Regresión de un caso de linfosarcoma canino tras un tratamiento inmunoquimioterápico

Presentamos un caso clínico de un linfosarcoma multicéntrico en un perro y su evolución con un tratamiento inmunoquimioterápico, apreciándose una regresión del proceso tumoral al final del mismo.We have reported a case report about a multicentríc lymphosarcoma in a dog and its evolution with an immunochemotherapeutic protocol. We noticed a total regresion of the tumor at the end of the treatment

Endothelial damage, inflammation and immunity in chronic kidney disease

Chronic kidney disease (CKD) patients have an accelerated atherosclerosis, increased risk of thrombotic-ischemic complications, and excessive mortality rates when compared with the general population. There is also evidence of an endothelial damage in which the proinflammatory state, the enhanced oxidative stress, or the accumulation of toxins due to their reduced renal clearance in uremia play a role. Further, there is evidence that uremic endothelial cells are both involved in and victims of the activation of the innate immunity. Uremic endothelial cells produce danger associated molecular patterns (DAMPS), which by binding to specific pattern recognition receptors expressed in multiple cells, including endothelial cells, induce the expression of adhesion molecules, the production of proinflammatory cytokines and an enhanced production of reactive oxygen species in endothelial cells, which constitute a link between immunity and inflammation. The connection between endothelial damage, inflammation and defective immunity in uremia will be reviewed here

Allelic frequencies for SNP variants in the gene Nramp1 in bovine infected with Brucella abortus or classified by resistance to the pathogen

La resistencia natural a la brucelosis en bovinos ha sido asociada a factores genéticos, principalmente a algunos polimorfismos de nucleótido simple ubicados dentro del gen Nramp1. La presente investigación evalúa el efecto de variantes tipo polimorfismos de nucleótido simple presentes en regiones codificantes y en la región 3 UTR del gen Nramp1, en la clasificación de los animales como resistentes o susceptibles, además se determinan los genotipos predominantes en animales naturalmente infectados y comprobados como positivos por la presencia de anticuerpos anti Brucella abortus. Se establecieron las frecuencias genotípicas y alélicas para cinco polimorfismos de nucleótido simple identificados dentro del gen Nramp1 en animales de las razas blanco orejinegro (Bos taurus taurus) y cebú (Bos taurus indicus) y en muestras serológicamente positivas provenientes de animales cruzados (Bos taurus x Bos indicus). La determinación de genotipos se realizó mediante la metodología polimorfismo conformacional de cadena sencilla. Se realizó un ensayo de desafío infeccioso in vitro, para estimar la capacidad de los macrófagos bovinos para controlar la sobrevivencia bacterial, lo que permitió definir los individuos como resistentes o susceptibles. Los resultados sugieren una asociación significativa del SNP4 (p = 0,0506) con la variación para el fenotipo de susceptibilidad, pues se encontró el genotipo homocigoto (BB) en alta frecuencia en animales catalogados como resistentes y el genotipo heterocigoto (AB) en alta frecuencia en animales catalogados como susceptibles y en animales con títulos de anticuerpos anti Brucella abortus.;The natural resistance to brucellosis in cattle has been associated to genetic factors mainly to some single nucleotide polymorphism (SNP), located within Nramp1 gen. The current research has studied the effect of nucleotide variants to be found in coding regions and other one located in 3 non translated region of Nramp1 gene, on the animal classification as resistant or susceptible, moreover was identified the main genotypes to be found on the infected animals, confirmed as positives by antibody antibrucella titles. Was established the genotypic and allelic frequencies for five single nucleotide polymorphism in animals from blanco orejinegro (Bos taurus taurus) and zebu breeds (Bos taurus indicus) and serum samples belonging to positive crossbred animals (Bos taurus x Bos indicus). The genotype was defined by the methodology known as single strand conformational polymorphism . To estimate the macrophage capacity to control the bacterial survival, an in vitro assay was performed, which allowed define the phenotype as resistant or susceptible. The results suggest a significant association for SNP4 (p = 0.0506) with the phenotypic variation for resistant or susceptibility, because was found the genotype (BB) at higher frequency in susceptible animals and naturally infected animals, than those resistant animals.Ganado de leche-Ganadería lech

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever

Background Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. Methods Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. Results The incidence of NF among the groups was reduced (64%, 44%, and 24%; P2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). Conclusions G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.

Somatostatin receptor subtype 5 (SST5 ) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the [email protected] Study

Introduction: atherosclerosis, blood vessel disease, is the main cause of cardiovascular disease associated with aging; comprising modifiable risk factors that increase because of this when it exists.Objective: to evaluate atherogenic markers and metabolic syndrome in older adults, with cardiovascular risk living in urban areas, Pinar del Río province. Methods: observational, descriptive and cross-sectional study, from the service of Clinical Laboratory at Abel Santamaría Cuadrado Teaching General Hospital  Pinar del Río with 60 years old and older patients from the urban areas, during the period 2013 - 2014. The target group included 588 patients. The sample comprised 100 patients who have at least two risk factors previously established for this study.Results: ample predominance of women (61.0 %), the risk factors of higher incidence were hypertension 67 %, and sedentary lifestyle 65 %, followed by obesity 48 %, diabetes mellitus 40 % along with smoking habit 32 %, obese with increased diameters of waist circumference 48 %, and dyslipidemia 49 %, those with high glycemic values in fasting 50 % of the sample. It was considered that 63 % of the patients studied suffer from metabolic syndrome.Conclusions: a high number of white-skin women, the predominant risk factors were hypertension followed by sedentary lifestyle, obesity, diabetes mellitus and smoking habit. Approximately half of the sample was obese with increased diameters of the waist circumference, a large part suffered from dyslipidemia and half of them showed high fasting blood glucose levels. The prevalence of metabolic syndrome was detected.IIntroducción: aterosclerosis, enfermedad de los vasos sanguíneos, principal causa de enfermedad cardiovascular vinculada al envejecimiento, con factores de riesgo modificables que se incrementan cuando esta existe.Objetivo: evaluar marcadores aterogénicos y síndrome metabólico en adultos mayores, con riesgo cardiovascular residentes en zonas urbanas de la provincia Pinar del Río.Métodos: estudio observacional, descriptivo, transversal, servicio de Laboratorio Clínico Hospital General Docente “Abel Santamaría Cuadrado” Pinar del Río, pacientes de 60 años y más de zonas urbanas, durante período 2013 - 2014. Universo de 588 pacientes. Muestra de 100 pacientes que posean mínimo de dos factores de riesgo establecidos con anterioridad para este estudio.Resultados: amplio predominio de las mujeres (61 %). Factores de riesgo de mayor incidencia hipertensión arterial 67 %, y sedentarismo 65 %, seguidos por obesidad 48 %, diabetes mellitus 40 % y hábito de fumar 32 %, obesos con diámetros aumentados de la circunferencia de la cintura 48 %, presentaban dislipidemia 49 % y tenían elevados valores de glucemia en ayunas el 50 % de la muestra. Se consideró que 63 % de los pacientes estudiados presentaron síndrome metabólico.Conclusiones: elevado número de mujeres de piel blanca, con factor de riesgo predominante de hipertensión arterial seguido por sedentarismo, obesidad, diabetes mellitus y hábito de fumar. Alrededor de la mitad de la muestra fueron obesos con diámetros aumentados de la circunferencia de la cintura, gran parte presentaban dislipidemia y la mitad altos valores de glucemia en ayunas. Se detecta prevalencia de síndrome metabólico

Endocrinología celular y molecular

El correcto funcionamiento y homeostasis del organismo requieren un control de la secreción hormonal, cuyos defectos producen graves desórdenes endocrinos y metabólicos. Esta regulación mediada por la interacción hormona-receptor culmina en la modificación de la actividad celular, previa a la cual, se ven afectadas toda una serie de proteínas que participan en el control de la ruta de secreción regulada, facilitando el procesamiento, clasificación, tráfico intracelular y exocitosis de la hormona en cuestión. En relación al control de la secreción de la GH y a los factores reguladores de dicho proceso, se estudia el control de la secreción de la GH por la SRIF, así como su regulación por factores periféricos como la adiponectin

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

Background\ud In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.\ud \ud Methods\ud We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings.\ud \ud Results\ud Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls).\ud \ud Conclusions\ud Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases

Optimal ISW detection and joint likelihood for cosmological parameter estimation

We analyse the local variance effect in the standard method for detecting the integrated Sachs-Wolfe effect (ISW) via cross-correlating the cosmic microwave background (CMB) with the large-scale structure (LSS). Local variance is defined as the systematic noise in the ISW detection that originates in the realisation of the matter distribution in the observed Universe. We show that the local variance contributes about 11 per cent to the total variance in the standard method, if a perfect and complete LSS survey up to z ~ 2 is assumed. Due to local variance, the estimated detection significance and cosmological parameter constraints in the standard method are biased. In this work, we present an optimal method of how to reduce the local variance effect in the ISW detection by working conditional on the LSS-data. The variance of the optimal method, and hence the signal-to-noise ratio, depends on the actual realisation of the matter distribution in the observed Universe. We show that for an ideal galaxy survey, the average signal-to-noise ratio is enhanced by about 7 per cent in the optimal method, as compared to the standard method. Furthermore, in the optimal method there is no need to estimate the covariance matrix by Monte Carlo simulations as in the standard method, which saves time and increases the accuracy. Finally, we derive the correct joint likelihood function for cosmological parameters given CMB- and LSS-data within the linear LSS formation regime, which includes a small coupling of the two datasets due to the ISW effect.Comment: Proof added to appendix. Minor changes to text and formulae. Results and figures unchanged. Matches published MNRAS versio