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Fasted State (fasted + state)
Selected AbstractsResistance exercise increases leg muscle protein synthesis and mTOR signalling independent of sexACTA PHYSIOLOGICA, Issue 1 2010H. C. Dreyer Abstract Aim:, Sex differences are evident in human skeletal muscle as the cross-sectional area of individual muscle fibres is greater in men than in women. We have recently shown that resistance exercise stimulates mammalian target of rapamycin (mTOR) signalling and muscle protein synthesis in humans during early post-exercise recovery. Therefore, the aim of this study was to determine if sex influences the muscle protein synthesis response during recovery from resistance exercise. Methods:, Seventeen subjects, nine male and eight female, were studied in the fasted state before, during and for 2 h following a bout of high-intensity leg resistance exercise. Mixed muscle protein fractional synthetic rate was measured using stable isotope techniques and mTOR signalling was assessed by immunoblotting from repeated vastus lateralis muscle biopsy samples. Results:, Post-exercise muscle protein synthesis increased by 52% in the men and by 47% in the women (P < 0.05) and was not different between groups (P > 0.05). Akt phosphorylation increased in both groups at 1 h post-exercise (P < 0.05) and returned to baseline during 2 h post-exercise with no differences between groups (P > 0.05). Phosphorylation of mTOR and its downstream effector S6K1 increased significantly and similarly between groups during post-exercise recovery (P < 0.05). eEF2 phosphorylation decreased at 1- and 2 h post-exercise (P < 0.05) to a similar extent in both groups. Conclusion:, The contraction-induced increase in early post-exercise mTOR signalling and muscle protein synthesis is independent of sex and appears to not play a role in the sexual dimorphism of leg skeletal muscle in young men and women. [source] Effect of food on the antiviral activity of didanosine enteric-coated capsules: a pilot comparative study,HIV MEDICINE, Issue 4 2008B Hernández-Novoa Objectives To determine the effect of food on the antiviral activity of enteric-coated (EC) capsules of didanosine (ddI). Methods We conducted a pilot, randomized, open-label study of 28-day ddI-EC capsules monotherapy-administered in a fasted state (group 1, n=11) or with food (group 2, n=10) to treatment-naďve chronically HIV-1-infected individuals. To assess the antiviral efficacy, HIV-1 RNA was determined at baseline, day 3, day 7 and weekly thereafter. The area under the HIV-1 RNA curve minus baseline weighted by time (AUCMB/day) was calculated. Results Mean baseline HIV-1 RNA was 4.2 log10 copies/mL in group 1 and 3.8 log10 copies/mL in group 2. After 28 days, the mean HIV-1 RNA reduction was 0.99 log10 copies/mL [95% confidence interval (CI) 0.45,1.53] for group 1 and 0.89 log10 copies/mL (95% CI 0.38,1.40) for group 2. AUCMB/day values were 0.775 log10 copies/mL (95% CI 0.33,1.22) and 0.774 log10 copies/mL (95% CI 0.48,1.07), respectively, showing no difference in the rate of decrease of HIV-1 RNA (P=0.995). Mean ddI plasma levels at day 28 were 0.0234 mg/L for group 1 and 0.0227 mg/L for group 2 (P=0.96). Conclusions In this pilot study, the administration of food did not have any significant effect on the antiviral activity of ddI-EC capsules. [source] Plasma Agouti-Related Protein Level: A Possible Correlation with Fasted and Fed States in Humans and RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2002C.-P. Shen Abstract We measured plasma concentrations of agouti-related protein (AGRP) in humans and rats and determined whether these were affected by ingestion of a meal after fasting. In 17 healthy human subjects, the mean plasma concentration of AGRP was lower in the fed state than in the fasted state. Two hours after a breakfast meal, AGRP levels dropped by 39%. By contrast, a continued fast for 2 h increased the average AGRP concentration by 73%. In rats with diet-induced obesity, refeeding resulted in a 50% decrease in plasma AGRP concentrations following a fasting-refeeding protocol. Our results support the notion that plasma AGRP may serve as a biomarker for the transition from a fasted to the satiated state. [source] Scintigraphic study to investigate the effect of food on a HPMC modified release formulation of UK-294,315JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009J. Davis Abstract The objective of the study was to use the combined approach of gamma scintigraphy and pharmacokinetics, in order to understand the mechanisms explaining the pharmacokinetic differences observed for a modified release (MR) formulation, when administered either in the fed or fasted state. Ten healthy subjects were recruited into a randomized three period single dose study, each subject receiving UK-294,315 40 mg IR (fasted), 100 mg MR (fasted) or 100 mg MR (after a high fat meal). Cmax values were markedly higher for the MR tablet in the fed state versus fasted and mean residence time was about 3 h longer for fasted versus fed; there was little difference in apparent oral clearance. In the fasted state, average gastric emptying of the intact tablet occurred at 1.2 h postdose, with gastric emptying of intact tablet observed in all subjects. In the fed state, rapid disintegration of the MR tablet was observed by scintigraphy, with 7/9 subjects showing complete disintegration in the stomach. Complete disintegration occurred 10.1 h postdose in the fasted state versus 5.9 h after a high fat meal. The study showed that in the fed state, the MR tablet eroded more rapidly than in the fasted state, leading to an overall increase in the rate of absorption. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1568,1576, 2009 [source] Evaluation of drug precipitation of solubility-enhancing liquid formulations using milligram quantities of a new molecular entity (NME)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007Wei-Guo Dai Abstract A precipitation screening method using a 96-well microtiter plate was developed to evaluate in vitro drug precipitation kinetics of liquid formulations for poorly water-soluble compounds, using milligram quantities of compounds and milliliter volumes of biorelevant media. By using this method we identified three formulations showing distinct in vitro precipitation kinetics (fast, slow, and no precipitation) for a model new molecular entity (JNJ-25894934). The in vitro precipitation profiles in simulated intestinal fluid (SIF), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) were compared with those measured by a USP dissolution method, and with in vivo absorption at the fasted and fed states in canine pharmacokinetic (PK) studies. The precipitation kinetics of all three formulations in the initial hours measured by the screening method correlated to those determined by the USP method (R2,=,0.96). The PK results showed that the fast-precipitation formulation had the lowest bioavailability. However, a similar bioavailability was observed for the slow- and no-precipitation formulations. The oral bioavailability of JNJ-25894934 at the fed state was also significantly higher than that at the fasted state for all three formulations (p,<,0.05). In addition, the in vitro precipitation profiles in FeSSIF correlated better with in vivo absorption than those in SIF and FaSSIF. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2957,2969, 2007 [source] Stability of oleuropein in the human proximal gutJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2009Constantinos Markopoulos Abstract Objectives We aimed to assess the intralumenal stability of oleuropein in human gastric and small intestinal contents. We additionally aimed to assess the stability characteristics of oleuropein in media simulating the intralumenal conditions. Methods The intralumenal stability of oleuropein was assessed in aspirates from the stomach and the upper small intestine of healthy volunteers collected under both fasted and fed state conditions and in media simulating the intralumenal environment. Key findings Oleuropein degraded in aspirates collected in the fasted state. When the initial concentration was about 50 ,g/ml (close to expected intragastric concentration after single dose of commercially available products of oleuropein) the mean zero-order half-life of oleuropein in aspirates collected from the fasted small intestine was estimated to be 3.14 ± 0.08 h at 37°C (i.e. after oral administration in the fasted state, a substantial fraction of oleuropein degrades before reaching the intestinal mucosa). In contrast, oleuropein was stable in aspirates collected from the fed stomach; in small intestinal contents aspirated in the fed state the estimated zero-order degradation half-life was at least 12 h. Conclusions These data suggest that oleuropein should not have substantial intralumenal stability problems when administered in the fed state. Data collected in media simulating the intragastric and intraintestinal environment suggest that pH affects the stability of oleuropein only at low pH values (of about 2). At higher pHs degradation characteristics are at least partly affected by the presence of other scavengers of reactive oxygen species in the medium. [source] Involvement of NO in gastric emptying of semi-solid meal in conscious pigsNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2005R. A. Lefebvre Abstract, The influence of non-selective nitric oxide synthase (NOS) inhibition on gastric emptying of a semi-solid meal was studied in conscious pigs. Antro-duodenal motility and fundic compliance were also assessed to evaluate the mechanisms at the origin of potential alteration in gastric emptying pattern. NG -nitro- l -arginine methyl ester (l -NAME; 20 mg kg,1 i.v.) delayed gastric emptying (half-emptying time of 128.98 ± 16.86 min vs 73.74 ± 7.73 min after saline, P < 0.05, n = 6) as a result of decreased proximal gastric emptying. No changes were observed for distal gastric emptying as a result of unchanged antral motility. Similarly, no changes were noted on duodenal motor patterns either in the fasted or in the fed state. l -NAME decreased fundic compliance in fasted state (49 ± 11 mL mmHg,1vs 118 ± 15 mL mmHg,1 after saline, P < 0.05, n = 6). As this phenomenon is expected to increase emptying rate, the gastroparesis induced by NOS inhibition is thus likely to originate from distal resistive forces. It is concluded that NO positively modulates gastric emptying. [source] Investigation of some factors contributing to negative food effectsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2009Venugopal P. Marasanapalle Abstract A drug is defined as exhibiting negative food effects, if the co-administration of food statistically decreases its area under the curve, AUC, when compared with its administration on a fasted stomach. In this study, the role of biopharmaceutical factors that contribute to negative food effects was studied using furosemide, nadolol, tacrine and atenolol (as model compounds exhibiting negative food effects), and prednisolone, hydrochlorothiazide and ibuprofen (as model compounds that do not show any food effects). The physiological pH of the upper intestinal tract is lower, at pH 5, in the postprandial state when compared with the preprandial state, pH 6.5. Drugs that exhibited negative food effects had low apical to basolateral Caco-2 permeabilities, low pKa/pKb and Log P values of less than 1. The drugs exhibiting negative food effects had low distribution coefficients at the pH conditions of the fed and fasted states. Furosemide, being a hydrophilic, poorly soluble acidic drug showed lower solubility in the fed state when compared with the fasted state. Basic drugs, atenolol, nadolol and tacrine, are ionized to a higher extent in the fed state and exhibit lower permeability and lower absorption when compared with the fasted state. Thus, drugs were found to exhibit negative food effects owing to their decrease in solubility or permeability in the upper intestinal tract of the fed state when compared with the fasted state. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||