Muneyoshi Yoshida

Protective effect of probucol on alloxan diabetes in rats

The diabetogenic action of alloxan is known to be attenuated by several oxygen radical scavengers. The present study was conducted to see if probucol, a drug with strong free radical scavenger action, can reduce pancreatic B-cell damage induced by alloxan in male Wistar rats. After 2 weeks of a 1% probucol diet, 50 mg/kg alloxan was intravenously injected in rats (group PA, n = 34). Urine glucose of most of the injected rats not pretreated with probucol (group A, n = 22) was positive, while more than half of the rats of group PA failed to show urine glucose. The blood glucose level in group PA was significantly lower than that in group A (326 +/- 25 vs. 487 +/- 28 mg/dl, P less than 0.001). Histological examination revealed that most of the pancreatic islets of group A were degranulated, whereas a lot of islets remained unaffected in group PA. Thus, the in vivo diabetogenic action of alloxan was reduced by pretreatment with probucol, although the effect was incomplete. This effect can be explained by probucols strong free radical scavenger action. Since accumulation of free radicals can be an initial step of B-cell damage in animal models of type 1 (insulin-dependent) diabetes, the drug can be useful for the prevention of type 1 diabetes with its long-term clinical history of safety.

Effects of niceritrol on elevated serum lipoprotein Lp(a) levels in diabetic patients with or without overt proteinuria

Abstract Effects of 16 weeks of niceritrol therapy (750 mg/d for the first 8 weeks and 1500 mg/d for the remaining 8 weeks) on serum levels of lipids, apolipoproteins, and Lp(a) were examined in diabetic patients with and without overt proteinuria. Pre-niceritrol Lp(a) levels exceeded 30 mg/dL and were comparable in both groups of patients. Pretreatment levels of lipids and apolipoproteins also were similar in both groups. Nonproteinuric patients exhibited an 18% decrease in Lp(a) and a 22% reduction in triglycerides as well as increases in high-density lipoprotein cholesterol and apolipoprotein AI. In contrast, patients with overt proteinuria showed no significant changes in serum lipids, apolipoproteins, or Lp(a) in response to niceritrol therapy. These findings suggest that the presence of overt proteinuria may affect Lp(a) metabolism in diabetic patients.

Post-traumatic hypothalamic obesity--an autopsy case.

A 45‐year‐old housewife sustained a blow to the occipital region In a traffic accident about 2 years and 3 months prior to death. Autopsy revealed lesions of softening in the hypothalamus, left thalamus, frontal lobe (especially on the left), and base of the left temporal lobe. Following the head trauma, a marked Increase of appetite was noted, with obesity, hypogonadism, and mild elevation of temperature. No diabetes insipidus was noted whatsoever. Based on data from physical and pathological examination, the relationship between function and morphology in the human hypothalamus was discussed.

Effects of long-term high-fiber diet on macrovascular changes and lipid and glucose levels in STZ-induced diabetic SD rats

The effects of long-term high-fiber diet on lipid and glucose levels and the histological changes in the coronary arteries and thoracic aorta in STZ-induced diabetic SD rats were investigated. During the first 4 weeks of the study period, all diabetic rats were given regular chow plus water after which, all were grouped according to the following diet regimen: group II, no added cholesterol and glucomannan; group III, no added cholesterol but with glucomannan supplement, group IV, with added cholesterol but no glucomannan supplement; and group V, with both cholesterol and glucomannan supplements. 15% weight of glucomannan and 1.5% weight of cholesterol in regular rat chow were used as supplements when indicated. Non-diabetic rats which received only regular chow served as the control group (group I). In the 18th week all rats were sacrificed and weight gain, glucose, total cholesterol, HDL-cholesterol, triglyceride and lipid peroxidase concentrations were determined. Selected portions of the heart and thoracic aorta were histologically examined. Weight gain was higher in rats supplemented with glucomannan than in those without glucomannan supplements, but the difference is not significant. A lowering tendency in glucose levels was likewise observed. Furthermore, total cholesterol and HDL-cholesterol levels were lower and higher, respectively in diabetic rats receiving glucomannan. Although the triglyceride levels were similar in all rats, lipid peroxidase levels were significantly lower in rats with high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effects of bezafibrate on in vivo VLDL-triglyceride production in the rat

Long-term effects of bezafibrate on in vivo production of VLDL-triglyceride were studied in the rat. Bezafibrate given at a daily dose of 30 mg/kg body weight for 14 days produced a decrease not only in triglyceride by 51% but in cholesterol by 28% and phospholipid by 18%. Despite a marked reduction in plasma triglyceride concentrations, there was no significant change in the rate of VLDL-triglyceride secretion from the liver into the circulation between bezafibrate-treated and control animals (1113 +/- 58 and 1234 +/- 63 micrograms/min, respectively). In addition, bezafibrate produced no change in lipid composition in VLDL. These results suggest that bezafibrate enhances triglyceride removal from the circulation, which leads to reduction in plasma triglyceride.

Morphological study of nervous system in vacor-induced diabetic rats

Patients with Vacor diabetes mellitus frequently developed diabetic ketoacidosis and neuropathy in the early stage of the disease; however, the mechanism of the development of diabetes and its neurologic complications is not known. In this study, oral administration of 100 mg Vacor/kg of body weight was used in Wistar male rats. The rats were sacrificed 6 h after administration to avoid natural expiration. Light microscopy revealed focal hemorrhage and edematous change in the periventricular area of the brain, scattered hemorrhage in the posterior and anterior horns, spongy degeneration and demyelinization in th fasciculus gracilis and cuneatus of the white matter, early degenerative changes in the sciatic nerve, and no change of the vagus. Electron microscopy showed necrosis of the axon, myelin sheaths and glia cells in the spinal cord, while the organelles of the peripheral nerves were unchanged. These findings indicate that Vacor produces various neurotoxicities in the acute toxic phase.