While hypertension disrupts the blood-brain barrier (BBB) integrity within the paraventricular nucleus of hypothalamus (PVN) and increases the leakage into the brain parenchyma, exercise training (T) was shown to correct it. Since there is scarce and contradictory information on the mechanism(s) determining hypertension-induced BBB deficit and nothing is known about T-induced improvement, we sought to evaluate the paracellular and transcellular transport across the BBB within the PVN in both conditions. SHR and WKY submitted to 4-weeks aerobic T or sedentary (S) protocol were chronically catheterized for hemodynamic recordings at rest and intra-arterial administration of dyes (Rhodamine-dextran 70kDa + FITC-dextran 10kDa). Brains were harvesting for FITC leakage examination, qPCR evaluation of different BBB constituents and protein expression of Caveolin-1 and Claudin-5, the main markers of transcytosis and paracellular transport, respectively. Hypertension was characterized by increased arterial pressure and heart rate, augmented sympathetic modulation of heart and vessels, and reduced cardiac parasympathetic control, marked FITC extravasation into the PVN which was accompanied by increased caveolin-1 gene and protein expression, without changes in claudin-5 and others tight junctions' components. SHR-T vs. SHR-S showed a partial pressure reduction, resting bradycardia, improvement of autonomic control of the circulation simultaneously with correction of both FITC leakage and caveolin-1 expression; there was a significant increase in claudin-5 expression. Caveolin-1 content was strongly correlated with improved autonomic control after exercise. Data indicated that within the PVN the transcytosis is the main mechanism governing both hypertension-induced BBB leakage as well as the exercise-induced correction.

Objective: The classic criterion for VO2máx plateau identification was proposed by Taylor et al. (1955), however, there are many critiques of this method. In this paper, we propose a new statistic-based VO2max plateau identification methodology. In addition, we aim to test for eventual differences between characteristics of the individuals who presented and those who did not present the maximum VO2max plateau. Method: Forty-one (n = 41) physically active men participated. The subjects underwent a cardiopulmonary exercise test using ramp protocol to measure the VO2max and other physiological variables. The identification of VO2max plateau was performed by segmented linear regression with unknown breakpoints for each individual. Results: Although 58.54% (24) of the sample presented VO2max plateau, no significant differences were observed in metabolic, ventilatory and velocity variables between the groups. Conclusion: The methodology presents advantages, since it is adequate to analyze VO2 variations individually and because it is based on statistical techniques, which considers the continuous records of the maximal effort test, not segmenting it in sections for analysis. The comparison between groups, according to the occurrence of the plateau, showed no differences between them.

Hypertension augments while exercise training corrects the increased vesicle trafficking (transcytosis) across the blood-brain barrier (BBB) within preautonomic areas and the autonomic imbalance. There is no information on possible mechanism(s) conditioning these effects. Knowing that Mfsd2a is the major transporter of docosahexaenoic acid (DHA) and that Mfsd2a knockout mice exhibited leaky BBB, we sought to identify its possible involvement in hypertension- and exercise-induced transcytosis across the BBB. SHR and Wistar rats were submitted to treadmill training (T) or kept sedentary (S) for 4 weeks. Resting hemodynamic/autonomic parameters were recorded in conscious chronically cannulated rats. BBB permeability within the hypothalamic paraventricular nucleus (PVN) was evaluated in anesthetized rats. Brains were harvested for Mfsd2a and caveolin-1 (an essential protein for vesicle formation) expression. SHR-S vs. Wistar-S exhibited elevated arterial pressure (AP) and heart rate (HR), increased vasomotor sympathetic activity, reduced cardiac parasympathetic activity, greater pressure variability, reduced HR variability and depressed baroreflex control. SHR-S also showed increased BBB permeability, reduced Mfsd2a and increased caveolin-1 expression. SHR-T vs. SHR-S exhibited increased Mfsd2a density, reduced caveolin-1 protein expression, normalized PVN BBB permeability, which were accompanied by resting bradycardia, partial AP drop, reduced sympathetic and normalized cardiac parasympathetic activity, increased HR variability and reduced pressure variability. No changes were observed in Wistar-T vs. Wistar-S. Training is an efficient tool to rescue Mfsd2a expression, which by transporting DHA into the endothelial cell reduces caveolin-1 availability and vesicles' formation. Exercise-induced Mfsd2a normalization is an important mechanism to correct both BBB function and autonomic control in hypertensive subjects.

Introduction: Chronic hypertension is accompanied by either blood-brain barrier (BBB) leakage and autonomic dysfunction. There is no consensus on the mechanism determining increased BBB permeability within autonomic areas. While some reports suggested tight junction’s breakdown, others indicated the involvement of transcytosis rather than paracellular transport changes. Interestingly, exercise training was able to restore both BBB permeability and autonomic control of the circulation. We sought now to clarify the mechanism(s) governing hypertension- and exercise-induced BBB permeability.Methods: Spontaneously hypertensive rats (SHR) and normotensive controls submitted to 4-week aerobic training (T) or sedentary protocol (S) were chronically cannulated for baseline hemodynamic and autonomic recordings and evaluation of BBB permeability. Brains were harvested for measurement of BBB function (FITC-10 kDa leakage), ultrastructural analysis of BBB constituents (transmission electron microscopy) and caveolin-1 expression (immunofluorescence).Results: In SHR-S the increased pressure, augmented sympathetic vasomotor activity, higher sympathetic and lower parasympathetic modulation of the heart and the reduced baroreflex sensitivity were accompanied by robust FITC-10kDa leakage, large increase in transcytotic vesicles number/capillary, but no change in tight junctions’ density within the paraventricular nucleus of the hypothalamus, the nucleus of the solitary tract and the rostral ventrolateral medulla. SHR-T exhibited restored BBB permeability and normalized vesicles counting/capillary simultaneously with a normal autonomic modulation of heart and vessels, resting bradycardia and partial pressure reduction. Caveolin-1 expression ratified the counting of transcellular, not other cytoplasmatic vesicles. Additionally, T caused in both groups significant increases in tight junctions’ extension/capillary border.Discussion: Data indicate that transcytosis, not the paracellular transport, is the primary mechanism underlying both hypertension- and exercise-induced BBB permeability changes within autonomic areas. The reduced BBB permeability contributes to normalize the autonomic control of the circulation, which suppresses pressure variability and reduces the occurrence of end-organ damage in the trained SHR. Data also disclose that hypertension does not change but exercise training strengthens the resistance of the paracellular pathway in both strains.

Rápidos avanços na tecnologia têm trazido para o mercado a necessidade de sistemas de software mais complexos e de maior criticidade desenvolvidos em curto tempo. Entrega de software de qualidade dentro do tempo e prazo especificado no cenário atual de TI tem se tornado um grande desafio para as empresas de TI. Procurando minimizar este problema diante do mercado, empresas de TI estão dedicando mais tempo para a verificação e validação de seus produtos, investindo esforços para que suas estruturas de testes de software sejam bem definidas. Porém, um grande número dessas empresas falham na primeira iniciativa por não conhecerem os tipos de estruturas existentes e os riscos envolvidos em cada uma delas. Este artigo relatará uma experiência na implantação de três estruturas organizacionais de testes: Equipe Independente de Testes, Equipe Integrada de Testes e Terceirização, em quatro projetos do C.E.S.A.R.(Centro de Estudos e Serviços Avançados do Recife), descrevendo como cada estrutura foi implementada, enfatizando as dificuldades, os benefícios encontrados e fornecendo um comparativo entre as três estruturas.