Capacity In Healthy Subjects Research Articles

Ketone Bodies Improve Human CD8+ Cytotoxic T-Cell Immune Response During COVID-19 Infection.

Severe COVID-19 is characterized by profound CD8+ T-cell dysfunction, which cannot be specifically treated to date. We here investigate whether metabolic CD8+ T-cell reprogramming by ketone bodies could be a promising strategy to overcome the immunoparalysis in COVID-19 patients. This approach was triggered by our recent pioneering study, which has provided evidence that CD8+ T-cell capacity in healthy subjects could be significantly empowered by a Ketogenic Diet. These improvements were achieved by immunometabolic rewiring toward oxidative phosphorylation. We here report similar strengthening of CD8+ T cells obtained from severely diseased COVID-19 patients: Flow cytometry and ELISA revealed elevated cytokine expression and secretion (up to + 24%) upon ketone treatment and enhanced cell lysis capacity (+ 21%). Metabolic analyses using Seahorse technology revealed upregulated mitochondrial respiratory chain activity (+ 25%), enabling both superior energy supply (+ 44%) and higher mitochondrial reactive oxygen species signaling. These beneficial effects of ketones might represent evolutionary conserved mechanisms to strengthen human immunity. Our findings pave the road for metabolic treatment studies in COVID-19.

Effects of wearing facemasks on the sensation of exertional dyspnea and exercise capacity in healthy subjects.

Due to the currently ongoing pandemic of coronavirus disease 2019 (COVID-19), it is strongly recommended to wear facemasks to minimize transmission risk. Wearing a facemask may have the potential to increase dyspnea and worsen cardiopulmonary parameters during exercise; however, research-based evidence is lacking. We investigated the hypothesis that wearing facemasks affects the sensation of dyspnea, pulse rate, and percutaneous arterial oxygen saturation during exercise. Healthy adults (15 men, 9 women) underwent a progressive treadmill test under 3 conditions in randomized order: wearing a surgical facemask, cloth facemask, or no facemask. Experiment was carried out once daily under each condition, for a total of 3 days. Each subject first sat on a chair for 30 minutes, then walked on a treadmill according to a Bruce protocol that was modified by us. The experiment was discontinued when the subject’s pulse rate exceeded 174 beats/min. After discontinuation, the subject immediately sat on a chair and was allowed to rest for 10 minutes. Subjects were required to rate their levels of dyspnea perception on a numerical scale. Pulse rate and percutaneous arterial oxygen saturation were continuously monitored with a pulse oximeter. These parameters were recorded in each trial every 3 minutes after the start of the exercise; the point of discontinuation; and 5 and 10 minutes after discontinuation. The following findings were obtained. Wearing a facemask does not worsen dyspnea during light to moderate exercise but worsens dyspnea during vigorous exercise. Wearing a cloth facemask increases dyspnea more than wearing a surgical facemask during exercise and increases pulse rate during vigorous exercise, but it does not increase pulse rate during less vigorous exercise. Wearing a surgical facemask does not increase pulse rate at any load level. Lastly, wearing a facemask does not affect percutaneous arterial oxygen saturation during exercise at any load level regardless of facemask type.

Polyphenol Bioavailability and Plasma Antiradical Capacity in Healthy Subjects after Acute Intake of Pigmented Rice: A Crossover Randomized Controlled Clinical Trial.

Health-promoting effects of plant foods have been emphasized in the last few decades and ascribed to the bioactive phytochemicals present therein—in particular, phenylpropanoids. The latter have been investigated for a number of preclinical biological activities, including their antioxidant power. Due to the paucity of human studies, in this randomized intervention trial, we investigated whether the acute intake of pigmented rice could increase the plasma bioactive levels and antiradical power in twenty healthy subjects. A crossover randomized controlled clinical trial was conducted on 19 volunteers. Artemide and Venere black rice cultivars were tested, while brown rice Carnaroli was used as a control. Each patient received randomly one serving (100 g) of rice on three different experimental days, separated by a 7-day washout period. After baseline blood withdrawal, time-course changes of plasma polyphenols, flavonoids and radical-scavenging capacity were determined at 30, 60, 120 and 180 min post rice intake. Compared to Carnaroli rice, the two black rice cultivars significantly increased the plasma levels of polyphenols and flavonoids at 60 and 120 min and, correspondingly, the plasma antiradical power at 60 min after consumption. Pigmented rice consumption can contribute to diet-related health benefits in humans.

A Single 60.000 IU Dose of Erythropoietin Does Not Improve Short-Term Aerobic Exercise Performance in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial.

Erythropoietin (EPO) boosts exercise performance through increase in oxygen transport capacity following regular administration of EPO but preclinical study results suggest that single high dose of EPO also may improve exercise capacity. Twenty-nine healthy subjects (14 males/15 females; age: 25 ± 3 years) were included in a randomized, double-blind, placebo-controlled crossover study to assess peak work load and cardiopulmonary variables during submaximal and maximal cycling tests following a single dose of 60.000 IU of recombinant erythropoietin (EPO) or placebo (PLA). Submaximal exercise at 40%/60% of peak work load revealed no main effect of EPO on oxygen uptake (27.9 ± 8.7 ml min–1⋅kg–1/ 37.1 ± 13.2 ml min–1⋅kg–1) versus PLA (25.2 ± 3.7 ml min–1⋅kg–1/ 33.1 ± 5.3 ml min–1⋅kg–1) condition (p = 0.447/p = 0.756). During maximal exercise peak work load (PLA: 3.5 ± 0.6 W⋅kg–1 vs. EPO: 3.5 ± 0.6 W kg–1, p = 0.892) and peak oxygen uptake (PLA: 45.1 ± 10.4 ml⋅min–1 kg–1 vs. EPO: 46.1 ± 14.2 ml⋅min–1 kg–1, p = 0.344) reached comparable values in the two treatment conditions. Other cardiopulmonary variables (ventilation, cardiac output, heart rate) also reached similar levels in the two treatment conditions. An interaction effect was found between treatment condition and sex resulting in higher peak oxygen consumption (p = 0.048) and ventilation (p = 0.044) in EPO-treated males. In conclusion, in a carefully conducted study using placebo-controlled design the present data failed to support the hypothesis that a single high dose of EPO has a measurable impact on work capacity in healthy subjects.

Plasma asymmetric dimethylarginine concentrations are not related to differences in maximal oxygen uptake in endurance trained and untrained men.

What is the central question of this study? Is there an association of plasma concentration of asymmetric dimethylarginine, which is related to exercise capacity in patients with cardiovascular diseases, with oxygen delivery and subsequently exercise capacity in healthy subjects in the absence of the potentially confounding influence of inflammation and oxidative stress? What is the main finding and its importance? Plasma asymmetric dimethylarginine concentrations are not related to exercise capacity in healthy subjects, while O2 delivery in the working skeletal muscle during the maximal graded-exercise test is not associated with any of the l-arginine analogues. ADMA alone does not play a crucial role in local muscle perfusion and in maintaining exercise capacity. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis that could limit oxygen (O2 ) delivery in the working skeletal muscles by altering endothelium-dependent vasodilatation. Exercise capacity is associated with plasma ADMA concentrations in patients with cardiovascular diseases, but this issue has still not been investigated in healthy subjects. We aimed to determine whether plasma ADMA concentrations were negatively associated with exercise capacity in young healthy male subjects. Ten men with maximal oxygen uptake ( )> 65mLkg-1 min-1 were included in the high exercise capacity group (HI-FIT), and 10 men with < 45mLkg-1 min-1 were included in the low exercise capacity group (LO-FIT). Plasma ADMA and other l-arginine analogue concentrations were measured before and after a maximal graded-exercise test by liquid chromatography-tandem mass spectrometry. Microvascular O2 delivery during exercise was estimated through the pattern from the sigmoid model of muscle deoxygenation in the vastus lateralis measured by near infrared spectroscopy. was 60% higher in the HI-FIT group (median: 70.2mLkg-1 min-1 ; IQR: 68.0-71.9mLkg-1 min-1 ) than in the LO-FIT group (median: 43.8mLkg-1 min-1 ; IQR: 34.8-45.3mLkg-1 min-1 ). Plasma ADMA concentrations did not differ between the LO-FIT and HI-FIT groups before (0.50± 0.06 vs. 0.54± 0.07μmolL-1 , respectively) and after the maximal incremental exercise test (0.49± 0.08 vs. 0.55± 0.03μmolL-1 , respectively). There was no significant association of plasma ADMA concentrations with the pattern of local muscle deoxygenation and exercise capacity. Exercise capacity and microvascular O2 delivery are not related to plasma ADMA concentrations in young healthy male subjects. Our findings show that ADMA does not play a crucial role in local muscle perfusion and in maintaining exercise capacity without pathological conditions.

Disturbed blood flow induces endothelial apoptosis without mobilizing repair mechanisms in hypertension

AimsThe influence of blood flow disturbances on vascular function, endothelial activation and repair capacity has not been fully elucidated either in physiological conditions or in cardiovascular disease. We aimed to determine the impact of increases in retrograde blood flow (RBF) on vascular function, endothelial biomarkers and repair capacity in healthy subjects and patients with hypertension. Main methodsIn seven healthy (CT; 32 ± 15 yr) and eight hypertensive (HT; 34 ± 23 yr) men, flow mediated-dilation (FMD) was assessed before and 10 min after a 30-min maneuver to increase brachial artery RBF in which a pneumatic cuff was inflated to 75 mm Hg on forearm. Blood samples were obtained at rest and during the last minute of the maneuver. Key findingsEndothelial activation, apoptosis and endothelial progenitor cells (EPC) were measured by flow cytometry; nitrite was measured by ozone-chemiluminescence. No significant disparities were observed in FMD, endothelial activation and circulating EPC between groups at baseline (p > 0.05). However, HT presented higher resting endothelial apoptosis (p = 0.01 vs CT). Exacerbated RBF induced reductions in FMD (p = 0.02 vs baseline) and increases in endothelial activation in both groups (p = 0.049 vs baseline). Endothelial apoptosis increased only in HT (p = 0.02 vs baseline; p = 0.004 vs CT), whereas EPC (p = 0.02 vs baseline; p = 0.03 vs HT) and nitrite (p = 0.04 vs baseline; p = 0.004 vs HT) increased only in CT during the maneuver. SignificanceWhile findings indicate that increased RBF impairs endothelial function and triggers the EPC mobilization in healthy subjects, patients with hypertension presented greater apoptosis and impaired repair capacity in response to RBF.

Acute effect of Clitoria ternatea flower beverage on glycemic response and antioxidant capacity in healthy subjects: a randomized crossover trial

BackgroundClitoria ternatea L., a natural food-colorant containing anthocyanin, demonstrated antioxidant and antihyperglycemic activity. The aim of this study was to determine the effects of Clitoria ternatea flower extract (CTE) on postprandial plasma glycemia response and antioxidant status in healthy men.MethodsIn a randomized, crossover study, 15 healthy men (ages 22.53 ± 0.30 years; with body mass index of 21.57 ± 0.54 kg/m2) consumed five beverages: (1) 50 g sucrose in 400 mL water; (2) 1 g CTE in 400 mL of water; (3) 2 g CTE in 400 mL of water; (4) 50 g sucrose and 1 g CTE in 400 mL of water; and (5) 50 g sucrose and 2 g CTE in 400 mL of water. Incremental postprandial plasma glucose, insulin, uric acid, antioxidant capacities and lipid peroxidation were measured during 3 h of administration.ResultsAfter 30 min ingestion, the postprandial plasma glucose and insulin levels were suppressed when consuming sucrose plus 1 g and 2 g CTE. In addition, consumption of CTE alone did not alter plasma glucose and insulin concentration in the fasting state. The significant increase in plasma antioxidant capacity (ferric reducing ability of plasma (FRAP), oxygen radical absorbance capacity (ORAC), trolox equivalent antioxidant capacity (TEAC), and protein thiol) and the decrease in malondialdehyde (MDA) level were observed in the subjects who received 1 g and 2 g CTE. Furthermore, consumption of CTE protected sucrose-induced reduction in ORAC and TEAC and increase in plasma MDA.ConclusionsThese findings suggest that an acute ingestion of CTE increases plasma antioxidant capacity without hypoglycemia in the fasting state. It also improves postprandial glucose, insulin and antioxidant status when consumed with sucrose.Trial registrationThai Clinical Trials Registry: TCTR20170609003. Registered 09 September 2017.‘retrospectively registered’.

Fontan Circulation over Time

The unique, unphysiological Fontan circulation is associated with an impaired functional status of the patients that is suggested to deteriorate over time. Unfortunately, previous studies did not integrate both pulmonary and cardiac determinants of functional status. In addition, a comparison with the natural decrease in exercise capacity in healthy subjects (in both children and adults) is lacking. This single-center study aims to investigate the functional status in a cohort of Fontan patients in relation to time since Fontan completion and to identify its determinants, including cardiac characteristics and pulmonary characteristics. Eighty-five consecutive Fontan patients ≥10years who performed adequate cardiopulmonary exercise testing (respiratory exchange ratio >1.01) were included. Mean time since Fontan completion was 15 ± 9years (range 2 to 37years). New York Heart Association functional class was I in 36 patients (42%), II in 41 patients (48%), and III in 8 patients (9%). Peak oxygen uptake during exercise (VO2 index) was 25.7 ± 7.9ml/min/m2 (58 ± 14% of predicted). New York Heart Association functional class and peak VO2 index both correlated with time since the Fontan operation; however, peak VO2 as percentage of predicted (VO2(pred)) did not. In multivariate analyses, peak VO2(pred) was independently associated with maximum heart rate, oxygen pulse at peak exercise, and forced expiratory volume in 1second (R2= 0.579) but not with cardiac output in rest. In conclusion, the present data suggest that functional status in Fontan patients is impaired already shortly after Fontan completion, whereas its subsequent deterioration seems to follow the natural decline of aging. Furthermore, functional status in Fontan patients correlates with pulmonary function and cardiac functional parameters during exercise but not with conventional cardiac measurements at rest.

The Effect of Isomaltulose Together with Green Tea on Glycemic Response and Antioxidant Capacity: A Single-Blind, Crossover Study in Healthy Subjects.

Isomaltulose, a naturally-occurring isomer of sucrose, is commonly used as an alternative sweetener in foods and beverages. The goal of this study was to determine the effect of isomaltulose together with green tea on postprandial plasma glucose and insulin concentration, as well as antioxidant capacity in healthy subjects. In a randomized, single-blind, crossover study, 15 healthy subjects (eight women and seven men; ages 23.5 ± 0.7 years; with body mass index of 22.6 ± 0.4 kg/m2) consumed five beverages: (1) 50 g sucrose in 400 mL water; (2) 50 g isomaltulose in 400 mL of water; (3) 400 mL of green tea; (4) 50 g sucrose in 400 mL of green tea; and (5) 50 g isomaltulose in 400 mL of green tea. Incremental area under postprandial plasma glucose, insulin, ferric reducing ability of plasma (FRAP) and malondialdehyde (MDA) concentration were determined during 120 min of administration. Following the consumption of isomaltulose, the incremental 2-h area under the curve (AUC0–2 h) indicated a higher reduction of postprandial glucose (43.4%) and insulin concentration (42.0%) than the consumption of sucrose. The addition of green tea to isomaltulose produced a greater suppression of postprandial plasma glucose (20.9%) and insulin concentration (37.7%). In accordance with antioxidant capacity, consumption of sucrose (40.0%) and isomaltulose (28.7%) caused the reduction of green tea-induced postprandial increases in FRAP. A reduction in postprandial MDA after drinking green tea was attenuated when consumed with sucrose (34.7%) and isomaltulose (17.2%). In conclusion, green tea could enhance the reduction of postprandial glucose and insulin concentration when consumed with isomaltulose. In comparison with sucrose, isomaltulose demonstrated less alteration of plasma antioxidant capacity after being consumed with green tea.

The association between right ventricular free wall strain and exercise capacity for health check-up subjects

BackgroundRight ventricular (RV) function has been found to be a major factor of exercise capacity in patients with heart failure. However, the role of RV function in exercise capacity in healthy subjects has not been well studied. This study aims to validate the role of RV strain derived from speckle tracking echocardiography for exercise capacity for health check-up subjects.MethodsThis study prospectively recruited subjects from a routine health examination. All of them were symptom free. RV function represented by RV strain was derived from speckle tracking echocardiography in addition to traditional echocardiography parameters. Functional capacity was determined by a symptom limited treadmill exercise test with the Bruce protocol.ResultsAmong 164 recruited subjects (age 52.2 ±9.2 years, 66.4% male), 32 subjects represented impaired functional capacity (MET<8), which was significantly correlated with age, left ventricular mass index, left ventricular filling pressure (E/e’), global longitudinal strain of the left ventricle (LVGLS) (-16.0±2.5% vs. -18.9±3.8%, p < 0.001) and RV free wall strain (RVLS_FW) (-17.0±4.9% vs. -21.9±3.2%, p <0.001). After multivariate logistic regression, RVS_FW was an independent predictor for impaired functional capacity (OR 1.62, CI 1.32–1.98; p <0.001).ConclusionsIn conclusion, RV strain is independently associated with exercise capacity for health check-up subjects. RV function is an important factor for functional capacity.

Field tests in cardiac rehabilitation

Assessment of physical capacity is a major concern, given the increasing prevalence of chronic disabling conditions due cardiovascular disease, usually associated with an intolerance to effort leading to reduced physical activity. Maximal exercise tests remain the reference because they can rule out contra-indications to retraining, help in drug prescription optimization, measure the maximal capacity in terms of heart rate, maximum power or peak VO 2 . However, they require specific technical and human resources, and therefore imply a financial burden limiting which their repeatability in clinical practice. In addition, they may not be well-tolerated in patients with severe cardiovascular impairement, multiple co-morbidities, and/or the older ones. Moreover, they are not representative of the actual functional capabilities in ecological conditions. As a result, field tests, associated with a collection of physiological parameters, can represent an alternative to assess exercise intolerance in cardiac rehabilitation (CR). The most used are walk tests, designed to evaluate the safety and exercise capacity in healthy subjects and patients from a speed or walking distance. These tests can be maximal (most often imposed with increasing speed), in order to get an idea of the prognosis (prediction of peak VO 2 ) or submaximal at a constant speed or a self-selected comfortable speed (6-minute walk, for example). Submaximal tests are considered as valuable benchmarks for measuring the response to a standardized activity typically encountered in everyday life. This performance evaluation can be performed before and after an intervention (surgery, medication, rehabilitation) in order to assess its effects. It can also help to assess the quality of life and could be a tool to personnalize training programs. Field tests have the advantage of being simple to perform, well-tolerated, require few expertise and equipment, and appear well-connected with daily activities. However, they have usually a modest correlation with peak VO 2 , and appear strongly influenced by familiarity and influence the motivation of the subject. The aim of this update is to describe the main walk tests used in the cardiac rehabilitation, their psychometric properties and interests in clinical practice, performed in addition to or instead of maximal stress tests.

Inspiratory Capacity as an Indirect Measure of Immediate Effects of Positive Expiratory Pressure and CPAP Breathing on Functional Residual Capacity in Healthy Subjects.

Positive expiratory pressure (PEP) and CPAP are used to enhance breathing parameters such as functional residual capacity (FRC) in patients. Studies comparing effects of PEP and CPAP on FRC are few and variable. One reason for this may be that sophisticated equipment, not suitable in the clinical setting, is required. Because total lung capacity (TLC) consists of inspiratory capacity (IC) and FRC, a change in IC should result in a corresponding change in FRC given constant TLC. We aimed to evaluate the effects of different PEP and CPAP devices on IC as an indirect measure of induced changes in FRC from these devices in healthy subjects. Twenty healthy subjects breathed with 2 PEP devices, a PEP mask (flow resistor) and a PEP bottle (threshold resistor), and 2 CPAP devices, a flow resistor and a threshold resistor, in a randomized order. The measurement sequence consisted of 30 breaths with an IC measurement performed before and immediately after the 30th breath while the subjects were still connected to the breathing device. Perceived exertion of the 30 breaths was measured with the Borg category ratio 10 scale. Three of the 4 breathing devices, the PEP mask and the 2 CPAP devices, significantly decreased IC (P < .001). Median perceived exertion was quite low for all 4 breathing devices, but the difference in perceived exertion among the different breathing devices was large. Provided that TLC is constant, we found that measurements of changes in IC could be used as an indirect measure of changes in FRC in healthy subjects. All investigated breathing devices except the PEP bottle decreased IC, as an indirect measure of increased FRC.

Cardiac autonomic modulation is determined by gender and is independent of aerobic physical capacity in healthy subjects.

BackgroundAerobic physical capacity plays an important role in reducing morbidity and mortality rates in subjects with cardiovascular diseases. This action is often related to an improvement in the autonomic modulation of heart rate variability (HRV). However, controversies remain regarding the effects of physical training on cardiac autonomic control in healthy subjects. Therefore, our objective was to investigate whether aerobic capacity interferes with the autonomic modulation of HRV and whether gender differences exist.MethodsHealthy men and women (N=96) were divided into groups according to aerobic capacity: low (VO2: 22-38 ml/kg-1 min-1), moderate (VO2: 38-48 ml/kg-1 min-1) and high (VO2 >48 ml/kg-1 min-1.) We evaluated the hemodynamic parameters and body composition. The autonomic modulation of HRV was investigated using spectral analysis. This procedure decomposes the heart rate oscillatory signal into frequency bands: low frequency (LF=0.04-0.15Hz) is mainly related to sympathetic modulation, and high frequency (HF=0.15-0.5Hz) corresponds to vagal modulation.ResultsAerobic capacity, regardless of gender, determined lower values of body fat percentage, blood pressure and heart rate. In turn, the spectral analysis of HRV showed that this parameter did not differ when aerobic capacity was considered. However, when the genders were compared, women had lower LF values and higher HF values than the respective groups of men.ConclusionThe results suggest that aerobic physical capacity does not interfere with HRV modulation; however, the cardiac modulatory balance differs between genders and is characterized by a greater influence of the autonomic vagal component in women and by the sympathetic component in men.

Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: central actor and therapeutic target

Muscle dysfunction is a common complication and an important prognostic factor in chronic obstructive pulmonary disease (COPD). As therapeutic strategies are still needed to treat this complication, gaining more insight into the process that leads to skeletal muscle decline in COPD appears to be an important issue. This review focuses on mitochondrial involvement in limb skeletal muscle alterations (decreased muscle mass, strength, endurance and power and increased fatigue) in COPD. Mitochondria are the main source of energy for the cells; they are involved in production of reactive oxygen species and activate an important pathway that leads to apoptosis. In COPD patients, skeletal muscles are characterized by decreased mitochondrial density and biogenesis, impaired activity and coupling of mitochondrial respiratory chain complexes, increased mitochondrial production of reactive oxygen species and, possibly, increased apoptosis. Of particular interest, a sedentary lifestyle, hypoxia, hypercapnia, tobacco smoking, corticosteroid therapy and, possibly, inflammation participate in this mitochondrial dysfunction, which is accessible to conventional therapies, such as exercise and tobacco cessation, as well as, potentially, to more innovative approaches, such as antioxidant treatment and supplementation with polyunsaturated fatty acids.

Decreased Sudomotor Function is Involved in the Formation of Atopic Eczema in the Cubital Fossa

Eczema in the cubital fossa, which is susceptible to sweat, is frequently observed in atopic dermatitis (AD). However, there has been no direct evidence that sweating causes eczema in the cubital fossa. To investigate this issue, axon reflex-mediated sweating volume (AXR) and skin barrier function in the cubital fossa were measured in subjects with AD and in healthy volunteers, and were applied to clinical feature of the cubital fossa. AXR in the cubital fossa decreased in AD subjects; it positively correlated only with water-holding capacity in healthy subjects but not in patients with in AD. Furthermore, AD subjects with lichenoid eczema and either prurigo or papules over the cubital fossa showed extremely decreased AXR. These results suggest that decreased sweating is a major source of water in the stratum corneum, and decreased sudomotor function may be involved in both the cause and aggravation of representative atopic eczema in the cubital fossa.

Blood antioxidant capacity change in patients with the «dry» form of age-related macular degeneration treated with polarized polychromatic non-coherent light and dynamic electromyostimulation

Aim. To assess the antioxidant capacity in patients with the «dry» form of age-related macular degeneration before and after combined treatment with polarized polychromatic non-coherent light and dynamic electromyostimulation. Methods. Two groups of patients with the «dry» form of age-related macular degeneration were examined. 40 patients (80 eyes) from the main group were treated using combined treatment and 39 patients (78 eyes) in the group of control who were treated conventionally. The integral blood antioxidant capacity was measured by galvanometry. Results. Blood antioxidant capacity in healthy subjects is 26.0 kC/l. In patients of the main group blood antioxidant capacity before the treatment was equal to 22.81±0.27 kC/l, compared to 22.17±0.20 kC/l in control group (total mean value 22.49±0.27 kC/l). There was a relevant elevation of the blood antioxidant capacity at the late stages after the treatment - up to 12 months, compared to only 2 months in the control group. Visual acuity in patients of the main group before the treatment was 0.87±0.02, after the treatment was finished - 0.96±0,01 (p 0.001), 2 months after the treatment - 0.95±0.01 (p 0.001), 6 months after the treatment - 0.96±0.01 (p 0.001), 12 months after the treatment - 0.95±0.01 (p 0.001). Visual acuity in patients of the control group before the treatment was 0.91±0.02, after the treatment was finished - 0.95±0.02 (p 0.05), 2 months after the treatment - 0.94±0.02 (p 0.05), 6 months after the treatment - 0.92±0.02 (p 0.05). 12 months after the treatment the visual acuity deteriorated compared to the treatment start and was measured as 0.89±0.02. Conclusion. There is a decrease of blood antioxidant capacity (22.49±0.27 kC/l) in patients with the «dry» form of age-related macular degeneration; a relevant increase of blood antioxidant capacity and visual acuity can be observed up to 12 months after the treatment with polarized polychromatic non-coherent light and dynamic electromyostimulation.

PKCα is genetically linked to memory capacity in healthy subjects and to risk for posttraumatic stress disorder in genocide survivors

Strong memory of a traumatic event is thought to contribute to the development and symptoms of posttraumatic stress disorder (PTSD). Therefore, a genetic predisposition to build strong memories could lead to increased risk for PTSD after a traumatic event. Here we show that genetic variability of the gene encoding PKCα (PRKCA) was associated with memory capacity--including aversive memory--in nontraumatized subjects of European descent. This finding was replicated in an independent sample of nontraumatized subjects, who additionally underwent functional magnetic resonance imaging (fMRI). fMRI analysis revealed PRKCA genotype-dependent brain activation differences during successful encoding of aversive information. Further, the identified genetic variant was also related to traumatic memory and to the risk for PTSD in heavily traumatized survivors of the Rwandan genocide. Our results indicate a role for PKCα in memory and suggest a genetic link between memory and the risk for PTSD.

Chester Step Test in Patients With COPD: Reliability and Correlation With Pulmonary Function Test Results

The 5-stage Chester step test assesses aerobic capacity in healthy subjects. It has not been tested in patients with COPD. To determine the reliability of the Chester step test in patients with COPD and correlation with pulmonary function test and exercise test results. Thirty-two patients (mean ± SD FEV(1) 46 ± 15% of predicted) undertook 2 Chester step tests and two 6-min walk tests, on different days, in random order. A subgroup of 11 patients performed incremental cycle ergometry. Thirty-one patients performed stage 1 of the Chester step test. Nineteen patients performed stage 2 of the Chester step test. The number of steps was highly reproducible: 66 ± 41 steps vs 68 ± 41 steps. There was no difference in heart rate or S(pO(2)) between the 2 Chester step tests at the peak of exercise or at the end of each stage. There was a significant correlation between number of steps and FEV(1) (r = 0.43, P = .02), and 6-min walk distance (r = 0.60, P = .001). Heart rate increased according to advanced stages of the Chester step test, up to 81 ± 13% of predicted. There was a significant correlation between number of steps and peak heart rate (r = 0.55, P = .001). In the 11 patients who performed the incremental cycling test there was a significant correlation between number of steps and peak work load (r = 0.69, P = .02). In the 6 patients in whom oxygen uptake could be estimated from the Chester step test, oxygen uptake was higher than that measured at the peak of the cycling test (30.8 ± 5.1 mL/kg/min vs 17.4 ± 4.5 mL/kg/min, respectively, P = .001). Despite being highly reproducible, the Chester step test had a very short duration in patients with COPD. The number of steps incremented in each stage seems to be too large for these patients. An adaptation of the Chester step test should be considered for patients with COPD.

Effects of Beta‐Blockade on Exercise Performance at High Altitude: A Randomized, Placebo‐Controlled Trial Comparing the Efficacy of Nebivolol versus Carvedilol in Healthy Subjects

Exposure to high altitude (HA) hypoxia decreases exercise performance in healthy subjects. Although β-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective β-adrenergic blockade on exercise performance in healthy subjects acutely exposed to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. In this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL) residents (15 males, age 38.3 ± 12.8 years) were randomized to placebo (n = 9), carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary endpoints were measures of exercise performance evaluated by cardiopulmonary exercise testing at sea level without treatment, and after at least 3 weeks of treatment, both at SL and shortly after arrival at HA (4559 m). HA hypoxia significantly decreased resting and peak oxygen saturation, peak workload, VO(2) , and heart rate (HR) (P < 0.01). Changes from SL (no treatment) differed among treatments: (1) peak VO(2) was better preserved with nebivolol (-22.5%) than with carvedilol (-37.6%) (P < 0.01); (2) peak HR decreased with carvedilol (-43.9 ± 11.9 beats/min) more than with nebivolol (-24.8 ± 13.6 beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol (-9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes independently predicted changes in peak VO(2) at multivariate analysis (R= 0.62, P < 0.01). Exercise performance is better preserved with nebivolol than with carvedilol under acute exposure to HA hypoxia in healthy subjects.

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 µmol/L. After single oral administration, the maximum plasma concentration (C(max)) and area under the curve (AUC(0-∞)) were 84.7 ± 25.2 µmol/L and 2,676.4 ± 708.3 µmol/L·h, respectively. The half-life and the time required to reach the C(max) was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.