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Young Healthy Subjects (young + healthy_subject)
Selected AbstractsAcute Effects of Low Doses of Red Wine on Cardiac Conduction and Repolarization in Young Healthy SubjectsALCOHOLISM, Issue 12 2009Matteo Cameli Background:, Moderate to high blood concentrations of ethanol have been shown to yield acute changes in cardiac electrophysiological properties, but the effect of low concentrations have never been assessed. The role of concomitant changes in clinical variables or cardiac dimensions is also still unknown. This study aimed at exploring the acute effects of low doses of ethanol, administered as Italian red wine, on conduction, depolarization, and repolarization electrocardiographic (ECG) intervals in a population of healthy subjects. Methods:, Forty healthy young volunteers drank a low quantity of red wine (5 ml/kg), and an equal volume of fruit juice in separate experiments. Heart rate, P-wave duration, PR interval, QRS duration, QT interval, corrected QT interval, QT dispersion, and corrected QT dispersion were assessed at baseline and after 60 minutes from challenge. Results:, Mean blood ethanol concentration after drinking was 0.48 ± 0.06 g/l. Compared to the control challenge, significant changes after red wine intake were observed in P-wave duration (from 101 ± 11 to 108 ± 14 milliseconds, p = 0.0006), PR interval (from 153 ± 15 to 167 ± 17 milliseconds, p < 0.0001), QT interval (from 346 ± 28 to 361 ± 24 milliseconds, p < 0.0001), and corrected QT interval (from 388 ± 24 to 402 ± 30 milliseconds, p = 0.0006). None of these changes showed correlations with modifications in clinical or echocardiographic variables. In multivariate analyses aimed at exploring predictors of ECG changes, none of the variables entered the final models. Conclusions:, Low doses of red wine acutely slow cardiac conduction and prolong repolarization in normal individuals. These changes are poorly predictable. The potential arrhythmogenic impact of these effects is worthy of exploration. [source] Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populationsCYTOMETRY, Issue 2 2006Rebecca Gusic Shaffer Abstract Background: Age and cardiovascular disease status appear to alter numbers and function of circulating endothelial progenitor cells (EPCs). Despite no universal phenotypic definition, numerous studies have implicated progenitors with apparent endothelial potential in local responses to vascular injury and with cardiovascular disease in general. To further define the role of this lineage in peripheral artery disease (PAD), we developed a multiparameter flow cytometry assay to analyze multiple phenotypic definitions of progenitor cells (PCs), EPCs, and mature endothelial cells (ECs) and evaluate effects of age and PAD on baseline levels of each subset. Methods: Blood was collected from young healthy subjects (N = 9, mean age 33 ± 8 years), older healthy subjects (N = 13, mean age 66 ± 8 years), and older subjects with PAD (N = 15, mean age 69 ± 8 years). After ammonium chloride lysis, cells were stained and analyzed on a Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33 (lineage panel), PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion, and only viable, low to medium side scatter lineage-negative singlets were analyzed. In some studies, cells were sorted for morphological studies. Subsets were defined as indicated later. Results: Our results, using a comprehensive flow cytometric panel, indicate that CD133+, CD34+, and CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older individuals, both healthy and with PAD. However, the number of EPCs and mature ECs did not significantly differ among the three groups. Assessment of endothelial colony forming units and dual acLDL-lectin staining supported the flow cytometric findings. Conclusions: We describe a comprehensive flow cytometric method to detect circulating mature and progenitor endothelial populations confirmed by conventional morphological and functional assays. Our findings suggest that aging may influence circulating levels of PCs, but not EPCs or ECs; PAD had no effect on baseline levels of any populations investigated. This study provides the basis for evaluating the potential effects of acute stress and therapeutic intervention on circulating progenitor and endothelial populations as a biomarker for cardiovascular status. © 2005 International Society for Analytical Cytology [source] Pharmacokinetics of dipeptidylpeptidase-4 inhibitorsDIABETES OBESITY & METABOLISM, Issue 8 2010A. J. Scheen Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug,drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [source] Age-related alterations of gene expression patterns in human CD8+ T cellsAGING CELL, Issue 1 2010Jia-Ning Cao Summary Aging is associated with progressive T-cell deficiency and increased incidence of infections, cancer and autoimmunity. In this comprehensive study, we have compared the gene expression profiles in CD8+ T cells from aged and young healthy subjects using Affymetrix microarray Human Genome U133A-2 GeneChips. A total of 5.2% (754) of the genes analyzed had known functions and displayed statistically significant age-associated expression changes. These genes were involved in a broad array of complex biological processes, mainly in nucleic acid and protein metabolism. Functional groups, in which down-regulated genes were overrepresented, were the following: RNA transcription regulation, RNA and DNA metabolism, intracellular (Golgi, endoplasmic reticulum and nuclear) transportation, signaling transduction pathways (T-cell receptor, Ras/MAPK, JNK/Stat, PI3/AKT, Wnt, TGF,, insulin-like growth factor and insulin), and the ubiquitin cycle. In contrast, the following functional groups contained more up-regulated genes than expected: response to oxidative stress and cytokines, apoptosis, and the MAPKK signaling cascade. These age-associated gene expression changes may be responsible for impaired DNA replication, RNA transcription, and signal transduction, possibly resulting in instability of cellular and genomic integrity, and alterations of growth, differentiation, apoptosis and anergy in human aged CD8+ T cells. [source] Role of mastication and swallowing in the control of autonomic nervous activity for heart rate in different posturesJOURNAL OF ORAL REHABILITATION, Issue 12 2003E. Nitta summary, Mastication and swallowing increase the heart rate, and posture change and respiration also modulate the heart rate. To clarify the role of mastication and swallowing in the modulation of the autonomic nervous activity, we investigated how they interact with modulation of the heart rate by changing body positions and respiration in young healthy subjects. R,R intervals of electrocardiogram at rest were significantly changed with different body positions, compared with supine and standing. A net shortening by mastication of a chewing gum base was similar in various postures. Respiration induced a periodic change in the R,R intervals, depending on the body postures, but mastication did not markedly change them in each posture. Dry swallowing at rest and spontaneous swallowing during the mastication in the sitting position induced a similar transient shortening and suppressed the respiration-induced changes after the swallowing. The net transient shortening by dry swallowing at rest was similar in the different postures. These results suggest that signals from mastication and swallowing are summated with those from body positions and respiration for shortening the R,R intervals and that signals from swallowing suppress the respiration-induced periodic changes. [source] Measuring the acute effect of insulin infusion on ATP turnover rate in human skeletal muscle using phosphorus-31 magnetic resonance saturation transfer spectroscopyNMR IN BIOMEDICINE, Issue 8 2010Ee Lin Lim Abstract Mitochondrial dysfunction has been proposed to underlie the insulin resistance of type 2 diabetes. However, the relative time course of insulin action in stimulating ATP turnover rate and glucose uptake in skeletal muscle has not been examined. These two parameters were measured in young healthy subjects using the 31P MRS saturation transfer method in conjunction with the euglycaemic hyperinsulinaemic clamp technique respectively. Glucose infusion rate rose rapidly from 0 to 2.90,±,0.11,mg/kgffm/min during the first 10,min of insulin infusion and further to 6.17,±,0.57,mg/kgffm/min between 15 and 45,min. In contrast, baseline ATP turnover rate was 9.0,±,0.4,µmol/g/min of muscle and did not change during the first 45,min of insulin infusion. Between 50 and 80,minutes ATP turnover rate increased by 8% and remained steady to 150,minutes (9.7,±,0.5 µmol/g/min of muscle, p,=,0.03 vs baseline). The in vivo time course of insulin stimulation of skeletal muscle ATP turnover rate is not consistent with a rate limiting effect upon the initiation of insulin-stimulated glycogen synthesis. Copyright © 2010 John Wiley & Sons, Ltd. [source] A pilot study on the differences in wavefront aberrations between two ethnic groups of young generally myopic subjectsOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2008Alejandro Cerviño Abstract A comparative population-based cross-sectional study design was used to examine the prevalence of wavefront patterns in two different ethnic groups, and the relationship of these patterns with ocular biometrics and gender. The Shin,Nippon SRW5000 open field autorefractor, the Wavefront Analysis Supported Customized Ablation (WASCA) wavefront analyser and the IOLMaster were used to determine wavefront aberrations, mean spherical equivalent (SE) refractive error and axial length (AL). Seventy-four eyes from 74 young healthy subjects (44 British Asians, 30 Caucasians; 36 men, 38 women; mean age 22.51 ± 3.89 years) with mean SE averaging ,1.90 ± 2.76 D (range ,10.88 to +2.19 D) were examined. Relationships between ethnicity, gender, AL and SE, against the wavefront high-order root mean square, and aberration components up to the fifth order, were assessed by using multiple regression and correlation analysis. AL on its own accounted for 4.7% of the variance in trefoil component (F1,72 = 4.602; p = 0.035), 13.7% of coma component (F1,72 = 12.536; p = 0.001), 6.1% of trefoil component (F1,72 = 5.705; p = 0.020) and 9.8% of coefficient (F1,72 = 8.908; p = 0.004). A significant model emerged (F2,71 = 6.164; p = 0.003) for ethnicity and axial length, accounting for 12.4% of variance in primary spherical aberration with ethnicity accounting for 8.4% of that variance. For Caucasian subjects, a significant correlation was found between axial length and (Pearson's correlation coefficient ,0.500; p = 0.005) and (Pearson's correlation coefficient ,0.423; p = 0.020). For British Asian subjects, AL was only correlated with coefficient (Pearson's correlation coefficient ,0.358; p = 0.017). Ethnicity is a factor to be considered in the variability of wavefront aberration, particularly spherical aberration. Relationship between AL and wavefront aberrations seems to vary between ethnicities. If higher order aberrations play a role in the emmetropization process, this may be different for different populations. [source] Compensation for light loss due to filtering by macular pigment: relation to hue cancellationOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 3 2007James M. Stringham Abstract Background:, A long-standing question in colour vision research is how the visual system is able to correct for the significant absorbance of short wave light by the crystalline lens and macular pigment (MP). Such compensation must be required in order to maintain colour constancy across the retina where MP levels are changing quickly and dramatically. Objective:, We studied this compensation mechanism by measuring MP spatial density profiles and hue cancellation functions across the central retina in a sample of six young healthy subjects. Method:, Yellow (Y, 575 nm)/blue (B, 440 nm) and red (R, 600 nm)/green (G, 501 nm) cancellation functions were obtained at 0, 1, 1.75, 3 and 7° eccentricity. The MP optical density at 460 nm was measured at these same eccentricities using heterochromatic flicker photometry. One subject was assessed repeatedly over a 4-month period during daily supplementation with 30 mg of lutein (L). Results:, Hue cancellation values for the Y/B system did not change across the retina (r = 0.09). In contrast, R/G sensitivity changed as a direct function of MP absorbance (r = 0.99). The Y/B values did not change in the one subject supplemented with 30 mg L daily, despite increases in MP of about 50% over 4 months. Conclusions:, Despite large variations in MP across the retina, hue cancellation values for the Y-B system across the central retina were constant. For example, one subject's MP density declined from a central peak of 0.99 to near zero at 7° (near 90% transmission difference) yet thresholds for the Y/B system were unaffected. In contrast, the G lobe of the R/G system was directly correlated with MP density. Taken together, these results confirm that the Y/B system compensates for MP density, but the R/G system does not. [source] Feasibility of T and Z scores from magnetic resonance imaging data for quantification of cartilage loss in osteoarthritisARTHRITIS & RHEUMATISM, Issue 10 2003R. Burgkart Objective T scores (an indicator of the difference between patients and young healthy subjects) and Z scores (an indicator of the difference between patients and age-matched healthy subjects) are used in the diagnosis of osteoporosis and form the current basis for the definition of osteoporosis by the World Health Organization. We tested the feasibility of using T and Z scores derived from quantitative cartilage imaging with magnetic resonance imaging (MRI) for the diagnosis of osteoarthritis (OA). Methods High-resolution MR images of tibial cartilage were acquired from 126 young healthy adults (ages 20,35 years), 24 age-matched elderly healthy adults (ages 50,75 years), 7 OA patients prior to tibial osteotomy, and 7 OA patients prior to knee arthroplasty. Cartilage volume, thickness, surface area, and original joint surface area (before onset of disease) were determined in the medial and lateral tibia. Results The cartilage volume of the medial tibia of osteotomy patients with varus malalignment displayed moderate T scores (,1.0), and more negative T scores (,3.8) were observed in knee arthroplasty patients with varus malalignment. Normalization of the cartilage volume to the original joint surface area substantially enhanced the scores in patients undergoing osteotomy (,2.3) and in patients undergoing knee arthroplasty (,5.5), and this was superior to the normalization ratios of cartilage volume to body height and cartilage volume to body weight, in terms of distinguishing the loss of articular cartilage. Conclusion Quantitative analysis of OA by MRI is feasible using T and Z scores. However, cartilage volume should be normalized to the individual joint surface area in order to maximize the discriminatory power of this technique for the diagnosis of OA. [source] Population modelling of the effect of inogatran, at thrombin inhibitor, on ex vivo coagulation time (APTT) in healthy subjects and patients with coronary artery diseaseBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2001Marie Cullberg Aims, The purpose of this study was to characterize the relationship between the degree of anticoagulation, assessed by APTT, and the plasma concentration of inogatran in healthy subjects and in patients with coronary artery disease. Methods, Data from five phase I studies in 78 healthy males and two phase II multicentre studies in 948 patients of both sexes with unstable angina pectoris or non-Q-wave myocardial infarction were evaluated. A total of 3296 pairs of concentration-APTT samples were obtained before, during, and after intravenous infusions of inogatran. Mixed effects modelling was used for population pharmacodynamic analysis of the drug effect and for describing the variability in baseline APTT. Results, The population mean baseline APTT was 29 s, but large variations between individuals (s.d. 3.6 s) were observed. The variability between studies (1.3 s) and centres (1.8 s) were of less importance, though statistically significant. APTT increased in a nonlinear manner with increasing inogatran concentration and the relationship was well described by a combined linear and Emax model. A significant part of the overall variability could be ascribed to the APTT reagent and equipment used at the different study centres. These method-dependent differences were compensated for by including the lower limit of the normal reference range as a covariate, affecting both baseline and Emax, in the model. For the typical healthy subject and patient, the method-corrected population mean parameters were: APTTbaseline 35 and 31 s, slope 8.0 and 5.8 s l µmol,1, Emax 36 and 34 s, and EC50 0.54 and 0.72 µmol l,1, respectively. The model predicted plasma concentration needed to double the APTT from the baseline value was 1.25 and 1.45 µmol l,1 in the healthy volunteer and patient, respectively. Conclusions, The nonlinear relationship between APTT and inogatran concentration in plasma was well described by a combined linear and Emax model. Pooling of data was made possible by incorporating a centre-specific characteristic of the assay method in the model. Patients had lower baseline APTT and appeared to have less pronounced effect of inogatran than young healthy subjects. [source] Reliability results of straylight measurements using the C-QuantACTA OPHTHALMOLOGICA, Issue 2008A CERVINO Purpose Assessment of repeatability and reproducibility of straylight measures with the C-Quant straylightmeter (Oculus AG, Germany), effect of age on reliability measures and correlation of measures determined with new methods of scatter determination. Methods Results from different studies will be presented. For repeatability assessment, 20 eyes (age 26.9±2.7 years) were examined with the C-Quant, taking 10 consecutive readings. 5 subjects were also examined on 5 consecutive days to assess reproducibility. Repeated measures from 84 subjects, age range 19-86 years, were analysed to assess the effect of patient's age. Software was developed to quantify scatter from centroid patterns obtained using a clinical aberrometer(WASCA, Zeiss) based on previous work by Donnelly & Applegate, and 3 values were obtained on 10 eyes. 3 measures were also made with the C-Quant. Preliminary results comparing the C-Quant and the StarLight hallometer will also be presented. Results Results failed to show differences between readings taken within the same session (mean SD 0.07, p>0.05) or between sessions (mean SD 0.05, p>0.05). Variability of intrasession measurements was not significant for subjects of different age (p=0.094). After removal of incomplete patterns, good correlation was achieved between psychometric and objective measures despite small sample size (n=6; r= -0.831, p=0.040). Conclusion The C-Quant straylightmeter is repeatable and reliable for retinal straylight assessment on human eyes. Age does not decrease repeatability eventhough they feel more insecure about their ability to perform the test. Psychometrical determination of straylight showed remarkably high correlation with objective measures of scatter on young healthy subjects. [source] Effect of graded leg cycling on postischaemic forearm blood flow in healthy subjectsCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 1 2008Marc Charles Summary This study assessed in healthy subjects, the effect of leg cycling on the forearm vascular responses to ischaemia to confirm previous results showing that exercise-induced sympathetic activation during leg cycling reduced postischaemic forearm hyperaemia. Seven young healthy subjects performed two bouts of cycling exercises at 50% and 80% of their maximal aerobic capacity (Ex50, Ex80 respectively) during which forearm arterial blood flow was successively occluded for 40, 90 and 180 s. Control forearm blood flow (FBF) and postischaemic forearm blood flow (pi-FBF) measured at the release of arterial occlusions were assessed using plethysmography. Digital arterial pressure was continuously monitored allowing calculation of control and postischaemic forearm conductance (FC and pi-FC respectively). At rest, pi-FBF increased with the duration of ischaemia (5 ± 1, 19 ± 3, 29 ± 3, 31 ± 4 ml min,1 100 ml,1 after 0, 40, 90 and 180 s of ischaemia respectively). During Ex50, FBF and pi-FBF did not change significantly although pi-FC was significantly reduced (,pi-FC = ,39%, ,33%, ,27% for 40, 90, 180 s of ischaemia respectively). During Ex80, there was a further dramatic decrease in pi-FC (,53%, ,66%, ,62% from rest) and pi-FBF were largely blunted (13 ± 4 versus 19 ± 3, 14 ± 4 versus 29 ± 3, 17 ± 5 versus 31 ± 4 ml min,1 100 ml,1). These results demonstrated that forearm responses to ischaemia depended on leg activities. It was suggested that exercise-induced sympathetic activation may have interfered on local vasodilatation because of ischaemia. [source] | |||||||||||||