Home About us Contact
|
Home About us Contact | ||
|
|
||
Healthy Humans (healthy + human)
Terms modified by Healthy Humans Selected AbstractsGlobal classification of human facial healthy skin using PLS discriminant analysis and clustering analysisINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2001C Guinot Synopsis Today's classifications of healthy skin are predominantly based on a very limited number of skin characteristics, such as skin oiliness or susceptibility to sun exposure. The aim of the present analysis was to set up a global classification of healthy facial skin, using mathematical models. This classification is based on clinical, biophysical skin characteristics and self-reported information related to the skin, as well as the results of a theoretical skin classification assessed separately for the frontal and the malar zones of the face. In order to maximize the predictive power of the models with a minimum of variables, the Partial Least Square (PLS) discriminant analysis method was used. The resulting PLS components were subjected to clustering analyses to identify the plausible number of clusters and to group the individuals according to their proximities. Using this approach, four PLS components could be constructed and six clusters were found relevant. So, from the 36 hypothetical combinations of the theoretical skin types classification, we tended to a strengthened six classes proposal. Our data suggest that the association of the PLS discriminant analysis and the clustering methods leads to a valid and simple way to classify healthy human skin and represents a potentially useful tool for cosmetic and dermatological research. Résumé Les classifications actuelles qui définissent une peau saine sont fondées principalement sur un nombre très limité de caractéristiques cutanées telles que l'aspect gras de la peau ou sa sensibilité au soleil. Cette analyse a pour but d'établir une classification globale de la peau humaine saine du visage à l'aide de modèles mathématiques. Une recherche de typologie a été effectuée à partir des caractéristiques cliniques et biophysiques de la peau du visage des individus tout en tenant compte d'une classification théorique, reflet de l'expertise des dermatologues, appréciée sur les zones frontale et malaire du visage. Pour accroître l'efficacité prédictive des modèles avec un minimum de variables, la méthode d'analyse discriminante PLS (Partial Least Square) a été utilisée. Des méthodes de classification ont été appliquées aux composantes PLS obtenues afin de déterminer le nombre le plus vraisemblable de classes et pour regrouper les sujets selon leurs proximités. Grâce à cette approche, quatre composantes PLS ont pu être construites et six classes se sont avérées pertinentes. Ce travail a abouti à une proposition de classification à six classes plus vraisemblable et acceptable que les 36 combinaisons possibles de la classification théorique proposée. Nos données suggèrent que l'association de l'analyse discriminante PLS aux méthodes de classification permet d'obtenir de façon simple et appropriée une classification de la peau humaine saine et représente un outil potentiel utile dans le domaine de la recherche en cosmétologie et en dermatologie. [source] Twenty-four-hour non-invasive monitoring of systemic haemodynamics and cerebral blood flow velocity in healthy humansACTA PHYSIOLOGICA, Issue 1 2002M. DIAMANT ABSTRACT Acute short-term changes in blood pressure (BP) and cardiac output (CO) affect cerebral blood flow (CBF) in healthy subjects. As yet, however, we do not know how spontaneous fluctuations in BP and CO influence cerebral circulation throughout 24 h. We performed simultaneous monitoring of BP, systemic haemodynamic parameters and blood flow velocity in the middle cerebral artery (MCAV) in seven healthy subjects during a 24-h period. Finger BP was recorded continuously during 24 h by Portapres and bilateral MCAV was measured by transcranial Doppler (TCD) during the first 15 min of every hour. The subjects remained supine during TCD recordings and during the night, otherwise they were seated upright in bed. Stroke volume (SV), CO and total peripheral resistance (TPR) were determined by Modelflow analysis. The 15 min mean value of each parameter was assumed to represent the mean of the corresponding hour. There were no significant differences between right vs. left, nor between mean daytime vs. night time MCAV. Intrasubject comparison of the twenty-four 15-min MCAV recordings showed marked variations (P < 0.001). Within each single 15-min recording period, however, MCAV was stable whereas BP showed significant short-term variations (P < 0.01). A day,night difference in BP was only observed when daytime BP was evaluated from recordings in the seated position (P < 0.02), not in supine recordings. Throughout 24 h, MCAV was associated with SV and CO (P < 0.001), to a lesser extent with mean arterial pressure (MAP; P < 0.005), not with heart rate (HR) or TPR. These results indicate that in healthy subjects MCAV remains stable when measured under constant supine conditions but shows significant variations throughout 24 h because of activity. Moreover, changes in SV and CO, and to a lesser extent BP variations, affect MCAV throughout 24 h. [source] Short-term nocturnal hypoglycaemia increases morning food intake in healthy humansDIABETIC MEDICINE, Issue 2 2008S. M. Schmid Abstract Aims Hypoglycaemia during wakefulness increases hunger and food intake. Patients with Type 1 diabetes mellitus are at high risk of recurrent hypoglycaemia and weight gain. Given the background of frequent hypoglycaemic episodes during night-time sleep in diabetic patients, we investigated morning food intake after nocturnal hypoglycaemia. Methods We tested 16 healthy normal-weight subjects (eight women) on three nights. A linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60 min was induced by insulin infusion immediately after sleep onset (,early hypo') or after about 3.5 h of sleep (,late hypo'). On a control night, no hypoglycaemia was induced. Spontaneous food intake at a breakfast buffet was registered on the subsequent morning. Results Compared with the control condition (700 ± 93 kcal), subjects ate more after ,late hypo' (867 ± 108 kcal; P = 0.041), but not after ,early hypo' (852 ± 111 kcal; P = 0.130). Analyses of macronutrient fractions revealed that in comparison with the control condition, subjects ate significantly more carbohydrates after both ,late hypo' (277 ± 25 kcal vs. 206 ± 23 kcal, P < 0.001) and ,early hypo' (245 ± 23 kcal, P = 0.048), with this effect being more pronounced after late than early nocturnal hypoglycaemia (P = 0.026). Conclusions In healthy subjects, nocturnal hypoglycaemia during sleep stimulates spontaneous food intake the following morning, with carbohydrate intake being especially affected. Effects were more pronounced after ,late hypo', suggesting the influence of temporal dynamics. Although healthy non-diabetic subjects were studied, similar mechanisms may contribute to the frequently observed body weight gain in insulin-treated diabetic patients. [source] Do horses suffer from irritable bowel syndrome?EQUINE VETERINARY JOURNAL, Issue 9 2009J. O. HUNTER Summary Irritable bowel syndrome (IBS) in man is not a single entity but has several causes. One of the most common forms has similarities with colic and laminitis in horses. Undigested food residues may pass from the small intestine into the colon where bacterial fermentation produces chemicals that lead to disease. In horses the consequences may be disastrous, but in healthy humans such malabsorption may not be harmful. After events such as bacterial gastroenteritis or antibiotic treatment, an imbalance of the colonic microflora with overgrowth of facultative anaerobes may arise, leading to malfermentation and IBS. It is not known whether such subtle changes may likewise be present in the microflora of horses who are susceptible to colic and laminitis. Metabolomic studies of urine and faeces may provide a suitable way forward to identify such changes in the horse's gut and thus help to identify more accurately those at risk and to provide opportunities for the development of improved treatment. [source] Red Cell Pulmonary Transit Times Through the Healthy Human LungEXPERIMENTAL PHYSIOLOGY, Issue 2 2003G. S. Zavorsky It has previously been postulated that rapid red cell capillary transit through the human lung plays a role in the mechanism of diffusion limitation in some endurance athletes. Methodological limitations currently prevent researchers from directly measuring pulmonary capillary transit times in humans during exercise; however, first pass radionuclide cardiography allows direct measurement of red blood cell (RBC) transit times through the whole lung at various exercise intensities. We examined the relationship between mean whole lung red cell pulmonary transit times (cardiopulmonary transit times or CPTT) and different levels of flow in 88 healthy humans (76 males, 12 females) from several studies (mean age 31 years). The pooled data suggest that the relationship between CPTT and cardiac index (CI), beginning at rest and progressing through to maximum exercise demonstrates that CPTT reaches its minimum value when CI is about 8.1 l m2 min,1 (2.5-3 times the CI value at rest), and does not significantly change with further increases in CI. Cardiopulmonary blood volume (CPBV) index also does not change significantly until CI reaches 2.5 to 3 times the CI value at rest and then increases roughly linearly after that point. Consequently, the systematic increase in CPBV index with increasing pulmonary blood flow between 8.1 and 20 l m2 min,1 displays an adaptive response of the cardiopulmonary system by augmenting CPBV (and perhaps pulmonary capillary blood volume through distension and recruitment) to offset the reduction in CPTT, as no significant difference in mean CPTT is observed between these levels of flow (P > 0.05). Therefore, these data demonstrate that CPBV does not reach maximum capacity during strenuous or maximum exercise. This does not support the principle of quarter-power allometric scaling for flow when explaining modifications during exercise. Therefore, we speculate that the observed relationships between CPTT, CBPV index and flow may prevent mean CPTT (and perhaps mean pulmonary capillary transit times) from decreasing below the threshold time required for oxygenation. [source] Interactions between salivary Bifidobacterium adolescentis and other oral bacteria: in vitro coaggregation and coadhesion assaysFEMS MICROBIOLOGY LETTERS, Issue 2 2008Seiji Nagaoka Abstract Coaggregation assays were performed to investigate interactions between oral Bifidobacterium adolescentis and other oral bacterial species. Bifidobacterium adolescentis OLB6410 isolated from the saliva of healthy humans did not coaggregate with Actinomyces naeslundii JCM8350, Streptococcus mitis OLS3293, Streptococcus sanguinis JCM5708, Veillonella parvula ATCC17745 or Porphyromonas gingivalis OB7124, but it did coaggregate with Fusobacterium nucleatum JCM8532. Subsequent examination of biofilm formation on saliva-coated hydroxyapatite discs using FISH revealed that B. adolescentis OLB6410 could not directly adhere to the coated discs. It did, however, adhere to biofilms of A. naeslundii, V. parvula, and F. nucleatum, although it did not coaggregate with A. naeslundii nor with V. parvula. These results suggest that the adhesion of B. adolescentis to tooth surfaces is mediated by other oral bacteria. Heat- or proteinase K-treated F. nucleatum could not coaggregate with B. adolescentis. Similarly, the coaggregation and coadhesion of proteinase K-treated B. adolescentis were strongly inhibited. It is therefore probable that proteinaceous factors on the cellular surface of B. adolescentis and F. nucleatum are involved in their interaction. The data presented in this study add to our understanding of bifidobacterial colonization in the human oral cavity. [source] New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humansFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2004M. Trellu Abstract Thiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re-investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C-labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de-glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3-O-glucuronidated aglycone (M1) obtained after glucuro-conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax = 1 h) and was eliminated with an apparent terminal half-life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax = 0.4 h) and eliminated with an apparent terminal half-life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half-life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly investigate the PK and bioequivalence of TCC, the biological samples obtained must be assayed with a bioanalytical method able to specifically analyse TCC and its active metabolite M1. [source] Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humansHUMAN BRAIN MAPPING, Issue 4 2008Ariel Graff-Guerrero Abstract The D2 receptors exist in either the high- or low-affinity state with respect to agonists, and while agonists bind preferentially to the high-affinity state, antagonists do not distinguish between the two states. [11C]-(+)-PHNO is a PET D2agonist radioligand and therefore provides a preferential measure of the D2high receptors. In contrast, [11C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D2 high- and low-affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [11C]-(+)-PHNO and [11C]raclopride in volunteers using a within-subject design. Both radioligands accumulated in brain areas rich in D2/D3 -receptors. However, [11C]-(+)-PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [11C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [11C]raclopride, equal in the ventral-striatum (3.4 vs. 3.3), and higher in the globus pallidus for [11C]-(+)-PHNO (1.8 vs. 3.3). Moreover [11C]-(+)-PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [11C]-(+)-PHNO in the globus pallidus and ventral-striatum could be the presence of a greater proportion of high- vs. low-affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D3 -over-D2 with [11C]-(+)-PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. Hum Brain Mapp 2008. © 2007 Wiley-Liss, Inc. [source] Verbal memory performance improved via an acute administration of D -amphetamineHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2007Inge Zeeuws Abstract Background An improved long-term retention of verbal memory was observed after an acute D -amphetamine administration. It was proposed that D -amphetamine modulates consolidation, but a possible drug effect on retrieval could not be rejected. Objectives We want to provide additional support for the consolidation hypothesis, and investigate whether an influence on intervening retrieval can be refuted. Methods Thirty-six male paid volunteers participated in a double blind, counterbalanced, placebo-controlled design in which the number of intermediate free recall tests was manipulated. Results A significant D -amphetamine facilitation effect on recall performance emerged 1 h and 1 day after list learning. In line with the consolidation hypothesis, no effect was found on immediate tests. Importantly, the number of intermediate retrievals did not affect the magnitude of the drug effect, suggesting that the D -amphetamine facilitation effect is independent of retrieval. Conclusion The D -amphetamine facilitation effect on verbal memory does not involve a modulation of the initial encoding or short-term memory (STM) processes. Moreover, the drug does not enhance long-term retention by acting on intervening retrieval processes. The current findings are in line with the conjecture of an involvement of the consolidation process in the D -amphetamine facilitation effect on verbal memory in healthy humans. Copyright © 2007 John Wiley & Sons, Ltd. [source] Relationship between stroke volume, cardiac output and filling of the heart during tiltACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009M. BUNDGAARD-NIELSEN Background: Cardiac function curves are widely accepted to apply to humans but are not established for the entire range of filling of the heart that can be elicited during head-up (HUT) and head-down tilt (HDT), taken to represent minimal and maximal physiological filling of the heart, respectively. With the supine resting position as a reference, we assessed stroke volume (SV), cardiac output (CO) and filling of the heart during graded tilt to evaluate whether SV and CO are maintained during an assumed maximal physiological filling of the heart elicited by 90° HDT in healthy resting humans. Methods: In 26 subjects, central blood volume was manipulated with graded tilt from 60° HUT to 90° HDT. We measured SV, CO (Finometer®) and cardiac filling by echocardiography of the left ventricular end-diastolic volume (LVEDV; n=12). Results: From supine rest to 60° HUT, SV and CO decreased 23 ml [confidence intervals (CI): 16,30; P<0.001; 23%] and 0.9 l/min (0.4,1.4; P<0.0001; 14%), respectively, but neither SV nor CO changed during HDT up to 70°. However, during 90° HDT, SV decreased 12 ml (CI: 6,19; P<0.0001; 12%), with an increase of 21 ml (9,33; P=0.002; 16%) in LVEDV because HR increased 3 bpm and CO decreased 0.5 l/min (ns). Conclusion: This study confirmed that SV and CO are maximal in resting, supine, healthy humans and decrease during HUT. However, 90° HDT was associated with increased LVEDV and induced a reduction in SV. [source] Iloprost inhalation redistributes pulmonary perfusion and decreases arterial oxygenation in healthy volunteersACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009D. RIMEIKA Background: Previous studies have shown that ventilation,perfusion matching is improved in the prone as compared with that in the supine position. Regional differences in the regulation of vascular tone may explain this. We have recently demonstrated higher production of nitric oxide in dorsal compared with ventral human lung tissue. The purpose of the present study was to investigate regional differences in actions by another vasoactive mediator, namely prostacyclin. The effects on gas exchange and regional pulmonary perfusion in different body positions were investigated at increased prostacyclin levels by inhalation of a synthetic prostacyclin analogue and decreased prostacyclin levels by unselective cyclooxygenase (COX) inhibition. Methods: In 19 volunteers, regional pulmonary perfusion in the prone and supine position was assessed by single photon emission computed tomography using 99mTc macro-aggregated albumin before and after inhalation of iloprost, a stable prostacyclin analogue, or an intravenous infusion of a non-selective COX inhibitor, diclofenac. In addition, gas distribution was assessed in seven subjects using 99mTc-labelled ultra-fine carbon particles before and after iloprost inhalation in the supine position. Results: Iloprost inhalation decreased arterial PaO2 in both prone (from 14.2±0.5 to 11.7±1.7 kPa, P<0.01) and supine (from 13.7±1.4 to 10.9±2.1 kPa, P<0.01) positions. Iloprost inhalation redistributed lung perfusion from non-dependent to dependent lung regions in both prone and supine positions, while ventilation in the supine position was distributed in the opposite direction. No significant effects of non-selective COX inhibition were found in this study. Conclusions: Iloprost inhalation decreases arterial oxygenation and results in a more gravity-dependent pulmonary perfusion in both supine and prone positions in healthy humans. [source] Long-term effects of calorie restriction on serum sex-hormone concentrations in menAGING CELL, Issue 2 2010Roberto Cangemi Summary Calorie restriction (CR) slows aging and consistently reduces circulating sex hormones in laboratory animals. However, nothing is known regarding the long-term effects of CR with adequate nutrition on serum sex-hormone concentration in lean healthy humans. In this study, we measured body composition, and serum total testosterone, total 17-,-estradiol, sex hormone,binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S) concentrations in 24 men (mean age 51.5 ± 13 years), who had been practicing CR with adequate nutrition for an average of 7.4 ± 4.5 years, in 24 age- and body fat,matched endurance runners (EX), and 24 age-matched sedentary controls eating Western diets (WD). We found that both the CR and EX volunteers had significantly lower body fat than the WD volunteers (total body fat, 8.7 ± 4.2%; 10.5 ± 4.4%; 23.2 ± 6.1%, respectively; P = 0.0001). Serum total testosterone and the free androgen index were significantly lower, and SHBG was higher in the CR group than in the EX and WD groups (P , 0.001). Serum 17,-estradiol and the estradiol:SHBG ratio were both significantly lower in the CR and EX groups than in the WD group (P , 0.005). Serum DHEA-S concentrations were not different between the three groups. These findings demonstrate that, as in long-lived CR rodents, long-term severe CR reduces serum total and free testosterone and increases SHBG concentrations in humans, independently of adiposity. More studies are needed to understand the role of this CR-mediated reduction in sex hormones in modulating the pathogenesis of age-associated chronic diseases such as cancer and the aging process itself. [source] Expression of p16INK4a in peripheral blood T-cells is a biomarker of human agingAGING CELL, Issue 4 2009Yan Liu Summary Expression of the p16INK4a tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16INK4a expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16INK4a expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16INK4a, but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16INK4a expression did not independently correlate with gender or body-mass index, but was significantly associated with tobacco use and physical inactivity. In addition, p16INK4a expression was associated with plasma interleukin-6 concentration, a marker of human frailty. These data suggest that p16INK4a expression in PBTL is an easily measured, peripheral blood biomarker of molecular age. [source] Subtractive Screening for Probiotic Properties of Lactobacillus Species from the Human Gastrointestinal Tract in the Search for New ProbioticsJOURNAL OF FOOD SCIENCE, Issue 8 2007S. Delgado ABSTRACT:, In the search for new probiotics, 61 Lactobacillus spp. isolates, belonging to 12 species and isolated as dominant lactic acid bacteria from the feces of healthy humans, were subjected to a subtractive system of in vitro analyses, which included desirable and undesirable traits. Twenty-four isolates were able to grow in 2% bovine bile, of which 13 grew in acidified broth at pH 3.5 in acidified cysteine-containing MRS broth. Intrinsic resistance to certain antimicrobial agents (cefoxitin, metronidazole, vancomycin) was observed in most isolates, but atypical resistances to erythromycin, clindamycin, or tetracycline were also found in 5 strains. Undesirable traits such as ,-chymotrypsin or N-acetyl-,-glucosaminidase activities were not detected, but low ,-glucuronidase and moderate ,-glucosidase activities were recorded in 2 strains. Two Lactobacillus gasseri and 2 Lactobacillus paracasei selected strains inhibited several intestinal pathogens in an agar spot test, including strains of Escherichia coli, Listeria monocytogenes, Salmonella typhimurium, and Staphylococcus aureus. They also adhered to human Caco-2 and HT-29 epithelial cells in a manner comparable to Lactobacillus rhamnosus strain GG, and were unable to degrade pig gastric mucin in a plate assay. Together, these results suggest these 4 strains to be good probiotic candidates, concluding that the subtractive screening devised in this work could be a valuable tool in large-scale surveys for probiotics. [source] Influence of Dissolved Oxygen Concentration on the Pharmacokinetics of Alcohol in HumansALCOHOLISM, Issue 5 2010In-hwan Baek Background:, Ethanol oxidation by the microsomal ethanol oxidizing system requires oxygen for alcohol metabolism, and a higher oxygen uptake increases the rate of ethanol oxidation. We investigated the effect of dissolved oxygen on the pharmacokinetics of alcohol in healthy humans (n = 49). The concentrations of dissolved oxygen were 8, 20, and 25 ppm in alcoholic drinks of 240 and 360 ml (19.5% v/v). Methods:, Blood alcohol concentrations (BACs) were determined by converting breath alcohol concentrations. Breath samples were collected every 30 min when the BAC was higher than 0.015%, 20 min at BAC ,0.015%, 10 min at BAC ,0.010%, and 5 min at BAC ,0.006%. Results:, The high dissolved oxygen groups (20, 25 ppm) descended to 0.000% and 0.050% BAC faster than the normal dissolved oxygen groups (8 ppm; p < 0.05). In analyzing pharmacokinetic parameters, AUCinf and Kel of the high oxygen groups were lower than in the normal oxygen group, while Cmax and Tmax were not significantly affected. In a Monte Carlo simulation, the lognormal distribution of mean values of AUCinf and t1/2 was expected to be reduced in the high oxygen group compared to the normal oxygen group. Conclusions:, In conclusion, elevated dissolved oxygen concentrations in alcoholic drinks accelerate the metabolism and elimination of alcohol. Thus, enhanced dissolved oxygen concentrations in alcohol may have a role to play in reducing alcohol-related side effects and accidents. [source] A Critical Evaluation of Influence of Ethanol and Diet on Salsolinol Enantiomers in Humans and RatsALCOHOLISM, Issue 2 2010Jeongrim Lee Background:, (R/S)-Salsolinol (SAL), a condensation product of dopamine (DA) with acetaldehyde, has been speculated to have a role in the etiology of alcoholism. Earlier studies have shown the presence of SAL in biological fluids and postmortem brains from both alcoholics and nonalcoholics. However, the involvement of SAL in alcoholism has been controversial over several decades, since the reported SAL levels and their changes after ethanol exposure were not consistent, possibly due to inadequate analytical procedures and confounding factors such as diet and genetic predisposition. Using a newly developed mass spectrometric method to analyze SAL stereoisomers, we evaluated the contribution of ethanol, diet, and genetic background to SAL levels as well as its enantiomeric distribution. Methods:, Simultaneous measurement of SAL enantiomers and DA were achieved by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Plasma samples were collected from human subjects before and after banana (a food rich in SAL) intake, and during ethanol infusion. Rat plasma and brain samples were collected at various time points after the administration of SAL or banana by gavage. The brain parts including nucleus accumbens (NAC) and striatum (STR) were obtained from alcohol-non-preferring (NP) or alcohol-preferring (P) rats as well as P-rats which had a free access to ethanol (P-EtOH). Results:, Plasma SAL levels were increased significantly after banana intake in humans. Consistently, administration of banana to rats also resulted in a drastic increase of plasma SAL levels, whereas brain SAL levels remained unaltered. Acute ethanol infusion did not change SAL levels or R/S ratio in plasma from healthy humans. The levels of both SAL isomers and DA were significantly lower in the NAC of P rats in comparison to NP rats. The SAL levels in NAC of P rats remained unchanged after chronic free-choice ethanol drinking. There were decreasing trends of SAL in STR and DA in both brain regions. No changes in enantiomeric ratio were observed after acute or chronic ethanol exposure. Conclusions:, SAL from dietary sources is the major contributor to plasma SAL levels. No significant changes of SAL plasma levels or enantiomeric distribution after acute or chronic ethanol exposure suggest that SAL may not be a biomarker for ethanol drinking. Significantly lower SAL and DA levels observed in NAC of P rats may be associated with innate alcohol preference. [source] When What You See Isn't What You Get: Alcohol Cues, Alcohol Administration, Prediction Error, and Human Striatal DopamineALCOHOLISM, Issue 1 2009Karmen K. Yoder Background:, The mesolimbic dopamine (DA) system is implicated in the development and maintenance of alcohol drinking; however, the exact mechanisms by which DA regulates human alcohol consumption are unclear. This study assessed the distinct effects of alcohol-related cues and alcohol administration on striatal DA release in healthy humans. Methods:, Subjects underwent 3 PET scans with [11C]raclopride (RAC). Subjects were informed that they would receive either an IV Ringer's lactate infusion or an alcohol (EtOH) infusion during scanning, with naturalistic visual and olfactory cues indicating which infusion would occur. Scans were acquired in the following sequence: (1) Baseline Scan: Neutral cues predicting a Ringer's lactate infusion, (2) CUES Scan: Alcohol-related cues predicting alcohol infusion in a Ringer's lactate solution, but with alcohol infusion after scanning to isolate the effects of cues, and (3) EtOH Scan: Neutral cues predicting Ringer's, but with alcohol infusion during scanning (to isolate the effects of alcohol without confounding expectation or craving). Results:, Relative to baseline, striatal DA concentration decreased during CUES, but increased during EtOH. Conclusion:, While the results appear inconsistent with some animal experiments showing dopaminergic responses to alcohol's conditioned cues, they can be understood in the context of the hypothesized role of the striatum in reward prediction error, and of animal studies showing that midbrain dopamine neurons decrease and increase firing rates during negative and positive prediction errors, respectively. We believe that our data are the first in humans to demonstrate such changes in striatal DA during reward prediction error. [source] The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in healthALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010B. S. Wong Aliment Pharmacol Ther 2010; 32: 884,893 Summary Background, The short-term effects of methylnaltrexone (MNTX), a peripherally acting ,-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. Aim, To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. Methods, In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. Results, Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t1/2 (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). Conclusion, Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health. [source] Recognition of coagulation factor VIII by CD4+ T cells of healthy humansJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2003G-L. Hu Summary., Hemophilia A patients treated with coagulation factor (F)VIII may develop an anti-FVIII immune response. Anti-FVIII antibodies may occur also in healthy subjects. To understand the extent to which an immune response to FVIII occurs in healthy subjects, we investigated the proliferative response of blood CD4+ T cells from 90 blood donors to FVIII and to pools of overlapping synthetic peptides spanning the sequences of individual FVIII domains (A1,A3, C1,C2). Most subjects responded to FVIII and several FVIII domains. Men had stronger responses to FVIII than women, and older subjects than younger subjects. The domain-induced responses were weaker than the FVIII-induced responses, yet their intensity in individual subjects correlated with that of the response to FVIII. We examined whether Th1 and/or Th2 cells responded to FVIII in 68 subjects, by determining the CD4+ T cells that secreted interferon-, (IFN-,) or interleukin (IL)-5 after stimulation with FVIII: 25 subjects had FVIII-specific IFN-,-secreting cells, and seven of them had also FVIII-specific IL-5-secreting cells. None had only IL-5-secreting cells. Thus, a CD4+ T cell response to FVIII, which first involves Th1 cells, is common among subjects with a normal procoagulant function. [source] Continuous distal oesophageal acidification decreases postprandial gastric acidity in healthy human subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009K. BLONDEAU Summary Background, Previously, we hypothesized that exposing the distal oesophagus to acid signals the stomach to decrease gastric acidity. Aim, To test the hypothesis that exposing the distal oesophagus to acid signals the stomach to decrease gastric acidity. Methods, Twenty-two healthy humans ingested a standard meal containing [14C]octanoic acid and [13C]glycine over 30 min on 2 separate occasions. Gastric pH was measured for 90 min before and 240 min after the meal. 10 mm HCl was infused continuously at 1 mL/min into either the distal oesophagus or stomach in a 2-way crossover fashion for 60 min before and 240 min after the meal. Gastric emptying of solid and liquid were determined with breath tests. Results, Compared to gastric infusion, oesophageal infusion significantly decreased gastric acidity after the meal, but not before the meal and the magnitude of the decrease varied directly with gastric acidity. Gastric emptying of solid or liquid with oesophageal infusion was not significantly different from that with gastric infusion. Conclusions, These findings support the hypothesis of the existence of a physiological oesophago-gastric feedback mechanism that might contribute to regulation of postprandial gastric acidity. Oesophageal acidification might decode gastric information and signal the stomach to decrease gastric acidity. Further studies are needed to assess the characteristics of such feedback mechanism in-patients with gastro-oesophageal reflux disease (GERD). [source] Stroke volume of the heart and thoracic fluid content during head-up and head-down tilt in humansACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2005J. J. Van Lieshout Background:, The stroke volume (SV) of the heart depends on the diastolic volume but, for the intact organism, central pressures are applied widely to express the filling of the heart. Methods:, This study evaluates the interdependence of SV and thoracic electrical admittance of thoracic fluid content (TA) vs. the central venous (CVP), mean pulmonary artery (MPAP) and pulmonary artery wedge (PAWP) pressures during head-up (HUT) and head-down (HDT) tilt in nine healthy humans. Results:, From the supine position to 20° HDT, SV [112 ± 18 ml; mean ± standard deviation (SD)], TA (30.8 ± 7.1 mS) and CVP (3.6 ± 0.9 mmHg) did not change significantly, whereas MPAP (from 13.9 ± 2.7 to 16.1 ± 2.5 mmHg) and PAWP (from 8.8 ± 3.4 to 11.3 ± 2.5 mmHg; P < 0.05) increased. Conversely, during 70° HUT, SV (to 65 ± 24 ml) decreased, together with CVP (to 0.9 ± 1.4 mmHg; P < 0.001), MPAP (to 9.3 ± 3.8 mmHg; P < 0.01), PAWP (to 0.7 ± 3.3 mmHg; P < 0.001) and TA (to 26.7 ± 6.8 mS; P < 0.01). However, from 20 to 50 min of HUT, SV decreased further (to 48 ± 21 ml; P < 0.001), whereas the central pressures did not change significantly. Conclusions:, During both HUT and HDT, SV of the heart changed with the thoracic fluid content rather than with the central vascular pressures. These findings confirm that the function of the heart relates to its volume rather than to its so-called filling pressures. [source] Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humansALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006J. L. MADSEN Summary Background, Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. Aim, To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. Methods, Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion of glyceryl trinitrate 1 ,g/kg × min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. Results, Glyceryl trinitrate did not change gastric mean emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. Conclusions, Intravenous infusion of glyceryl trinitrate 1 ,g/kg × min does not induce major changes in gastric or small intestinal motor function after a 1600-kJ meal in healthy volunteers. [source] Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2004A. Russo Summary Background :,KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans. Aim :,To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis. Methods :,Twenty-nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and ,meal-related' symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days. Results :,KC 11458 had no statistically significant or clinically relevant effect on gastric emptying of either the solid intragastric retention at 100 min (T100) (P = 0.87) or liquid 50% emptying time (T50) (P = 0.17) components of the meal. KC 11458 slightly worsened (P = 0.04) upper gastrointestinal symptoms when compared with placebo. The magnitude of the change in solid gastric emptying correlated with the change in the blood glucose concentration (r = 0.49; P < 0.05). Conclusions :,KC 11458, in a dose of 8 mg t.d.s. for 8 days, does not accelerate gastric emptying in patients with diabetic gastroparesis. The absence of efficacy may relate to an effect of hyperglycaemia. [source] Mild hypothermia inhibits IL-10 production in peripheral blood mononuclear cellsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2004T. Matsui Background:, Hypothermia is often associated with compromised host defenses and infections. Deterioration of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. Therefore, we determined whether mild hypothermia affects the production of several types of cytokines in peripheral blood mononuclear cells (PBMCs), and the balance between pro-inflammatory and anti-inflammatory states. Methods:, PBMCs obtained from 12 healthy humans were cultured with phytohemagglutinin (PHA) in normothermic (37°C: control) or hypothermic (33°C) conditions for 24 h. The production levels of tumor necrosis factor (TNF)-,, the interleukins (ILs) IL-6, IL-8 and IL-10, and interferon (IFN)-, in the culture supernatants were measured by means of enzyme-linked immunosorbent assay (ELISA). Results:, Under hypothermic conditions (33°C), PHA-induced production of IL-10 and IFN-, in PBMCs was significantly lower, by 34% and 84%, respectively, when compared with controls, while production of TNF-,, IL-6 and IL-8 did not change. The magnitude of reduction of IL-10 in hypothermic conditions resulted in IL-10/pro-inflammatory cytokine ratios decreasing to approximately 30,45% of those of controls. Conclusions:, The present study clearly demonstrates that mild hypothermia (33°C) inhibits IL-10 and IFN-, production in cultured PBMCs. The profound inhibition of IL-10 and the pro-inflammatory reaction-dominated state induced suggests that the host defense mechanism against secondary infection may be maintained rather than inhibited in hypothermia. Thus, the reduction of IL-10 could be an important characteristic of immune responses in mild hypothermia. [source] Contractile properties of human motor units in health, aging, and diseaseMUSCLE AND NERVE, Issue 9 2001FRCPC, K. Ming Chan MD Abstract The primary function of skeletal muscle is to produce force for postural control and movement. Although the contractile properties of the whole muscle are useful functional indicators, they do not accurately reflect the heterogeneity of the constituent motor units (MUs) and their changes in health and disease. However, data on the contractile properties of human MUs, in comparison to other animal species, are relatively sparse. This, in part, is due to greater methodological challenges of in vivo studies of MUs in the human. The purpose of this review is to critically appraise the methods used in humans; to describe the normative data from different muscle groups; to discuss differences between data from healthy humans and other animal species; and, last, to characterize changes of the MU contractile properties in aging, disease, and in response to intervention. Because the spike-triggered averaging technique can only be used to study the twitch properties, other methods were subsequently developed to measure a wider range of contractile properties. Although there is general agreement between human data and those from other animal species, major differences do exist. Potential reasons for these discrepancies include true biological differences, but differences in the techniques used may also be responsible. Although limited, measurement of MU contractile properties in humans has provided insight into the changes associated with aging and motoneuronal diseases and provides a means of gauging their adaptive capacity for training and immobilization. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1113,1133 [source] Effect of acute acoustic stress on anorectal function and sensation in healthy humans,NEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2005S. Gonlachanvit Abstract, Little is known about the effects of acute acoustic stress on anorectal function. To determine the effects of acute acoustic stress on anorectal function and sensation in healthy volunteers. Ten healthy volunteers (7 M, 3 F, mean age 34 ± 3 years) underwent anorectal manometry, testing of rectal compliance and sensation using a barostat with and without acute noise stress on separate days. Rectal perception was assessed using an ascending method of limits protocol and a 5-point Likert scale. Arousal and anxiety status were evaluated using a visual analogue scale. Acoustic stress significantly increased anxiety scores (P < 0.05). Rectal compliance was significantly decreased with acoustic stress compared with control (P < 0.000001). In addition, less intraballoon volume was needed to induce the sensation of severe urgency with acoustic stress (P < 0.05). Acoustic stress had no effect on hemodynamic parameters, anal sphincter pressure, threshold for first sensation, sensation of stool, or pain. Acute acoustic stimulation increased anxiety scores, decreased rectal compliance, and enhanced perception of severe urgency to balloon distention but did not affect anal sphincter pressure in healthy volunteers. These results may offer insight into the pathogenesis of stress-induced diarrhoea and faecal urgency. [source] Effects of duodenal fat, protein or mixed-nutrient infusions on epigastric sensations during sustained gastric distension in healthy humansNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2002C. FEINLE Duodenal fat modulates sensory and motor responses to gastric distension and raises plasma cholecystokinin compared with glucose. The effects of protein (also releasing cholecystokinin), or mixed nutrients (with a balanced macronutrient composition), on gastrointestinal sensations in relation to gastric relaxation and plasma cholecystokinin concentrations are not known. The aim of this study was therefore to compare the effects of duodenal infusion of fat, protein or mixed nutrients during sustained gastric distension (mimicking the intragastric presence of food) on these parameters. In 10 healthy subjects, gastric distension to fullness was maintained for 90 min, while gastric volume, sensations and plasma cholecystokinin were monitored during duodenal infusion of isotonic saline or nutrients (2 kcal min,1). During saline infusion, all parameters remained unchanged for 90 min. Initially, only lipid increased plasma cholecystokinin, gastric volume and scores for sensations. Cholecystokinin and gastric volume responses to protein and mixed nutrients were delayed and not associated with significant changes in sensations. In conclusion, the intensity of gastrointestinal sensations is related to, but not entirely explained by, the magnitude in intragastric volume and plasma cholecystokinin changes. Our results offer new insights into the role of dietary nutrient composition in gastrointestinal sensations, and may have implications for the dietary management of digestive symptoms. [source] Gonadal steroids and salivary IgA in healthy young women and menAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Sari M. Van Anders Empirical evidence from clinical, nonhuman animal, and in vitro studies point to links between immune function and gonadal steroids, including potential androgenic immunosuppression and estrogenic immunoenhancement. This study was designed to test links between steroids and one marker of mucosal humoral immunity,immunoglobulin A (IgA) in healthy individuals, to facilitate comparisons with other species and clinical populations, as there are few existing studies with healthy humans that also allow gender/sex investigations. Participants (86 women, 91 men) provided a saliva sample for measurement of testosterone (T), estradiol (E2), and IgA. Results showed that E2 was significantly and positively correlated with IgA in women, and group analyses by E2 quartile showed that this association was linear. No significant correlations or nonlinear associations were seen between T and IgA in men or women, or E2 and IgA in men. Evidence from this study indicates that IgA and E2 are significantly associated in healthy premenopausal women. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] The effect of whole-body sunbed ultraviolet A exposure on the pharmacokinetics of the photolabile drug nifedipinePHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2000H. S. Al-Ajmi The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and readily photodegrades in vitro to a toxic nitroso-pyridine photoproduct. We examined whether whole body exposure of normal subjects to sunbed UVA radiation would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian volunteers (phototypes I,III) participated in this ethically approved, randomised, cross-over study. Each subject attended on 2 occasions, one week apart, and on each occasion was given a single oral dose (10 mg) of nifedipine following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a whole-body UVA (sunbed comprising Philips R-UVA lamps) dose of 70% of the individual's predetermined minimal phototoxic dose was delivered over a period of 17,36 min. Plasma nifedipine levels were measured using a standard reverse-phase high-performance liquid chromatography method. The area under the plasma concentration-time curve (AUC) of nifedipine during the UVA irradiation session (median 206 ng,·,ml,1,·,h,1) was significantly higher than during the non-irradiation control session (median 174.5 ng,·,ml,1,·,h,1) (P=0.03; 95% C.I. for difference in medians 9.9 to 55.9 ng,·,ml,1,·,h,1). UVA irradiation did not significantly affect any of the other measured pharmacokinetic parameters (Cmax, t1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to in vivo photodegradation of nifedipine in healthy humans after a single dose. The apparent increase in AUC during UVA irradiation may be due to slightly slower metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood distribution changes affecting liver blood flow. [source] AKAP10 (I646V) functional polymorphism predicts heart rate and heart rate variability in apparently healthy, middle-aged European-AmericansPSYCHOPHYSIOLOGY, Issue 3 2009Serina A. Neumann Abstract Previous evidence suggests that the dual-specific A kinase-anchoring protein 2 functional polymorphism (AKAP10 (A/G) I646V) influences heart rate (HR) and heart rate variability (HRV) in mice and humans (N=122) with cardiovascular disease. Here, we asked whether this AKAP10 variant predicts HR and HRV in a large sample of healthy humans. Resting HR and short-term time and frequency domain measures of HRV (5 min during paced and unpaced respiration conditions) were assessed in a U.S. community sample (N=1,033) of generally healthy men and women (age 30,54) of European ancestry. Each person was genotyped for the AKAP10 variant. As with previous work, the AKAP10 Val allele predicted greater resting HR (Paced p<.01; Unpaced p<.03) and diminished HRV (Paced ps <.05) suggesting that this variant may modulate the sensitivity of cardiac pacemaker cells to autonomic inputs, possibly conferring risk for arrhythmias and sudden cardiac death. [source] | |||||||||||||||||||||||||||||||