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Biomedical subjects

M Kuroda

Publications and source records attributed to M Kuroda.

At least 505 records · Page 28Linked to original sources
PubMed1979

Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals.

ML-263B (compactin), a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, is very effective in lowering serum cholesterol levels in animal species such as hens, dogs, monkeys and man. In the present studies, the effect of this drug on cholesterol metabolism in several strains of mice and rats was studied. The results indicate that, when administered for a longer period, the drug showed no hypocholesterolemic activity in these species under either normo- or hypercholesterolemic conditions, except for rats treated with the detergent Triton WR-1339. The administration of ML-236B caused a significant decrease in fecal excretion of bile acids and in the hepatic levels of cholesterol 7 alpha-hydroxylase, and produced a marked increase in hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase activity, resulting in no inhibition of hepatic sterol synthesis, even in the presence of the drug in the active form(s). It is concluded that the lack of hypocholesterolemic activity of ML-236B in mice and rats could, at least partly, be explained by these unexpected results.

Animals↗
PubMed1979

Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The fungal metabolite ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, has been shown to be significantly effective in lowering serum cholesterol levels in cynomolgus monkeys at doses of 20-50 mg/kg per day. Levels of serum phospholipids and triglycerides were, however, not significantly changed by the administration of the drug. Of the serum lipoprotein fractions, a beta-lipoprotein corresponding to low density lipoprotein was preferentially reduced by the drug treatment. Fecal excretion of neutral sterols was unaffected but that of bile acids and slightly elevated by the administration of ML-236B.

Animals↗
PubMed1979

Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, significantly reduced both serum cholesterol and phospholipid levels in dogs, when used at a dosage higher than 10 mg/kg per day. Triglyceride levels were not consistently changed, but beta- and pre-beta-lipoproteins were preferentially reduced. Serum cholesterol levels were reduced by 44--45% at the higher dosage of 100--400 mg/kg per day (for 5 weeks) but ML-236B caused no significant changes in the cholesterol content of the liver and aorta and in the activities of serum GOT, GPT, CPK and lecithin : cholesterol acyltransferase. Fecal excretion of neutral sterols was unaffected but that of bile acids was markedly elevated by the drug. Under these conditions, hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, showed no detectable changes.

Animals↗
PubMed1979

A unique affinity and adaptation of renomedullary interstitial cells for hypertonic medium.

Collagenase-dispersed cells of renal papillary tissue from adult mongrel dogs were directly inoculated in a modified M.E.M. (Eagle's) giving an osmolality of approximately 1,000 mOsm/L by addition of urea and sodium chloride, and were cultured in an atmosphere of 95% air-5%CO2 at 37 degrees C. Within twelve hours after inoculation, spindle-shaped cells attached firmly to the surface of culture dishes, while the other cellular components of the inner medulla remained floating in the medium. After several days in culture, the colonies grew to form a confluent cell layer, which was composed of almost homogenous cells giving spindle-shape. These cells kept on the major characteristics of renomedullary interstitial cell (RIC) in morphology as well as in function to produce prostaglandin E. These results appear to be principally attributable to the unique characteristics of RIC, one of which is affinity for high osmolality and the other is different behavior in attachment to the dish. As the procedure proposed here was relatively simple and did not require a long period up to the development of monolayer, it would provide a promising model "in vitro" to study the humoral regulation of prostaglandin production.

Animals↗
PubMed1978

Hyperuricemia associated with hypertension. A 4-year follow-up study of hyperuricemic hypertensives.

We investigated the prognosis of 153 hypertensive patients, whose initial concentration of serum uric acid had been evaluated. One hundred and seventeen subjects could be followed up after 4 years and 16 of them died during the follow-up period. Cerebrovascular disease was seen in 6 subjects, 4 of whom died from the disease. Myocardial infarction and heart failure occurred in 9 and 7 of them died as a result. The frequency of these diseases was greater among the hyperuricemic group and 8 of the 11 who died belonged to this group. Four men were struck by gouty attacks. They were all hyperuricemic and had been proven to have at least one family member with asymptomatic hyperuricemia and/or gout. It is reasonable to regard the presence of hyperuricemia as one of the poor risk factors for vascular diseases. I addition, we must investigate more closely personal and family histories of gout when we see hyperuricemic subjects, regardless of absence of gouty symptoms.

Adolescent↗