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Biomedical subjects

J Ostrowski

Publications and source records attributed to J Ostrowski.

At least 145 records · Page 8Linked to original sources
PubMed1984

Intravenous and oral administration of molsidomine, a pharmacodynamic and pharmacokinetic study.

In 12 healthy male volunteers, molsidomine 1, 2 and 4 mg i.v. increased resting heart rate and decreased systolic blood pressure, the latter still being affected after 8 hours. After single oral doses of 1 and 2 mg, systolic pressure tended to be reduced for 90 minutes and exercise heart rate tended to be increased. After oral treatment with 2 mg molsidomine three times daily for 1 week, the pharmacokinetic parameters and the effects on heart rate and blood pressure after the final dose were not different from those after the first dose. The terminal half-life was independent of dose and route of administration. Clearance and distribution volume were not dose-dependent. The bioavailability of a 2 mg oral dose of molsidomine was 44%. Inter-individual variation in heart rate, blood pressure and pharmacokinetics was observed.

Administration, Oral↗
PubMed1984

The function and morphology of the liver in porphyria cutanea tarda.

The aminopyrine breath test, postprandial serum bile acids, and routine liver tests were assessed as indicators of liver dysfunction in 38 patients with porphyria cutanea tarda. In 17 patients needle biopsy specimens of the liver were obtained. Bile acids were increased in almost all the patients studied (97%) but impairment of aminopyrine demethylation was found in only 45%. More than 50% of cases had elevated activities of serum alanine aminopeptidase, leucine aminopeptidase, gammaglutamyl transpeptidase (GGTP), and alanine aminotransferase (ALAT). All liver biopsy specimens showed fluorescence characteristic of porphyrins. Histologic examination of biopsy material revealed cellular lesions in all cases, the most common pathological findings being fatty degeneration of varying degree and iron accumulation. The most frequent electronmicroscopic changes in the liver were fat droplets, granules containing bile material, and siderosomes in the cytoplasm of hepatocytes. However, there was no evident relationship between morphological and functional liver changes.

Adult↗
PubMed1984

Urinary porphyrins in liver disease.

By use of quantitative thin-layer chromatography, urinary porphyrins were examined in 40 healthy volunteers, 38 patients with prophyria cutanea tarda (PCT), and 139 patients with various liver diseases. Significant elevations not only of coproporphyrin but also of some other porphyrins were found in many patients with liver disease. However, there was no evident relationship between porphyrin disturbances and functional or clinical findings, and all of these non-PCT patients who initially demonstrated intense uroporphyrinuria, when re-studied apparently had more normal porphyrin excretion. It seems, therefore, that whereas porphyrin estimations are useful in porphyrias, no clinically important conclusions can be drawn from urinary findings in patients with liver disease. The origin of defective haem biosynthesis in liver disease remains obscure. It can only be speculated that transient and reversible urocoproporphyrinuria may occur in patients with defective hepatic uroporphyrinogen decarboxylase activity who clinically and biochemically are not porphyric.

Adult↗
PubMed1984

[Lipoprotein regulatory effect of molsodomine in rats].

The antianginal drug N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine, Corvation) was orally administered (dose range 10(-5) - 10 mg/kg) to Wistar rats over 7 d once a day. The concentration of low density lipoprotein (LDL)-cholesterol in serum was decreased (40-45%) by therapeutic relevant dosages of molsidomine corresponding to an increase (80%) of the vasoprotective index high density lipoprotein (HDL)/LDL. HDL-cholesterol stayed unchanged. Clofibrate did not change the concentration of the lipoproteins in rat serum under equimolar conditions.

Animals↗
PubMed1983

Abnormalities in liver function and morphology and impaired aminopyrine metabolism in hereditary hepatic porphyrias.

The aminopyrine breath test and measurement of postprandial serum bile acids were performed in 67 patients with well-documented hereditary hepatic porphyria. Elevated postprandial serum bile acids levels were found in 75% and the aminopyrine breath test was abnormal in 42% of the patients studied. These function tests exhibited a statistically significant correlation with the excretion of porphyrin precursors in patients with acute intermittent porphyria. Furthermore, all 12 patients with acute intermittent porphyria who had a liver biopsy because of abnormalities in the aminopyrine breath test or postprandial serum bile acids measurement, or both, were found to have diffuse, moderately severe, but nonspecific ultrastructural changes of hepatocytes, indicative of significant subcellular damage. While a direct relationship between functional and morphologic abnormalities is speculative, it is possible that the defective heme biosynthesis, perhaps related to the reduced aminopyrine demethylation, could form the basis for the ultrastructural hepatic changes in porphyria. This, in turn, could be the cause of the elevated postprandial serum bile acids levels.

Adult↗
PubMed1981

Effect of DNA gyrase inhibitors on gene expression of the cysteine regulon.

Nalidixic acid inhibits the expression of those cysteine genes which are regulated by the cysB product, it has no affect, however, on the constitutively-expressed cysE gene. The expression of cysteine genes in a strain carrying a mutation in the nalA locus is resistant to this drug. Novobiocin affects the expression of cysteine genes similarly to nalidixic acid. The effect of nalidixic acid on the expression of genes in a cysteine constitutive mutant was studied.

Acetyltransferases↗
PubMed1981

Absorption and disposition of [14C]-molsidomine in laboratory animals.

14C-Labelled N-ethoxycarbonyl-3-morpholinosyndnonomine(14C-molsidomine, Corvaton) was administered orally to mouse, rat, rabbit, dog and rhesus monkey, and i.v. to rat and dog, at a dose level of 6 mg/kg-1. The rates and routes of excretion of radioactivity were determined. The oral dose was well-absorbed in all species and most (greater than 75%) of the radioactive dose was excreted in urine. In rat and dog less than 1% of the dose was present as expired 14CO2. In dog and rhesus monkey, small amounts of radioactivity were eliminated relatively slowly. In rat, dog and rhesus monkey, the three species examined in detail, radioactivity was generally distributed throughout the body 4-10 days after dosing. Levels were highest in liver, pelt, blood and the gastrointestinal tract. Whole-body autoradiographic studies in rat and rhesus monkey showed that at 4 days post-dose, radioactivity was highest in stomach wall and was distributed into other tissues in lesser amounts. In view of its mode of action, it was interesting that radioactivity was also associated with the heart muscle and aorta walls.

Animals↗