Núria Monzonís Martínez

Loss of adaptation to oxidative stress as a mechanism for aortic damage in aging rats

Cells are armed with a vast repertoire of antioxidant defence mechanisms to prevent the accumulation of oxidative damage. The cellular adaptive response is an important antioxidant mechanism against physiological and pathophysiological oxidative alterations in a cell’s microenvironment. The aim of this paper was to study, in the rat aorta, whether this adaptive response and the inflammation associated with oxidative stress were expressed throughout the aging process. We examined the rat aorta, as it is a very sensitive tissue to oxidative stress. Male Wistar rats of 1.5, 3, 12, 18 and 24 months of age were used. Superoxide anion (O2−) generation; levels of two antioxidant enzymes, superoxide dismutase (SOD) and catalase; and the levels of prostaglandin E2 (PGE2), an inflammatory marker, were measured. The results for rats at different ages were compared with those for 3 months of age. A balance between production of O2− and SOD activity was found in the aorta of rats from 1.5 to 12 months old. Oxidative stress was present in the aorta of old animals (18–24) months), due to a failure in the mechanisms of adaptation to oxidative stress. The observed increase in PGE2 levels in these rats reflected an inflammatory response. All together suggest that vascular oxidative stress and the inflammatory process observed in the old groups of rats could be closely related to vascular aging. Our results also remark the importance of the adaptative response to oxidative stressResumenLas células están equipadas con una amplia gama de mecanismos de defensa antioxidante para prevenir la acumulación de lesiones oxidativas. La respuesta celular de adaptación constituye un importante mecanismo antioxidante para prevenir las alteraciones en el microentorno celular tanto a nivel fisiológico como patofisiológico. El propósito de este trabajo fue estudiar en aorta de rata si la respuesta de adaptación así como la inflamación, asociadas ambas con el estrés oxidativo, se expresan a lo largo del proceso de envejecimiento. Se ha empleado aorta de rata ya que constituye un tejido muy sensible al estrés oxidativo. Se utilizaron ratas macho Wistar de 1,5,3,12,18 y 24 meses de edad y se estudiaron la producción de anion superoxido (O2−), los niveles de dos enzimas antioxidantes, superoxido dismutasa (SOD) y catalasa, así como los niveles de prostaglandina E2 (PGE2), un indicador de la inflamación. Los resultados obtenidos a las diferentes edades se compararon con los obtenidos con las ratas de 3 meses de edad. Nuestros resultados demostraron un equilibrio entre producción de O2− y actividad de SOD en las ratas de entre 1,5 y 12 meses de edad. En la aorta de los animales viejos (18–24 meses) se detectó mayor estrés oxidativo debido a un fallo en los mecanismos de adaptación al mismo, mientras que el aumento observado en los niveles de PGE2 en estos animales refleja una respuesta inflamatoria. En conjunto, nuestros resultados sugieren que tanto el estrés oxidativo vascular, como el proceso inflamatorio observados en los grupos de ratas viejas podrían estar fuertemente relacionados con el envejecimiento vascular. Nuestros resultados remarcan también la importancia de la respuesta de adaptación al estrés oxidativo.

Oxidative stress, nitric oxide and prostaglandin E2 levels in the gastrointestinal tract of aging rats

Objectives To evaluate the presence of oxidative stress and alterations in the levels of two cytoprotective agents, prostaglandin E2 and nitric oxide, in the gastrointestinal tract of aging rats.

Comparison of three prognostic scoring systems in a series of 146 cases of chronic myelomonocytic leukemia (CMML): MD Anderson prognostic score (MDAPS), CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model. A detailed review of prognostic factors in CMML

Although specific prognostic models for chronic myelomonocytic leukemia (CMML) exist, few are based on large series of patients. MD Anderson prognostic score (MDAPS) has been the most useful for CMML risk assessment. Due to recent emergence of CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model, we compared the three scores. One hundred forty-six CMML patients diagnosed between 1998 and 2014 were retrospectively analyzed. Univariate analysis was performed to assess prognostic impact on overall survival (OS) and leukemia-free survival (LFS) of the variables composing the scores and all items showed prognostic value on OS with the exception of the presence of circulating immature myeloid cells. Regarding LFS, only CPSS variables, bone marrow blast ≥10% and an absolute monocyte count >10×109/L had an impact. When the scores were applied, all showed an impact on OS and retained their significance in multivariate analysis. By using ROC curves and C-index, CPSS showed a slightly better predictive value for mortality and leukemia transformation. Variables composing the three indexes were compared in multivariate analysis and only CPSS parameters and platelets<100×109/L retained their significance. Based on these findings, by adding platelet count to CPSS, a new score was implemented (CPSS-P) showing the best risk prediction capability in our series. This study reinforces the validity of the tested scores.