検索

Neuroprotective therapy for Parkinson's disease (PD) is a treatment intended to prevent or reduce neuronal degeneration. Since clinical studies to evaluate such an effect would be prolonged, the choice of agents for use as possible neuroprotective therapy is based on the results of in vitro and animal experiments. Free radicals are currently regarded as the most important factor in the progression of PD. One current possible neuroprotective therapy is reduction of levodopa dose, since levodopa is a source of free radical formation. Dopamine (DA) metabolism inhibition, and administration of the DA agonist bromocriptine that eliminates hydroxyl free radicals have neuroprotective effects experimentally. The other candidates for neuroprotective agents are still under development. However, those whose clinical use is permitted should be considered for use, since patients with long-standing PD cannot wait until the neuroprotective efficacy of these agents is confirmed by clinical study.

Leucine decarboxylation in rat brain was investigated during acute hepatic failure, induced by partial hepatectomy after carbon tetrachloride (CCl4) pretreatment of rats. These rats presented metabolic alkalosis, and had significantly higher levels of arterial blood and brain ammonia than control and CCl4-treated rats. Brain leucine decarboxylation was elevated in rats with hepatic failure. This alteration correlated with arterial blood ammonia concentrations, and probably with elevated brain ammonia levels, as brain ammonia levels were directly related to arterial blood ammonia.

L-Cysteine (5.0 mmol per kg of body weight) was intraperitoneally injected into rats fed a 25% casein or 5% casein diet. Concentrations of acidic and neutral amino acids in various tissues were determined 2 h later. In the rats fed the 25% casein diet there was a tendency for tissue amino acid and glutathione levels to be slightly lower than controls. In the 5% casein diet group, however, concentrations of tissue amino acids and glutathione generally increased after L-cysteine administration. S-(2-Hydroxy-2-carboxyethylthio)cysteine (HCETC,3-mercaptolactate-cysteine disulfide), though in trace amounts, was detected in kidney and blood plasma in the 5% casein diet group. Increases in cysteine-glutathione disulfide in liver, kidney and erythrocytes in the 5% casein diet group were considerable. These results indicate that L-cysteine was rapidly metabolized in the 25% casein diet group through the oxidative pathway, while in the 5% casein diet group, in which liver cysteine dioxygenase activity is supposed to be quite low, the oxidative metabolism of L-cysteine decreased and part of the L-cysteine was metabolized through the transaminative pathway. Administration of 15.0 mmol L-cysteine per kg of body weight to rats fed the 25% casein diet resulted in an increase in cysteine-glutathione disulfide in liver, kidney and erythrocytes, and the appearance of HCETC in blood plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

A single injection of ferric nitrilotriacetate (Fe3+-NTA) caused a transitory increase in plasma immunoreactive insulin (IRI) and plasma immunoreactive glucagon (IRG) in rats. They reached maximum levels at 2 days after injection and returned to the normal range at 10 days. At 2 days after Fe3+-NTA injection, blood glucose level was normal but the glucose tolerance test (GTT) was impaired. There was a further increase in plasma IRI level and IRG level was suppressed after glucose loading. At 10 days after Fe3+-NTA injection, glucose tolerance was normal and IRI also returned to the normal range. No degenerative changes were found on H.E.-stained rat pancreatic tissue sections after Fe3+-NTA injection. Histochemical staining, however, showed a reduction in beta-granules and heavy metals (Timm's granules) from islet cells in the central area of the rat pancreatic islet 1 to 3 days after injection of Fe3+-NTA. The fading remained in some islets even at 10 days after injection, but by then the beta-granule distribution was restored in most islet cells. The results indicate a single Fe3+-NTA injection induced transitory instability of the pancreatic islet beta-cell granules and the glucose intolerance with a hyperresponse of IRI.

The present study investigated the brain catecholamine metabolism of rats with liver injury induced either by malnutrition or with CCl4. In the malnutrition group, the plasma tyrosine concentration was low, while it showed a tendency to be high in the cerebral cortex. Dopamine concentrations were low in both the cerebral cortex and diencephalon. Norepinephrine concentrations were low in the cerebral cortex, striatum and diencephalon. Tyrosine hydroxylase activity was elevated while monoamine oxidase activity was decreased in the striatum. In the CCl4 group, tyrosine concentrations in the plasma and cerebral cortex did not change. The dopamine concentration in the cerebral cortex increased five days after, and the norepinephrine concentration in the diencephalon increased 24 h after the last administration of CCl4. These data suggest that catecholaminergic neurons in the brain may be substantially affected by liver injury. It may be considered that malnutrition disturbs brain development, particularly in young rats.

Two cases of chronic unconjugated hyperbilirubinemia and marked retention of indocyanine green (ICG) are described. Since bilirubin uridine diphosphate (UDP)-glucuronyl transferase activities were depressed in their liver, the patients seemed to have bilirubin metabolism similar to that in Gilbert's syndrome. However, the ICG fractional disappearance rates of the cases were rather low (0.018 and 0.019) compared to the rates reported for Gilbert's syndrome. These results suggest that the patients had a new metabolic disorder which results in constitutional unconjugated hyperbilirubinemia and ICG intolerance.

Transaminative metabolism of L-cysteine was investigated using homogenates of guinea pig liver and kidney. L-Cysteine was transaminated in the presence of 2-oxoglutarate and the homogenate of either liver or kidney. S-(2-Hydroxy-2-carboxyethylthio)cysteine (HCETC) (3-mercaptolactate-cysteine disulfide) was formed by liver homogenate, but the amount was very small. On the other hand, a relatively large amount of HCETC was formed in the presence of kidney homogenate. Transamination between 3-mercaptopyruvate and certain amino acids was catalyzed actively by both liver and kidney homogenates in the presence of L-glutamate. However, more half-cysteine was formed by liver than kidney, and more HCETC was produced by kidney than liver. L-Glutamate was the most potent amino donor, and L-aspartate strongly inhibited the reaction. Results indicate that L-cysteine can be transaminated both in liver and kidney of the guinea pig, and that kidney is more active than liver. 2-Oxoglutarate is the most active 2-oxo acid for cysteine transamination. Oxaloacetate (and aspartate in the reverse reaction) is inhibitory to the reaction. These results are in agreement with the previous conclusion that cysteine aminotransferase is identical with aspartate aminotransferase.