Ventilatory response to peripheral chemoreflex and muscle metaboreflex during static handgrip in healthy humans: evidence of hyperadditive integration.

NEW FINDINGS: What is the central question of this study? What is the effect of peripheral chemoreflex and muscle metaboreflex integration on ventilation regulation, and what is the effect of integration on breathing-related sensations and emotions? What is the main finding and its importance? Peripheral chemoreflex and muscle metaboreflex coactivation during isocapnic static handgrip exercise appeared to elicit a hyperadditive effect with regard to ventilation and an additive effect with regard to breathing-related sensations and emotions. These findings reveal the nature of the integration between two neural mechanisms that operate during small-muscle static exercise performed under hypoxia. ABSTRACT: Exercise augments the hypoxia-induced ventilatory response in an exercise intensity-dependent manner. A mutual influence of hypoxia-induced peripheral chemoreflex activation and exercise-induced muscle metaboreflex activation might mediate the augmentation phenomenon. However, the nature of these reflexes' integration (i.e., hyperadditive, additive or hypoadditive) remains unclear, and the coactivation effect on breathing-related sensations and emotions has not been explored. Accordingly, we investigated the effect of peripheral chemoreflex and muscle metaboreflex coactivation on ventilatory variables and breathing-related sensations and emotions during exercise. Fourteen healthy adults performed 2-min isocapnic static handgrip, first with the non-dominant hand and immediately after with the dominant hand. During the dominant hand exercise, we (a) did not manipulate either reflex (control); (b) activated the peripheral chemoreflex by hypoxia; (c) activated the muscle metaboreflex in the non-dominant arm by post-exercise circulatory occlusion (PECO); or (d) coactivated both reflexes by simultaneous hypoxia and PECO use. Ventilation response to coactivation of reflexes (mean ± SD, 13 ± 6 l/min) was greater than the sum of responses to separated activations of reflexes (mean ± SD, 8 ± 8 l/min, P = 0.005). Breathing-related sensory and emotional responses were similar between coactivation of reflexes and the sum of separate activations of reflexes. Thus, the peripheral chemoreflex and muscle metaboreflex integration during exercise appeared to be hyperadditive with regard to ventilation and additive with regard to breathing-related sensations and emotions in healthy adults.

Mediation Analysis in Manual Therapy Research.

Objective: The purpose of this study was to illustrate the applicability of mediation analysis in the manual therapy field by assessing whether pain intensity, duration of pain, or the change in systolic blood pressure mediated the heart rate variability (HRV) of patients with musculoskeletal pain who received manual therapy. Methods: A secondary data analysis from a 3-arm, parallel, randomized, placebo-controlled, assessor-blinded, superiority trial was performed. Participants were randomized into spinal manipulation, myofascial manipulation, or placebo groups. Cardiovascular autonomic control was inferred from resting HRV variables (low-high frequency power ratio; LF/HF) and blood pressure responsiveness to a sympathoexcitatory stimulus (cold pressor test). Pain intensity and duration were assessed. Mediation models analyzed whether pain intensity, duration, or blood pressure independently affected the improvement of the cardiovascular autonomic control of patients with musculoskeletal pain after intervention. Results: The first assumption of mediation was met for LF/HF with statistical evidence of a total effect of spinal manipulation, as compared with placebo on HRV outcomes (ß = 0.77 [0.17-1.30]); second and third assumptions showed no statistical evidence of a relationship between the intervention and pain intensity (ß = -5.30 [-39.48 to 28.87]), pain intensity, and LF/HF (ß = 0.00 [-0.01 to 0.01]). Conclusion: In this study of causal mediation analysis, the baseline pain intensity, duration of pain, and responsiveness of the systolic blood pressure to a sympathoexcitatory stimulus did not mediate the effects of the spinal manipulation on the cardiovascular autonomic control of patients with musculoskeletal pain. Accordingly, the immediate effect of spinal manipulation on the cardiac vagal modulation of patients with musculoskeletal pain may more likely be related to the intervention rather than the mediators investigated.

How much does sleep deprivation impair endurance performance? A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to investigate the effect of sleep deprivation on endurance performance, as well as possible effect-modifying factors. Searches were done in Pubmed, Web of Science, Embase, and Scopus on 12 July 2022. We additionally searched the bibliographic references and citations on Google Scholar of the papers whose full text was analyzed. Eligible studies were randomized and non-randomized controlled trials that compared sleep deprivation and habitual-sleep night effects on endurance performance in healthy humans. The studies' quality was examined by the Cochrane Collaboration's risk of bias tool. We calculated the pooled standardized mean differences (pooled SMD) and 95% confidence interval (95%CI) by a random-effects model. A mixed-effects model analyzed subgroups. Thirty-one studies were analyzed (n = 478), generating 38 effect sizes in full. The overall risk of bias was low in 8% of the studies, unclear in 74%, and high in 18%. Sleep deprivation in general had a moderate negative effect on endurance performance (polled SMD [95%CI] = -0.52 [-0.67; -0.38]). Training status, sleep deprivation magnitude, assessment time, exercise mode, and endpoint type did not influence the sleep deprivation effect, whereas longer exercises (>30 min) were more affected by sleep deprivation than shorter ones (P = 0.035). Therefore, the available evidence supports that sleep deprivation's deleterious effect on endurance performance is of moderate size and depends on exercise duration. This information can be useful to estimate the performance decrement of endurance exercise practitioners under sleep deprivation in training routines and competitions.PROSPERO registration number CRD42021229717.

Sleep deprivation causes a moderate deleterious effect on endurance performance.Sleep deprivation similarly impairs endurance performance in untrained, recreationally-trained, and trained people, but its effect on well-trained and professional endurance athletes is unknown.One or more nights of partial sleep deprivation or one night of total sleep deprivation similarly compromise endurance performance. Uncertainties about the effect of more than one night of total sleep deprivation warrant more studies.Sleep deprivation impairs walking, running, and cycling endurance performance regardless of the exercise endpoint being unknown (i.e. incremental or constant load tests) or known (i.e. time trial tests) and assessment time. However, sleep deprivation causes a more deleterious effect on endurance performance in exercises lasting more than 30 min.

Resistance Training Improves Sleep and Anti-Inflammatory Parameters in Sarcopenic Older Adults: A Randomized Controlled Trial.

Sleep and exercise have an important role in the development of several inflammation-related diseases, including sarcopenia. Objective: To investigate the effects of 12 weeks of resistance exercise training on sleep and inflammatory status in sarcopenic patients. Methods: A randomized controlled trial comparing resistance exercise training (RET) with a control (CTL) was conducted. Outcomes were obtained by physical tests, polysomnography, questionnaires, isokinetic/isometric dynamometry tests, and biochemical analysis. Results: Time to sleep onset (sleep latency) was reduced in the RET group compared to the CTL group (16.09 ± 15.21 vs. 29.98 ± 16.09 min; p = 0.04) after the intervention. The percentage of slow-wave sleep (N3 sleep) was increased in the RET group (0.70%, CI: 7.27−16.16 vs. −4.90%, CI: 7.06−16.70; p = 0.04) in an intention to treat analysis. Apnea/hour was reduced in the RET group (16.82 ± 14.11 vs. 7.37 ± 7.55; p = 0.001) and subjective sleep quality was improved compared to the CTL (−1.50; CI: 2.76−6.14 vs. 0.00; CI: 1.67−3.84 p = 0.02) in an intention-to-treat analysis. Levels of interleukin-10 (IL-10) (2.13 ± 0.80 vs. 2.51 ± 0.99; p < 0.03) and interleukin-1 receptor antagonist (IL-1ra) (0.99 ± 0.10 vs. 0.99 ± 0.10 ng/mL; p < 0.04; delta variation) were increased in the RET group. Conclusions: RET improves sleep parameters linked to muscle performance, possibly due to an increase in anti-inflammatory markers in older sarcopenic patients.

Perceived Exertion: Revisiting the History and Updating the Neurophysiology and the Practical Applications.

The perceived exertion construct creation is a landmark in exercise physiology and sport science. Obtaining perceived exertion is relatively easy, but practitioners often neglect some critical methodological issues in its assessment. Furthermore, the perceived exertion definition, neurophysiological basis, and practical applications have evolved since the perceived exertion construct's inception. Therefore, we revisit the careful work devoted by Gunnar Borg with psychophysical methods to develop the perceived exertion construct, which resulted in the creation of two scales: the rating of perceived exertion (RPE) and the category-ratio 10 (CR10). We discuss a contemporary definition that considers perceived exertion as a conscious perception of how hard, heavy, and strenuous the exercise is, according to the sense of effort to command the limbs and the feeling of heavy breathing (respiratory effort). Thus, other exercise-evoked sensations would not hinder the reported perceived exertion. We then describe the neurophysiological mechanisms involved in the perceived exertion genesis during exercise, including the influence of the peripheral feedback from the skeletal muscles and the cardiorespiratory system (i.e., afferent feedback) and the influence of efferent copies from the motor command and respiratory drive (i.e., corollary discharges), as well as the interaction between them. We highlight essential details practitioners should consider when using the RPE and CR10 scales, such as the perceived exertion definition, the original scales utilization, and the descriptors anchoring process. Finally, we present how practitioners can use perceived exertion to assess cardiorespiratory fitness, individualize exercise intensity prescription, predict endurance exercise performance, and monitor athletes' responses to physical training.

One Session of Spinal Manipulation Improves the Cardiac Autonomic Control in Patients with Musculoskeletal Pain: A Randomized Placebo-Controlled Trial.

STUDY DESIGN: Three-arm, parallel, randomized, placebo-controlled, assessor-blinded trial. OBJECTIVE: To compare the immediate effect of manual therapy at the upper thoracic spine on the cardiovascular autonomic control of patients with musculoskeletal pain. SUMMARY OF BACKGROUND DATA: Musculoskeletal pain increases the risk of cardiovascular events. Thus, manual therapy applied to the upper thoracic region is likely efficient to improve the cardiac autonomic control. METHODS: The study included 59 patients with musculoskeletal pain enrolled at an outpatient clinic. Participants were randomly assigned to spinal manipulation (n = 19), myofascial manipulation (n = 20), or placebo (n = 20) administered to the upper thoracic region. Resting heart rate variability provided indexes of the cardiac autonomic control, and the blood pressure response to the cold pressor test as a proxy of the sympathetic responsiveness to a stressor stimulus. RESULTS: Groups were similar for baseline variables except for blood pressure. Two-way repeated-measures one-way analysis of covariance (ANCOVA) revealed that only spinal manipulation induced immediate increase of the square root of the mean squared differences of successive RR intervals (RMSSD), absolute (ms2), and normalized units (n.u.) of the high-frequency power (HF) as compared with pre-intervention evaluation, indicating an improvement in the parasympathetic activity to the heart. Normalized units of low-frequency power (LF) and the LF/HF ratio reduced after the spinal manipulation solely, suggesting a reduction of the sympathetic activity to the heart. There were no significant differences in the blood pressure responsiveness among the three treatments. There were no adverse events. CONCLUSION: In patients with musculoskeletal pain, spinal manipulation on the upper thoracic spine led to an immediate improvement in the resting cardiac autonomic control without an effect on the blood pressure responsiveness to a sympathoexcitatory stimulus. Myofascial manipulation or placebo did not change cardiovascular autonomic control.Level of Evidence: 2.

Diagnostic accuracy of the clinical indicators to identify central sensitization pain in patients with musculoskeletal pain.

BACKGROUND: The identification of central sensitization (CS) is an important aspect in the management of patients with chronic musculoskeletal pain. Several methods have been developed, including clinical indicators and psychophysical measures. However, whether clinical indicators coincide with the psychophysical test of CS-related sign and symptoms is still unknown. Therefore, the present study aimed to analyze the diagnostic accuracy of the clinical indicators in identifying CS-related sign and symptoms in patients with musculoskeletal pain. METHODS: One-hundred consecutive patients with musculoskeletal pain were included. Clinical indicators (index method) based on a combination of patient self-report pain characteristics and physical examination were used to identify the phenotype of patients with musculoskeletal pain and the predominance of the CS-related sign and symptoms. Conditioned pain modulation (CPM) was assessed by the Cold Pressor Test (reference standard), which is a psychophysical test used to detect impairment of CPM. Measurements of the diagnostic accuracy were performed. RESULTS: Twenty-seven patients presented predominance of CS-related sign and symptoms in the assessment of the clinical indicators, and 20 had impairment of CPM. Clinical indicators showed high accuracy (75.0%; 95% confidence interval = 65.3 to 83.1), high specificity (80.0%; 95% confidence interval = 69.6 to 88.1), high negative predictive value (87.7%; 95% confidence interval = 81.2 to 92.1), and a relevant positive likelihood ratio (2.8, 95% confidence interval = 1.5 to 5.0) when compared to the Cold Pressor Test. CONCLUSION: Clinical indicators demonstrated a valuable tool for detecting the impaired CPM, which is a remarkable feature of the CS-related sign and symptoms. Clinicians are encouraged to use the clinical indicators in the management of patients with musculoskeletal pain.

Clinical utility of ventilatory and gas exchange evaluation during low-intensity exercise for risk stratification and prognostication in pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Peak oxygen consumption (pVO2 ), determined from CPET, provides a valuable indication of PAH severity and patient prognosis. However, CPET is often contraindicated in severe PAH and frequently terminated prior to achievement of a sufficient exercise effort. We sought to determine whether in PAH low-intensity [i.e. freewheeling exercise (FW)] exercise reveals abnormal VE /VCO2 and PET CO2 responses that are associated with pVO2 and serve as indices of PAH risk stratification and mortality. METHODS: Retrospective analysis of CPET from 97 PAH patients and 20 age-matched controls was undertaken. FW VE /VCO2 and PET CO2 were correlated with pVO2 % age-predicted. Prognostication analysis was conducted using pVO2 > 65% age-predicted, as known to represent a low mortality risk. Primary outcome was mortality from any cause. RESULTS: FW PET CO2 was correlated with pVO2 (P < 0.0001; r = 0.52), while FW VE /VCO2 was not (P = 0.13; r = -0.16). ROC curve analyses showed that FW PET CO2 (AUC = 0.659), but not FW VE /VCO2 (AUC = 0.587), provided predictive information identifying pVO2 > 65% age-predicted (best cut-off value of 28 mm Hg). By Cox analysis, FW PET CO2 < 28 mm Hg remained a predictor of mortality after adjusting for age and PAH aetiology (HR: 2.360, 95% CI: 1.144-4.866, P = 0.020). CONCLUSION: Low PET CO2 during FW is associated with reduced pVO2 in PAH and provides predictive information for PAH risk stratification and prognostication.

Relationship between symptoms and imagenological signs of degenerative temporomandibular joint disorders using the Research Diagnostic Criteria for Temporomandibular Disorders and cone-beam computed tomography / Relação entre sintomas e sinais imagenológicos das disfunções degenerativas da articulação temporomandibular com o Research Diagnostic Criteria for Temporomandibular Disorders e a tomografia computadorizada de feixe cônico

ABSTRACT BAKGROUND AND OBJECTIVES: Arthralgia is a common complaint among patients with temporomandibular osteodegeneration, however, for the accurate diagnosis of osteodegeneration, it is suggested the adoption of imaging tests associated with standardized clinical diagnosis protocols. The objective of this study was to evaluate patients with degenerative changes in the temporomandibular joint previously visualized by cone beam computed tomography, relating these changes with the clinical diagnoses and symptoms of temporomandibular disorders, in order to conclude which of the degenerative changes develop more painful symptomatology. METHODS: A cross-sectional observational descriptive study. Thirty-eight patients who had previously done the cone beam computed tomography exam were evaluated. Subjects were grouped according to clinical diagnosis of temporomandibular joint changes using the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire. The presence of pain was considered during lateral palpation; intra-articular palpation; excursive movements; and active mouth opening. RESULTS: Among the purely clinical diagnoses, only 10.5% were conclusive, classifying patients as suffering from osteoarthritis/osteoarthrosis. Painful joint symptoms were found in all groups, with no statistically significant difference. Similarly, the presence of degenerative disorders, including flattening, osteophytes, sclerosis, and erosion were found in similar proportions in all diagnosis groups. CONCLUSION: 89.5% of the degenerative changes were clinically underdiagnosed. There was a positive association between the presence of symptoms and the number of correct clinical diagnoses of osteoarthritis/osteoarthrosis obtained with the Research Diagnostic Criteria for Temporomandibular Disorders.

RESUMO JUSTIFICATIVA E OBJETIVOS: Entre os pacientes com osteodegeneração cortical temporomandibular, a artralgia é uma queixa comum, entretanto, para o diagnóstico preciso de osteodegeneração sugere-se a adoção de exames de imagem associados a protocolos de diagnóstico clínico padronizados. O objetivo deste estudo foi avaliar pacientes com alterações degenerativas da articulação temporomandibular previamente visualizados por tomografia computadorizada de feixe cônico, relacionando essas alterações com os diagnósticos e sintomas clínicos da disfunção temporomandibular, a fim de concluir quais das alterações degenerativas se associam ao sintoma álgico. MÉTODOS: Trata-se de um estudo observacional descritivo transversal. Foram avaliados 38 pacientes que já haviam realizado realizado a tomografia computadorizada de feixe cônico. Os indivíduos foram agrupados de acordo com o diagnóstico clínico de alterações na articulação temporomandibular, utilizando o questionário Research Diagnostic Criteria for Temporomandibular Disorders. A presença de dor foi considerada durante: palpação lateral; palpação intra-articular; movimentos excursivos; e abertura ativa da boca. RESULTADOS: Entre os diagnósticos puramente clínicos, apenas 10,5% foram conclusivos, classificando os pacientes como portadores de osteoartrite/osteoartrose. Sintomas articulares dolorosos foram encontrados em todos os grupos, sem diferença estatisticamente significante. Da mesma forma, a presença de distúrbios degenerativos, incluindo achatamento, osteófitos, esclerose e erosão, foi encontrada em proporções semelhantes em todos os grupos de diagnóstico. CONCLUSÃO: 89,5% das alterações degenerativas foram clinicamente subdiagnosticadas. Houve associação positiva entre a presença de sintomas e o número de diagnósticos clínicos corretos de osteoartrite/osteoartrose obtidos com o Research Diagnostic Criteria for Temporomandibular Disorders.

No Sex Difference in Mental Fatigue Effect on High-Level Runners' Aerobic Performance.

PURPOSE: Some evidence suggests that sedentary women may be more vulnerable to cognitive task-induced mental fatigue. Mental fatigue, in turn, may worse aerobic exercise performance, presumably via increased perceived effort. However, it remains unclear whether acute mental fatigue induction increases perceived effort and worsens endurance performance in high-level professional athletes and whether such effects are influenced by sex. METHODS: We studied 30 athletes (15 women and 16 men) in a single-blinded, randomized, controlled and crossover protocol. In separate visits, athletes either performed a 45-min cognitive task (Stroop's color-word conflict test) to induce mental fatigue or watched a 45-min documentary as control. Then athletes performed a time-to-exhaustion test on a treadmill. RESULTS: Perceptual measures and cognitive performance indicated that the prolonged cognitive task induced a similar mental fatigue state in women and men. Cardiorespiratory and metabolic responses to the TEE did not change with mental fatigue in both sexes. Mental fatigue increased perceived effort during the time-to-exhaustion test, anticipated attainment of maximal effort, and shortened time to exhaustion similarly in women and men (mean ± SE, -27.3 ± 20.9 s for women vs -26.7 ± 15.1 s for men; P = 0.98). CONCLUSIONS: The prolonged cognitive task provoked mental fatigue, anticipated attainment of maximal perceived effort, and worsened aerobic performance in professional runners with no sex differences. Although we did not contrasted athletes with nonathletes, our results suggest that being an athlete may somehow prevent women from developing greater mental fatigue and suffering more from its underlying effects compared with men.

Ischemic preconditioning boosts post-exercise but not resting cardiac vagal control in endurance runners.

PURPOSE: High cardiac vagal control in endurance athletes has been generally associated with adequate recovery from training and readiness to cope high-intensity training. A method that improves cardiac vagal control in endurance athletes could therefore be advantageous. Accordingly, we sought to test whether ischemic preconditioning (IPC) could enhance cardiac vagal control in endurance runners. METHODS: Fifteen subjects underwent IPC, sham ultrasound (SHAM) or control (CT), in random order. Subjects were informed both IPC and SHAM would be beneficial vs. CT (i.e., similar placebo induction), and IPC would be harmless despite ischemia sensations (i.e., nocebo avoidance). Resting cardiac vagal control was assessed via respiratory sinus arrhythmia (RSA) and heart rate variability (HRV) indexes. Post-exercise cardiac vagal control was assessed via heart rate recovery [HR time constant decay (T30) and absolute HR decay (HRR30s)] during 30-s breaks of a discontinuous incremental test. Capillary blood samples were collected for lactate threshold identification. RESULTS: RSA and HRV were similar among interventions at pre- and post-intervention assessments. Lactate threshold occurred at 85 ± 4% of maximal effort. T30 was similar among interventions, but IPC increased HRR30s at 70% and 75% of maximal effort vs. SHAM and CT (70%: IPC = 31 ± 2 vs. SHAM = 26 ± 3 vs. CT = 26 ± 2 bpm, mean ± SEM, P < 0.01; 75%: IPC = 29 ± 2 vs. SHAM = 25 ± 2 vs. CT = 24 ± 2 bpm, P < 0.01). CONCLUSION: IPC did not change resting cardiac vagal control, but boosted fast post-exercise cardiac vagal reactivation at exercise intensities below lactate threshold in endurance runners.

Adults with initial metabolic syndrome have altered muscle deoxygenation during incremental exercise.

OBJECTIVE: Reduced aerobic power is independently associated with metabolic syndrome (MetS) incidence and prevalence in adults. This study investigated whether muscle deoxygenation (proxy of microvascular O2 extraction) during incremental exercise is altered in MetS and associated with reduced oxygen consumption ( V˙O2peak ). METHODS: Twelve men with initial MetS (no overt diseases and medication-naive; mean ± SD, age 38 ± 7 years) and 12 healthy controls (HCs) (34 ± 7 years) completed an incremental cycling test to exhaustion, in which pulmonary ventilation and gas exchange (metabolic analyzer), as well as vastus lateralis deoxygenation (near infrared spectroscopy), were measured. RESULTS: Subjects with MetS, in contrast to HCs, showed lower V˙O2peak normalized to total lean mass, similar V˙O2 response to exercise, and earlier break point (BP) in muscle deoxygenation. Consequently, deoxygenation slope from BP to peak exercise was greater. Furthermore, absolute V˙O2peak was positively associated with BP in correlations adjusted for total lean mass. CONCLUSIONS: MetS, without overt diseases, altered kinetics of muscle deoxygenation during incremental exercise, particularly at high-intensity exercise. Therefore, the balance between utilization and delivery of O2 within skeletal muscle is impaired early in MetS natural history, which may contribute to the reduction in aerobic power.

Enteropathy Associated with Olmesartan.

The recognition of an enteropathy caused by olmesartan is recent. It was first described in 2012 by the Mayo Clinic, which presented 22 clinical cases. Olmesartan is a highly prescribed drug and the differential diagnosis of a sprue-like enteropathy is very wide, so it is important to be aware of this pathology. We report a case of a 67-years-old man, with arterial hypertension under treatment with olmesartan, with a 4-months history of diarrhea and weight lost. He was admitted three times in our Department during this period of time. An initial diagnosis was made of lymphocytic colitis but he did not respond to treatment with corticosteroids. There was a high suspicion of celiac disease, so the patient started a gluten-free diet but still there were no symptomatic changes. The patient underwent several blood and imaging tests which were negative. Due to the suspicion of an enteropathy caused by drugs, olmesartan was stopped and the patient showed a significant improvement of his symptoms. The exact pathophysiology of this entity remains to be elucidated. It may affect all gastrointestinal tract and mimic a refractory celiac disease as well as a lymphocytic colitis due to similar symptoms and histology. It is expected more cases like this in the future due to high use of olmesartan in current clinical practice. So, it is important to all gastroenterologists to be aware of this pathology and take it into consideration when putting together a differential diagnosis.

A enteropatia por Olmesartan não estava reconhecida até ao ano de 2012 quando a "Mayo Clinic" apresentou 22 casos. Apesar de existirem poucos casos publicados, é importante familiarizar os clínicos com aspectos referentes a esta patologia, visto tratar-se de um fármaco muito prescrito e o diagnóstico diferencial da enteropatia "sprue-like" ser muito amplo.Apresentamos o caso de um paciente em tratamento com Olmesartan por hipertensão arterial. É internado 3 vezes num prazo de 4 meses por quadro de diarreia e perda importante de peso. Inicialmente, é diagnosticado de colite linfocítica que não responde ao tratamento com corticóides e, posteriormente, de provável doença celíaca que não responde a dieta sem glúten. Realizam-se inúmeros exames complementários, analíticos e de imagem, sem concluir-se nenhum diagnóstico. Perante a suspeita de uma enteropatia por Olmesartan, retira-se o fármaco definitivamente e reinicia-se o glúten na dieta, confirmando-se uma melhoria espectacular do quadro clínico. Durante os internamentos não tomava Olmesartan, sendo o motivo da melhoria clínica durante os mesmos.Os mecanismos associados a esta patologia são desconhecidos. Pode afectar todo o aparelho digestivo e mimetizar uma doença celíaca refractária e/ou colite linfocítica devido a semelhança dos sintomas e da anatomia patológica. Devido à elevada prescrição deste medicamento, é esperável que no futuro se diagnostiquem mais casos, motivo pelo qual, os clínicos, principalmente os gastroenterologistas, devem de considera-la no diagnóstico diferencial.

Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents.

During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed.

Aplicacao da tecnica por cromatografia a gas para investigacao da formacao de sub produtos da desinfeccao em agua potavel / Application of gas chromatographic technique for investigation of the formation of by products in drinking water disinfection

O uso do cloro para a desinfecção e/ou oxidação nas estações de tratamento de água favorece a formação de subprodutos orgânicos halogenados (SOH), muitos deles carcinogênicos. O objetivo desta pesquisa foi validar uma metodologia analítica proposta para a quantificação simultânea de 12 subprodutos da desinfecção por cromatografia a gás com detector de captura de elétrons (CG-DCE). O método apresentou linearidade (r>0,998), repetibilidade menor que 0,15%, limites de detecção de 1 a 6 µg.L-1 e de quantificação de 3 a 21 Î1/4g.L-1, precisão (<10%), exatidão (93-120%) e recuperação (87-117%). Os resultados indicam que o método pode ser empregado para a investigação de SOH em água, garantindo confiabilidade analítica nos resultados.

The use of chlorine for disinfection and/or oxidation at drinking water treatment plants favors the formation of halogenated organic by-products (HOB), many of them carcinogenic. The purpose of this research was to validate an analytical method for the simultaneous quantification of 12 HOB from disinfection by gas chromatograph with electrons capture detector (GC-ECD). The method provided linearity (r>0.998), repeatability lower than 0.15%, limits of detection from 1 to 6 Î1/4g.L-1 and of quantification from 3 to 21 Î1/4g.L-1, precision (<10%), accuracy (93-120%) and recovery (87-117%). The results indicate that the method can be employed to investigate the formation of HOB in water, yielding analytically reliable results.

The 894G>T endothelial nitric oxide synthase genetic polymorphism affects hemodynamic responses to mental stress performed before and after exercise.

Nitric oxide is the primary mediator of vasodilation during mental stress. Since genetic polymorphisms in the nitric oxide synthase (eNOS) gene seem to impair the production of NO, this study aimed to evaluate the effect of an exercise bout on hemodynamic responses to mental stress in subjects with the 894G>T polymorphism of eNOS. Subjects without (wild-type group; n = 16) or with (polymorphic-type group; n = 19) the 894G>T polymorphism underwent a mental stress challenge before and after a maximal cardiopulmonary exercise test. Blood pressure was measured by auscultation and forearm blood flow by venous occlusion plethysmography. The groups were similar regarding anthropometric, metabolic, resting blood pressure and exercise variables. Before exercise, systolic blood pressure response during mental stress was higher in the polymorphic-type group (∆wild-type: 8.0 ± 2.0% vs. ∆polymorphic-type: 12.5 ± 1.8%, P = 0.01), while the increase in forearm vascular conductance was similar between the groups (∆wild-type 90.8 ± 26.4% vs. ∆polymorphic-type: 86.3 ± 24.1%, P = 0.44). After exercise, the systolic blood pressure at baseline and during mental stress was lower than before exercise in the whole group (P < 0.05), but the pressure response during mental stress was still higher in the polymorphic-type group (∆wild-type: 5.8 ± 1.5% vs. ∆polymorphic-type: 10.2 ± 1.4%, P = 0.01). The increase in forearm vascular conductance was inhibited only in the polymorphic-type group (∆before exercise 86.3 ± 24.1% vs. ∆after exercise: 41.5 ± 12.6%, P = 0.04). In conclusion, these results suggest the 894G>T eNOS polymorphism is associated with altered hemodynamic responses to mental stress both before and after a single bout of dynamic exercise with potential clinical implications.

Impaired hemodynamic response to mental stress in subjects with prehypertension is improved after a single bout of maximal dynamic exercise.

INTRODUCTION: High blood pressure during mental stress in subjects with prehypertension is associated with blunted vasodilation in skeletal muscles, which might be improved by an acute bout of exercise. OBJECTIVE: To investigate the hemodynamic responses to mental stress before and after a bout of exercise in subjects with prehypertension. METHOD: Eighteen subjects with prehypertension and 16 with normotension underwent a mental stress test before and after a maximal cardiopulmonary exercise test on a treadmill. Blood pressure was measured by auscultation, and forearm blood flow was measured by venous occlusion plethysmography; from these measurements, the vascular conductance was calculated. RESULTS: Subjects with prehypertension had a higher mean blood pressure during mental stress (prehypertension 112 ± 2 vs. normotension 101 ± 3 mm Hg, p<0.05), and their vascular conductance did not increase (baseline 0.025 ± 0.004 vs. mental stress 0.022 ± 0.003 a.u., p.0.05). After the exercise bout, the mean blood pressure during mental stress was lower in subjects with prehypertension (before exercise 112 ± 2 vs. after exercise 107 ± 2 mm Hg, p<0.05), and vascular conductance increased (baseline 0.011 ± 0.001 vs. mental stress 0.024 ± 0.004 a.u., p<0.05). CONCLUSION: Subjects with prehypertension had elevated blood pressure and a blunted vasodilator response during mental stress, but their blood pressure was attenuated and their vasodilator response was normalized after a single bout of maximal dynamic exercise.

Comparação entre métodos de avaliação da modulação vagal cardíaca / Comparison of assessment methods of cardiac vagal modulation

FUNDAMENTO: Diversos métodos têm sido utilizados para avaliar a modulação vagal cardíaca; entretanto, há lacunas quanto a associação e acurácia desses métodos. OBJETIVO: Investigar a associação entre três métodos válidos, reprodutíveis e comumente utilizados para avaliação da modulação vagal cardíaca, e comparar as suas acurácias. MÉTODOS: Trinta homens saudáveis (23 ± 4 anos) e 15 homens com coronariopatia (61 ± 10 anos) foram avaliados em ordem contrabalanceada pela Variabilidade da Frequência Cardíaca (VFC; variáveis: domínio do tempo = pNN50, DPNN e RMSSD, domínio da frequência = AF ms² e AF u.n.), Arritmia Sinusal Respiratória (ASR) e Teste de Exercício de 4 segundos (T4s). RESULTADOS: Indivíduos saudáveis apresentaram maior modulação vagal nos três métodos (p < 0,05). No grupo saudável houve correlação (p < 0,05) entre os resultados da VFC (pNN50 e DPNN) e da ASR, mas não houve correlação entre o T4s e os outros dois métodos estudados. No grupo com coronariopatia houve correlação entre os resultados da VFC (pNN50, DPNN, RMSSD, AF ms² e AF u.n.) e da ASR. Em adição, houve correlação entre o T4s e a ASR. Por fim, os métodos ASR e T4s apresentaram tamanho do efeito mais preciso e melhor acurácia (p < 0,05) comparados à VFC. CONCLUSÃO: A VFC e a ASR geraram resultados parcialmente redundantes em indivíduos saudáveis e em pacientes com coronariopatia, enquanto o T4s gerou resultados complementares a VFC e ASR em indivíduos saudáveis. Além disso, os métodos ASR e T4s foram mais precisos para discriminar a modulação vagal cardíaca entre indivíduos saudáveis e pacientes com coronariopatia comparados à VFC.

BACKGROUND: Several methods have been used to assess cardiac vagal modulation, but there are gaps regarding the association and accuracy of these methods. OBJECTIVE: To investigate the association between three valid, reproducible and commonly methods used to assess cardiac vagal modulation and compare their accuracies. METHODS: Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced design by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced order by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). RESULTS: Healthy subjects had higher vagal modulation by the three methods (p <0.05). There was a correlation in the healthy group (p <0.05) between the results of HRV (SDNN and pNN50 and RSA, but there was no correlation between the T4s and the other two methods. In the group with coronary artery disease, there was a correlation between the results of HRV (pNN50, SDNN, RMSSD, HF ms² and HF n.u.) and RSA. In addition, there was a correlation between the RSA and T4s. Finally, the T4s and RSA methods presented more accurate effect size and better accuracy (p <0.05), when compared to the HRV. CONCLUSION: HRV and RSA generated partially redundant results in healthy subjects and in patients with coronary artery disease, while the T4s generated results that were complementary to HRV and RSA in healthy subjects. In addition, RSA and T4s methods were more accurate when discriminating cardiac vagal modulation between healthy subjects and patients with coronary artery disease, when compared to HRV.