En reconocimiento a la labor de los revisores. ¿Cómo podemos mejorar? / Recognizing the reviewer's contribution. How can we improve?

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Genetics of type 1 diabetes: recent progress and future perspectives

Type 1 diabetes (T1D) is a chronic immune-mediated disease, characterisedby a selective loss of insulin-producing b-cells in the pancreaticislets. Susceptibility is determined by interactions of multiple genes withunknown environmental factors. Around 50% of the genetic risk of thedisease is explained by HLA, although other genes with a smaller effectare also involved. Most of the known risk genes for T1D play a role inimmunity, mostly through T-cell regulation (CTLA4, PTPN22, IL-2RA)and cytokine production or modulation (VDR, SUMO4). The insulin gene(INS) represents and exception to this, and is probably the only genespecifi cally associated with T1D and not with other autoimmune diseases.Ongoing genome-wide association studies are providing evidenceof multiple known and previously unknown risk genes. New analyticaltools are continuously being developed to handle the vastamounts of data produced, as well as to account for multiple comparisonsand assess combined effects such as gene-gene and gene-environmentinteractions. In this review, we will give an overview of the mostimportant genes identifi ed to date, analyse the genetic evidence supportingthem as T1D susceptibility genes and discuss the mechanismsmediating their contribution to the pathogenesis of the disease(AU)

Dislipemia diabética: nuevas evidencias para un correcto enfoque diagnóstico / Diabetic dyslipidaemia: new evidences for a correct diagnostic approach

La dislipemia diabética hace referencia a las alteraciones lipídicas características de los pacientes con diabetes tipo 2. Se define por la presencia de colesterol LDL (cLDL) normal o levemente aumentado, la tríada aterogénica que incluye hipertrigliceridemia moderada, colesterol HDL bajo (cHDL) y predominio de partículas LDL pequeñas y densas (fenotipo B de las LDL), y también un aumento del número de partículas aterogénicas (de densidad muy baja [VLDL], intermedia [IDL] y baja [LDL]), que se refleja en un aumento en las concentraciones de apolipoproteína B (hiperapoB) y del colesterol no HDL. La dislipemia diabética es uno de los principales factores de riesgo que contribuyen al aumento del riesgo cardiovascular en los pacientes con diabetes mellitus tipo 2 y, por tanto, requiere de una evaluación precisa para establecer objetivos terapéuticos adecuados y seleccionar el tratamiento más apropiado. La evaluación inicial de la dislipemia diabética incluye la cuantificación de los triglicéridos, cHDL y LDL, descartar otras causas de dislipemia secundaria y las dislipemias familiares, en especial cuando los niveles de cLDL son >160 mg/dL (4,43 mmol/L). Si la concentración de triglicéridos excede los 150 mg/dL (1,7 mmol/L), puede existir una abundancia anormal de partículas LDL pequeñas y densas. En este contexto, la determinación de apolipoproteína B y el cálculo del colesterol no HDL permitirá obtener una estimación del número de partículas aterogénicas circulantes

Diabetic dyslipidaemia is defined as the lipid abnormalities typically found in patients with type 2 diabetes. These include normal or slightly increased LDL-cholesterol, the so-called atherogenic triad which contains moderate hypertriglyceridaemia, low HDL-cholesterol and a predominance of small dense LDL particles (also known as phenotype B) and an increase in the number of atherogenic particles (VLDL, IDL and LDL), displayed as high apolipoprotein B and non-HDL-cholesterol concentrations. Diabetic dyslipidaemia is one of the major risk factors which contribute to the increased cardiovascular risk of type 2 diabetic patients. Therefore, it is highly relevant to properly assess its components and establish optimal therapeutic goals and interventions. The initial evaluation of diabetic dyslipidaemia includes triglycerids, HDL-cholesterol and HDL-cholesterol levels determination, and the exclusion of other causes of secondary dyslipidaemia or familial hyperlipidaemia, especially when LDL cholesterol concentrations exceed 160 mg/dl (4.43 mmol/l). If triglycerid concentrations exceed 150 mg/dl (1.7 mmol/l), there is an elevated risk for the presence of an abnormally high proportion of small, dense LDL particles. In this context, the measurement of apolipoprotein B and the determination of non-HDL cholesterol concentrations can be especially useful in assessing the number of circulating atherogenic particles

Dislipemia diabética: evaluación y tratamiento / Diabetic dyslipemy: assessment and treatment

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Red Europea de Genética de la Diabetes Tipo 1 / European Type 1 Diabetes genetics network

Incluso los estudios genéticos más amplios realizados hasta el momento tienen un poder estadístico insuficiente para detectar genes que confieren un riesgo (o protección) moderado de desarrollar una diabetes tipo 1.Para solventar esta limitación, se ha establecido el Consorcio Internacional de Genética de la Diabetes Tipo 1 (T1DGC), cuyo objetivo es reclutar a 2.800 parejas de hermanos con diabetes tipo 1 en todo el mundo. La Red Europea de Genética de la Diabetes Tipo 1 está formada por más de 100 centros de 28 países, 6 de ellos españoles, que colaboran con el fin de estudiar la genética y la patogenia de la diabetes tipo 1.Como parte del Consorcio Internacional, el primer objetivo de la Red Europea es incluir a 1.200 familias con, al menos, 2 hermanos con diabetes tipo 1 diagnosticada antes de los 35 años de edad, aunque el fin último es conseguir una colaboración más estrecha entre los países europeos participantes, con transferencia de conocimientos de unos centros a otros e intercambio de recursos. Aunque la participación española es significativa, aún existen muchos centros que podrían hacer una buena aportación a este proyecto y obtener los beneficios de una colaboración internacional de estas características. La participación sigue abierta y la inclusión de pacientes continuará hasta diciembre de 2006 (AU)

Previous studies searching for genesassociated with type 1 diabetes have been limited by sample size. To identify genesassociated with a moderate risk of developing the disease (or conferring protection against it), the Type 1 Diabetes Genetics Consortium (T1DGC) has been established with the aim of recruiting 2800sib-pair families around the world. The European Type 1 Diabetes Genetics Network (ET1DGN) is a collaborative venture that involves more than 100European centers, including six from Spain, whose aim is to study the genetics and pathogenesis of type 1 diabetes. As part of the T1DGC, its main objective is to recruit 1200 families in which at least two siblings have type 1 diabetes diagnosed before the age of 35. The ultimate goal is to promote further and closer collaboration between the European centres involved, which will include transferring knowledge from some centers to others and sharing resources. Although there is already a significant level of participation in Spain, there are still many centers that could contribute to the aims of this project, aswell as enjoy the benefits of taking part in an international endeavor of this kind. Participation is still open, and family recruitment will continue until December2006 (AU)

Dislipidemia diabética: significación clínica y actitud terapéutica / Diabetic dyslipidemia: clinical signification and therapeutic attitude

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The role of the alternative oxidase in stabilizing the in vivo reduction state of the ubiquinone pool and the activation state of the alternative oxidase

A possible function for the alternative (nonphosphorylating) pathway is to stabilize the reduction state of the ubiquinone pool (Qr/Qt), thereby avoiding an increase in free radical production. If the Qr/Qt were stabilized by the alternative pathway, then Qr/Qt should be less stable when the alternative pathway is blocked. Qr/Qt increased when we exposed roots of Poa annua (L.) to increasing concentrations of KCN (an inhibitor of the cytochrome pathway). However, when salicylhydroxamic acid, an inhibitor of the alternative pathway, was added at the same time, Qr/Qt increased significantly more. Therefore, we conclude that the alternative pathway stabilizes Qr/Qt. Salicylhydroxamic acid increasingly inhibited respiration with increasing concentrations of KCN. In the experiments described here the alternative oxidase protein was invariably in its reduced (high-activity) state. Therefore, changes in the reduction state of the alternative oxidase cannot account for an increase in activity of the alternative pathway upon titration with KCN. The pyruvate concentration in intact roots increased only after the alternative pathway was blocked or the cytochrome pathway was severely inhibited. The significance of the pyruvate concentration and Qr/Qt on the activity of the alternative pathway in intact roots is discussed.

In vivo ubiquinone reduction levels during thermogenesis in araceae

In vivo ubiquinone (UQ) reduction levels were measured during the development of the inflorescences of Arum maculatum and Amorphophallus krausei. Thermogenesis in A. maculatum spadices appeared not to be confined to a single developmental stage, but occurred during various stages. The UQ pool in both A. maculatum and A. krausei appendices was approximately 90% reduced during thermogenesis. Respiratory characteristics of isolated appendix mitochondria did not change in the period around thermogenesis. Apparently, synthesis of the required enzyme capacity is regulated via a coarse control upon which a fine control of metabolism that regulates the onset of thermogenesis is imposed.