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Biomedical subjects

L J Fischer

Publications and source records attributed to L J Fischer.

At least 73 records · Page 4Linked to original sources
PubMed1976

Studies on the biological disposition of diethylstilbestrol in rats and humans.

Studies were conducted to elucidate the processes involved in the biological disposition of diethylstilbestrol (DES). The apparent biological half-life of [14C] DES decreased with increasing age in immature rats. The half-life of DES in adult rats (14 min) was reached between the 15th and 25th day after birth. Comparison of the intestinal absorption of [14C] DES and [14C]DES monoglucuronide showed the unconjugated drug to be absorbed much more rapidly. Hydrolysis of the conjugate took place in the lower intestine, and this permitted the drug to undergo enterohepatic cycling.

Age Factors↗
PubMed1976

Binding of thiopental to plasma proteins: effects on distribution in the brain and heart.

Thiopental-14C (30 mg and 10 muCi/kg) was injected intravenously into rats 36-48 hours following bilateral nephrectomy and one minute after pretreatment with sulfadimethoxine (30 mg/kg, iv). Control groups of normal and sham-operated animals were used. The distributions of radioactivity in plasma, brain, and heart 1, 5, and 30 minutes after injection were examined. Uremic and sulfonamide-pretreated rats showed significantly higher levels of 14C in brain and heart and more free thiopental in plasma at each time than did control animals. There was a significant correlation between the free thiopental in plasma and total drug concentrations in the brain and heart. Uremic rats bound less thiopental in plasma compared with controls in spite of normal total plasma protein and albumin concentrations. It is concluded that reduced protein binding of thiopental leads to accelerated distribution and increased drug concentrations in the brain and and heart.

Animals↗
PubMed1975

Synthesis of an active hydroxylated glutethimide metabolite and some related analogs with sedative-hypnotic and anticonvulsant properties.

Two synthetic pathways are described for the preparation of 4-hydroxy-2-ethyl-2-phenylglutarimide (2), an active hydroxylated metabolite of glutethimide (1). Fourteen other glutethimide analogs were also synthesized and tested for biological activity. Most of the analogs exhibited sedative-hypnotic properties and compound 2 possessed the greatest activity compared to the parent drug. 4-Amino-2-ethyl-2-phenylglutarimide and 4-hydroxy-2-ethyl-2-phenylglutaconimide (13) exhibited the greatest potential as anticonvulsant agents. The structure-activity relationships of the series are discussed.

Animals↗
PubMed1975

Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro.

Pancreatic islet cell vacuolization, hyperglycemia, and glucose intolerance develop in rats after oral administration of cyproheptadine (CPH). In order to determine whether these effects were associated with abnormal insulin secretion, pancreas segments from CPH-treated and control rats were compared for their ability to secrete insulin in response to several stimuli. Oral administration of CPH (45 mg/kg/day) to rats for 1 or 8 days inhibited glucose-mediated insulin secretion from pancreas segments obtained 3 and 24 hr after the last dose of the drug. Insulin secretion had returned to normal by 48 hr after drug administration. Intraperitoneal administration of the drug was less effective than oral administration in inhibiting in vitro insulin secretion. Other stimuli for insulin secretion (tolbutamide, glucagon, L-leucine, and dibutyryl 3',5'cyclic AMP), like glucose, were incapable of releasing normal amounts of insulin from pancreas segments of CPH-treated rats. CPH and a metabolite, desmethyl-CPH, inhibited glucose-stimulated insulin secretion when added in vitro to pancreas segments from control rats. This suggests that the inhibition of insulin secretion in pancreas segments taken from animals treated with CPH could be due, at least in part, to the presence of drug and its metabolite in the tissue. A previously observed reduction in the pancreatic content of insulin in CPH-treated rats may also contribute to the abnormal insulin release in animals given the drug.

Administration, Oral↗
PubMed1975

Cyproheptadine-induced depletion of insulin in the rat.

The pancreotoxicity of cyproheptadine (CPH) in rats was characterized through measurement of proinsulin and insulin levels in the pancreas as well as plasma immunoreactive insulin (IRI) and glucose levels at various times during and after drug treatment. Daily oral doses of CPH (45 mg/kg) depleted pancreatic IRI to 25% of control within 3 days. Pancreatic IRI levels showed no further decrease during the rest of a 2-week treatment period and returned to normal levels 2 days after withdrawal of the drug. Pancreatic proinsulin levels were not significantly changed by CPH treatment, and the decrease in pancreatic IRI can be ascribed primarily to a decrease in insulin. Nonfasting hyperglycemia was evident after two doses of CPH and persisted throughout the treatment period. Plasma IRI was not significantly altered compared to control and was inappropriately low for the hyperglycemia that was produced by CPH. Daily doses of CPH given i.p. (45 mg/kg) caused a transient decrease in pancreatic IRI, but hyperglycemia did not occur. Lower i.p. doses (22.5 mg/kg/day) caused a sustained decrease in pancreatic IRI content to 45% of control after 2 weeks and hyperglycemia was evident throughout the treatment period. No changes in pasma IRI were observed as a result of drug treatment even though blood glucose was elevated. These results suggest that biochemical changes affecting insulin synthesis and/or storage are associated with previously reported CPH-induced morphologic alterations in the rat beta-cell.

Animals↗