Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases

<p>Abstract</p> <p>Background</p> <p>Selenoprotein S (SelS) protects the functional integrity of the endoplasmic reticulum against the deleterious effects of metabolic stress. <it>SEPS1/SelS </it>polymorphisms have been involved in the increased release of pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in macrophages. We aimed at investigating the role of the <it>SEPS1 </it>variants previously associated with higher plasma levels of these cytokines and of the <it>SEPS1 </it>haplotypes in the susceptibility to develop immune-mediated diseases characterized by an inflammatory component.</p> <p>Results</p> <p>Six polymorphisms distributed through the <it>SEPS1 </it>gene (rs11327127, rs28665122, rs4965814, rs12917258, rs4965373 and rs2101171) were genotyped in more than two thousand patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases and 550 healthy controls included in the case-control study.</p> <p>Conclusion</p> <p>Lack of association of <it>SEPS1 </it>polymorphisms or haplotypes precludes a major role of this gene increasing predisposition to these inflammatory diseases.</p

Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer

BACKGROUND: Brain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions. MATERIALS AND METHODS: At a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period. RESULTS: A total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1–14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%. CONCLUSION: In patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations

Geología y geodinámica en la quebrada Qenqo: aluviones que afectaron Zurite-Cusco (2010)

En la quebrada Qenqo del distrito de Zurite, provincia de Anta, departamento del Cusco; el día 28 de enero del 2010 ocurrió un fenómeno geodinámico de movimientos en masa. En efecto, en la parte alta del cerro Llamacancha la reactivación de un deslizamiento de tipo rotacional, originó una serie de flujos de detritos que descendieron por la quebrada Qenqo, los cuales continuaron los días 6 y 13 de febrero, pero cada uno de los cuales tuvo distintas intensidades. Estos fenómenos produjeron múltiples daños y afectó a gran parte de la población de Zurite, ya que destruyó viviendas, terrenos de cultivo e infraestructura urbana, tales como puentes, vías asfaltadas, postes, canales, etc. El documento presenta el diagnóstico y evaluación de este fenómeno, identificando las causas que lo originaron y propone algunas recomendaciones

Susceptibility to type 1 diabetes conferred by the PTPN22 C1858T polymorphism in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The protein tyrosine phosphatase N22 gene (<it>PTPN22</it>) encodes a lymphoid-specific phosphatase (LYP) which is an important downregulator of T cell activation. A <it>PTPN22 </it>polymorphism, C1858T, was found associated with type 1 diabetes (T1D) in different Caucasian populations. In this study, we aimed at confirming the role of this variant in T1D predisposition in the Spanish population.</p> <p>Methods</p> <p>A case-control was performed with 316 Spanish white T1D patients consecutively recruited and 554 healthy controls, all of them from the Madrid area. The <it>PTPN22 </it>C1858T SNP was genotyped in both patients and controls using a TaqMan Assay in a 7900 HT Fast Real-Time PCR System.</p> <p>Results</p> <p>We replicated for the first time in a Spanish population the association of the 1858T allele with an increased risk for developing T1D [carriers of allele T vs. CC: OR (95%) = 1.73 (1.17–2.54); p = 0.004]. Furthermore, this allele showed a significant association in female patients with diabetes onset before age 16 years [carriers of allele T vs. CC: OR (95%) = 2.95 (1.45–6.01), female patients vs female controls p = 0.0009]. No other association in specific subgroups stratified for gender, HLA susceptibility or age at onset were observed.</p> <p>Conclusion</p> <p>Our results provide evidence that the <it>PTPN22 </it>1858T allele is a T1D susceptibility factor also in the Spanish population and it might play a different role in susceptibility to T1D according to gender in early-onset T1D patients.</p

Evidence for the association of the SLC22A4 and SLC22A5 genes with Type 1 Diabetes: a case control study

BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (χ(2 )= 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41–0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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