Systematic Review of the Serotonergic System in the Pathophysiology of Severe Dengue: The Theory of Thrombocytopenia and Vascular Extravasation.

BACKGROUND: Severe dengue is characterized by thrombocytopenia, hemorrhaging, and/or capillary extravasation and may be linked to a reduced plasma concentration of serotonin (5-hydroxytriptamine, or 5-HT). OBJECTIVE: The aim of the current contribution was to conduct a systematic bibliographic review of reports on the role of the peripheral serotonergic system in the pathophysiology of severe dengue. METHODS: A bibliographic review was carried out of in vivo/in vitro models, clinical trials, and case series studies from 2010-2019. The selective criteria were the use of treatments with serotonin reuptake inhibitors and/or agonists/antagonists of 5-HT receptors and their impact on inflammation, coagulation, and endothelium. Moreover, cross-sectional and cohort studies on the relationship between intraplatelet and plasma 5-HT levels in patients with dengue were also included. The risk of bias in the selected reports was examined with domain-based assessment utilizing Cochrane-type criteria. The main results are summarized in Tables and Figures. RESULTS: Based on descriptions of the effect of serotonergic drugs on 5-HT levels and the findings of clinical trials of dengue treatment, most receptors of the peripheral serotonergic system, and especially 5-HT2A, seem to participate in regulating serum 5-HT during severe dengue. Therefore, the peripheral serotonergic system probably contributes to thrombocytopenia and capillary extravasation. CONCLUSION: Regarding dengue, 5-HT may be a key parameter for predicting severity, and an understanding of 5-HT-related mechanisms could possibly facilitate the development of new therapies. These proposals require further research due to the limited number of publications on the role of serotonergic receptors at the peripheral level.

Comparative analysis of anthropometric indicators for diagnosing obesity and predicting cardiometabolic risk in Mexican adolescents.

Introduction: Introduction: obesity is a cardiometabolic risk (CMR) factor in adolescents. It represents a public health problem that requires simple diagnostic strategies based on the determination of anthropometric indicators (AIs) such as body mass index (BMI), waist circumference (WC), conicity index (CONI), waist-to-height ratio (WHtR), and body fat percentage (BFP). The purpose of the current contribution was to analyze the utility of the aforementioned AIs for evaluating obesity as a CMR factor in Mexican adolescents. Materials and methods: the design of the study is descriptive and cross-sectional. Nutritional status was established by using various AIs and as a CMR factor under the criteria of WHtR. Participating in the present investigation were 2,000 adolescents from 15 to 17 years of age, of which 1,079 (53.9 %) were female and 921 (46.1 %) were male. All were high school students in Tuxtla Gutiérrez, Chiapas, Mexico. Results and conclusion: the prevalence of obesity was influenced by gender. With the WHtR and BFP, male students exhibited a greater prevalence of obesity, while with the BMI and CONI, the percentage of obesity was similar between the two genders. BMI was significantly correlated with BFP, WC and WHtR, and was one of the AIs with the greatest area under the curve, showing a good capacity to predict cardiometabolic risk. BMI is a simple and adequate tool for diagnosing obesity and predicting CMR in adolescents.

Introducción: Introducción: la obesidad es un factor de riesgo cardiometabolico (RCM) en los adolescentes y representa un problema de salud pública que requiere estrategias diagnosticas sencillas, basadas en la determinación de indicadores antropométricos (IA) como el índice de masa corporal (IMC), la circunferencia de la cintura (CC), el índice de conicidad (ICONI), el índice de cintura-talla (ICT) y el porcentaje de grasa corporal (PGC). El propósito del presente estudio fue analizar la utilidad de diversos IA (IMC, CC, ICONI, ICT y PGC) para evaluar la obesidad como factor de RCM en adolescentes mexicanos. Materiales y métodos: el diseño del estudio fue descriptivo y transversal. Se analizó el estado nutricional mediante varios IA y el factor de RCM bajo los criterios del ICT. Este estudio fue conducido en 2000 adolescentes de entre 15 y 17 años, de los cuales 1079 (53,9 %) eran mujeres y 921 (46,1 %) varones, todos ellos estudiantes de nivel medio superior de Tuxtla Gutiérrez, Chiapas, México. Resultados y conclusión: la prevalencia de la obesidad estuvo influenciada por el género: los varones presentaron una mayor prevalencia de obesidad con ICT y PGC, mientras que con IMC e ICONI, el porcentaje de obesidad fue similar entre ambos géneros. El IMC se correlacionó significativamente con el PGC, la CC y el ICT, y fue uno de los IA con mayor área bajo la curva, mostrando una buena capacidad para predecir el RCM. El IMC representa una herramienta sencilla y adecuada para el diagnóstico de obesidad y predecir el RCM en adolescentes.

Impact of Exposure to Environmental Enrichment on the Anxiety-Like Behavior of Ovariectomized Mice.

Objective: The aim of this study was to explore the influence of short-term (2-week) exposure to social (SE) and/or physical enrichment (PE) on the anxiety-like behavior of ovariectomized (OVX) NIH Swiss mice. Method : One week after surgery, each OVX mouse was housed under one of 4 social conditions: (1) isolated, (2) accompanied by an intact female, (3) accompanied by an intact male, or (4) in a community of 10 OVX individuals. The animals in each of these environments were divided into 2 subgroups, consisting of the presence and absence of PE. Following a 2-week exposure to the respective conditions, each OVX mouse was subjected to either the light/dark exploration test (LDT) or the elevated plus maze (EPM) to examine anxiety-like behavior. Results: The LDT and EPM showed very similar patterns. Compared to an impoverished environment, PE elicited a significant anxiolytic effect for OVX mice housed alone or in companion of an intact female (F [1, 54] = 16.11, P = 0.001). By contrast, mice living in community but without PE displayed anxiogenic-like behavior, perhaps due to crowding, compared to the animals living in isolation (F [1, 36] = 5.64, P = 0.023). Conclusion: This study emphasized the importance of taking housing conditions into account during the screening of new anxiolytic agents and the critical role of OVX in the regulation of anxiety.

Effect of ketamine administration, alone and in combination with E-6837, on climbing behavior.

Some types of schizophrenia have been associated with repetitive movements lacking specific purpose, also known as stereotyped behavior. Dopamine agonists (D2) and noncompetitive N-methyl-D-aspartate receptor antagonists (e.g. ketamine) have been administered in rodent models to induce stereotyped behavior that resembles some motor symptoms of schizophrenia. Recently, a relationship has been found between 5-HT6 receptors (5-HT6Rs) and dopaminergic activity. The present study evaluates the effect of ketamine (5 and 10 mg/kg), alone and in combination with the 5-HT6R agonist E-6837, on the climbing behavior of male mice. Ketamine was administered with an acute (1 day) and subchronic (5 day) scheme. Later, these doses and schemes were combined with an acute scheme of E-6837 (5 and 10 mg/kg). With both the acute and the subchronic schemes, ketamine increased climbing behavior at a dose of 10 mg/kg, and this effect was reversed by E-6837 (at 5 and 10 mg/kg). The present results suggest that there is an interaction between N-methyl-D-aspartate and 5-HT6 receptors in the regulation of climbing behavior. Further research is necessary to provide more evidence on this interaction.

Interacción de los receptores NMDA - 5-HT6 en la investigación preclínica de las alteraciones cognitivas relacionadas con la esquizofrenia / Interaction of nmda AND 5-HT6 receptors in the preclinical investigation of schizophrenia-related cognitive changes

Diversos antagonistas del receptor N-metil-D-aspartato (RNMDA) como la fenciclidina o la ketamina estudiados en roedores han permitido inducir alteraciones cognitivas similares a las observadas en la esquizofrenia. Casualmente, uno de los receptores a serotonina, el 5-HT6, ha cobrado interés en la búsqueda de nuevos fármacos con propiedades procognitivas. Con la finalidad de comprender mejor la interacción de ambos receptores (NMDA y 5-HT6) en la regulación cognitiva se realizó una revisión exhaustiva en la literatura. Varios estudios con esquemas agudos o subcrónicos de los antagonistas NMDA en roedores fueron evaluados en distintas pruebas, en donde se encontró deterioro cognitivo. Fue común que el esquema agudo de diversos fármacos serotoninérgicos 5-HT6 revirtiera el deterioro cognitivo inducido por la administración previa de los antagonistas del RNMDA. Por el contrario y sorprendentemente, la inyección aguda y combinada tanto de los antagonistas NMDA como de los fármacos serotoninérgicos 5-HT6 lograron fortalecer la memoria. El esquema subcrónico de los antagonistas NMDA representa el modelo más integrador para el estudio de las alteraciones cognitivas asociadas a la esquizofrenia. Aunque el deterioro y el efecto procognitivo mediados por estos receptores pudieran ser explicados mediante la regulación conjunta que ejercen ambos receptores sobre la liberación de distintos neurotransmisores como el glutamato, es una situación compleja que se requiere continuar investigando para fundamentar mejor estas ideas (AU)

Diverse antagonists of the NMDA receptor studied in rodents, such as phencyclidine or ketamine, have enabled researchers to induce cognitive changes similar to those found in schizophrenia. Interestingly, one of the serotonin receptors, 5-HT6, has attracted much attention for the development of new drugs with pro-cognitive properties. With the aim of better understanding the interaction of both NMDA and 5-HT6 in cognitive regulation, an exhaustive review of the literature was carried out. Various studies have found cognitive impairment, evaluated in rodents using different tests, after applying acute or sub-chronic schemes of NMDA antagonists. An acute scheme of applying different serotogenic 5-HT6 receptors has often reversed the cognitive impairment induced by the previous administration of NMDA antagonists. Surprisingly, an acute injection of a combination of suboptimal doses of NMDA and 5-HT6 antagonists resulted in strengthening memory. The sub-chronic scheme of NMDA antagonists represents the most reliable model for the study of cognitive changes associated with schizophrenia. Cognitive impairment, as well as a pro-cognitive effect mediated by NMDA and 5-HT6, may be explained by a joint regulation of these receptors to modulate the release of distinct neurotransmitters, such as glutamate. This represents a complex interaction that requires ongoing research to clarify the mechanisms at play (AU)