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Biomedical subjects

R N Saunders

Publications and source records attributed to R N Saunders.

53 records · Page 3Linked to original sources

Assessment of diabetogenic drug activity in the rat: 5,5-diphenyl-2-thiohydantoin.

The diabetogenic activity of 5,5-diphenyl-2-thiohydantoin (DPTH) via oral administration was assessed in both normal and streptozotocin diabetic rats. Rats were fed powdered chow diet with and without 0.1% (w/w) DPTH. Food consumption and body weight were recorded every other day; whole blood glucose concentrations were determined at the start of the study and at the midpoint. At sacrifice, liver and pancreas were excised and blood samples were collected. Protein and lipid levels were determined in liver; insulin in pancreas; and glucose, insulin, and lipid in blood. DPTH treatment caused decreased food consumption and body weight gain. The drug dose, calculated from the food consumption data, was 76.5 mg/kg/day for the normal rats and 107 mg/kg/day for the diabetic rats. DPTH increased liver weight and liver lipid content in both normal and diabetic rats, and markedly lowered serum triglyceride concentration in normal rats but not in diabetic rats. Serum fatty acid concentration was not altered by DPTH. DPTH produced a significant elevation of blood glucose concentration of the diabetic rats that was not, however, correlated with altered pancreatic insulin concentration. In vitro, DPTH infusion inhibited insulin secretion by the perfused pancreas.

Animals↗

Metabolism cage for carbon dioxide trapping studies.

This report describes the design and construction of a metabolism cage that allows for separation of urine and feces and for trapping expired CO2. Such a cage could find use in pharmacokinetic studies of drug excretion rates where potential metabolism to CO2 should be considered. To demonstrate the separation qualities of this cage design, the radioactivity appearing in the urine, feces, and exhaust gases was determined daily for 14 days after the single oral administration of 26-[14C]cholesterol. Less than 1% of the administered radioactivity appeared in the urine, whereas 61% appeared in the feces and 19% in the expired CO2.

Animals↗

The retired breeder rat as a new model for antiplatelet drug discovery.

Spontaneous circulating platelet aggregates were observed in male retired breeder rats but in nonbred males of the same age and strain. Fasting serum lipid, platelet serotonin, and platelet rich plasma cyclic guanosine monophosphate levels were similar in retired breeders and nonbred rats. The in vitro response of platelets from retired breeder and nonbred rats to adenosine diphosphate and collagen were also similar. Administration of prostaglandin E1 and antiplatelet drugs (acetylsalicylic acid, sulfinpyrazone, and dipyridamole) reduced the number of circulating platelet aggregates in the breeder rats. It was concluded that the retired breeder rat may be a useful model for identification of new anti-platelet drugs.

Animals↗

Influence of 1,3-butanediol on blood glucose concentration and pancreatic insulin content of streptozotocin-diabetic rats.

Male rats were made diabetic by intravenous administration of 75 mg/kg of streptozotocin and were fed, via a pair-feeding regimen, high-fat diets +/- 1,3-butanediol (BD) at 13.5 and 27% of the dietary calories for 30 days and 31 days, respectively. 1,3-Butanediol was added to the diets primarily as a replacement for fat. Food consumption and rat weight were recorded daily. Whole blood glucose concentrations were determined weekly. At sacrifice, liver, pancreas and epididymal fat pads were excised and blood samples were collected. Liver was analyzed for protein and lipid; pancreas was weighed and analyzed for insulin; fat pads were weighed and discarded; and blood was analyzed for glucose and lipid. The 13.5% BD diet increased the beta-hydroxybutyrate, acetoacetate and cholesterol concentrations, decreased the glucose concentration in blood, and increased the insulin content of the pancreas. The BD diets did not affect the concentrations of phospholipid, triglyceride, cholesterol and fatty acid in the liver; fatty acid concentrations in the blood; or the epididymal fat pad weight. The results suggest that BD produced a slight amelioration of the diabetic condition, which may have resulted from an increased capacity of the pancreas to synthesize insulin. In addition, the data provide further evidence suggesting that in the rat BD is oxidized to the ketone bodies, beta-hydroxybutyrate and acetoacetate.

Acetoacetates↗

The biological properties of aspartame. V. Effects on a variety of physiological parameters related to inflammation and metabolism.

Aspartame (APM), L-aspartyl-L-phenylalanine methyl ester, is a low calorie sweetening agent 180 times sweeter than sucrose. As part of a series of studies designed to determine the potential effects of ingestion of excesses of APM on a wide spectrum of physiological processes, experiments were conducted in which high multiples (mg/kg basis) of the projected maximum daily human intake (20 mg/kg) were administered intragastrically to laboratory rats. Doses up to 16 times the maximum intake had no effect on inflammation parameters including carrageenin-induced paw edema, connective tissue formation and adjuvant arthritis. APM, likewise, showed no antihistamine activity in vitro. Even higher multiples (up to 103 times) of the maximum intake had no effect on various parameters of carbohydrate and lipid metabolism. These results indicate that APM ingested in great excess would not be expected to significantly impair inflammatory processes nor influence carbohydrate and lipid metabolism.

Animals↗