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Biomedical subjects

A H Stark

Publications and source records attributed to A H Stark.

9 recordsLinked to original sources

Hyperglycemia reduces nitric oxide synthase and glycogen synthase activity in endothelial cells.

Hyperglycemia is considered a primary cause of diabetic vascular complications. A hallmark of vascular disease is endothelial cell dysfunction characterized by diminished nitric-oxide (NO)-dependent phenomena such as vasodilation, angiogenesis, and vascular maintenance. This study was designed to investigate the effects of a high level of D-glucose on endothelial NO response, oxidative stress, and glucose metabolism. Bovine aortic endothelial cells (BAECs) were pretreated with a high concentration of glucose (HG) (22 mmol/L) for at least 2 weeks and compared with control cells exposed to 5 mmol/L glucose (NG). The effect of chronic hyperglycemia on endothelial NO-synthase (eNOS) activity and expression, glycogen synthase (GS) activity, extracellular-signal-regulated kinase (ERK 1,2), p38, Akt expression, and Cu/Zn superoxide-dismutse (SOD-1) activity and expression were determined. Western blot analysis showed that eNOS protein expression decreased in HG cells and was accompanied by diminished eNOS activity. The activity of GS was also significantly lower in the HG cells than in NG cells, 25.0+/-17.4 and 89+/-22.5 nmol UDP-glucose.mg protein(-1)x min(-1), respectively. Western blot analysis revealed a 40-60% decrease in ERK 1,2 and p38 protein levels, small modification of phosphorylated Akt expression, and a 30% increase in SOD-1 protein expression in HG cells. Although SOD expression was increased, no change was observed in SOD activity. These results support the findings that vascular dysfunction due to exposure to pathologically high D-glucose concentrations may be caused by impairment of the NO pathway and increased oxidative stress accompanied by altered glucose metabolism.

Animals↗

Adaptation of Sprague Dawley rats to long-term feeding of high fat or high fructose diets.

BACKGROUND: Present animal models used to emulate type 2 diabetes may not accurately reflect the metabolic changes that occur in humans. AIM OF THE STUDY: The purpose of this research was to evaluate diets reported to induce insulin resistance and impaired glucose metabolism in rats as a potentially useful model for studying type 2 diabetes. METHODS: Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. Glucose tolerance tests were carried out in week 3 and week 9 of the experiment. At the termination of the experiment, serum insulin, glucose, cholesterol and triacylglycerols were measured. Glucose incorporation into glycogen and glycogen synthase activity were measured in soleus muscles. RESULTS: Similar weight gain was observed for all three groups of rats. Glucose tolerance curves and fasting glucose levels were not significantly different at any time point in the experiment. Insulin levels were unchanged for the controls (171+/-21 pM), high fructose (164+/-16 pM) and high fat (181+/-30 pM) diets. Fasting serum triacylglycerols and cholesterol levels were not significantly elevated by dietary treatment. In soleus muscles, rats on all three diets had a significant increase in glycogen synthesis in response to insulin, but synthesis was similar in all three groups. Glycogen synthase activity was also not significantly affected by long-term dietary intervention. CONCLUSIONS: In this study, healthy Sprague Dawley rats fed high fat or high fructose diets for 3 months adapted to the nutritional intervention without developing classical signs of insulin resistance and impaired glucose tolerance.

Adaptation, Biological↗

Soluble polysaccharide and biomass of red microalga Porphyridium sp. alter intestinal morphology and reduce serum cholesterol in rats.

The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44% in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29%). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food.

Analysis of Variance↗

Cataract development in sand and galactosemic rats fed a natural tomato extract.

This study investigated the effect of a natural tomato extract (TE) on cataract formation in two animal models. A TE containing 5% lycopene was included in the diet of diabetic sand rats at 0.2%, and Sprague Dawley rats were fed a high-galactose diet (30 g/100 g of diet), supplemented with either the lycopene-rich extract at concentrations of 0.2, 0.4, and 0.8% or BHT (0.2%). TE had no significant effect on plasma glucose levels or cataract development in sand rats; however, in rats maintained on a diet rich in galactose, both BHT and TE decreased cataract incidence, and grades were lower than in control animals. In addition, lens protein and reduced glutathione levels were higher and aldose reductase activity was lower than in the control group. The results suggest that antioxidants act as protective agents when oxidative stress is a primary cause of cataract formation but may be less effective in preventing cataracts in hyperglycemic animals.

Analysis of Variance↗

Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study.

High dietary fiber intake has been hypothesized to lower blood estrogen concentrations, an effect thought to be beneficial for decreasing breast cancer risk. This study investigated the association between dietary supplementation of wheat bran and circulating estrogen levels in postmenopausal African-American women participating in a community intervention trial. Seventeen postmenopausal women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was assessed and blood and 24-hour urine samples were collected before and after five to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin confirmed that all postmenopausal participants adhered to the intervention protocol. Nine of the 17 postmenopausal women were taking some form of estrogen replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs. 113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml), and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l) levels remained constant. In the eight postmenopausal women who were not receiving exogenous hormones (PM), wheat bran consumption was not associated with predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml), estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/- 0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/- 6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and postintervention levels of estradiol and SHBG significantly higher and androstenedione significantly lower than those not receiving ERT. No association between wheat bran supplementation and hormone levels was found in PM or PM-ERT African-American participants. These results in postmenopausal women are in contrast to findings of earlier studies in premenopausal women indicating that wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal women are only 5-10% of those in premenopausal women; therefore, a high wheat bran fiber diet alone may not be sufficient to depress these low levels even further.

Aged↗

Development of a urinary riboflavin adherence marker for a wheat bran fiber community intervention trial.

Development of a reliable marker of adherence to high-fiber diets is essential for accurately assessing dietary fiber intake in community interventions and clinical trials. The objective of this study was to evaluate the feasibility of using a riboflavin tracer incorporated into wheat bran cereal to determine fiber intake and compare results to the more traditional methodology of measuring stool weight. The inpatient phase of the study established that the excretion of urinary riboflavin was highly correlated with the dose of the riboflavin-spiked wheat bran cereal (r = 0.95, P < 0.005) and could be used as a biomarker to validate fiber supplement intake. The outpatient clinical intervention included a group of seven African-American men and women, who were asked to incorporate 1/2 cup of wheat bran cereal (11.6 g of dietary fiber) into their daily diet for a 6-week period. The cereal was spiked with a 28-mg dose of riboflavin. Baseline measurements of urinary riboflavin and stool weight were compared to postintervention levels. Comparison of pre- and postintervention measures of riboflavin excretion showed a significant increase (0.8 +/- 0.1 versus 6.0 +/- 0.6 mg/day, P < 0.02), which confirmed a high level of adherence to the dietary intervention. Although wet stool weights at baseline were significantly lower than postintervention (106 +/- 20 versus 146 +/- 23 g/day; P < 0.03), differences in dry stool weights did not reach significant levels (28 +/- 4 versus 33 +/- 5 g/day, P < 0.30). Furthermore, pre- and poststool measurements overlapped and could not provide definitive data on participant adherence. These results indicate that the riboflavin tracer was a more sensitive biomarker of wheat bran fiber supplementation than stool weight and provided an accurate method for validating adherence to the dietary intervention. A riboflavin marker provides a valid technique for adherence assessment in large-scale community trials, in which collection of 3-day fecal samples is not a manageable option.

Aged↗

In vitro production of short-chain fatty acids by bacterial fermentation of dietary fiber compared with effects of those fibers on hepatic sterol synthesis in rats.

The aim of this study was to determine the effects of fiber feeding on short-chain fatty acid (SCFA) production in laboratory rats and in an in vitro fermentation model using fecal inocula from rats adapted to a high fiber diet. In addition, the effect of fiber intake on endogenous sterol synthesis was evaluated. Twenty male Sprague-Dawley rats were divided into four groups and fed a control or 30% fiber diet (cellulose, pectin or pea fiber) for 4 wk. In vitro fermentation was compared with measurements of cecal SCFA content of fiber-adapted rats. Sterol synthesis in isolated hepatocytes was determined in groups of five to seven rats fed 15% dietary fiber for 4 wk. Cellulose was poorly fermented in both the in vitro and in vivo experiments. Pectin fermentation produced high levels of propionate, whereas pea fiber was associated with notable butyrate production. Adaptation to pectin produced seven times more SCFA in rat cecal contents (515 +/- 78 mumol) in comparison to a fiber-free diet (70.6 +/- 4.9 mumol), with similar results observed in vitro. Sterol synthesis in hepatocytes of rats fed pectin was significantly greater than in those of control or cellulose-fed rats. Despite significantly higher rates of SCFA production in pectin-fed rats, cholesterol synthesis was not inhibited, suggesting that SCFA are not the cholesterol-lowering factor of highly fermentable fiber sources.

Acetates↗

Psychological functioning after halothane or enflurane anesthesia.

Halothane and enflurane anesthesia were administered without surgery to young volunteer subjects who were compared with unanesthetized control subjects. All subjects were tested for intellectual function, visual-motor coordination, and personality characteristics, and they were asked to complete a symptom checklist on three occasions: before anesthesia, 2 days after anesthesia, and 2 weeks after anesthesia. Except for slight temporary effects in a few individuals, anesthesia altered neither intellectual or visual-motor measures nor personality characteristics. Although both anesthetics induced a number of symptoms persisting for 2 days after anesthesia, malaise was clearly greater following halothane than enflurane. Halothane was specifically associated with difficulty in remembering things, difficulty in concentrating, faintness or dizziness, and having to do things slowly to do them right. These symptoms were absent at the 2-week test.

Enflurane↗