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The effect of a 48 h fast on the physiological responses to food ingestion in normal-weight women.

The thermogenic, cardiovascular and metabolic responses to a 30 kJ/kg body-weight test meal were studied in eight normal-weight, healthy female subjects after a 6 or 48 h fast. There was no significant change in metabolic rate following the 48 h fast, but plasma glucose, insulin, noradrenaline and respiratory exchange ratio were all reduced, and plasma beta-hydroxybutyrate was increased. Forearm blood flow was increased, with reduction in diastolic blood pressure. After the 48 h fast, there was a reduction in the metabolic rate response 40-90 min after food (control + 0.54 (SE 0.05), 48 h fast + 0.27 (SE 0.12) kJ/min, P less than 0.01), and in forearm blood flow and diastolic blood pressure responses, but increases in heart rate, blood glucose and plasma insulin responses to the ingestion of the test meal. There was no significant relationship between plasma catecholamine concentration and food ingestion or metabolic rate. Fasting induced considerable adaptation in these subjects and altered some of the physiological responses to food ingestion.

Adaptation, Physiological↗

cDNA encoding sequences for myostatin and FGF6 in sea bass (Dicentrarchus labrax, L.) and the effect of fasting and refeeding on their abundance levels.

Fish have the ability to compensate for set-backs in growth as a result of fasting. When food levels are restored, growth in these fish can increase over and above normal rates. This phenomenon, known as "compensatory growth", has been studied with respect to enhancing food conversion efficiency. However, the mechanisms by which food intake activates an increase in somatic growth, and especially in muscle growth, are not well understood. In this study, we report first on the isolation of two complete cDNAs sequences encoding sea bass (Dicentrarchus labrax) myostatin and fibroblast growth factor 6 (FGF6), which have been shown to be major genetic determinants of skeletal muscle growth. The open reading frames of myostatin (376 amino acids) and FGF6 (209 amino acids) showed 97-63% and 87-62% sequence identity with other vertebrate myostatins and FGF6s, respectively. We also report on the expression profile of myostatin and FGF6 in sea bass skeletal muscle in response to different feeding regimens, as quantified by real-time RT-PCR. Nutritional status significantly influenced the myostatin expression levels in muscle, inducing an up-regulation during fasting and a down-regulation during the recovery from fasting, whereas the muscular FGF6 mRNA levels were not significantly affected by the feeding status of the animals. These findings suggest that myostatin has an inhibitory role in muscle growth in response to different feeding regimens, whereas FGF6 is not involved in the muscle compensatory growth induced by refeeding.

Amino Acid Sequence↗

The effect of food on the relative bioavailability of deflazacort.

The effect of high- and low-fat meals on the relative bioavailability of deflazacort tablets was investigated in 12 healthy, adult males who were administered 36 mg deflazacort under fasted and fed conditions in a crossover fashion. Serial plasma samples were drawn up to 24 h post-dose and quantified for the active metabolite 21-desacetyl deflazacort (DFZ 21-OH) by a rapid and sensitive HPLC method. Following deflazacort administration with high-fat and low-fat meals and under fasted conditions, DFZ 21-OH area under the curve to infinity averaged 508.39 +/- 131.70, 510.05 +/- 148.30 and 511.90 +/- 188.16 ng.h/ml. DFZ 21-OH Cmax averaged 156.31 +/- 33.31, 156.85 +/- 40.17 and 188.05 +/- 53.35 ng/ml for high-fat, low-fat and fasted treatments, respectively. Differences in Cmax between the fed versus fasted treatments were statistically significant (P < 0.05). The decrease in Cmax under fed conditions was accompanied by an increase in mean Tmax of approximately 17-85% compared to fasted conditions. As expected, terminal half-life was not affected. These data indicate that co-administration of deflazacort tablets with high-fat and low-fat meals leads to a small decrease in rate but does not affect its extent of absorption.

Administration, Oral↗

Effect of food on the pharmacokinetics of multiple-dose oral voriconazole.

AIMS: Voriconazole is a new triazole antifungal agent with activity against a range of clinically important and emerging pathogens. This study determined the effect of food on the pharmacokinetics of voriconazole in healthy volunteers. METHODS: This was an open, randomized, two-way crossover, multiple-dose study in male volunteers. Twelve subjects received voriconazole 200 mg twice daily for 6.5 days. Each dose was administered either with food or in the fasted state, i.e. not within 2 h of food. Treatment periods were separated by a minimum 7-day washout period. Plasma samples were taken for the estimation of voriconazole plasma concentrations on days 1 and 7. Safety and toleration were assessed by monitoring of both laboratory safety tests and adverse events. RESULTS: Administering voriconazole with food significantly decreased both day 7 AUCtau and Cmax by approximately 35% (9598-7520 ng.h ml-1; P = 0.003) and 22% (2038-1332 ng ml-1; P = 0.008), respectively. Administering voriconazole with food statistically significantly delayed absorption, evident from tmax values; the mean difference for tmax on day 7 was 1.1 h. The terminal phase rate constant was unchanged by administering voriconazole with food. The fasted terminal phase half-life was 7.3 h compared with 6.6 h for the fed state. Visual inspection of Cmin values suggests that steady state was achieved after 5 days in both dietary states. Voriconazole accumulation, as assessed by ratios of Cmax and AUCtau on days 1 and 7, was statistically significantly greater when administered with food (Cmax, P = 0.010, AUCtau, P = 0.006). Mean Cmax accumulation in the fasted state was 2.1-fold compared with 3.5-fold in the fed state. AUCtau accumulation in the fasted state was 3.1-fold compared with 4.2-fold in the fed state. There were no discontinuations due to adverse events or laboratory abnormalities. Treatment-related mild-to-moderate visual disturbances were experienced by six out of 12 subjects. CONCLUSIONS: The bioavailability of twice-daily 200 mg voriconazole is reduced by approximately 22% as measured by AUCtau after multiple dosing when taken with food, compared with fasting.

Administration, Oral↗

The effect of beta-adrenergic blockade upon basal and pentagastrin-stimulated gastric acid secretion and upon gastrin response to food.

Beta-adrenergic blockade with 10 mg of propanolol had no significant effect upon the spontaneous gastric acid secretion, while the maximum (pentagastrin) acid secretion was depressed in healthy subjects and patients with duodenal ulcer. The gastrin response to food was significantly higher during beta-adrenergic blockade. It is suggested that a minor part of the maximum acid secretion may be due to activation of beta-receptors, while the gastrin response to food is probably not related to activation of beta-receptors.

Depression, Chemical↗

Diet quality and food limitation affect the dynamics of body composition and digestive organs in a migratory songbird (Zonotrichia albicollis).

Migrating songbirds interrupt their feeding to fly between stopover sites that may vary appreciably in diet quality. We studied the effects of fasting and food restriction on body composition and digestive organs in a migratory songbird and how these effects interacted with diet quality to influence the rate of recovery of nutrient reserves. Food limitation caused white-throated sparrows to reduce both lean and fat reserves, with about 20% of the decline in lean mass represented by a decline in stomach, small intestine, and liver. During refeeding on diets similar in nutrient composition to either grain or fruit, food-limited grain-fed birds ate 40% more than did control birds, and they regained body mass, with on average 60% of the increase in body mass composed of lean mass including digestive organs. In contrast, food-limited fruit-fed birds did not eat more than did control birds and did not regain body mass, suggesting that a digestive constraint limited their food intake. The interacting effects of food limitation and diet quality on the dynamics of body composition and digestive organs in sparrows suggest that the adequacy of the diet at stopover sites can directly influence the rate of recovery of body reserves in migrating songbirds and hence the pace of their migration.

Analysis of Variance↗

6-Thioguanine in children with acute lymphoblastic leukaemia: influence of food on parent drug pharmacokinetics and 6-thioguanine nucleotide concentrations.

AIMS: Since relatively little is known about the pharmacokinetics of 6-thioguanine (6TG) in children receiving 6-thioguanine for maintenance therapy of acute lymphoblastic leukaemia (ALL), we studied plasma drug concentrations under standardized conditions and investigated the effect of food on parent drug pharmacokinetics and the accumulation of the active metabolites 6-thioguanine nucleotides (6-TGNs) in red cells. METHODS: Single oral doses of 40 mg of 6-TG were administered both in the fasting and fed state to children with ALL. Pharmacokinetic sampling was performed up to 6 h post dose. Daily oral doses of 40 mg m(-2) of 6-TG were administered both fasting and after food over two 4 week periods. Twice weekly samples were taken for metabolite concentrations. The study design was cross-over with each child receiving dosing in either fasted or after food over a 4 week period in each phase. RESULTS: Eleven patients were studied. A wide interindividual variation in Cmax (median 313 pmol ml(-1), range 51-737) and AUC (median 586 pmol ml(-1) h, range 156-1306) was observed in the fasted state. Concomitant food administration resulted in a significant reduction in Cmax (median 71 vs 313 pmol ml(-1), P = 0.006, CI from 36 to 426), AUC (median 200 vs 586 pmol ml(-1) h, P = 0.006, 95% CI from 109 to 692), and time to reach Cmax (median 1.5 vs 3 h, P = 0.013, 95% CI from 0.74 to 2.73). There was no difference in the steady state concentration of red cell 6-TGNs observed after a 4 week period of 6-TG administered fasting or after food. CONCLUSIONS: Children with ALL demonstrate significant interindividual variation in 6-TG pharmacokinetics. Although there would appear to be a reduction in parent drug Cmax and AUC with food there was no difference in 6-TGN concentrations after 4 weeks of 6-TG. Taking the drug on an empty stomach may not be necessary.

Administration, Oral↗

Human cortical specialization for food: a functional magnetic resonance imaging investigation.

Although specialized cortical pathways that process specific sensory stimuli and/or execute cognitive functions have been identified, the neuro-specificity for food-related stimuli has not been clearly demonstrated. We employed functional magnetic resonance imaging (fMRI) to compare neural systems associated with the appreciation of foods and nonfoods. Healthy, normal weight, right-handed men and women (n = 12; age 29.8 +/- 1.8 y, BMI 21.8 +/- 0.8 kg/m(2)) were imaged by fMRI while fasting. Real food and nonfood items were presented to subjects both visually and tactilely, during scanning. Subjects were instructed to pay attention to the items. A randomized 2 x 2 block design consisted of 4 conditions: visual food, visual nonfood, tactile food, and tactile nonfood. Brain regions that were significantly activated to a greater extent during the presentation of foods compared with nonfood items included the anterior cingulate, superior temporal gyrus, parahippocampal gyrus, hippocampus, and the insula. These findings support the claim that the presence of food (either seen or felt) elicits a unique cortical response that is differentiated from nonfood items. This neural substrate specialized for processing of foods informs models of food-related behavior.

Adult↗

Studies on antidiabetic effects of cortex Moutan polysaccharide-2b in type 2 diabetes mellitus rats.

AIM: To study the antidiabetic effects of cortex Moutan polysaccharide-2b (CMP-2b) in type 2 diabetes mellitus (T2DM) rats. METHODS: The T2DM model rats were induced by a single intravenous injection of low dose streptozotocin (STZ) and intake of high sucrose-fat diet. CMP-2b was given to T2DM rats daily through gavage for 4-5 weeks. The body weight, water and food intake, fasting blood glucose (FBG), glucose tolerance, plasma lipids, serum insulin, and insulin receptor (Ins R) were determined. RESULTS: Oral administration of CMP-2b significantly decreased water and food intake, FBG, total cholesterol (Tch), and triglyceride (TG), improved the impaired glucose tolerance (IGT), and remarkably raised the number of low affinity InsR and insulin sensitivity index (ISI) in T2DM rats. CONCLUSION: CMP-2b may be useful for treating T2DM and its complications.

Animals↗

Influence of food and fluid ingestion on aspirin bioavailability.

The influence of test meals and accompanying fluid volume on aspirin bioavailability from commercial tablets was determined following single oral doses to healthy male volunteers. Plasma aspirin and salicylate levels were determined simultaneously using a GLC end-point. Area analysis indicated that approximately 5--8% of absorbed drug entered the systemic circulation as unchanged aspirin in nonfasted subjects compared to 16--18% in fasted individuals. Food tended to reduce the appearance rate of aspirin into the circulation, resulting in lower and somewhat more sustained levels than with fasting. Plasma salicylate levels were not influenced markedly by the various treatments, although levels were higher in fasted than in nonfasted subjects during the 1st hr after dosing. After this time, fat pretreatment tended to produce higher levels than other treatments.

Adult↗

Effects of aging and food restriction on the antioxidant enzyme activity of rat livers.

The effects of aging and food restriction on the activities and mRNA levels of antioxidant enzymes in rat livers were examined. Rats were fed ad libitum every day (AL) or ad libitum on every other weekday (FR). At 30 months of age, the catalase and glutathione peroxidase activities were lower, whereas the thiobarbituric acid (TBA) value, an index of lipid peroxidation of the AL rats, was higher than that at younger ages. At 33 months of age, copper/zinc superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase activities increased, and the TBA value of the FR rats remained unchanged as compared with those at younger ages. Until old age, food restriction gave rather decreasing effects on antioxidant enzyme activities. Furthermore, antioxidant enzyme activities and the TBA values of the FR rats were higher at the end of a fasting period than those at the end of a feeding period.

Aging↗

Resistance of hepatic glycogen to depletion in obese Zucker rats.

Glycogen stores (liver and carcass) have been studied in lean and obese Zucker rats. The animals were submitted to one of three feeding conditions: ad libitum, a 48-h fast, or a 48-h fast and food ad libitum for 24 h, and to two environmental conditions, either thermoneutrality or an acute cold exposure (2 days at 4-7 degrees C). After a 2-day fast at 25 degrees C, the liver glycogen store was reduced by 45 times in the lean rats, while it was decreased by only 3 times in the obese rats. Under these conditions, the liver glycogen store was 45 times higher in the obese than in the lean rats. After 2 days in the cold, liver glycogen store was 4.4 times higher in obese rats than in lean rats. After a 2-day fast in the cold, the liver glycogen store in the obese rats was 30 times higher than in the lean rats. In comparison to fasting at thermoneutrality, fasting in the cold did not lead to a further reduction in hepatic glycogen in obese Zucker rats. The differences observed in the mobilization of the hepatic glycogen store between obese and lean rats have not been found in the mobilization of the carcass glycogen store. Drastic conditions, such as a 2-day fast in the cold, did not exhaust the glycogen store in obese Zucker rats. The present observations point out that obese Zucker rats cannot mobilize the entire hepatic glycogen store, as seen in lean control rats. The role of this abnormality in the high hyperlipogenesis that maintains the obese state is still to be evaluated.

Analysis of Variance↗

Suppression of food intake induced by corticotropin-releasing factor family in neonatal chicks.

Corticotropin-releasing factor (CRF), urocortin and urotensin I share amino acid sequences, and they inhibit food intake in mammals. CRF plays a potent role in decreasing food intake in avian species, but the effects of urocortin and urotensin I have not been investigated. Therefore, the effect of these three peptides on food intake in the neonatal chick was compared. In Experiment 1, birds were injected intracerebroventricularly (i.c.v.) with either 0, 0.01, 0.1 or 1 microg of urocortin following a 3-h fast, and food intake was measured for 2 h post-injection. Food intake was suppressed in a dose-dependent manner. Using a similar design in Experiment 2, the effect of urotensin I was investigated. Urotensin I appeared to suppress food intake in neonatal chicks more than urocortin did. In Experiment 3, the efficacy of CRF, urocortin and urotensin I was directly compared using one dose, 0.1 microg. The results indicated that the suppressive effect on food intake was strongest for CRF followed by urotensin I, then urocortin. These results suggest that the structure of receptors for the CRF family in chicks may be somewhat different than in mammals.

Animals↗