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PubMed1985

[Circulating immune complexes, specific IgE against food and inhalation allergens, serum histamine levels and disorders of intestinal permeability in atopic patients before and after test meals].

Specific IgE antibodies against 25 food and 3 respiratory allergens were investigated in 35 AD patients and 26 healthy controls before and after challenge meals (CM). The frequency of positive results showed a significant increase after CM (+ 58%) with no influence on reaction specificity. Increased serum CIC levels with IgG, IgE and IgM were recorded in 34, 47 and 54% of the 35 AD patients respectively, whereby only the IgE-CIC demonstrated an increase of frequency and mean levels after CM. In 4 out of 5 atopic patients, significant higher histamine values were registered half an hour after CM, furthermore 23 out of 61 fasted patients demonstrated increased serum histamine levels. However, no direct correlation could be noticed between the increased intestinal permeability of the investigated patients on the one hand and the serum histamine levels or the presence of IgE-CIC on the other hand. The relations between single parameters as well as their clinical significance in AD patients after CM administrations are discussed.

Adolescent↗

PubMed1998

Prolonged decreases in plasma nitrate levels at early postoperative phase after hepato-pancreato-biliary surgery.

Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and metabolic alterations. To evaluate the clinical significance of .NO production under surgical stress, serial measurements of plasma nitrite plus nitrate levels were performed in 45 surgical patients. Group A included 19 patients who underwent major surgery with uneventful postoperative courses. Group B included 18 patients who underwent laparoscopic cholecystectomy. Group C included 8 patients whose surgery was complicated by intra-abdominal abscesses. Eight healthy volunteers served as controls. Plasma nitrate levels were determined with a redox chemiluminescence .NO analyzer and coincided with measurements made by high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples). During laparotomy, arterial nitrate levels correlated well with peripheral, portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949, respectively; p < 0.0001). A significant decrease in nitrate from preoperative levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days after surgery. Plasma nitrate levels in groups A and B were significantly different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in group A (p < 0.005). Plasma nitrate levels measured before and after fasting or food intake were not significantly different. These results suggest that surgical stress leads to a decrease in the end product of .NO in the whole body, and that the greater the surgical stress the longer the duration of decreased .NO production.

Adult↗

PubMed1977

Preliminary studies of absorption and excretion of benoxaprofen in man.

1 Benoxaprofen is a new acidic anti-inflammatory compound which was well absorbed after oral administration to man. 2 Single doses of 100, 200 and 400 mg produced mean peak concentrations in the plasma of 13.0, 33.5 and 45.3 microgram respectively, and the plasma half-life of the compound was between 30 and 35 hours. 3 Multiple dosing with 25 and 50 mg every 24 h achieved an equilibrium conentration in the plasma after 6-8 days, while dosing with 100 mg every 12 h enabled equilibrium to be reached in 3-6 days. Plasma concentrations between 35 and 45 microgram/ml were achieved by giving 100 mg doses every 12 hours. 4 Absorption of benoxaprofen was delayed when the drug was given with food, but the total amount absorbed remained the same. 5 The effect of milling the material to small particle size (19 micron) was to increase the rate of absorption compared to that of unmilled material (58 micron). 6 Benoxaprofen was well tolerated by healthy male subject in the doses given.

Adult↗

PubMed1983

Pituitary hormone release in response to food ingestion: evidence for neuroendocrine signals from gut to brain.

The synchrony of PRL and cortisol release with feeding is now well established. To delineate further the neuroendocrine mechanisms involved, meal-related pituitary and adrenal cortical activities were investigated in seven normal men in a series of experiments conducted in random sequence at 1-week intervals. Ingestion of a standardized mixed meal elicited a consistent acute release of PRL and cortisol at noon (1200 h), but not at breakfast (0800 h). No measurable changes in other pituitary hormones were observed. The relative magnitudes of PRL and cortisol release in response to lunch were not significantly influenced by a preceding breakfast. These responses appear unrelated to the cephalic or oral phases of food ingestion. However, the composition of the meals was found to be important. Whereas carbohydrate meals had no discernible effects, high protein meals induced a large increase in both PRL and cortisol; high fat meals caused selective release of PRL. Ingestion of L-tyrosine and L-tryptophan induced remarkable increments in serum concentrations of both PRL and cortisol, suggesting that these essential amino acids may be active components of the high protein meal. Choline had no effect. Meal-mediated PRL and cortisol release was unaffected by prior receptor blockade of the opioidergic and cholinergic systems with naloxone and atropine, respectively. These observations indicate that the protein component of the meal was responsible for the midday surges of PRL and cortisol and that the cephalic-vagal pathway was not required in food-entrained pituitary hormone release. Further, our data suggest that the neurotransmitter substrates in the protein meal may serve to link the gut and brain by modifying central catecholamine and serotonin biosynthesis, and thereby influence the hypothalamic factors controlling pituitary PRL and ACTH secretion. The possibility that gastrointestinal hormones may also influence the hypothalamic-pituitary system remains to be explored.

Adult↗

PubMed1979

Indobufen (K 3920), a new inhibitor of platelet aggregation: effect of food on bioavailability, pharmacokinetic and pharmacodynamic study during repeated oral administration to man.

The effect of food on bioavailability of indobufen tablets was investigated in 6 healthy volunteers. Subsequently, the same subjects took 100 mg b.i.d. for 7 days. Plasma levels and urinary excretion of indobufen were determined by GLC. Platelet aggregation induced by several concentrations of adrenaline was determined turbidimetrically at various times after the first and last doses. The absorption of indobufen tablets was not substantially impaired by the presence of food in the GI tract, although peak plasma levels and AUCs were slightly reduced after food. Pharmacokinetic analysis of plasma and urinary levels of indobufen did not indicate any change in drug disposition after repeated dosing. Adrenaline-induced platelet aggregation was markedly inhibited for up to 12 h after the first dose and the intensity and duration of this effect did not change after repeated administration. A twice-daily dosing appears suitable for clinical trials.

Adult↗

PubMed1999

Role of growth hormone (GH)-releasing hormone and somatostatin on leptin-induced GH secretion.

Leptin is a hormone secreted by the adipocytes that regulates food intake and energy expenditure. It is known that growth hormone (GH) secretion is markedly influenced by body weight, being suppressed in obesity and cachexia, and recent data have demonstrated that GH release is regulated by leptin levels. Although one of the sites of action of leptin is likely to be the hypothalamus, since leptin receptor mRNA is particularly abundant in several hypothalamic nuclei, the mechanisms by which leptin regulates GH secretion are not yet known. The aim of the present study was to investigate whether leptin could act at the hypothalamic level modulating somatostatin and GH-releasing hormone (GHRH) expression. The administration of anti-GHRH serum (500 microl, i.v.) completely blocked leptin-induced GH release in fasting rats. In contrast, the treatment with anti-somatostatin serum (500 microl, i.v.) significantly increased GH release in this condition. Furthermore, leptin administration (10 microg, i.c.v.) to intact fasting animals reversed the inhibitory effect produced by fasting on GHRH mRNA levels in the arcuate nucleus of the hypothalamus, and increased somatostatin mRNA content in the periventricular nucleus. Finally, leptin administration (10 microgram, i.c.v.) to hypophysectomized fasting rats increased GHRH mRNA levels, and decreased somatostatin mRNA content, indicating an effect of leptin on hypothalamic GHRH- and somatostatin-producing neurons. These findings suggest a role for GHRH and somatostatin as mediators of leptin-induced GH secretion.

Animals↗

PubMed2005

Metabolic adaptations of liver mitochondria during restricted feeding schedules.

Food anticipatory activity (FAA) is an output of the food-entrained oscillator (FEO), a conspicuous biological clock that expresses when experimental animals are under a restricted food schedule (RFS). We have shown that the liver is entrained by RFS and exhibits an anticipatory response before meal time in its oxidative and energetic state. The present study was designed to determine the mitochondrial oxidative and phosphorylating capacity in the liver of rats under RFS to further support the biochemical anticipatory role that this organ plays during the food entrainment (9). Metabolic and functional parameters of liver mitochondria were characterized before (0800 h), during (1100 h), and after (1400 h) FAA. The main results were as follows. First, there was an enhancement during FAA (1100 h) in 1) oxidative capacity (site I of the electron transport chain), 2) phosphorylating ability (estimated by ATP synthesis), and 3) activities of NADH shuttles. Second, after rats were fed (1400 h), the phosphorylating capacity remained high, but this was not the case for the respiratory control ratio for site I. Finally, in the three experimental conditions before, during, and after FAA, an increment was detected in the H(+) electrochemical potential, due to an elevation in mitochondrial membrane potential, and in mitochondrial yield. Most of the changes in mitochondrial properties related to RFS were also present when results were compared with those from the 24-h fasted group. In conclusion, the results support the notion that a distinctive rheostatic state is installed in the metabolic activity of the liver when FEO is being expressed.

Animals↗

PubMed2004

Effects of ghrelin on food intake and neuroendocrine function in sheep.

Ghrelin, a novel acylated peptide, is the endogenous ligand for growth hormone secretagogue (GHS) receptor. Ghrelin is produced mainly in the oxyntic glands of the stomach, but also produced in the intestines, kidneys, hypothalamus and pituitary gland. Circulating ghrelin levels have been shown to rise before a meal and fall afterwards, suggesting that anticipation of a meal may stimulate secretion. In some species, ghrelin administration has been shown to stimulate growth hormone (GH) secretion, and to cause weight gain by increasing food intake and reducing metabolic utilization of fat. Furthermore, intracerebroventricular and intravascular administration of ghrelin increases gastric acid output in a dose-dependent manner. Thus, ghrelin may play an important role in controlling feeding behavior and energy homeostasis. We have investigated the role of ghrelin in the control of feeding and neuroendocrine function in ruminants using sheep as an experimental model. This mini review describes mechanisms regulating ghrelin secretion at feeding time, and also focuses on the neuroendocrine functions of ghrelin.

Animals↗

PubMed1976

After vagotomy atropine suppresses gastrin release by food.

Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement.

Animals↗

PubMed2005

Inverse shift in circulating corticosterone and leptin levels elevates hypothalamic deiodinase type 2 in fasted rats.

During food deprivation, plasma T(4) and T(3) levels are decreased. Under this metabolic condition, hypothalamic deiodinase type 2 (D2) activity and mRNA levels are elevated, whereas TRH mRNA levels are suppressed. Systemic T(4) administration does not reverse these hypothalamic changes. The mechanism(s) that underlies this paradoxical regulation of D2 during fasting is unknown. We hypothesize that leptin and/or glucocorticoids play a role in these mechanisms, and their interactions may be an important regulator of the hypothalamic-pituitary-thyroid axis. Thus, we assessed the effects of these hormones on D2 activity levels of food-deprived as well as fed animals using enzyme activity measurements. In food-deprived animals, corticosterone replacement reversed the inhibitory effect of adrenalectomy (ADX) on D2 induction, whereas ADX and ADX plus corticosterone replacement did not significantly affect D2 activity levels in rats fed ad libitum. Leptin administration to fed animals did not change D2 activity, whereas in fasted rats, leptin decreased D2 activity by reducing corticosterone plasma levels. When leptin was administered to fasted animals that were either ADX or ADX plus corticosterone treated at a high dose, D2 activity did not increase. Our results show that during fasting, diminishing leptin levels play a permissive role to enable glucocorticoid-induced up-regulation of D2. Thus, our observations suggest that appropriate induction of D2 activity during negative energy balance is dependent upon both leptin and glucocorticoid signaling.

Adrenalectomy↗

PubMed2004

Media to simulate the postprandial stomach I. Matching the physicochemical characteristics of standard breakfasts.

To better predict food effects on the bioavailability/bioequivalence of drugs and drug products from in-vitro data, a dissolution medium that simulates the initial composition of the postprandial stomach was developed. First, the physical parameters of two homogenized standard breakfasts often administered to assess food effects in pharmacokinetic studies were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Subsequently, the match of the physical parameters of several commercially available liquid meals, including long-life milk, Ensure and Ensure Plus to those of the breakfasts was evaluated. Of the three liquid meals studied, Ensure Plus had the closest physicochemical behaviour to that of homogenized standard breakfasts. By increasing the viscosity of Ensure Plus with 0.45% pectin, it was possible to obtain a medium that closely resembles the FDA standard breakfast.

Animals↗

PubMed2004

Reproductive switch and aging: the case of leptin change in dietary restriction.

We have proposed that normal food intake is geared toward optimizing the internal milieu for reproduction, despite some components of this milieu being detrimental to health. In dietary restriction, the animal is prevented from eating enough to attain or maintain reproductive capacity and this particular milieu does not materialize. Life extension occurs as a by-product. This idea provides a framework for exploring biomolecular changes in dietary restriction and their relevance to aging. Leptin is a case in point: here, a decrease in leptin level in dietary restriction is explored in the light of leptin's role in the complex signaling system of reproductive switch.

Adipose Tissue↗

PubMed1990

Fluoride pharmacokinetics: its implications in the fluoride treatment of osteoporosis.

This report reviews some aspects of fluoride pharmacokinetics in relation to the treatment of osteoporosis. The bioavailability of conventional plain NaF tablets has been shown to be close to 100, for sustained-release NaF tablets close to 90%, and for enteric-coated NaF tablets 65%. The simultaneous intake of food and/or calcium tablets reduces the bioavailability by 30 to 40%. Fluoride renal clearance is influenced by both urinary pH and flow and the clinical consequences of this is discussed. Studies on plasma kinetics of fluoride during chronic fluoride intake suggests that a plasma sample taken at mid-dosage intervals will give reproducible "mean steady-state" levels. It is suggested that improvements of the clinical benefit of fluoride therapy in osteoporosis might be achieved if the dosage regimen were based on the pharmacokinetic properties of the fluoride preparation used as well as plasma fluoride monitoring.

Biological Availability↗

PubMedDate not supplied

Pharmacokinetics and concentration--effect relationships of bevantolol (CI-775) in normal volunteers.

The pharmacokinetic handling of the beta 1 selective adrenoceptor blocking drug, bevantolol, was studied in 12 healthy volunteers. After intravenous (i.v.) administration of 50 mg of the drug, there was a biexponential decline in plasma levels with a terminal elimination half life (t1/2) of 1.9 h (range 1.4-2.3 h) and a total apparent volume of distribution at equilibrium of 62 L. After oral administration of the same dose, the bioavailability averaged 57% (range 26-98%) and peak plasma levels varied over a threefold range. On average, less than 1% of the dose was eliminated unchanged in the urine, indicating that the clearance of the drug was accounted for almost entirely by metabolism. Plasma levels after oral dosing with food showed an average 75-min delay in achievement of peak plasma levels and an average 14% increase in the extent of bioavailability of the drug. A positive correlation (r = 0.79) existed between the logarithm of the plasma bevantolol level and the percentage of reduction in postexercise heart rate. A plasma drug level of approximately 200 ng/ml produced a 10% reduction in postexercise heart rate. Pharmacological studies using guinea pig atrial and tracheal tissue demonstrated that the beta-blocking potency and beta-selectivity of bevantolol were intermediate between those of metoprolol and atenolol.

Adrenergic beta-Antagonists↗

PubMed1991

The glycemic index: methodology and clinical implications.

There is controversy regarding the clinical utility of classifying foods according to their glycemic responses by using the glycemic index (GI). Part of the controversy is due to methodologic variables that can markedly affect the interpretation of glycemic responses and the GI values obtained. Recent studies support the clinical utility of the GI. Within limits determined by the expected GI difference and by the day-to-day variation of glycemic responses, the GI predicts the ranking of the glycemic potential of different meals in individual subjects. In long-term trials, low-GI diets result in modest improvements in overall blood glucose control in patients with insulin-dependent and non-insulin-dependent diabetes. Of perhaps greater therapeutic importance is the ability of low-GI diets to reduce insulin secretion and lower blood lipid concentrations in patients with hypertriglyceridemia.

Blood Glucose↗

PubMed1994

The relation of reported alcohol ingestion to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States).

We undertook a cross-sectional study in 107 premenopausal women in Maryland (United States) of alcohol intake and hormonal status in order to evaluate whether plasma hormone levels might mediate the reported positive relation between alcohol ingestion and breast cancer risk. Alcohol ingestion was estimated using a drinking pattern questionnaire, a food frequency questionnaire, and seven-day food records. Fasting blood specimens were collected on days 5-7, 12-15, and 21-23 of each participant's menstrual cycle and pooled to create follicular, midcycle, and luteal phase samples, respectively, for analysis. Estrone, estrone sulfate, estradiol, androstenedione, and dehydroepiandrosterone sulfate (DHEAS) in plasma were measured by radioimmunoassay, and sex-hormone binding globulin (SHBG) was measured by an immunoradiometric assay. After adjusting for age, weight, and total energy intake, alcohol ingestion was not associated with plasma estrogens in the follicular, midcycle, or luteal phases of the menstrual cycle, nor with the level of SHBG or DHEAS in plasma averaged from the three phases of the cycle. Alcohol, however, was significantly positively associated with the average level of plasma androstenedione. Based on these cross-sectional findings among premenopausal women, the increased risk of breast cancer related to alcohol ingestion does not appear to be mediated by elevated plasma estrogen levels. Androstenedione, however, may mediate the alcohol/breast cancer-association.

Adult↗

PubMed1991

Regional effects of ceruletide, a cholecystokinin-8 analog, on the striatal monoaminergic systems in food-deprived mice.

To clarify the pharmacological mechanism by which ceruletide affects involuntary movements, we used 20-h food-deprived mice to examine the acute effects of ceruletide (600 micrograms/kg, i.p.) on the histochemistry of striatal dopaminergic and serotonergic systems. The latter was unchanged but a reduction in catecholamine fluorescence was seen which was restricted to the ventrolateral (VL) portion of the striatum. Biochemical assays also indicated decreased levels of dopamine (DA) and its metabolites in this restricted region of the striatum with little or no change in noradrenaline, serotonin or their metabolites. In all regions examined, except the dorsomedial part of the mid-striatum, the ratio of dopamine metabolites to dopamine was higher in the ceruletide-treated group than in controls, suggesting increased DA release. Further pharmacological experiments showed that, compared to results in mice receiving only ceruletide: the ceruletide-induced decreases in DA and dihydroxyphenylacetic acid (DOPAC) in VL were less after alpha-methyl-p-tyrosine treatment; ceruletide caused no significant decrease in either DA or DOPAC after pargyline pretreatment, although the low levels of homovanillic acid (HVA) were still further significantly reduced; and the ceruletide-induced decrease of DA was reduced, that of DOPAC was abolished and that of HVA enhanced by nomifensine pretreatment. These results suggested that ceruletide might induce a more rapid degradation of DA in VL and increased efflux of HVA through the blood-brain barrier. This evidence suggests that ceruletide has a regionally specific effect on the striatal dopaminergic system which may relate to the amelioration of involuntary movements.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

The glycaemic index values of Vietnamese foods.

OBJECTIVE: To determine and compare the glycaemic index (GI) values of a range of Vietnamese foods in two racial groups. DESIGN AND SUBJECTS: Twelve healthy subjects (six Asian and six Caucasian) consumed 50 g carbohydrate portions of a reference food (glucose sugar) and nine Vietnamese foods (three rices, three noodle products and three sweet foods) in random order after an overnight fast. The reference food was tested on two separate occasions, and the Vietnamese foods were each tested once. Capillary blood samples were taken at time 0 (fasting), 15, 30, 45, 60, 90 and 120 min from the start of each meal. Samples were analysed for plasma glucose and the incremental areas under the plasma glucose curves (AUC) were used to calculate the GI values of the test foods, using glucose as the reference food (ie GI value of glucose=100). The mean GI value of each food was calculated for the entire group of subjects (n=12) and for both racial groups (n=6). RESULTS: The three rices had surprisingly high GI values (86-109), whereas the noodle products had relatively low GI values (39-61). The sugar-rich foods produced intermediate GI values (54-79). The GI values for the nine foods calculated separately for the two racial groups were not significantly different from each other (P=0.26). CONCLUSIONS: The GI values derived from Caucasian subjects are likely to be applicable to Asian populations. Varieties of imported rice from Thailand were found to have high GI values. Alternative low-GI staples, such as rice noodles, may be preferable for Asian/Vietnamese people with diabetes. SPONSORSHIP: This study was funded by the University of Sydney.

Animals↗