Mental stress induces endothelial dysfunction by AT1R-mediated redox imbalance in overweight/obese men

The main goal of this study was to determine whether oxidative imbalance mediated by AT1 receptor (AT1R) is responsible for deleterious endothelial responses to mental stress (MS) in overweight/obese class I men. Fifteen overweight/obese men (27±7 years old; 29.8±2.6 kg/m2) participated in three randomized experimental sessions with oral administration of the AT1R blocker olmesartan (40 mg; AT1R blockade) or ascorbic acid (AA; 3g) infusion or placebo [both intravenously (0.9% NaCl) and orally]. After two hours, endothelial function was determined by flow-mediated dilation (FMD) before (baseline), 30 min (30MS), and 60 min (60MS) after a five-minute acute MS session (Stroop Color Word Test). Blood was collected before (baseline), during MS, and 60 min after MS for redox homeostasis profiling: lipid peroxidation (TBARS; thiobarbituric acid reactive species), protein carbonylation, and catalase activity by colorimetry and superoxide dismutase (SOD) activity by an ELISA kit. At the placebo session, FMD significantly decreased 30MS (P=0.05). When compared to baseline, TBARS (P<0.02), protein carbonylation (P<0.01), catalase (P<0.01), and SOD (P<0.01) increased during the placebo session. During AT1R blockade, FMD increased 30 min after MS (P=0.01 vs baseline; P<0.01 vs placebo), while AA infusion increased FMD only 60 min after MS. No differences were observed during MS with the AT1R blockade and AA regarding TBARS, protein carbonylation, catalase, and SOD. AT1R-mediated redox imbalances played an important role in endothelial dysfunction to mental stress.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Short isocapnic hyperoxia affects indices of vascular remodeling and intercellular adhesion molecules in healthy men

In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24±3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16±0.85 vs normoxia: 3.51±0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40±3.84 vs normoxia: 5.73±2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53±0.11 vs normoxia: 0.68±0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling.

Effects of disturbed blood flow during exercise on endothelial function: a time course analysis

This study aimed to examine the time course of endothelial function after a single handgrip exercise session combined with blood flow restriction in healthy young men. Nine participants (28±5.8 years) completed a single session of bilateral dynamic handgrip exercise (20 min with 60% of the maximum voluntary contraction). To induce blood flow restriction, a cuff was placed 2 cm below the antecubital fossa in the experimental arm. This cuff was inflated to 80 mmHg before initiation of exercise and maintained through the duration of the protocol. The experimental arm and control arm were randomly selected for all subjects. Brachial artery flow-mediated dilation (FMD) and blood flow velocity profiles were assessed using Doppler ultrasonography before initiation of the exercise, and at 15 and 60 min after its cessation. Blood flow velocity profiles were also assessed during exercise. There was a significant increase in FMD 15 min after exercise in the control arm compared with before exercise (64.09%±16.59%, P=0.001), but there was no change in the experimental arm (-12.48%±12.64%, P=0.252). FMD values at 15 min post-exercise were significantly higher for the control arm in comparison to the experimental arm (P=0.004). FMD returned to near baseline values at 60 min after exercise, with no significant difference between arms (P=0.424). A single handgrip exercise bout provoked an acute increase in FMD 15 min after exercise, returning to near baseline values at 60 min. This response was blunted by the addition of an inflated pneumatic cuff to the exercising arm.

Plasticity of neutrophils reveals modulatory capacity

Neutrophils are widely known as proinflammatory cells associated with tissue damage and for their early arrival at sites of infection, where they exert their phagocytic activity, release their granule contents, and subsequently die. However, this view has been challenged by emerging evidence that neutrophils have other activities and are not so short-lived. Following activation, neutrophil effector functions include production and release of granule contents, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). Neutrophils have also been shown to produce a wide range of cytokines that have pro- or anti-inflammatory activity, adding a modulatory role for this cell, previously known as a suicide effector. The presence of cytokines almost always implies intercellular modulation, potentially unmasking interactions of neutrophils with other immune cells. In fact, neutrophils have been found to help B cells and to modulate dendritic cell (DC), macrophage, and T-cell activities. In this review, we describe some ways in which neutrophils influence the inflammatory environment in infection, cancer, and autoimmunity, regulating both innate and adaptive immune responses. These cells can switch phenotypes and exert functions beyond cytotoxicity against invading pathogens, extending the view of neutrophils beyond suicide effectors to include functions as regulatory and suppressor cells.

Intercostal and forearm muscle deoxygenation during respiratory fatigue in patients with heart failure: potential role of a respiratory muscle metaboreflex

The purpose of this study was to determine the effect of respiratory muscle fatigue on intercostal and forearm muscle perfusion and oxygenation in patients with heart failure. Five clinically stable heart failure patients with respiratory muscle weakness (age, 66±12 years; left ventricle ejection fraction, 34±3%) and nine matched healthy controls underwent a respiratory muscle fatigue protocol, breathing against a fixed resistance at 60% of their maximal inspiratory pressure for as long as they could sustain the predetermined inspiratory pressure. Intercostal and forearm muscle blood volume and oxygenation were continuously monitored by near-infrared spectroscopy with transducers placed on the seventh left intercostal space and the left forearm. Data were compared by two-way ANOVA and Bonferroni correction. Respiratory fatigue occurred at 5.1±1.3 min in heart failure patients and at 9.3±1.4 min in controls (P<0.05), but perceived effort, changes in heart rate, and in systolic blood pressure were similar between groups (P>0.05). Respiratory fatigue in heart failure reduced intercostal and forearm muscle blood volume (P<0.05) along with decreased tissue oxygenation both in intercostal (heart failure, -2.6±1.6%; controls, +1.6±0.5%; P<0.05) and in forearm muscles (heart failure, -4.5±0.5%; controls, +0.5±0.8%; P<0.05). These results suggest that respiratory fatigue in patients with heart failure causes an oxygen demand/delivery mismatch in respiratory muscles, probably leading to a reflex reduction in peripheral limb muscle perfusion, featuring a respiratory metaboreflex.

Determinação simultânea de resíduos de etinilestradiol e gestodeno em superfícies de equipamentos de produção / Simultaneous determination of ethynylestradiol and gestodene residues on manufacturing equipment surfaces

Um método de validação de limpeza foi desenvolvido e validado, baseado na amostragem por swab e na determinação cromatográfica simultânea de resíduos de gestodeno e etinilestradiol. O método apresenta limite de quantificação de 0,036µg/mL de etinilestradiol e 0,009µg/mL de gestodeno. Este foi considerado seletivo, preciso, exato e robusto de acordo com as normas da ANVISA. O fator de recuperação para etinilestradiol foi 90,45% e para gestodeno foi 83,52% em superfície de inox e 87,31% para etinilestradiol e 81,21% para gestodeno em superfície emborrachada. O método foi aplicado com sucesso no teste de amostragem por swab de todos os pontos de superfície dos equipamentos. O método de limpeza foi considerado validado...

A cleaning technique validation method was developed and validated, based on swab sampling and simultaneous chromatographic determination of gestodene and ethynyl estradiol residues. The method exhibited limits of quantitation (LOQs) of 0.036µg/mL for ethynyl estradiol and 0.009µg/mL for gestodene. It was considered selective, precise, accurate and robust, according to the standards set by ANVISA, the Brazilian regulatory agency. Mean swab recovery factors were 90.45% for ethynyl estradiol and 83.52 % for gestodene on an inox surface and 87.31% for ethynyl estradiol and 81.21 % for gestodene on a rubberized surface. The method was successfully applied to the assay of actual swab samples collected from all points on equipment surfaces. The cleaning method was validated...

Hemodynamic mechanisms of the attenuated blood pressure response to mental stress after a single bout of maximal dynamic exercise in healthy subjects

To determine the hemodynamic mechanisms responsible for the attenuated blood pressure response to mental stress after exercise, 26 healthy sedentary individuals (age 29 ± 8 years) underwent the Stroop color-word test before and 60 min after a bout of maximal dynamic exercise on a treadmill. A subgroup (N = 11) underwent a time-control experiment without exercise. Blood pressure was continuously and noninvasively recorded by infrared finger photoplethysmography. Stroke volume was derived from pressure signals, and cardiac output and peripheral vascular resistance were calculated. Perceived mental stress scores were comparable between mental stress tests both in the exercise (P = 0.96) and control (P = 0.24) experiments. After exercise, the blood pressure response to mental stress was attenuated (pre: 10 ± 13 vs post: 6 ± 7 mmHg; P < 0.01) along with lower values of systolic blood pressure (pre: 129 ± 3 vs post: 125 ± 3 mmHg; P < 0.05), stroke volume (pre: 89.4 ± 3.5 vs post: 76.8 ± 3.8 mL; P < 0.05), and cardiac output (pre: 7.00 ± 0.30 vs post: 6.51 ± 0.36 L/min; P < 0.05). Except for heart rate, the hemodynamic responses and the mean values during the two mental stress tests in the control experiment were similar (P > 0.05). In conclusion, a single bout of maximal dynamic exercise attenuates the blood pressure response to mental stress in healthy subjects, along with lower stroke volume and cardiac output, denoting an acute modulatory action of exercise on the central hemodynamic response to mental stress.

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

The cardiovascular electrophysiologic basis for the action of pyridostigmine, an acetylcholinesterase inhibitor, has not been investigated. The objective of the present study was to determine the cardiac electrophysiologic effects of a single dose of pyridostigmine bromide in an open-label, quasi-experimental protocol. Fifteen patients who had been indicated for diagnostic cardiac electrophysiologic study underwent two studies just before and 90-120 min after the oral administration of pyridostigmine (45 mg). Pyridostigmine was well tolerated by all patients. Wenckebach nodal anterograde atrioventricular point and basic cycle were not altered by pyridostigmine. Sinus recovery time (ms) was shorter during a 500-ms cycle stimulation (pre: 326 ± 45 vs post: 235 ± 47; P = 0.003) but not during 400-ms (pre: 275 ± 28 vs post: 248 ± 32; P = 0.490) or 600-ms (pre: 252 ± 42 vs post: 179 ± 26; P = 0.080) cycle stimulation. Pyridostigmine increased the ventricular refractory period (ms) during the 400-ms cycle stimulation (pre: 238 ± 7 vs post: 245 ± 9; P = 0.028) but not during the 500-ms (pre: 248 ± 7 vs post: 253 ± 9; P = 0.150) or 600-ms (pre: 254 ± 8 vs post: 259 ± 8; P = 0.255) cycle stimulation. We conclude that pyridostigmine did not produce conduction disturbances and, indeed, increased the ventricular refractory period at higher heart rates. While the effect explains previous results showing the anti-arrhythmic action of pyridostigmine, the clinical impact on long-term outcomes requires further investigation.

Subacute effects of a maximal exercise bout on endothelium-mediated vasodilation in healthy subjects

We evaluated vascular reactivity after a maximal exercise test in order to determine whether the effect of exercise on the circulation persists even after interruption of the exercise. Eleven healthy sedentary volunteers (six women, age 28 ± 5 years) were evaluated before and after (10, 60, and 120 min) a maximal exercise test on a treadmill. Forearm blood flow (FBF) was measured by venous occlusion plethysmography before and during reactive hyperemia (RH). Baseline FBF, analyzed by the area under the curve, increased only at 10 min after exercise (P = 0.01). FBF in response to RH increased both at 10 and 60 min vs baseline (P = 0.004). Total excess flow for RH above baseline showed that vascular reactivity was increased up to 60 min after exercise (mean ± SEM, before: 526.4 ± 48.8; 10 min: 1053.0 ± 168.2; 60 min: 659.4 ± 44.1 ml 100 ml-1 min-1 . s; P = 0.01 and 0.02, respectively, vs before exercise). The changes in FBF were due to increased vascular conductance since mean arterial blood pressure did not change. In a time control group (N = 5, 34 ± 3 years, three women) that did not exercise, FBF and RH did not change significantly (P = 0.07 and 0.7, respectively). These results suggest that the increased vascular reactivity caused by chronic exercise may result, at least in part, from a summation of the subacute effects of successive exercise bouts.

Cholinergic stimulation with pyridostigmine reduces the QTc interval in coronary artery disease

Parasympathetic dysfunction is an independent risk factor in patients with coronary artery disease; thus, cholinergic stimulation is a potential therapeutic measure that may be protective by acting on ventricular repolarization. The purpose of the present study was to determine the effects of pyridostigmine bromide (PYR), a reversible anticholinesterase agent, on the electrocardiographic variables, particularly QTc interval, in patients with stable coronary artery disease. In a randomized double-blind crossover placebo-controlled study, simultaneous 12-lead electrocardiographic tracings were obtained at rest from 10 patients with exercise-induced myocardial ischemia before and 2 h after the oral administration of 45 mg PYR or placebo. PYR increased the RR intervals (pre: 921 ± 27 ms vs post: 1127 ± 37 ms; P<0.01) and, in contrast with placebo, decreased the QTc interval (pre: 401 ± 3 ms vs post: 382 ± 3 ms; P<0.01). No other electrocardiographic variables were modified (PR segment, QT interval, QT and QTc dispersions). Cholinergic stimulation with PYR caused bradycardia and reduced the QTc interval without important side effects in patients with coronary disease. These effects, if confirmed in studies over longer periods of administration, may suggest a cardioprotection by cholinergic stimulation with PYR

Resting and reflex heart rate responses during cholinergic stimulation with pyridostigmine in humans

Dysfunction of the autonomic nervous system is of prognostic value for sudden death after acute myocardial infarction. Although the use of beta-blockers to counteract the adrenergic hyperactivity has been shown to decrease mortality in these patients, there have been no reports on the role of cholinomimetic drugs in the prognosis of patients after myocardial infarction. The present study was designed to investigate the effect of the administration of pyridostigmine bromide, a reversible anti-cholinesterase agent, on cardiac cholinergic activity assessed by the resting and reflex heart rate responses. Eight healthy volunteers were submitted to a conventional 12-lead electrocardiogram to obtain resting heart rate, and to three non-invasive cardiovascular tests: respiratory sinus arrhythmia, Valsalva maneuver and 4-sec exercise test. On two different days and following a randomized crossover double-blind protocol, the experiments were performed before and 120 min after oral administration of either pyridostigmine bromide (30 mg) or placebo. Pyridostigmine increased (P<0.05) the duration of the R-R intervals at rest (pre: 898 ñ 30 msec; post: 1019 ñ 45 msec; pre-placebo: 916 ñ 26 msec; post: 956 ñ 28 msec; P>0.05). Although the duration of the R-R intervals during the autonomic tests was also increased (P<0.05), the derived indexes of maximal fluctuation during the maneuvers did not change. These results indicate that oral pyridostigmine produces tonic cardiac cholinergic stimulation while exerting no effect on its reflex changes. Further studies are needed to address the potential role of the administration of pyridostigmine in the prognosis of patients with acute myocardial infarction.

Relative roles of the sympathetic and parasympathetic systems in the 4-s exercise test

To evaluate the relative influence of the two branches of the autonomic nervous nervous system on the 4-s exercise test which measures heart rat acceleration at the onset of exercise, 6 healthy male subjects performed the 4-s test under sympathetic blockade with propranolol, parasympathetic blockade with atropine and dual blockade. The magnitude of the 4-s test results (meams ñ SD) was significantly different only between the conditions with and without atropine (1.04 ñ 0.03 vs 1.53 ñ 0.33, respectively), with no differences between the control (1.60 ñ 0.25) and the test under sympathetic blockade (1.51 ñ 0.33). These results support the conclusion that the 4-s exercise test is a specific method for the evaluation of parasympathetic activity

Vagal activity: effect of age, sex and physical activity pattern

Heart rate response to a short (4 s) bicycle exercise test during maximal inspiratory apnea was used to assess vagal activity (VA). This study aims to evaluate the role of age, sex and physical activity pattern on VA. A total of 148 subjects, divided into athletes (N = 90) and non-athletes (N = 58) were tested. No correlation was found between age (range from 15 to 42 years) and VA in the male and female athletes (P>0.05). No gender effect could be identified. In spite of a slight tendency toward higher VA in athletes, no significant differences could be found between the two groups

Impressao basilar e tumor cervical.Relato de caso. / Basilar impression and cervical tumor. Case report

E analisado 1 caso de impressao basilar e malformacao de Arnold-Chiari associado a tumor cervical alto. A sintomatologia clinica era provocada tanto pelo tumor como pelas malformacoes craniocervicais