treadmill test. For the maximal exercise, there was a significant correlation (r = 0.88, P < 0.01) between VO2 max and 12-min running distance (speed). In addition, the oxygen intake and heart rate at AerT and AT in the submaximal exercise were linearly correlated with running speed. Three levels of training intensity at the submaximal exercise were termed: light, moderate, and heavy. Since AerT was the lower limit intensity and AT was the upper limit, we took the middle of their values as the moderate intensity. The end point for the determination of the training intensity at the submaximal exercise was estimated to be 85% VO2 max and 180 beats.min-1.

The contribution of age groups and causes of death to the sex difference in life expectancy (SDLE) at birth in Japan and Scotland was estimated for the period 1965-1990. The purpose was to determine the particular age groups and causes of death responsible for the opposite trend of SDLE in the two countries. SDLE has been widening and narrowing in Japan and Scotland, respectively. The availability of complete and reliable data for these two developed countries facilitated the study. A method of decomposing the total SDLE into age and cause of death components was employed. About 40-60% contribution to SDLE was observed for ages after 65 years. Marked increase in the contribution of the 75+ age group and marked decrease in the contribution of ages 45-64 for Japan and Scotland, respectively, had a major effect on the widening and narrowing of SDLE in the two countries, respectively. The contribution of diseases of the circulatory system was the maximum until 1980 in Japan (< or = 1.8 years or 33.6%; cerebrovascular disease alone < or = 23.4%) and until 1990 in Scotland (< or = 3.1 years or 47.0%; ischemic heart disease alone < or = 42.0%). In Japan, the contribution of malignancy had a marked increased from 0.7 year (12.3%) to 2.0 years (32.6%), particularly for the trachea, bronchus and lung, while there was only a small increase in Scotland from 1.0 year (16.6%) to 1.2 years (19.8%) with an increase in the negative contribution of female breast malignancy. In Japan, the contribution of diseases of the respiratory system increased considerably from 0.5 year (8.5%) to 1.1 years (18.1%) while it decreased in Scotland from 1.0 year (16.5%) to 0.6 year (10.7%). About 60-75% of SDLE is due to the above three groups of causes of death. Malignancy and diseases of the respiratory system had a persistently increased contribution in Japan with resultant widening of SDLE by 0.9 year. Diseases of the circulatory system have always had a high contribution. On the contrary, in Scotland the contribution of diseases of the circulatory system and malignancy was practically unchanged and diseases of the respiratory system had a decrease with a consequent narrowing of SDLE by 0.4 year. Further epidemiological study is necessary to detect and analyze in detail the internal gradients (environmental and genetic-biological) of major contributor diseases to SDLE in Japan and Scotland.

A study of 1,254 laparoscopic cholecystectomies performed at 17 hospitals affiliated with the Liver, Gallbladder, and Pancreas Research Group of the First Department of Surgery at Okayama University was undertaken to assess the current status and safety of this procedure. The data for 336 patients, comprising the initial 20 laparoscopic cholecystectomies performed at each institution, were compared with the data from the remaining 918 patients. Comparison of the two groups revealed the following: 1. the rates of intraoperative conversion to open cholecystectomy were 11.3% and 5.1% (P < 0.05), 2. the complication rates were 5.7% and 3.4%, and 3. the rates of bile duct injury were 2.4% and 1.1%, respectively. Compared with the first group, the bile duct injuries resulting from a lack of experience decreased in the second group, however, the incidence of these injuries occurring during avulsion of the gallbladder in difficult cases increased. These results suggest that the experience acquired during the initial 20 laparoscopic cholecystectomies led to a reduction in the rate of intraoperative conversion to open cholecystectomy, but it did not reduce the rate of complications, and that the risk of bile duct injury was always present.

Chinese ant extract preparations (CAEP) are a Chinese traditional medicine which is mainly used as a health food or drink for the treatment of rheumatism, rheumatoid arthritis, chronic hepatitis, sexual hypofunction, and antiaging in China. The effects on free radicals were examined by electron spin resonance spectrometry using the spin trapping agent 5.5-dimethyl-1-pyrroline-1-oxide (DMPO). Superoxide radicals (3.35 x 10(15) spins/ml) were quenched 50% by the extract at 0.5 mg/ml. The CAEP extract at 0.7 mg/ml inhibited 50% of hydroxyl radicals (52.0 x 10(15) spins/ml) generated by the Fenton reaction. Against DPPH radical, the scavenging action of CAEP was observed at 1.8 mg/ml of the extract and 50% of the DPPH radicals (8.14 x 10(15) spins/ml) were quenched. In vitro tests showed that CAEP inhibited the production of thiobarbituric acid-reactive substances, an index of lipid peroxidation, in rat brain homogenate.

This study was conducted to retrospectively analyzed the outcome of 192 total knee arthroplasties in 132 patients with rheumatoid arthritis (118 women, 14 men). The Okayama Mark II prosthesis, which requires the posterior cruciate ligament (PCL) to be resected, was used in 83 knees (group I), the Mark II prosthesis, which allows the PCL to be retained, was used in 68 knees (group II), and the new Okayama PCL-R prosthesis, which also allows the PCL to be retained, was used in 41 (group III). According to the Japanese Orthopaedic Association knee scoring system, the clinical outcome of groups I, II and III at 1 year after the operation were 64.9, 71.2 and 72.3 points, respectively, and the average flexion angles in each group at 1 year were 78.4, 92.6 and 101.3 degrees. Postoperative flexion in groups III was significantly greater than in groups I and II. These results suggest that postoperative flexion is greater when the posterior cruciate ligament is retained.

Localization of the glycosaminoglycans (GAG) was examined in the synovial membranes of patients with osteoarthritis under light microscopy using a fine cationic colloidal iron staining method combined with enzymatic digestion. Our staining method was very useful for demonstrating the difference in the localization of GAG in regions of the inflammatory site in the osteoarthritic synovial membrane. Hyaluronic acid was mainly located in connective tissues in the surface intercellular and perivascular spaces, chondroitin sulfate A/C in the highly fibrous part of and connective tissue around blood vessels, dermatan sulfate (chondroitin sulfate B) in the subsurface interstitium and vascular endothelial cells and heparan sulfate in part of vascular endothelial cells. No keratan sulfate was detected. GAG is reported to have an important role in cell movement, adherence and aggregation in the inflammatory sites. These findings should be useful for understanding the role of GAG in physiological and pathologic processes of secondary synovitis.

Etoposide (VP-16), one of the topoisomerase II (TopoII) inhibitors, interferes with TopoII by inducing the formation of and stabilizing a cleavable enzyme-DNA complex. VP-16 has been demonstrated to induce apoptosis in murine thymocytes. To clarify the mechanism of action of VP-16, we examined the in vitro effect of a non-cleavable-complex-forming type TopoII inhibitor, ICRF-193 which inhibits the DNA strand breakage induced by VP-16, on murine thymocytes in which apoptosis had been induced with VP-16. DNA fragmentation is characteristic of apoptosis. In the early stages, ICRF-193 decreased DNA fragmentation induced by VP-16, although this inhibitory effect decreased in the later. These data suggest that TopoII inhibitors induce apoptosis in murine thymocytes in two ways: with DNA-strand breaks in the early stage or without them. ICRF-193 itself induced apoptosis in murine thymocytes. The time course of DNA fragmentation caused by ICRF-193 was different from that of VP-16.

In this study, we measured free radicals and thiobarbituric acid-reactive substances (TBARS) in hepatocellular carcinoma and in non-cancerous liver parenchyma. There was a higher concentration of free radicals in malignant tissue than in non-cancerous tissue. In contrast, the level of TBARS was significantly (P < 0.01) lower than non-cancerous liver parenchyma. These paradoxical results suggested that antioxidative enzyme activity and/or inhibition of lipid peroxidation were higher in hepatocellular carcinoma.

Examination was made of the in vitro response of human peripheral blood mononuclear cells (PBNMCs) to phytohemagglutinin (PHA) following treatment with varicella zoster virus (VZV) or herpes simplex virus type 1 (HSV 1). Cell proliferation was determined by colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide. The response to PHA was depressed in all cases by virus infection of PBMNCs prior to PHA treatment. When the infection with the viruses was after PHA treatment, PHA response differed. For VZV infection, the response increased in four out of six samples, but was reduced in the other two. The response to PHA was depressed in all six samples by HSV 1 infection.