Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate

Here we describe a new non-human primate model of temporal lobe epilepsy (TLE) to better investigate the cause/effect relationships of human TLE. Status epilepticus (SE) was induced in adult marmosets by pilocarpine injection (250 mg/kg; i.p.). The animals were divided in 2 groups: acute (8 h post-SE) and chronic (3 and 5 months post-SE). To manage the severity of SE, animals received diazepam 5 min after the SE onset (acute group: 2.5 or 1.25 mg/kg; i.p.; chronic group/; 1.25 mg/kg; i.p). All animals were monitored by video and electrocorticography to assess SE and subsequent spontaneous recurrent seizures (SRS). To evaluate brain injury produced by SE or SRS we used argyrophil III, Nissl and neo-Timm staining techniques. Magnetic resonance image was also performed in the chronic group. We observed that pilocarpine was able to induce SE followed by SRS after a variable period of time. Prolonged SE episodes were associated with brain damage, mostly confined to the hippocampus and limbic structures. Similar to human TLE, anatomical disruption of dentate gyrus was observed after SRS. Our data suggest that pilocarpine marmoset model of epilepsy has great resemblance to human TLE, and could provide new tools to further evaluate the subtle changes associated with human epilepsy.FAPESPCNP

Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats

Background/Aims: Physical training has beneficial effects on endothelial function and can influence the regeneration of the endothelial cell. We investigated the effect of physical training on cisplatin (CP)-induced acute kidney injury and assessed the impact of training on endothelial structure and function, and on the inflammatory processes in rats. Methods: We injected male Wistar rats subjected to previous physical training in treadmill running (trained, TR) or not (sedentary, SED) with CP (5 mg/kg) (TR+CP and SED+CP groups, respectively). Five days after the injections, blood and urine samples were collected to evaluate renal function and kidneys were harvested for morphological, immunohistochemical, enzyme-linked immunosorbent assay, and analysis of nitric oxide (NO) levels. Results: Rats treated with CP showed increased levels of plasma creatinine and sodium and potassium fractional excretion. These alterations were associated with increase in tubulointerstitial lesions and macrophage number, reduction of endothelial cells, and increased VEGF, vimentin, and α-smooth muscle actin expression in the outer renal medulla in the SED+CP group. We also found increased levels of renal IL-1β and increased excretion of monocyte chemoattractant protein-1 and transforming growth factor-β compared with controls. These changes were milder in trained rats, associated with increased levels of renal tissue NO, and increased expression of p-eNOS and stromal cell-derived factor-1α (a chemokine involved in kidney repair) in the kidneys of CP-injected trained rats. Conclusions: The protective effect of previous training in CP-treated rats was associated with reduced endothelial cell lesions and increased renal production of NO in trained rats

Effects of 12 weeks of aerobic training on autonomic modulation, mucociliary clearance, and aerobic parameters in patients with COPD

Marceli Rocha Leite,1 Ercy Mara Cipulo Ramos,1 Carlos Augusto Kalva-Filho,2 Ana Paula Coelho Figueira Freire,1 Bruna Spolador de Alencar Silva,1 Juliana Nicolino,1 Alessandra Choqueta de Toledo-Arruda,3 Marcelo Papoti,4 Luiz Carlos Marques Vanderlei,1 Dionei Ramos1 1Department of Physiotherapy, São Paulo State University, Presidente Prudente, 2Program in Rehabilitation and Functional Performance, São Paulo University, Ribeirão Preto, 3Department of Medicine, São Paulo University, 4School of Physical Education and Sport of Ribeirão Preto, São Paulo University, Ribeirão Preto, São Paulo, Brazil Introduction: Patients with chronic obstructive pulmonary disease (COPD) exhibit aerobic function, autonomic nervous system, and mucociliary clearance alterations. These parameters can be attenuated by aerobic training, which can be applied with continuous or interval efforts. However, the possible effects of aerobic training, using progressively both continuous and interval sessions (ie, linear periodization), require further investigation.Aim: To analyze the effects of 12-week aerobic training using continuous and interval sessions on autonomic modulation, mucociliary clearance, and aerobic function in patients with COPD.Methods: Sixteen patients with COPD were divided into an aerobic (continuous and interval) training group (AT) (n=10) and a control group (CG) (n=6). An incremental test (initial speed of 2.0 km·h-1, constant slope of 3%, and increments of 0.5 km·h-1 every 2 minutes) was performed. The training group underwent training for 4 weeks at 60% of the peak velocity reached in the incremental test (vVO2peak) (50 minutes of continuous effort), followed by 4 weeks of sessions at 75% of vVO2peak (30 minutes of continuous effort), and 4 weeks of interval training (5×3-minute effort at vVO2peak, separated by 1 minute of passive recovery). Intensities were adjusted through an incremental test performed at the end of each period.Results: The AT presented an increase in the high frequency index (ms2) (P=0.04), peak oxygen uptake (VO2peak) (P=0.01), vVO2peak (P=0.04), and anaerobic threshold (P=0.02). No significant changes were observed in the CG (P>0.21) group. Neither of the groups presented changes in mucociliary clearance after 12 weeks (AT: P=0.94 and CG: P=0.69).Conclusion: Twelve weeks of aerobic training (continuous and interval sessions) positively influenced the autonomic modulation and aerobic parameters in patients with COPD. However, mucociliary clearance was not affected by aerobic training. Keywords: COPD, exercise, aerobic treatment, mucociliary clearanc

Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate

Here we describe a new non-human primate model of temporal lobe epilepsy (TLE) to better investigate the cause/effect relationships of human TLE. Status epilepticus (SE) was induced in adult marmosets by pilocarpine injection (250 mg/kg; i.p.). the animals were divided in 2 groups: acute (8 h post-SE) and chronic (3 and 5 months post-SE). To manage the severity of SE, animals received diazepam 5 min after the SE onset (acute group: 2.5 or 1.25 mg/kg; i.p.; chronic group/; 1.25 mg/kg; i.p). All animals were monitored by video and electrocorticography to assess SE and subsequent spontaneous recurrent seizures (SRS). To evaluate brain injury produced by SE or SRS we used argyrophil III, Nissl and neo-Timm staining techniques. Magnetic resonance image was also performed in the chronic group. We observed that pilocarpine was able to induce SE followed by SRS after a variable period of time. Prolonged SE episodes were associated with brain damage, mostly confined to the hippocampus and limbic structures. Similar to human TLE, anatomical disruption of dentate gyrus was observed after SRS. Our data suggest that pilocarpine marmoset model of epilepsy has great resemblance to human TLE, and could provide new tools to further evaluate the subtle changes associated with human epilepsy. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Fis Sao Carlos IFSC, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Fis Sao Carlos IFSC, BR-04023062 São Paulo, BrazilWeb of Scienc

Utilização do intercepto-y na avaliação da aptidão anaeróbia e predição da performance de nadadores treinados El uso del intercepto-y en la evaluación de adaptacion anaeróbica en la predicción de la performance de nadadores especializados Use of the y-intercept in the evaluation of the anaerobic fitness and performance prediction of trained swimmers

O objetivo desse estudo foi verificar a utilização do intercepto-y na avaliação da aptidão anaeróbia e predição da performance de nadadores treinados. Foram participantes do estudo 14 nadadores com idade entre 15 e 18 anos. Os atletas realizaram o teste de nado atado, performance máxima e velocidade crítica (VC) para determinação da capacidade de nado anaeróbio (CTA), todos em nado crawl em um período de três dias. 1) O teste de nado atado consistiu em realizar esforço máximo durante 30 segundos amarrado a um aparato de medição com células de carga para mensuração da força pico (Fpic), aptidão anaeróbia (AP ANA) e concentração de lactato pico ([la-]pic) conforme Papoti et al. (11); 2) Os participantes realizaram também performances máximas nas distâncias de 100, 200, 300, 400 e 600 m, com intervalo mínimo de duas horas entre cada nado; 3) E o teste de VC foi aplicado para determinação da CTA utilizando todas as combinações possíveis dos resultados das performances máximas, através do modelo de regressão linear entre distância versus tempo. Foi encontrada média de 25,07± 4,22 m nas 16 combinações de CTAs encontradas e coeficiente de regressão linear variando entre 0,99 e 1,00 e erro de coeficiente linear de 19,30± 5,9%. Não foram encontradas correlações significativas entre as CTAs e performances máximas, Fpic (227,81± 63,02 N), AP ANA (86,55± 13,05 N) e [la-]pic (6,80± 1,03 mM). Contudo, foram encontradas correlações significativas entre a AP ANA e as performances máximas. Desse modo, é possível concluir que a CTA representada pelo intercepto-y da relação distância versus tempo de nado, parece não ser um bom parâmetro na avaliação da aptidão anaeróbia e predição de performances entre 100 m e 600 m nado crawl.<br>El objetivo de ese estudio fue verificar el uso del intercepto-y en la evaluación anaeróbica de la aptitud y predicción de la performance de los nadadores especializados. Los participantes del estudio fueron 14 nadadores con edad entre 15 y 18 años. Los atletas realizaron la prueba de nado atado, máxima performance y velocidad crítica (VC) para la determinación de la capacidad de nado anaeróbico (CTA), todos en estilo crawl por un periodo de tres días. 1) La prueba de nado atado consistió en lograr el máximo esfuerzo durante 30 segundos atado a un aparato de medición con células de carga para la medida del pico de fuerza (Fpic), de la aptitud anaeróbica (AP ANA) y la concentración de pico del lactato ([la-]pic) según Papoti et al.(11). 2) Los participantes también lograron actuaciones al máximo en las distancias de 100, 200, 300, 400 y 600 m, con el intervalo mínimo de dos horas entre cada nado. 3) La prueba de VC se aplicó para la determinación de CTA que usa todas las posibles combinaciones de los resultados de las máximas actuaciones, a través del modelo de regresión lineal entre la distancia vs. tiempo. Se encontró un promedio de 25,07 &plusmn; 4,22 m en las 16 combinaciones de CTAs y se halló un coeficiente de regresión lineal que varía entre 0,99 y 1,00 con un error de coeficiente lineal de 19,30 &plusmn; 5,9%. No se encontraron en ellos correlaciones significantes entre CTAs y máximas performances, Fpic (227,81 &plusmn; 63,02 N), AP ANA (86,55 &plusmn; 13,05 N) y [la-]pic (6,80 &plusmn; 1,03 mm). Sin embargo, si se encontraron en ellos correlaciones significantes entre AP ANA y las máximas performances. De este modo, es posible concluir que la CTA representada por el intercepto-y de la distancia de la relación vs. tiempo de nado, parece no ser un parámetro bueno en la evaluación de la aptitud anaeróbica y la predicción de las actuaciones entre 100 m y 600 m del nado crawl.<br>The objective of this study was to verify the use of y-intercept from the critical velocity model in the evaluation of the anaerobic fitness and prediction of maximal performance in trained swimmers in crawl style. Fourteen swimmers with ages ranging from 15 to 18 years participated in this study. The athletes performed the tied swimming test, maximal performances tests and critical velocity (CV) for the determination of anaerobic swimming capacity (AWC). 1) The tied swimming test was applied through maximal effort during 30 seconds fixed to the equipment with load cells for the measurement of the peak force, anaerobic fitness and peak lactate. 2) The subjects also performed maximal performances at distances of 100, 200, 300, 400 and 600 meters with two hours interval between each swim. 3) AWC at CV model was determined utilizing all possible combinations by maximal performances applying the distance-time linear regression model. The AWC value obtained was of 25.07 ± 4.22 m, with linear regression coefficient between 0.99 and 1.00, and linear coefficient error of 19.30 ± 5.9%. AWC was not correlated with all maximal performances, peak force (227.81 ± 63.02 N), anaerobic fitness (85.55 ± 13.05 N), and peak lactate (6.80 ± 1.08 mM). However, the anaerobic fitness was correlated with all maximal performances. Thus, it was concluded that the AWC obtained by y-intercept of the distance/time of swim relation does not seem to be a good parameter for the anaerobic fitness evaluation neither to predict the maximal performances between 100 and 600 meters in crawl style

Demographic and clinical features of critically ill patients with COVID-19 in Greece: The burden of diabetes and obesity

Aims: The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece. Methods: In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13th 2020. Results: The median age of the patients was 65.5 (IQR 56–73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years. Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5–11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3–9) vs. 9 (IQR 7–14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors. Conclusions: Type 2 diabetes and obesity may have contributed to disease severity and mortality in COVID-19 critically ill patients in Greece. © 2020 Elsevier B.V