Recently, high carbohydrate diets were recommended for the treatment of diabetes mellitus. All aspects of these diets, however, have not been fully tested — particularly in insulin dependent diabetes mellitus (IDDM). The present study was designed to investigate the effects of high carbohydrate, low fat diets (HCLFD) on blood glucose regulation, lipoprotein and apoprotein concentrations and nutritional status in IDDM. Six women with IDDM were studied in the Clinical Research Center for ten weeks. The study was divided into a control diet (CD) with 45% CHO, 40% fat, and 15% protein for four weeks, and a HCLFD with 65% CHO, 20% fat, and 15% protein for six weeks. Subjects were allowed free selection of their carbohydrate and fiber sources during both diet periods. The resulting selections produced diets with approximately equal proportions of complex and simple carbohydrates (49% and 51%, respectively) and moderate quantities of dietary fiber (50 g) during the HCLFD. Weekly fasting and pre-prandial serum glucose and glycosylated hemoglobin, and daily 24 hr. urine glucose excretion and insulin dose were not significantly different between the two periods. Total plasma, LDL and HDL cholesterol concentrations (p<.05). and apopproteins AI (p<.001), B (p<.01) and CIII (p<.05) were significantly lower, VLDL cholesterol (p<.05), total plasma (p<.01) and VLDL (p<.001) triglycerides were significantly higher, and apoproteins AII and E were unchanged during the HCLFD. Lipoprotein and apoprotein concentrations were independent of glycemic control. There were no significant changes in any of the nutritional parameters tested. All except vitamin B₆ were within their respective normal ranges. Whole blood and plasma vitamin B₆, and pyridoxal 5'-phosphate fell below the lower limits, even though dietary intakes were adequate. The present study suggest that HCLFD did not adversely affect glycemic control in IDDM, and demonstrated a potentially beneficial lowering of total and LDL cholesterol concentrations independent of glycemic control. Finally, nutritional status appeared unaltered as a result of HCLFD. The lower levels of the B₆ vitamers in IDDM demonstrated in this study suggest that the relationship between diabetes and vitamin B₆ status needs to be investigated further. / Graduation date: 1982

Dietary protein intake has been observed to influence the induction of cancer in animals exposed to carcinogens, presumably by affecting the activities of enzyme systems which metabolize them. One such carcinogen is aflatoxin B₁ (AFB₁) a mold metabolite and frequent contaminant of foodstuffs. Variations in the levels of dietary proteins fed rats and rainbow trout (Salmo gairdneri) influence the induction of hepatocellular carcinoma by AFB, in these animals. The following work was undertaken to provide an explanation of these results in terms of AFB₁ in vitro metabolism. The effect of dietary casein and fish protein concentrate (FPC) levels upon the activities of potential AFB₁ metabolizing enzyme systems were studied in the rainbow trout (Salmo gairdneri). Hepatic subcellular protein and cytochrome P-450 contents, and the activities of glutathione-S-epoxide transferase (GTr) epoxide hydrase (EH) cytochrome c reductase and aldrin epoxidase (AE) enzymes were determined in trout fed varying levels of casein or FPC. In addition, the reduction of AFB₁ to aflatoxicol (AFL) and conversion to an active mutagen for Salmonella typhimurium TA 98 were examined. A prerequisite for this study was the adaptation of the Ames mutagen assay system for use with fish hepatic enzymes. Lowered hepatic GTr and AE activities and increased conversion of AFB₁ to AFL and to a microbial mutagen were noted in trout fed high protein diets relative to those fed low protein diets. Cytochrome P-450 content was observed to decrease with increasing dietary casein and increase with increasing dietary FPC. Hepatic EH activity remained constant and decreased in trout fed increasing levels of casein or FPC respectively. These changes in enzyme activity are discussed in relation to dietary influences upon AFB₁ carcinogenesis in the rainbow trout. / Graduation date: 1978

Gentamicin-induced nephrotoxicity varies temporally, with a peak being observed when this antibiotic is administered during the resting period and a trough when given during the activity period of rats. These variations are modified by fasting and by restricted feeding schedules. In this study, food and water intakes of adult female Sprague-Dawley rats were measured during pre-treatment (days 1 to 5) and during treatment (days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 h or 0100 h. A significantly higher level of serum creatinine was observed when gentamicin was administered at 1300 h compared to 0100 h, and a significantly lower creatinine clearance was found in rats treated with gentamicin at 1300 h compared to those treated with saline at the same time. Gentamicin treatment at 1300 h or 0100 h resulted in a decrease in the 24 h food intake. In addition, in the gentamicin-treated group at 0100 h, the maximal food intake observed at late dark during the pre-treatment period decreased during treatment, and early dark rather than late dark maximal intake occurred. Our data demonstrate that gentamicin induces a nephrotoxicity that varies temporally, and that gentamicin treatment inhibits food intake and alters its nocturnal variations.

Macronutrient composition of food was shown to have a potent impact in modulating circadian rhythms of gentamicin toxicity. In the present study, adult female Sprague-Dawley rats fully adapted to isocaloric 20 casein-containing, 20% soy-containing (both semi-purified with 10% safflower oil and 58.55% carbohydrate) or a standard chow diet (non-purified with 18.1% mixed proteins, 4.5% fat and 57.3% carbohydrate) were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution given in the middle of their resting period or in the middle of their activity period. Body weights, 24-h, 12-h light and 12-h dark food intakes were measured before (Days 1 to 5) and during treatment (Days 6 to 15). Gentamicin nephrotoxicity indices including serum creatinine, creatinine clearance, urinary proteins, urinary enzymes activities, corticocefular regeneration and cortical accumulation of gentamicin were measured at specific time points during the experiment. (Abstract shortened by UMI.)

All aminoglycosides have the potential to cause nephrotoxicity. Previous studies have shown that this toxicity was altered according to the macronutrient composition of dietary regimens offered to female rats. In a first study, adult female Sprague-Dawley rats adapted to a standard chow diet, the standard chow with 20% added casein or with 55% added casein were treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns and gentamicin nephrotoxicity indices were measured. In a second study, rats were fed the same diets, however, the treatment given was a sham injection. Results suggest that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and chow added with 20% casein were found to be more protective against gentamicin-induced nephrotoxicity than chow added with 55% casein.

Graduation date: 1979

No description available.

No description available.

No description available.

Abstract not available