Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; <EDGPIPP) from Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells. Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H2O2-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H2O2-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H2O2-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-NΩ-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.(AU)

Neuropéptidos en el encéfalo humano / Neuropeptides in the human brain

Resumen: los estudios en el encéfalo humano se han realizado con el fin de responder a varias preguntas de carácter científico relacionados con la neuroanatomía, neurofisiología, neurofarmacología,la neurología y la conducta. El encéfalo es el órgano en el que se encuentra la regulación de los reflejos y los mecanismos inconscientes como la transmisión del dolor, los cardiovasculares, los respiratorios, entre otros. Estos mecanismos están mediados por sustancias químicas tales como los neuropéptidos, que son cadenas cortas de aminoácidos que se han encontrado ampliamente distribuidos en el sistema nervioso central y periférico, además de ejercer acciones fisiológicas actuando como neurotransmisores, neuromoduladores (acciones paracrinas y autocrinas) y neurohormonas.En los últimos treinta años se ha incrementado el conocimiento sobre la distribución y función de los neuropéptidos en el sistema nervioso central de mamíferos (ratas, gatos, perros, alpacas, primates y humanos). Así, el objetivo de esta revisión se dirige a describir los datos más relevantes disponibles sobre los neuropéptidos en el encéfalo humano. Para ello se revisan aspectosimportantes de los neuropéptidos en el encéfalo humano como: a) La distribución, b) Las relaciones anatómicas, c) Las funciones fisiológicas, d) La coexistencia, y e) Las investigaciones futuras a realizar.

Abstract: the human brain has been used in laboratory as an experimental model in order to answer several scientific questions related to neuroanatomy, neurophysiology, neuropharmacology, neurology and behavior. The brain is the organ in which the regulation of reflexes and ®unconscious¼ mechanisms(transmission of pain, cardiovascular, respiratory, etc.) are carried out. These mechanisms are mediated by chemicals such as neuropeptides, which are shorter chains of amino acids that have been showed widely distributed in the central and peripheral nervous system and to exert physiologicalactions acting as neurotransmitters, neuromodulators (paracrine action and autocrine) and neurohormones.In the last thirty years, it has increased the knowledge on the distribution and function of neuropeptides in the central nervous system of mammals (rats, cats, dogs, alpaca, primates, and humans). Thus, the aim of this paper is to describe the most relevant information available about neuropeptides in the human brain. To do so will raise issues about neuropeptides in the human brain as: a) The distribution; b) The anatomical relationship; c) The physiological functions; d) The coexistence;and e) The related future research to make.

Staphylococcus aureus resistentes a meticilina (SARM) positivos para PVL aislados en individuos sanos de Montería-Córdoba / PVL positive methicillin-resistant Staphylococcus aureus (MRSAs) strains isolated from healthy individuals in Montería, Córdoba / Staphylococcus aureus resistente à meticilina (SARM) positivos para PVL isolados em indivíduos saudáveis de "Montería, Córdoba"

Objetivo. Estudiar cepas asociadas a la comunidad de SARM y productoras de PVL en individuos sanos de la ciudad de Montería. Materiales y métodos. Estudio descriptivo, prospectivo de corte transversal, a partir de un total de 253 muestras obtenidas de hisopados faríngeos en tres comunidades: 91 internos de la cárcel de Montería (19-58 años), 100 estudiantes adultos jóvenes de la Universidad de Córdoba (17-30 años) y 62 niños en edad escolar (4-9 años) del Colegio de la Universidad de Córdoba. Los individuos participantes no estuvieron hospitalizados en los últimos meses, ni recibieron tratamiento antimicrobiano y no presentaron signos y/o síntomas clínicos. Los aislamientos fueron identificados por pruebas convencionales microbiológicas y se determinó la susceptibilidad antimicrobiana para los diferentes antibióticos a través de MicroScan™ combo 1A (SIEMENS). Para la detección de los genes nuc, mecA y PVL se utilizaron los protocolos de Brakstad et al (5), Oliveira et al (6) y Gerard et al (7) respectivamente. Resultados. De las 253 muestras analizadas, 62 (24,5%) resultaron positivas para S. aureus, de éstas 4 (6,45%) fueron resistentes a meticilina, de las cuales 2 (25%) resultaron PVL positivas; 58 (93,54%) fueron sensibles y 6 (75%) positivas para PVL. Conclusiones. Los resultados obtenidos demuestran la colonización por SARM-AC en individuos sanos, la colonización fue mayor en la población infantil y adultos jóvenes.

Objective. To study SARM and PVL producing strains in healthy individuals of Montería city. Materials and methods. This was a descriptive, prospective and transversal study. A total of 253 samples from pharyngeal swabs in three communities were studied: 91 prisoners of the jail of Montería (19-58 years old), 100 young adult students of the University of Cordoba (17-30 years old) and 62 children in school age (4-9 years old) of the primary school of the University of Cordoba. Individuals analyzed had not been hospitalized, had not received any antimicrobial treatment and did not show any clinical signs or symptoms in the last months. The isolates were identified by conventional microbiological tests and the antimicrobial susceptibility was determined for different antibiotics with MicroScan™ kit 1A (SIEMENS). For the detection of the nuc, mecA and PVL genes, we followed the protocols of Brakstad et al., Oliveira et al. and Gerard et al. respectively. Results. Of the 253 analyzed samples, 62 (24.5%) were positive for S. aureus, out of those 4 (6.45%) were resistant to methicillin and 2 (25%) of them were PVL positive; 58 (93.54%) were sensitive to methicillin and 6 (75%) positive for PVL. Conclusions. Results obtained in this study show the colonization by SARM-AC of healthy individuals. Colonization was higher in young adults and children in school-age.

Objetivo. Estudar cepas associada à comunidade de SARM e produtoras de PVL em indivíduos saudáveis da cidade de Monteria. Materiais e métodos. Estudo descriptivo, prospectivo de corte transversal, de um total de 253 amostras obtidas em esfregaços faríngeos em três comunidades: 91 reclusos em Monteria (19-58 anos), 100 alunos adultos jovens da "Universidad de Córdoba" (17 - 30 anos) e 62 crianças em idade escolar (4-9 anos) do "Colégio de la Universidad de Córdoba". Os indivíduos envolvidos não foram internados nos últimos meses, ou receberam tratamento antimicrobiano e não tinham sinais e / ou sintomas clínicos. Os isolados foram identificados por testes microbiológicos convencionais e se determinou a susceptibilidade antimicrobiana aos diferentes antibióticos através de MicroScan™ combo 1A (SIEMENS). Para a detecção de genes nuc, mecA e LPV foram utilizados protocolos Brakstad et al (5), Oliveira et al (6) e Gerard et al (7), respectivamente. Resultados. De 253 amostras testadas, 62 (24,5%) foram positivas para S. aureus, destas 4(6,45%) foram resistentes à meticilina, dois das quais (25%) foram LPV positivas, 58 (93,54%) foram sensíveis e seis (75%) foram positivas para PVL. Conclusões. Os resultados demonstram a colonização de SARM-AC em indivíduos saudáveis, a colonização foi maior em crianças e adultos jovens.