La medicina hospitalaria del siglo XXI. ¿Qué está cambiando?

El objetivo de este artículo es analizar los cambios que se han producido en el ejercicio de la medicina en los últimos años. La irrupción de la tecnología en la actividad diaria ha supuesto grandes modificaciones en nuestra manera de diagnosticar y tratar a los pacientes y es muy probable que este impacto sea mayor en el futuro. Esto ha supuesto grandes ventajas en cuanto a la obtención y manejo de la información de la enorme cantidad de datos clínicos y analíticos que se generan cada día. Por otra parte, la tecnología también ha modificado el quehacer diario de los profesionales sanitarios, con cambios en la dedicación a diferentes tareas y nuevos sistemas organizativos y de realización de trabajo en equipo. No se pretende ir en contra de estos avances tan notables, pero creo necesario este análisis con el fin de situarnos en el contexto actual en el que se ejercen las profesiones sanitarias y por lo tanto poder prever que nos depara el futuro. Finalmente, comentaré las perspectivas que se vislumbran en el horizonte cercano respecto al diagnóstico, cuidados y tratamiento de nuestros enfermos.The aim of this paper is to analyze the changes in medical profession in the last decades. Technology has irrupted in the daily activity and has brought many modifications in the way that doctors diagnose and treat patients, and it is expected that his impact will be even greater in the future. Technology has involved many advantages with respect to the recovery and management of the huge quantity of clinical and analytical data generated in health institutions. Furthermore, technology has changed the daily work of health professionals, with modifications in tasks and new organizational systems and team-based activities. We are not against these important advances, but it is advisable to analyze these changes with the objective of knowing our actual situation and to facilitate the adaptation to these changes in the future. Finally, I will discuss the future perspectives related to diagnosis, care and treatment of our patients

Cyclosporine A-induced apoptosis in renal tubular cells is related to oxidative damage and mitochondrial fission

22 p.Cyclosporine A (CsA) nephrotoxicity has been linked to reactive oxygen species (ROS) production in renal cells. We have demonstrated that the antioxidant Vitamin E (Vit E) abolished renal toxicity in vivo and in vitro models. As one of the main sources of intracellular ROS are mitochondria, we studied the effects of CsA on several mitochondrial functions in LLC-PK1 cells. CsA induced ROS synthesis and decreased reduced glutathione (GSH). The drug decreased mitochondrial membrane potential (m) and induced physiological modifications in both the inner (IMM) and the outer mitochondrial membranes (OMM). In the IMM, CsA provoked mitochondrial permeability tran-sition pores (MPTP) and cytochrome c was liberated into the intermembrane space. CsA also induced pore formation in the OMM, allowing that intermembrane space contents can reach cytosol. Furthermore, CsA altered the mitochondrial dynamics, inducing an increase in mitochondrial fission; CsA increased the expression of dynamin related protein 1 (Drp1) that contributes to mitochondrial fission, and decreased the expression of mitofusin 2 (Mfn2) and optic atrophy protein 1 (Opa1), proteins involved in the fusion process. All these phenomena were related to apoptosis. These effects were inhibited when cells were treated with the antioxidant Vit E suggesting that they were mediated by the synthesis of ROS.Junta de Comunidades de Castilla la ManchaInstituto de Salud Carlos II

La ciclosporina a origina estrés oxidativo y disfunción mitocondrial en células tubulares renales

9 p.Estudiamos el efecto de la ciclosporina A (CsA) sobre la estructura y función mitocondrial en células LLC-PK1. Las células se incubaron durante 24 horas con CsA 1 µM y se analizó la producción de anión superóxido, contenido de NAD(P)H, oxidación de cardiolipina y potencial de membrana mitocondrial; además se estudió la formación de radicales libres y el contenido de glutatión reducido intracelular. Nuestros resultados demuestran que la CsA provocó un aumento del anión superóxido mitocondrial de modo paralelo al descenso de NAD(P)H; además, se produjo oxidación de la cardiolipina de la membrana interna y un descenso del potencial de membrana mitocondrial. Finalmente, observamos un aumento de la producción de radicales libres intracelulares y un descenso del glutatión reducido. En conclusión, la CsA produce modificaciones importantes en la fisiología y estructura mitocondrial con aumento de la síntesis de especies reactivas de oxígeno y descenso de la capacidad antioxidante, hechos que podrían justificar la toxicidad celular de la droga.Junta de Comunidades de Castilla-La Manch

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

27 p.Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondriaJunta de Comunidades de Castilla-La Manch

Intoxicaciones por setas ¿todavía existen hoy?

Presentamos el caso de una paciente de 55 años vegana, que ingresa por presentar cuadro de nauseas, vómitos y deterioro general secundario a la ingesta de Amanita próxima. La paciente sufrió un síndrome norleucínico con fracaso renal agudo oligoanúrico, que requirió tratamiento con hemodiálisis urgente. La evolución de la paciente fue satisfactoria con recuperación completa de la función renal al cabo de 3 semanas. A propósito de este caso revisamos los efectos tóxicos de las principales setas y su tratamiento.We treated a 55-year old patient with nausea, vomiting and general malaise secondary to the ingestion of Amanita proxima. Our patient suffered from a norleucinic syndrome, with oligoanuric acute kidney failure; she was treated with urgent hemodialysis. The clinical outcome of our patient was satisfactory and complete recovery of kidney function was observed after three weeks. We review of the main toxic effects of mushrooms and their treatment

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Efecto de diversas hormonas vasoactivas sobre la contracción glomerular y de las células mesangiales: modulación por el péptido natriurético atrial

Tesis doctoral inédita leída el 9-5-1988 en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología y Terapeutic

Efecto de diversas hormonas vasoactivas sobre la contraccion glomerular y de las celulas mesangiales Modulacion por el peptido natriuretico atrial

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai