Prolylcarboxypeptidase (PRCP) as a new target for obesity treatment.

Recently, we serendipitously discovered that mice with the deficiency of the enzyme prolylcarboxypeptidase (PRCP) have elevated alpha-melanocyte-stimulating hormone (alpha-MSH) levels which lead to decreased food intake and weight loss. This suggests that PRCP is an endogenous inactivator of alpha-MSH and an appetite stimulant. Since a modest weight loss can have the most profound influence on reducing cardiovascular risk factors, the inhibitors of PRCP would be emerging as a possible alternative for pharmacotherapy in high-risk patients with obesity and obesity-related disorders.

Effect of aldonic acids on the uptake of ascorbic acid by 3T3 mouse fibroblasts and human T lymphoma cells.

1. Previously, we reported that calcium L-threonate caused a dose-related increase in uptake of ascorbic acid (AA) by human T-lymphoma cells. Preincubation of mouse fibroblasts with calcium L-threonate also resulted in a dose-related augmentation in uptake of AA as compared to non-treated controls.

The effects of various levels of ascorbic acid on the response of the ODS rat to trimethyltin.

The effects of trimethyltin (TMT) on behavioral and histological parameters were investigated in rats maintained on low, mid, and high levels of ascorbic acid (AA). Male osteogenic disorder Shionogi (ODS) rats were used. Like man, ODS rats are unable to synthesize AA.

Effects of d-alpha-tocopherol supplementation on experimentally induced primate atherosclerosis.

Prevention and regression of induced atherosclerosis by d-alpha-tocopherol was investigated in 24 male M. fascicularis. One group received a basal diet, while three others consumed an atherogenic diet.

Inhibition of arylsulfatase B by ascorbic acid.

One hypothesis for atherosclerotic lesion formation is the response to injury hypothesis. If catabolism of the ground substance of the intima of blood vessels is viewed as an injury, then inhibition of this catabolism could lead to a decrease in atherosclerotic lesions. Arylsulfatase B catalyses the desulfation of glycosaminoglycans in the catabolism of the intimal ground substance.

Stimulatory action of calcium L-threonate on ascorbic acid uptake by a human T-lymphoma cell line.

The effects of preincubation of human T-lymphoma cells with increasing concentrations of calcium L-threonate on the uptake of L-[1-14C]ascorbic acid were examined. Calcium L-threonate (0-1,000 mg%) stimulated ascorbic acid (1.25 mg%) uptake in a dose-dependent manner.

Comparison of the anti-scorbutic activity of L-ascorbic acid and Ester C in the non-ascorbate synthesizing Osteogenic Disorder Shionogi (ODS) rat.

The Osteogenic Disorder Shionogi (ODS) rat, Clea Inc., Tokyo, Japan lacks the ability to synthesize L-ascorbic acid (AA). As with man, monkey and the guinea pig, this rat lacks L-gulonolactone oxidase necessary for the synthesis of AA from glucose.

Effect of cytochalasin B on the uptake of ascorbic acid and glucose by 3T3 fibroblasts: mechanism of impaired ascorbate transport in diabetes.

Hyperglycemia and/or hypoinsulinemia have been found to inhibit L-ascorbic acid cellular transport. The resultant decrease in intracellular ascorbic acid may de-inhibit aryl sulfatase B and increase degradation of sulfated glycosaminoglycans (sGAG). This could lead to a degeneration of the extracellular matrix and result in increased intimal permeability, the initiating event in atherosclerosis.

Clinical profile of a 4-year primate atherosclerosis model.

Twelve male M. fascicularis monkeys were divided into two groups of 6 animals each. One group (BASAL) was fed a diet containing 24% protein, 38% carbohydrate and 20% fat, while the other group (ATHER) received an identical diet with the addition of 4.

Intimal permeability evaluated in a short-term organ culture of diabetic guinea pig aorta.

A novel short-term organ culture system was used to evaluate intimal permeability changes by measuring aortic [14C]methylated albumin accumulation. Aortic plugs were removed from the upper thoracic aorta of male guinea pigs and maintained in serum-free media. The accumulation of [14C]albumin in the intimal-medial layer was determined after a 5 h incubation.

Selected physical and biochemical parameters in the streptozotocin-treated guinea pig: insights into the diabetic guinea pig model.

Since evidence suggests that ascorbic acid deficits may provoke certain diabetic complications, it becomes necessary to develop a diabetic animal model which, like man, is unable to synthesize this vitamin. To this end, the present study monitored the diabetogenic effects of streptozotocin (STZ, 150 mg/kg) in the male guinea pig, a species rarely used in diabetes research. Over a 3-week period, body weight and relative food intake were lower in the STZ group compared to controls.

An acute study on the relative gastro-intestinal absorption of a novel form of calcium ascorbate.

Several functions of L-ascorbic acid (vitamin C) have been suggested in addition to its role in the prevention of scurvy. Consequently, a controversy has arisen over the daily intake of the vitamin which will afford maximum benefits. Rapid cellular uptake and delayed renal excretion of ascorbic acid would be conducive to providing optimum cellular concentration for biochemical activity.

The effects of clonidine on food consumption and food competition in male stumptail macaques (Macaca arctoides).

The effects of clonidine on noncompetitive and competitive feeding were examined in three adult male stumptail macaques (Macaca arctoides). Noncompetitive feeding was examined when the subjects were individually-caged or group-caged. Clonidine (1.

Diet-induced changes in selected clinical chemistry parameters in M. fascicularis.

Thirty-six male M. fascicularis monkeys were fed a basal diet (180 g/day, 24% protein, 38% carbohydrate and 20% fat) for a period of 17 months. At that time, the animals were divided into two groups.

Normal serum biochemical, hematological, and EKG parameters in anesthetized adult male Macaca fascicularis and Macaca arctoides.

Selected serum enzymes, cholesterol, triglycerides, glucose, uric acid, protein, albumin, bilirubin, BUN, hematology, and electrocardiograms (EKG) were obtained from adult male cynomolgus (Macaca fascicularis) and adult male stumptailed (Macaca arctoides) macaques. Serum alkaline phosphatase, uric acid, albumin, bilirubin, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and monocytes were significantly lower in the cynomogus monkeys. This relationship was reversed for serum levels of triglycerides, phosphorus, red blood cell counts and lymphocytes.

Fruit and vegetable consumption and cardiovascular mortality.

A steady fall in mortality rates from cardiovascular diseases (CVD) has been reported recently in the United States. This study tests the hypothesis that fruits and vegetables had a protective effect against cardiovascular mortality among the American population from 1964-78. Special attention was focused on more specific groups of fruits and vegetables, especially those rich in vitamin C, to examine the effect of consumption of these foods on cardiovascular mortality rates.

The interaction of aortic glycosaminoglycans and 3H-inulin endothelial permeability in cholesterol induced rabbit atherogenesis.

Male Dutch-belted rabbits were fed a pelleted 0.5% cholesterol diet for 8 weeks. A control group was maintained on basal pelleted diet for the same period of time.

Effects of streptozotocin in the male guinea pig: a potential animal model for studying diabetes.

The effects of acutely administered streptozotocin in the male guinea pig were studied for a period of 18 days following treatment. A single intracardiac injection of streptozotocin (150 mg/kg) was administered on Day 0. On Day 2, plasma glucose concentrations were not significantly different from control levels.

The effects of glucose on ascorbic acid uptake in heart endothelial cells: possible pathogenesis of diabetic angiopathies.

Glucose in concentrations of 20 mg% (or greater) significantly inhibited 14C-labelled ascorbic acid (1.25 mg%) uptake in endothelial cells in the presence of insulin (1600 microU/ml). The absence of insulin also significantly reduced ascorbic acid uptake.

Changes in selected serum biochemical and EKG values with age in cynomolgus macaques.

Normal serum values for alkaline phosphatase were significantly higher in juvenile male cynomolgus monkeys compared to adults. Conversely, blood urea nitrogen (BUN) was significantly lower in juveniles than adults. A comparison of selected EKG parameters from each group revealed no significant differences; however, there was a trend towards mean left axis deviation in adult animals.

Effects of primaquine on serum biochemical and hematological parameters in anesthetized Macaca fascicularis.

Primaquine phosphate treatment (0.5 mg/kg/day, per os [p.o.

Reproductive toxicity of methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) in male Wistar rats.

Methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) is a systemic fungicide which has been implicated in producing damage to the testes. The present investigation was undertaken to evaluate the functional and behavioral significance of this reported benomyl-induced damage to male rats using a 70-day feeding study followed by a 70-day recovery study. Adult male Wistar rats were fed laboratory chow containing 1.