Daily reoxygenation decreases myocardial injury and improves post-ischaemic recovery after chronic hypoxia

Objective: In contrast to the clinical evidence, experimental studies showed that chronic hypoxia (CH) confers a certain degree of protection against ischaemia-reperfusion damage. We studied the effects of daily reoxygenation during CH (CHReox) on hearts exposed to ischaemia-reperfusion. We also separated the intrinsic effects on the myocardium of CH and CHReox from those related to circulatory and nervous factors. Methods: Fifty-one Sprague-Dawley rats were maintained for 15 days under CH (10% O2) or CHReox (10% O2+1hday−1 exposure to air). Normoxic (N, 21% O2) rats were the control. The animals were randomly assigned to one of the three following protocols: (1) protocol A: hearts (n=7 per group) were subjected to 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 3-h reperfusion, with measurement of the injury by tetrazolium staining; (2) protocol B: the end-diastolic pressure (EDP) and left ventricular developed pressure×heart rate (LVDP×HR) were measured in Langendorff-perfused isolated hearts (n=5 per group) during 30-min global ischaemia and 45-min reperfusion; and (3) protocol C: hearts (n=5 per group) were frozen for the determination of levels of endothelial nitric oxide synthase (eNOS) by Western blotting. Results: CHReox hearts displayed greater phosphorylation of the eNOS and enhanced plasma level of nitrates and nitrites in comparison to CH hearts (P≪0.0001, Bonferroni's post-test). The infarct size was greater in CH than in N hearts (P≪0.0001, Bonferroni's post-test) while it was reduced in CHReox in comparison to CH and N hearts (P≪0.0001). At the end of reperfusion, EDP was higher in CH than CHReox and N hearts (P=0.01, Bonferroni's post-test) while LVDP×HR was higher in CHReox and N than in CH hearts (P=0.03, Bonferroni's post-test). Conclusions: Exposure to CH results in impairment of myocardial tolerance to ischaemia-reperfusion, greater injury and reduced recovery of performance, in agreement with clinical evidence. Infarct size, diastolic contracture and myocardial performance have been reduced, respectively, by 63%, 64% and 151% with daily reoxygenation compared with chronic hypoxia by accelerating intrinsic adaptive change

Expression of carbohydrate-antigen sialyl-Lewis a on colon cancer cells promotes xenograft growth and angiogenesis in nude mice

We investigated the role of carbohydrate antigen sialyl-Lewis a (sLea), an E-selectin ligand and epitope of tumor marker CA19.9, in the development of xenografts in nude mice. To this end, animals were inoculated with the human colon cancer cell line HCT-15, expressing no Lewis antigens, or with a clone expressing sLea (HCT-15-T5). The size of HCT-15-T5 xenografts appeared larger than those of HCT-15 and their average weight was over twice bigger. In both xenografts the mitotic index was found elevated, as determined by Ki-67 assay, and no apoptosis was detected in the tumor cells by both caspase 8 or TUNEL assays. Some apoptotic signals were instead detected in the vessels. Conversely, microvessel density, determined through CD-31 immunohistochemistry, was found 3.2-folds bigger in HCT-15-T5 xenografts (p < 0.012). Only the membranes of HCT-15-T5 cells grown as xenografts reacted intensively with the anti CA19.9 antibody 1116-NS-19-9 by immunofluorescence, but not by immunohistochemistry. Unknown structures were instead stained by such technique in both xenografts, as were in mouse tissues not expressing the antigen and in human colon adenocarcinoma. We conclude that expression of sLea on the surface of colon cancer cells improves xenograft growth and is associated with enhanced angiogenesis, while immunohistochemistry with 1116-NS-19-9 antibody appears not suitable to determine CA19.9 expression

The Impact of Moderate Chronic Hypoxia and Hyperoxia on the Level of Apoptotic and Autophagic Proteins in Myocardial Tissue

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Brief reoxygenation episodes during chronic hypoxia enhance posthypoxic recovery of LV function: Role of mitogen-activated protein kinase signaling pathways

Children with congenital cyanotic heart defects have worse outcomes after surgical repair of their heart defects compared with noncyanotic ones. Institution of extracorporeal circulation in these children exposes the cyanotic heart to reoxygenation injury. Mitogen-activated protein kinase (MAPK) signaling cascades are major regulators of cardiomyocyte function in acute hypoxia and reoxygenation. However, their roles in chronic hypoxia are incompletely understood. We determined myocardial activation of the three major MAPKs, c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase-1/2 (ERK1/2), and p38-MAPK in adult rats exposed to hypoxia (FIO2=0.10) for varying periods of time. Myocardial function was analyzed in isolated perfused hearts. Acute hypoxia stimulated JNK and p38-MAPK activation. Chronic hypoxia (2weeks) was associated with increased p38-MAPK (but not JNK) activation, increased apoptosis, and impaired posthypoxic recovery of LV function. Brief normoxic episodes (1h/day) during chronic hypoxia abolished p38-MAPK activation, stimulated MEK-ERK1/2 activation modestly, and restored posthypoxic LV function. In vivo p38-MAPK inhibition by SB203580 or SB202190 in chronically hypoxic rats restored posthypoxic LV function. These results indicate that sustained hypoxemia maintains p38-MAPK in a chronically activated state that predisposes to myocardial impairment upon reoxygenation. Brief normoxic episodes during chronic hypoxia prevent p38-MAPK activation and restore posthypoxic recovery of myocardial functio

Adaptation to Hypoxia: A Chimera?

"The Chimera was, according to Greek mythology, a monstrous fire-breathing hybrid creature of Lycia in Asia Minor, composed of the parts of more than one animal [...]

Environmental health : reflexions of the Brazilian Association of Post-Graduation in Collective Health - ABRASCO

O Brasil, apesar de sua extraordinária biodiversidade e do enorme potencial instalado para desenvolver ações integradas na temática do ambiente, não tem dado, do ponto de vista programático, a prioridade que o tema ambiente merece. A Associação Brasileira de Pós-Graduação em Saúde Coletiva-ABRASCO reconheceu a importância de organizar um Grupo Temático “Saúde e Ambiente” para, de maneira mais organizada, participar da luta pelo desenvolvimento sustentável, através da ação política no campo da saúde coletiva, em busca de ambientes saudáveis e da promoção da saúde. O objetivo principal deste Grupo Temático-GT foi contribuir para que o tema da saúde ambiental seja internalizado no campo da Saúde Coletiva. Método: O Grupo escolheu três eixos para discussão em uma oficina do V Congresso Brasileiro de Epidemiologia, em Curitiba, no ano de 2002. O resultado resultado do debate ocorrido foi apresentado segundo três eixos: identificação do campo teórico-conceitual em Saúde Ambiente; a política de saúde e ambiente; o caminho metodológico. A conclusão foi apresentada no formato de uma agenda do GT para o biênio 2002-2004. _______________________________________________________________________________________ ABSTRACTNot with standing its extraordinary biodiversity and enormous installed potential to develop actions integrated in to the topic of environmental health, Brazil has not given the environmental the priority the subject deserves from the programmatic, point of view. The Brazilian Association of Post-Graduation in Collective Health - ABRASCO recognized the importance of organizing a Thematic Group “Health and Environment” in order to, in a more organized fashion, participate in the struggle for sustainable development, through political action in collective health, oriented to wards health environments and health promotion. The main objective of this Thematic Group was to facilitate the subject of the environmental health to be internalized in to the field of the Collective Health. Method: The theme was debated in a workshop during the V Brazilian Congress of Epidemiology in Curitiba, in 2002. Results were presented according to three axes: 1- Identification of the theoretical-conceptual field in Environmental Health; 2- the politics of health and environment; 3- methodological route. The general conclusion was presented as an agenda for ABRASCO’s Thematic Group in Environmental Health for the biennial 2002-2004

Blood gas transport at high altitude

As a model of human hypoxia, exposure to high altitudes causes a number of ventilatory, circulatory and hemopoietic adaptations. A review of the literature on blood gas transport responses to hypoxia indicates that they are influenced not only by altitude, but also by factors related to acclimatization. In addition, it appears that the need to oxygenate tissues conflicts with the need to maintain H+ homeostasis. Thus, the final situation represents a compromise between the respiratory adjustment aimed at increasing blood alkalosis in order to optimize the oxygen transport system, and the metabolic readjustment aimed at reestablishing normal blood pH. there are factors like red cell 2,3-diphosphoglycerate, a compound that decreases the hemoglobin affinity for oxygen, that can influence that balance by affecting arterial oxygen saturation through mechanisms independent of respiration

ELEMENTOS ONTOLÓGICOS PARA INVESTIGADORES Una introducción a las categorías puras de Inmanuel Kant

El nivel ontológico es sin lugar a dudas un presupuesto del actual debate epistemológico. Sobre la base de este reconocimiento, es el objetivo de este artículo aportar elementos para la construcción de una ontología que pueda dar cuenta de los conceptos privilegiados que articulan los desarrollos científicos contemporáneos, entre ellos, el concepto de “sistemas con historia”. Esos elementos se buscarán en el marco de la deducción metafísica de las categorías, tal como la presenta Kant en la Crítica de la razón pura. La deducción citada será entonces el hilo conductor de la exposición aquí presentada.Con la publicación de este extenso artículo me propongo dos objetivos: por una parte, facilitar a investigadores de diversas orientaciones profesionales el acceso al capítulo ontológico que presupone el debate epistemológico contemporáneo, a través de las ideas centrales del texto fundacional de la ontología crítica: la Crítica de la Razón Pura. Por otra parte, me propongo aportar argumentos a favor de una concepción ontológica que pueda ponerse en consonancia con los desarrollos científicos contemporáneos. En el cuadro de estos desarrollos se inscribe de manera privilegiada el concepto de sistemas complejos con historia; dejando de lado momentáneamente toda preocupación por el rigor académico que debe presidir un esfuerzo de exégesis del pensamiento de Kant. Imaginemos que alguien sin ninguna formación ni especial interés por la filosofía me pide que exponga las nuevas ideas que se pueden desprender de una lectura ingenua de las categorias kantianas. En esa circunstancia, diría aproximadamente lo que expreso a continuación

Noveles heterociclos con actividad anticonvulsivante derivados del myo-inositol y ácido valproico

El objetivo principal de esta investigación es el descubrimiento de nuevos fármacos antiepilépticos. La epilepsia es uno de los desórdenes neurológicos más comunes, la prevalencia mundial de esta enfermedad se estima en el 1% (más de 60 millones de personas), de las cuales más del 80 % de esta incidencia se da en los países subdesarrollados. Se estima que el 25-30 % de los pacientes con epilepsia son farmacorresistentes, esto quiere decir que la terapia de fármacos no es efectiva en ellos. Claramente surge la necesidad de desarrollar fármacos más eficaces que no infrinjan la calidad de vida de los pacientes. El objetivo particular de la presente tesis, es la síntesis y evaluación farmacológica de profármacos del Ácido Valproico. Para el desarrollo del presente trabajo, nuestra propuesta fue el diseño de noveles heterociclos derivados del myo-inositol, propuesto como transportador del agente anticonvulsivo acido valproico. En esta oportunidad se propuso introducir originalmente, el grupo funcional sulfato cíclico orientado a favorecer un aumento en la actividad del fármaco. Podemos enunciar los objetivos particulares de la siguiente manera: - Diseño de Profármacos del Ácido Valproico que posean como modulador una molécula libre de efectos adversos, que sea capaz de localizarse selectivamente en el sistema nervioso central, y tenga una química acorde para realizar con éxito la síntesis. - Síntesis de los profármacos planteados - Evaluación biológica de los compuestos sintetizados en modelos de epilepsia aguda en animales. - Aporte original a partir de los resultados obtenidos.Facultad de Ciencias Naturales y Muse