Incidencia de la enfermedad renal en pacientes diabéticos que consultan en Unidades Comunitarias de Salud Familiar en el municipio de Apastepeque, departamento de San Vicente, en el periodo de enero a abril de 2021

El presente informe indaga sobre de la incidencia de la enfermedad renal en pacientes diabéticos que consultan en las Unidades Comunitarias de Salud Familiar Básicas (UCSFB) que tienen como cede la Unidad Comunitaria de Salud Familiar Intermedia (UCSFI) Apastepeque, en el municipio de Apastepeque del departamento de San Vicente en el periodo de enero a abril de 2021. Con el propósito de conocer la estatificación y determinar el grado de daño renal en el que se encuentran los pacientes diabéticos, que contribuye a tener una apreciación más certera del sistema de morbimortalidad del país de esta enfermedad en el municipio de San Vicente, la información se recopiló mediante la lectura de Expedientes clínicos en la plataforma SIAP (Sistema Integrado de Atención a Pacientes) de las unidades comunitarias de salud familiar del municipio de Apastepeque, departamento de San Vicente, donde se encontraron la incidencia de enfermedad renal por edades, sexo, UCSF y el grado de función renal según la Tasa de Filtrado Glomerular (TFG) y albumina/creatinina, en el periodo de tiempo señalado para este trabajo de grado, el tipo de estudio es descriptivo, retrospectivo, de corte transversal y documental. Se comprobó que las UCSF con mayor incidencia de la enfermedad renal en pacientes diabéticos en el periodo de enero a abril de 2021 fueron: Apastepeque con un 43%, San Jacinto con un 20%, San Pedro con un 15%, San Felipe con un 9% y San Nicolás con un 8%. También se relacionaron los rangos de edades que presentan mayor incidencia de la enfermedad renal en pacientes diabéticos está entre los mayores de 60 años con un 41%, seguido por la población de entre 59 años con un 26%; mientras que en la variable sexo las mujeres fueron las más afectadas con un 83% y los hombres con un 17%. También se concluyó que podría deberse a que la población femenina tiene más riesgo en la juventud debido a la incidencia de los trastornos de la conducta alimentaria y de ánimo; en la edad fértil, embarazo; y en la edad madura, por la menopausia, por lo cual esta afectadas por la obesidad en todas las etapas de la vida. Además, las mujeres acuden con más frecuencia a las consultas de atención primaria. Por eso se recomienda que acudanii a consulta con su médico o a sitios de salud de primera atención, para una detección temprana. También realizar cambios en los hábitos diarios para que éstos sean saludables, como puede ser una alimentación balanceada, realizar ejercicio de forma regular, bajar de peso, suspender consumo de alcohol y tabaco

Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene

Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats.

Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress

<i>In vitro</i> (A) and <i>in vivo</i> (C) analyses of DNA methylation at the reelin gene promoter region in samples from control and stress groups.

<p>Genomic DNA obtained from both groups was cleaved with DNA methylation sensitive restriction enzyme HpaII and then amplified by conventional PCR using specific primers against a reelin promoter region containing an HpaII site (-786/-625). Undigested genomic DNA is included as amplification control in all PCR reactions. Efficient digestion of DNA samples using the HpaII enzyme was controlled by analyzing a region devoid of DNA methylation at the Ric-8B gene promoter containing several HpaII cleavage sites (digestion control). A region of the Runx2 gene promoter lacking HpaII sites was selected to show equal sample loading in each lane of the gels. Digestion with the isoschizomer restriction enzyme MspI (DNA methylation insensitive) was also performed to control for efficient cleavage at the reelin promoter sequence analyzed (Data not shown). DNA methylation differences between control and stress rats groups measured <i>in vivo</i> (<b>B</b>) and <i>in vitro</i> (<b>D</b>) were quantified by determining changes in pixel density at the bands amplified by PCR and visualized through conventional DNA electrophoresis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0117680#sec002" target="_blank">methods</a>). (<b>E</b>), diagram depicting the selected upstream promoter region with its putative methylation sites. The reelin promoter has several transcription site starts over the CpG island. Upstream the promoter is the HpaII/MspI restriction site that was selected for our analyses. Values are expressed as relative ratios between PCR amplifications of the reelin promoter sequence after digestion with HpaII over the amplifications of the Runx2 control promoter sequence (loading control). Values represent a mean ± SEM. N = 3 per group. *p<0.05.</p

Experimental design and reference map.

<p><b>A</b>, Experimental protocol of prenatal restraint stress. <b>B</b>, Map of neuronal quantification. The frontal (A), parietal (B), and caudal (C) cortical levels were subdivided in a medial (red square; 1), dorsal (blue square; 2) and dorsolateral (green square; 3) tiers. E = embryonic days; P = postnatal days.</p

Validation of stress in the pregnant rat.

<p><b>A</b>, The average adrenal gland weights were higher in stressed dams with respect to controls. <b>B</b>, analogously, in stressed rats the average body weight gain was 22.8% less than in controls. Values are mean ± SEM, n = 7 rats per group.</p

Primers used in each condition.

<p>Primers used in each condition.</p

Prenatal stress induces global decrease of reelin expressing neurons density in the prenatal (E20) rat brain (Left side) and no changes of NeuN neurons density (Right side).

<p>Immunohistochemistry results: All graphs show the immunoreactive neurons expressed in neurons/mm3. Opens bars represent control group and filled bars represent stress group. <b>A</b>, <b>B</b> and <b>C</b>, show the results of frontal, parietal and retrosplenial cortex respectively. Values are mean ± SEM, n = 7–10 rats per group (reelin analysis) and n = 3 rats per group (NeuN analysis).</p

<i>In vivo</i> (A) and <i>in vitro</i> (B) expression of Reelin and downstream elements in control and stress conditions analyzed by Western Blot.

<p>The left side of the panel shows the result of density pixel quantification, the right side shows a representative example of each protein expression. Expression levels observed <i>in vivo</i> are maintained after 5 DIV. Values are mean ± SEM. n = 8–12 per group at <i>in vivo</i> experiments, n = 3 per group at <i>in vitro</i> experiment. (<b>c</b>) Cdk5 kinase activity measured from protein extract from brain cortex of control (n = 5) and stressed (n = 4) rats. All data are presented as the mean and SEM. * p < 0.05.</p