TNF-α and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica

<p>Abstract</p> <p>Background</p> <p>Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress.</p> <p>Methods</p> <p>We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.</p> <p>Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-<it>α</it>, IFN-<it>γ</it>, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured.</p> <p>Results</p> <p>We found almost undetectable levels of TNF-<it>α</it>, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-<it>α </it>and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector – regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship.</p> <p>Conclusion</p> <p>These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis.</p

Papel crucial de la mitocondria en la muerte celular programada

La apoptosis se ha relacionado con importantes procesos, como el desarrollo embrionario y la órgano-génesis, el mantenimiento del número adecuado de células y la eliminación de aquellas dañadas, envejecidas o potencialmente peligrosas. Se realizó una revisión bibliográfica sobre el papel central que juega la mitocondria en la ejecución, amplificación y regulación de la apoptosis, las principales moléculas implicadas, las alteraciones morfológicas y bioquímicas que sufre esta organela durante este evento, entre ellas la liberación de proteínas desde el espacio ínter membranoso, cada una con funciones pro apoptóticas claves y destinos diferentes, la apertura del poro de transición de permeabilidad, las alteraciones en la homeostasis del Ca2+ y la formación del apoptosoma en el citosol. El conocimiento de todos los actores del proceso apoptótico y la profundización del papel exacto que ellos juegan, nos acerca al entendimiento de procesos fisiológicos y patológicos que cursan con incremento o inhibición de la apoptosis.The apoptosis has been related to significant processes including the embryo development and the organogenesis, the maintenance of the appropriate number of cells and the elimination of those damaged, aged or potentially dangers. A bibliographic review was made on the key role playing the mitochondria in the carrying out, amplification and regulation of apoptosis, the main implicated molecules, the morphological and biochemical alterations suffered by this organelle during this event, among them the release or proteins from the inter-membranous space, each with pro-apoptosis key functions and different fates, the opening of the permeability transition pore, the alterations of homeostasis of Ca2+, and the formation of apoptosome in cytosol. The knowledge of all participants of apoptosis process approach us to understanding of physiological and pathological processes accounting for apoptosis increase of inhibition

Mortalidad por sangrado digestivo alto en el Hospital «Enrique Cabrera» Mortality from upper digestive bleeding in «Enrique Cabrera» Hospital

INTRODUCCIÓN. El sangrado digestivo alto continúa siendo un problema de salud que conlleva una significativa morbilidad y mortalidad y un elevado consumo de recursos sanitarios. El presente estudio buscó caracterizar la mortalidad por sangrado digestivo alto en el período comprendido entre enero del 2003 y julio del 2007, en el Hospital «Enrique Cabrera» (La Habana). MÉTODO: Se realizó un estudio descriptivo, retrospectivo de corte transversal, donde se revisaron las fichas clínicas de los pacientes fallecidos por sangrado digestivo alto en el período señalado. RESULTADOS: Fallecieron 49 pacientes de un total de 320 ingresados por sangrado digestivo alto (15 %). El 80,6 % de los fallecidos eran mayores de 55 años. Es destacable el antecedente personal de elevado consumo de antiinflamatorios no esteroideos, de forma mantenida, presente en el 54,8 % de los casos, y le siguió la cirrosis hepática. La mitad de los diagnósticos clínicos iniciales fueron errados. El 64 % de los fallecidos se encontraban hemodinámicamente inestables en el momento del ingreso. Solo se intervino quirúrgicamente el 32,2 % de estos fallecidos. Todos los pacientes que no se operaron fallecieron en un cuadro de shock hipovolémico. CONCLUSIONES. Una actitud quirúrgica a tiempo podría salvar a estos enfermos.INTRODUCTION. Upper digestive bleeding is still a health problem leading to a significant morbidity and mortality and to an elevated consumption of health resources. The present study was aimed at characterizing mortality from upper digestive bleeding in «Enrique Cabrera» Hospital (Havana City) from January 2003 to July 2007. METHODS: A descriptive, retrospective and cross-sectional study was conducted to review the clinical cards of the dead patients due to upper digestive bleeding in this period. RESULTS: 49 patients died of a total of 320 admitted as a result of upper digestive bleeding (15 %). 80.6 % of the dead were over 55. It was stressed the personal history of the elevated mantained consumption of non-steroidal antiinflammatory drugs observed in 54.8 % of the cases, followed by liver cirrhosis. Half of the initial clinical diagnoses were wrong. 64 % of the dead were hemodinamically unstable on admission. Only 32.2 % of the dead had been operated on. All the patients that did not undergo surgery died of hypovolemic shock. CONCLUSIONS. A surgical procedure performed on time may save these patients

Mortalidad por sangrado digestivo alto en el Hospital “Enrique Cabrera” (2003 a 2007).

Enlaces originales: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0034-74932008000400006 https://www.researchgate.net/publication/262510937_Mortalidad_por_sangrado_digestivo_alto_en_el_Hospital_Enrique_CabreraINTRODUCCIÓN. El sangrado digestivo alto continúa siendo un problema de salud que conlleva una significativa morbilidad y mortalidad y un elevado consumo de recursos sanitarios. El presente estudio buscó caracterizar la mortalidad por sangrado digestivo alto en el período comprendido entre enero del 2003 y julio del 2007, en el Hospital «Enrique Cabrera» (La Habana). MÉTODO: Se realizó un estudio descriptivo, retrospectivo de corte transversal, donde se revisaron las fichas clínicas de los pacientes fallecidos por sangrado digestivo alto en el período señalado. RESULTADOS: Fallecieron 49 pacientes de un total de 320 ingresados por sangrado digestivo alto (15 %). El 80,6 % de los fallecidos eran mayores de 55 años. Es destacable el antecedente personal de elevado consumo de antiinflamatorios no esteroideos, de forma mantenida, presente en el 54,8 % de los casos, y le siguió la cirrosis hepática. La mitad de los diagnósticos clínicos iniciales fueron errados. El 64 % de los fallecidos se encontraban hemodinámicamente inestables en el momento del ingreso. Solo se intervino quirúrgicamente el 32,2 % de estos fallecidos. Todos los pacientes que no se operaron fallecieron en un cuadro de shock hipovolémico. CONCLUSIONES. Una actitud quirúrgica a tiempo podría salvar a estos enfermos.Hospital General Docente “Enrique Cabrera”

Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline

The pathology of Alzheimer's disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-β (Aβ). Using the APPPS1 Alzheimer's disease mouse model, we found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of the IL-12/IL-23 signaling molecules p40, p35 or p19, in which deficiency of p40 or its receptor complex had the strongest effect, resulted in decreased cerebral amyloid load. Although deletion of IL-12/IL-23 signaling from the radiation-resistant glial compartment of the brain was most efficient in mitigating cerebral amyloidosis, peripheral administration of a neutralizing p40-specific antibody likewise resulted in a reduction of cerebral amyloid load in APPPS1 mice. Furthermore, intracerebroventricular delivery of antibodies to p40 significantly reduced the concentration of soluble Aβ species and reversed cognitive deficits in aged APPPS1 mice. The concentration of p40 was also increased in the cerebrospinal fluid of subjects with Alzheimer's disease, which suggests that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer's disease pathology and cognitive deficits