Estudio anatomopatológico de aislados de Leptospira spp., provenientes de Nicaragua en Mesocricetus auratus como biomodelo

RESUMEN Objetivo. El objetivo de este trabajo fue caracterizar en el biomodelo Mesocricetus auratus la sintomatología y lesiones anatomopatológicas que provocan 5 aislados clínicos de Leptospira spp., provenientes de Nicaragua. Materiales y métodos. Con este fin se inocularon 50 hámster por vía i.p con 1mL del cultivo de cada una de las cepas en fase exponencial teniendo una concentración celular de 7.5 x 106 leptospira/mL (10 animales por cepa), evaluándose signos de la enfermedad, mortalidad durante 14 días, lesiones anatomopatológicas macroscópicas y microscópicas mediante tinción con hematoxilina-eosina y tinción de Warthyn Starryn. Resultados. Todas las cepas presentaron alta mortalidad, mostrando un cuadro tanto clínico, como lesional característico de la infección experimental. Además, causaron la muerte al 100% de los animales entre el tercer y décimo día postinfección. En el estudio anatomopatológico la cepa del serogrupo Ballum y la del serogrupo Pomona produjeron focos de hemorragias específicamente en el riñón y pulmones. De forma similar ocurrió una congestión hepática y renal, mientras que la hemorragia renal fue observada con mayor frecuencia en la cepa del serogrupo Pomona, diferenciándose del resto de las cepas que mostraron esta lesión con menos frecuencia. Conclusiones. Este trabajo permitió una mayor caracterización de estas cepas siendo utilizadas como futuras candidatas vacunales frente a una nueva epidemia de Leptospirosis en Nicaragua

"León Cuervo Rubio". Hospital y Médico. Reseña histórica para trabajadores y alumnos. Marzo 2007 / León Cuervo Rubio" Hospital and Doctors: Historical data for workers and students. March 2007

Partiendo de esta máxima y de la revolución actual en la educación que se lleva en Cuba para elevar a todos los niveles la cultura general integral, se defiende el criterio de que todo lo que se va a estudiar debe estar precedido por sus antecedentes históricos. Se planteó una investigación educacional de carácter histórico en el Hospital Clínico Quirúrgico "León Cuervo Rubio", realizada en el mes de septiembre de 2006 a inicios del curso escolar. Se emplearon métodos empíricos de investigación como: la encuesta, revisión documental y testimonios de familiares y amigos. El universo fue conformado por los 1200 trabajadores del hospital, seleccionados al azar y encuestados 700 para el 58.3%. Además 200 (57%) alumnos de Medicina de los años tercero, cuarto y quinto año del hospital, de un universo de 350. El universo de alumnos de Tecnología de la Salud del centro es de 100 alumnos, de los cuales fue encuestado el 100%. En la carrera de Enfermería, de 100 en Licenciatura fue encuestado el 100% de los alumnos, para una cifra total 1100 encuestados, conformándose la muestra de estudio. Se empleó el método estadístico porcentual y además se anexan testimonios históricos de la investigación al respecto. Los resultados fueron dirigidos a dar respuesta, mediante la confección de una reseña histórica, al problema del poco dominio de la historia de esta interesante personalidad pinareña. Palabras clave: ESTUDIANTES DE MEDICINA, RESEÑA HISTÓRICA, TRABAJADORES DE SALUD ABSTRACT Taking into consideration that every context to be understood needs to be preceded by its historical antecedents, an educational research having historical characteristics was conducted. The research took place at "León Cuervo Rubio" University hospital on September 2006 (at the beginning of the academic course), empiric methods of investigation were applied (inquiries, documental revisions and testimonies given by family and friends). The sample of the research was formed by 1200 workers at the hospital, 700 of them were enquired; 200 (57%) medical students enrolled on third, fourth and fifth academic years, 100 students from the Health Technology majors 8100% enquired), and 100 Nursing students 8100% enquired). The whole sample took 1100 people enquired. Percentage statistical method was used and historical testimonies were attached. Results were used to make a historical description of this interesting history in Pinar del Río. Key words: Medical Students, Historic Review, Health Workers

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Increased hippocampal accumulation of autophagosomes predicts short-term recognition memory impairment in aged mice

Constitutive macroautophagy involved in the turnover of defective long-lived proteins and organelles is crucial for neuronal homeostasis. We hypothesized that macroautophagic dysregulation in selective brain regions was associated with memory impairment in aged mice. We used the single-trial object recognition test to measure short-term memory in 18 aged mice compared to 22 young mice and employed immunohistochemistry to assess cellular distribution of proteins involved in the selective degradation of ubiquitinated proteins via macroautophagy. Values of the discrimination ratio (DR, a measure of short-term recognition memory performance) in aged mice were significantly lower than those in young mice (median, 0.54 vs. 0.67; p = 0.005, U test). Almost exclusively in aged mice, there were clusters of puncta immunoreactive for microtubule-associated protein 1 light chain 3 (LC3), ubiquitin- and LC3-binding protein p62, and ubiquitin in neuronal processes predominantly in the hippocampal formation, olfactory bulb/tubercle, and cerebellar cortex. The hippocampal burden of clustered puncta immunoreactive for LC3 and p62 exhibited inverse linear correlations with DR in aged mice (ρ = −0.48 and −0.55, p = 0.044 and 0.018, respectively, Spearman’s rank correlation). These findings suggest that increased accumulation of autophagosomes within neuronal processes in selective brain regions is characteristic of aging. The dysregulation of macroautophagy can adversely affect the turnover of aggregate-prone proteins and defective organelles, which may contribute to memory impairment in aged mice

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.This is the published version of the manuscript. It is available online from NPG in Cell Death and Differentiaiton here: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2014151a.html

Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase

Introduction Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. Objective Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. Methods Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. Results There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). Conclusion Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid

Data mining of high density genomic variant data for prediction of Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>The discovery of genetic associations is an important factor in the understanding of human illness to derive disease pathways. Identifying multiple interacting genetic mutations associated with disease remains challenging in studying the etiology of complex diseases. And although recently new single nucleotide polymorphisms (SNPs) at genes implicated in immune response, cholesterol/lipid metabolism, and cell membrane processes have been confirmed by genome-wide association studies (GWAS) to be associated with late-onset Alzheimer's disease (LOAD), a percentage of AD heritability continues to be unexplained. We try to find other genetic variants that may influence LOAD risk utilizing data mining methods.</p> <p>Methods</p> <p>Two different approaches were devised to select SNPs associated with LOAD in a publicly available GWAS data set consisting of three cohorts. In both approaches, single-locus analysis (logistic regression) was conducted to filter the data with a less conservative p-value than the Bonferroni threshold; this resulted in a subset of SNPs used next in multi-locus analysis (random forest (RF)). In the second approach, we took into account prior biological knowledge, and performed sample stratification and linkage disequilibrium (LD) in addition to logistic regression analysis to preselect loci to input into the RF classifier construction step.</p> <p>Results</p> <p>The first approach gave 199 SNPs mostly associated with genes in calcium signaling, cell adhesion, endocytosis, immune response, and synaptic function. These SNPs together with <it>APOE and GAB2 </it>SNPs formed a predictive subset for LOAD status with an average error of 9.8% using 10-fold cross validation (CV) in RF modeling. Nineteen variants in LD with <it>ST5, TRPC1, ATG10, ANO3, NDUFA12, and NISCH </it>respectively, genes linked directly or indirectly with neurobiology, were identified with the second approach. These variants were part of a model that included <it>APOE </it>and <it>GAB2 </it>SNPs to predict LOAD risk which produced a 10-fold CV average error of 17.5% in the classification modeling.</p> <p>Conclusions</p> <p>With the two proposed approaches, we identified a large subset of SNPs in genes mostly clustered around specific pathways/functions and a smaller set of SNPs, within or in proximity to five genes not previously reported, that may be relevant for the prediction/understanding of AD.</p

Ih Current Is Necessary to Maintain Normal Dopamine Fluctuations and Sleep Consolidation in Drosophila

HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep∶activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest∶activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels

Cuban scientific production in Medicine and Public Health: Scopus 2003-2011

El objetivo de este trabajo fue analizar la evolución del volumen y la visibilidad de la producción científica cubana en Salud Pública y en Medicina para determinar si siguen los mismos patrones de comunicación, y recomendar buenas prácticas de publicación. Se aplicaron indicadores bibliométricos de volumen, visibilidad y colaboración extraídos del portal SCImago Institutions Rankings a partir de datos de Scopus, para el área temática Medicine y la categoría Public Health, Environmental and Occupational Health, período 2003-2011. Cuba tiene una posición relativamente alta en los rankings de volumen de producción científica tanto en Medicina como en Salud Pública en los contextos internacionales y regionales, mientras que en impacto está entre los últimos países. La tendencia de la producción es al crecimiento, aunque en Salud Pública es más acelerado. El liderazgo es alto, pero la colaboración internacional está por debajo de lo esperado. La publicación en revistas de alto impacto (primer cuartil) y los artículos en el 10% más citado (excelencia) son escasos. Se concluye que el volumen y el impacto de la publicación no están acorde al potencial científico de salud cubana. Se recomienda incrementar la colaboración científica, la publicación de artículos en revistas de alto impacto, la preparación de los recursos humanos y seguir las recomendaciones internacionales sobre las buenas prácticas de edición y publicación científica.The aim of this study was to analyze the evolution of the quantity and visibility of Cuban scientific production in Public Health and Medicine to determine if they follow the same patterns of scientific communication and the recommended best practices for publication. Bibliometric indicators of quantity, visibility and cooperation were extracted from the SCImago Institutions Rankings website, which is based on Scopus data, in the field of Medicine and category of Public Health, Environmental and Occupational Health from 2003 to 2011.Cubahas a relatively high position in the rankings of scientific production in both Medicine and Public Health within the international and regional contexts, but its impact is ranked among the last countries. The production trend of both fields has increased, but public health is increasing faster. Leadership is high, but international collaboration is below expectations. Publication in high impact journals (first quartile) and articles in the set 10% most cited documents (excellence) are scarce. Thus, it may be concluded that the volume and impact of publication are not in accordance with the scientific potential of Cuban health. We recommend increasing scientific cooperation, publishing articles in high impact journals, training human resources and following the international recommendations for good editorial and scientific publication practices