Plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plants acting on the central nervous system: review plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plantas con acción sobre el sistema nervioso central incluidas en la lista nacional de plantas medicinales de interés para sus (RENISUS)

A depressão é uma doença grave que atinge a população em geral, estudos epidemiológicos estimam que a prevalência da depressão ao longo da vida no Brasil está em torno de 15,5%. Os fatores que desencadeiam o aparecimento da depressão incluem fatores sociais, psicológicos, biológicos e também fatores externos específicos como eventos estressantes, solidão, consumo de álcool e drogas, doenças crônicas e dar á luz (depressão pós-parto). O objetivo da presente pesquisa consistiu em realizar uma revisão bibliográfica sobre as principais plantas medicinais com ação antidepressiva. A ansiedade vem se tornando um dos principais problemas da atualidade, sendo intensificada pela pandemia causada pelo coronavírus, onde constatou-se que durante o pico da pandemia onde os casos confirmados de COVID-19 no Brasil ascenderam de 45.757 para 330.890, e as mortes, de 2.906 para 21.048, o sentimento de tristeza/depressão atingiu 40% dos adultos brasileiros. Os sintomas de depressão podem ser amenizados quando a disponibilidade sináptica de monoaminas são aumentadas, e esse aumento pode ocorrer através da diminuição da metabolização desses neurotransmissores. Neste sentido, busca-se através da farmacoterapia a utilização de antidepressivos que disponibilizem as monoaminas na fenda sináptica. A escolha do fármaco é feita com base nos sintomas da depressão e na boa resposta a uma determinada classe de antidepressivos. Em fevereiro de 2009 o Ministério da saúde lançou a Relação Nacional de Plantas Medicinais de Interesse ao SUS (RENISUS), contendo 71 espécies vegetais que são distribuídas de forma in natura nas unidades básicas de saúde (UBS). Destas, somente três espécies apresentam efeito antidepressivo e ansiolítico comprovados na literatura sendo Matricharia chamomilla, Erytrinum mulungu e a Passiflora incarnata que também fazem parte da RENISUS. Além destas, outras espécies como a Melissa officinalis, Lippia alba, Valeriana officinalis e Piper methysticum são utilizadas pela população para tratar ansiedade, insônia e depressão, sugerindo desta forma que estas espécies sejam incluídas na RENISUS.

Depression is a serious disease that affects the general population, epidemiological studies estimate that the prevalence of depression throughout life in Brazil is around 15.5%. The factors that trigger the onset of depression include social, psychological, biological and also specific external factors such as stressful events, loneliness, alcohol and drug consumption, chronic diseases and giving birth (postpartum depression). The objective of the present research was to carry out a literature review on the main medicinal plants with antidepressant action. Anxiety has become one of the main problems of today, being intensified by the pandemic caused by the coronavirus, where it was found that during the peak of the pandemic where confirmed cases of COVID-19 in Brazil rose from 45,757 to 330,890, and deaths, from 2,906 to 21,048, the feeling of sadness/depression reached 40% of Brazilian adults. Symptoms of depression can be alleviated when synaptic availability of monoamines is increased, and this increase can occur through decreased metabolization of these neurotransmitters. In this sense, the use of antidepressants that make monoamines available in the synaptic cleft is sought through pharmacotherapy. The choice of drug is based on symptoms of depression and good response to a particular class of antidepressants. In February 2009, the Ministry of Health launched the National List of Medicinal Plants of Interest to the SUS (RENISUS), containing 71 plant species that are distributed in natura form in basic health units (UBS). Of these, only three species have antidepressant and anxiolytic effects proven in the literature, being Matricharia chamomilla, Erytrinum mulungu and Passiflora incarnata, which are also part of RENISUS. In addition to these, other species such as Melissa officinalis, Lippia alba, Valeriana officinalis and Piper methysticum are used by the population to treat anxiety, insomnia and depression, thus suggesting that these species are included in RENISUS.

Los estudios epidemiológicos estiman que la prevalencia de la depresión a lo largo de la vida en Brasil es de alrededor del 15,5%. Los factores que desencadenan la aparición de la depresión son sociales, psicológicos, biológicos y también factores externos específicos, como los acontecimientos estresantes, la soledad, el consumo de alcohol y drogas, las enfermedades crónicas y el parto (depresión posparto). El objetivo de esta investigación fue realizar una revisión bibliográfica sobre las principales plantas medicinales con acción antidepresiva. La ansiedad se ha convertido en uno de los principales problemas de la actualidad, intensificándose por la pandemia causada por el coronavirus, donde se encontró que durante el pico de la pandemia donde los casos confirmados de COVID-19 en Brasil aumentaron de 45.757 a 330.890, y las muertes, de 2.906 a 21.048, el sentimiento de tristeza/depresión alcanzó el 40% de los adultos brasileños. Los síntomas de la depresión pueden aliviarse cuando se aumenta la disponibilidad sináptica de las monoaminas, y este aumento puede producirse mediante una disminución de la metabolización de estos neurotransmisores. En este sentido, se busca a través de la farmacoterapia el uso de antidepresivos que hagan disponibles las monoaminas en la hendidura sináptica. La elección del fármaco se hace en función de los síntomas de la depresión y de la buena respuesta a una clase concreta de antidepresivos. En febrero de 2009, el Ministerio de Salud lanzó la Lista Nacional de Plantas Medicinales de Interés para el SUS (RENISUS), que contiene 71 especies de plantas que se distribuyen in natura en unidades básicas de salud (UBS). De ellas, sólo tres especies tienen efectos antidepresivos y ansiolíticos probados en la literatura: Matricharia chamomilla, Erytrinum mulungu y Passiflora incarnata, que también forman parte del RENISUS. Además de éstas, otras especies como Melissa officinalis, Lippia alba, Valeriana officinalis y Piper methysticum son utilizadas por la población para tratar la ansiedad, el insomnio y la depresión, lo que sugiere que estas especies se incluyan en el RENISUS.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

VPA/PLGA microfibers produced by coaxial electrospinning for the treatment of central nervous system injury

The central nervous system shows limited regenerative capacity after injury. Spinal cord injury (SCI) is a devastating traumatic injury resulting in loss of sensory, motor, and autonomic function distal from the level of injury. An appropriate combination of biomaterials and bioactive substances is currently thought to be a promising approach to treat this condition. Systemic administration of valproic acid (VPA) has been previously shown to promote functional recovery in animal models of SCI. In this study, VPA was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microfibers by the coaxial electrospinning technique. Fibers showed continuous and cylindrical morphology, randomly oriented fibers, and compatible morphological and mechanical characteristics for application in SCI. Drug-release analysis indicated a rapid release of VPA during the first day of the in vitro test. The coaxial fibers containing VPA supported adhesion, viability, and proliferation of PC12 cells. In addition, the VPA/PLGA microfibers induced the reduction of PC12 cell viability, as has already been described in the literature. The biomaterials were implanted in rats after SCI. The groups that received the implants did not show increased functional recovery or tissue regeneration compared to the control. These results indicated the cytocompatibility of the VPA/PLGA core-shell microfibers and that it may be a promising approach to treat SCI when combined with other strategies.

Pharmacological effects of different chemotypes of Lippia alba (Mill.) N.E. Brown / Efectos farmacológicos de diferentes quimiotipos de Lippia alba (Mill.) N.E. Brown

The Lippia alba species consists of an aromatic plant used in Brazilian traditional medical practice and in the medical practice of several countries as well. Presenting a wide variability in its essential oil chemical composition, the Lippia alba is classified in chemotypes, or chemical races, according to the major constituents contained in its essential oil. Considering the quali and quantitative distribution of the components in the essential oil affect directly its pharmacological properties, which are presented in the medicinal species, this paper proposes a scientific literature review to correlate both biological and pharmacological properties presented by L. alba according to its chemical constitution.

Lippia alba es una planta aromática utilizada en la medicina tradicional de Brasil y de varios países. Con una gran variabilidad en la composición química de su aceite esencial, se clasifica en quimiotipos, o razas químicas, de acuerdo con los constituyentes mayoritarios presentes en el aceite esencial. Dado que la distribución cualitativa y cuantitativa de los componentes del aceite esencial afecta directamente a las propiedades farmacológicas presentadas por la especie medicinal, este trabajo propone realizar una revisión en la literatura científica para correlacionar las propiedades biológicas y farmacológicas de los quimiotipos presentes en el aceite essencial de la L. alba.

Ausencia de efectos adversos del SNC en tratamientos de más de tres años con efavirenz / Abscense of CNS adverse reactions of efavirenz therapy after three years of treatment

En el presente trabajo se seleccionaron pacientes adultos HIV en tratamiento antirretroviral que contenían efavirenz de más de tres años de duración que hubieron tenido efectos adversos del sistema nervioso central iniciales, comprobando la desaparición completa de los mismos en el 94% de los pacientes evaluados al cabo de 36 meses de tratamiento. Se empleó como método el análisis observacional retrospectivo, utilizando una encuesta de valoración de frecuencia temporal de efectos adversos del sistema nervioso central. Se tuvieron en cuenta los siguientes: mareos: depresión; trastornos del sueño; pesadillas e ideación suicida. De los efectos adversos del sistema nervioso central investigados, los más frecuente fue pesadillas 100% y mareos 81%. Esta frecuencia decreciente hasta su desaparición, fortalece la hipótesis del "fenómeno de tolerancia" similar al observado con ciertas indolaminas, debido a que efavirenz presenta una similitud estructural con estas e interacciona con algunos receptores de la superfamilia de receptores de 5 hidroxitriptamina (5HT). Además las diferencias interindividuales de efectos adversos del SNC podrían estar dadas por las diferencias alélicas en citocromo p 450 que determinan niveles plasmáticos de metabólitos hidroxilados neurotóxicos

In the present study, adult HIV patients were selected on antiretroviral treatment that contained efavirenz for more than three years that had adverse effects on the initial central nervous system, proving their complete disappearance in 94% of the patients evaluated after 36 months of treatment. A retrospective observational analysis was used as a method, using a survey of temporal frequency assessment of adverse effects of the central nervous system. The following were taken into account: dizziness; anxiety; depression; sleep disorders; nightmares and suicidal ideation. Of the adverse effects of the central nervous system investigated, the most frequent was nightmares 100% and dizziness 81%. This decreasing frequency until its disappearance, strengthens the hypothesis of the "tolerance phenomenon" similar to that observed with certain indolamines, because efavirenz has a structural similarity with these and interacts with some receptors of the superfamily of 5-hydroxytryptamine (5HT) receptors. In addition, the interindividual differences of CNS adverse effects could be due to allelic differences in cytochrome p 450 that determine plasma levels of neurotoxic hydroxylated metabolites.

Ethanol intake and toxicity: in search of new treatments / Ingesta de etanol y toxicidad: en búsqueda de nuevos tratamientos

Prolonged alcohol consumption has consequences on the liver, producing necrotic precipitates and fibrosis, on the pancreas, causing the pancreatic acini to atrophy and destroying insulin-producing cells, and on the central nervous system (CNS), causing the gray and white matter in the frontal lobes of the brain and cerebellum to atrophy. Generally, alcohol is metabolized via oxidative pathways, where the enzymes alcohol dehydrogenase and aldehyde dehydrogenase participate during its metabolization in the liver and CNS, or via non-oxidative pathways during its metabolization in the pancreas. Ethanol metabolism can produce oxidative stress and tissue damage mediated by free radicals, causing morphological and functional alterations in the liver. In the pancreas, it can cause progressive and irreversible damage affecting the endocrine and exocrine functions, a result of the activation of the stellate cells, which are activated directly by alcohol, causing pancreatic fibrosis. In the CNS ethanol can bind directly to proteins, nucleic acids and phospholipids to develop its pathogenesis. The effects produced by alcohol can be counteracted by supplementation with antioxidants, which reduce the inflammation and areas of focal necrosis in the liver, inhibit the activation of pancreatic stellate cells, and reduce oxidative stress in the CNS. Additionally, in order to reduce the negative effects associated with alcohol consumption, recent studies have suggested the administration of antioxidants as a treatment strategy.

El consumo prolongado de alcohol tiene consecuencias en hígado, produciendo precipitados necróticos y fibrosis; en páncreas, provocando atrofia del acino pancreático y destrucción de las células productoras de insulina, y en Sistema Nervioso Central (SNC) generando atrofia de la sustancia gris y blanca en lóbulos frontales del cerebro y cerebelo. En general, el metabolismo del alcohol se consigue mediante las vías oxidativas, donde participan las enzimas alcohol-deshidrogenasa y aldehído deshidrogenasa durante su metabolización en hígado y SNC; o bien, mediante las vías no oxidativas durante su metabolización en páncreas. El metabolismo del etanol es capaz de producir estrés oxidativo y daño tisular mediado por radicales libres, causando alteraciones morfológicas y funcionales del hígado; en el páncreas, puede causar daño progresivo e irreversible afectando las funciones endocrinas y exocrinas de este órgano producto de la activación de las células estrelladas que son activadas directamente por el alcohol generando fibrosis pancreática; mientras que, en SNC se puede unir directamente a proteínas, ácidos nucleicos y fosfolípidos para desarrollar su patogenia. Los efectos producidos por el alcohol pueden contrarrestarse mediante la suplementación con antioxidantes, que reducen la inflamación y las zonas de necrosis focal en el hígado, inhiben la activación de células pancreáticas estrelladas, y reducen el estrés oxidativo en SNC. Asimismo, para reducir los efectos negativos asociados al consumo de alcohol, estudios recientes han propuesto la administración de antioxidantes como estrategia terapéutica.

CYP2B6 516 G>T polymorphism and side effects of the central nervous system in HIV-positive individuals under Efavirenz treatment: Study of a sample from southern Brazil

ABSTRACT This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and evaluate its influence on central nervous system (CNS) side effect development in HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population from southern Brazil. Additionally, we performed a survey on the clinical and epidemiological characteristics of our sample. In addition to medical records evaluation, whole blood of 89 individuals was analyzed for viral load, T lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side effects of the CNS reported by individuals but without considering the genetic variables, no statistically significant association was noted between the adverse effects and the antiretroviral treatment (including or not EFV). In addition, no statistically significant difference was noted for the influence of genotype on the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals undergoing EFV treatment. This is the first study that investigated the impact of the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from southern Brazil. Its clinical significance indicates the need for prospective studies in this population.

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose / Efeitos da administração intracerebroventricular de rocurônio sobre o sistema nervoso central de ratos e determinação da dose indutora de crise epiléptica

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.

Aged Lewis rats exposed to low and moderate doses of rotenone are a good model for studying the process of protein aggregation and its effects upon central nervous system cell physiology / Ratos Lewis idosos expostos a baixa e moderada doses de rotenona são um bom modelo para estudar o processo de agregação proteica e seus efeitos sobre a fisiologia celular do sistema nervoso central

ABSTRACT Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.

RESUMO A fisiologia celular está prejudicada antes da agregação proteica podendo ser mais importante para a neurodegeneração do que as próprias inclusões. Assim, o objetivo deste estudo é caracterizar um modelo animal para analisar os mecanismos e efeitos da agregação proteica. Ratos Lewis com 10 meses de idade foram expostos a rotenona (1 ou 2 mg/kg/dia), administrada subcutaneamente, utilizando minibombas osmóticas. Os níveis de peptídeo beta-amiloide, TAU hiperfosforilada, alfa-sinucleína e proteínas carboniladas (indicativo de estresse oxidativo) foram avaliados por imunohistoquímica e western blot no hipocampo, substância negra e locus coeruleus. Foi demonstrado que 2 mg/kg/dia de rotenona promoveu aumento do peptídeo beta-amiloide, hiperfosforilação da TAU e alfa-sinucleína. Já 1 mg/kg/dia de rotenona não alterou os níveis dessas proteína nessas regiões. As proteínas carboniladas não se alteraram. Foi demonstrado que ratos Lewis idosos expostos a baixas doses de rotenona são modelo de estudo dos processos celulares antes da agregação proteica, enquanto 2 mg/kg/dia de rotenona permite estudos sobre os efeitos da agregação proteica.

A review on alcohol: from the central action mechanism to chemical dependency / Uma revisão sobre o álcool: do mecanismo de ação central à dependência química

SummaryIntroduction:alcohol is a psychotropic depressant of the central nervous system (CNS) that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations.Objectives:to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption.Methods:a literature review was conducted and articles published in different languages over the last 15 years were retrieved.Results:the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others), the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus.Discussion and conclusion:the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.

ResumoIntrodução:o álcool é uma substância psicotrópica depressora do sistema nervoso central (SNC), que promove alteração simultânea de inúmeras vias neuronais, gerando profundo impacto neurológico e traduzindo-se em diversas alterações biológicas e comportamentais.Objetivos:descrever as ações do álcool sobre o SNC, identificando as vias de sinalização modificadas e os efeitos biológicos gerados pelo seu consumo.Métodos:revisão bibliográfica, priorizando trabalhos multilinguísticos publicados nos últimos 15 anos.Resultados:são descritas ação direta do álcool em inúmeros receptores de neurotransmissores (ácido gama-aminobutírico – GABA, glutamato, endocanabinoides AEA e 2-AG, entre outros), ação indireta do álcool no sistema límbico e opioide, ação sobre canais de cálcio, potássio e proteínas reguladas por GABA no hipocampo, além de ações centrais mediadas pela deficiência de vitamina B1.Conclusão:a ação multifocal do álcool sobre o SNC resulta em efeito geral de depressão psicomotora, dificuldades no armazenamento de informações e no raciocínio lógico, incoordenação motora, além da estimulação do sistema de recompensa, o que pode explicar o desenvolvimento da dependência química. O conhecimento das vias de sinalização neuronais alteradas pelo álcool permite reconhecer a descrição de efetores que possam reduzir sua ação central e, assim, vislumbrar novas perspectivas terapêuticas para a reabilitação de adictos a essa substância.

Quality of life/spirituality, religion and personal beliefs of adult and elderly chronic kidney patients under hemodialysis / Qualidade de vida/espiritualidade, religião e crenças pessoais de adultos e idosos renais crônicos em hemodiálise / Calidad de vida/espiritualidad, religión y creencias personales de adultos y ancianos renales crónicos en hemodiálisis

OBJECTIVE: to assess the quality of life of chronic kidney patients undergoing hemodialysis, using the WHOQOL-bref and WHOQOL-SRPB. METHOD: a descriptive and cross-sectional study was undertaken at a kidney replacement therapy service in the interior of the state of SP. The 110subjects who complied with the inclusion criteria answered the Subject Characterization Instrument, the WHOQOL-bref and WHOQOL-SRPB. RESULTS: most of the respondents were male (67.27%), with a mean age of 55.65 years, Catholic (55.45%), with unfinished primary education (33.64%) and without formal occupation (79.08%). The WHOQOL-bref domains with the highest and lowest mean score were, respectively, "psychological" (µ=74.20) and "physical" (µ=61.14). The WHOQOL-SRPB domains with the highest and lowest mean score were, respectively, "completeness and integration" (µ=4.00) and "faith" (µ=4.40). CONCLUSIONS: the respondents showed high quality of life scores, specifically in the dimensions related to spirituality, religion and personal beliefs. Losses were evidenced in the physical domain of quality of life, possibly due to the changes resulting from the chronic kidney disease and hemodialysis treatment. .

OBJETIVO: avaliar a qualidade de vida de pacientes renais crônicos em hemodiálise, por meio do WHOQOL-bref e WHOQOL-Spirituality, Religion and Personal Beliefs. MÉTODO: trata-se de um estudo descritivo, de corte transversal, realizado em uma unidade de terapia renal substitutiva do interior do Estado de São Paulo. Os 110 sujeitos que atenderam os critérios de inclusão responderam ao Instrumento de Caracterização dos Sujeitos, ao WHOQOL-bref e WHOQOL-Spirituality, Religion and Personal Beliefs. RESULTADOS: a maioria dos respondentes era do sexo masculino (67,27%), com idade média de 55,65 anos, católica (55,45%), com ensino fundamental incompleto (33,64%) e sem ocupação formal (79,08%). Os domínios do WHOQOL-bref com maior e menor pontuação média foram, respectivamente, "psicológico" (µ=74,20) e "físico" (µ=61,14). Os domínios do WHOQOL-Spirituality, Religion and Personal Beliefs de menor e maior pontuação média foram, respectivamente, "totalidade e integração" (µ=4,00) e "fé" (µ=4,40). CONCLUSÕES: os respondentes apresentaram elevados escores de qualidade de vida, especificamente nas dimensões referentes à espiritualidade, religião e crenças pessoais. Evidenciaram-se prejuízos no domínio físico da qualidade de vida, possivelmente em decorrência das alterações resultantes da doença renal crônica e do tratamento hemodialítico. .

OBJETIVO: evaluar la calidad de vida de pacientes renales crónicos en hemodiálisis, por medio del WHOQOL-bref y WHOQOL-SRPB. MÉTODO: se trata de un estudio descriptivo, de corte transversal, realizado en una unidad de terapia renal substitutiva del interior del estado de SP. Los 110 sujetos que atendieron a los criterios de inclusión respondieron al Instrumento de Caracterización de los Sujetos, al WHOQOL-bref y WHOQOL-SRPB. RESULTADOS: la mayoría de los entrevistados era del sexo masculino (67,27%), con edad promedio de 55,65 años, católicos (55,45%), con enseñanza fundamental incompleta (33,64%) y sin ocupación formal (79,08%). Los dominios del WHOQOL-bref con mayor y menor puntuación promedio fueron, respectivamente: "psicológico" (µ=74,20) y "físico" (µ=61,14). Los dominios del WHOQOL-SRPB de menor y mayor puntuación promedio fueron, respectivamente: "totalidad e integración" (µ=4,00) y "fe" (µ=4,40). CONCLUSIONES: los entrevistados presentaron elevados puntajes de calidad de vida, específicamente en las dimensiones referentes a espiritualidad, religión y creencias personales. Se evidenciaron perjuicios en el dominio físico de la calidad de vida, posiblemente en consecuencia de las alteraciones resultantes de la enfermedad renal crónica y del tratamiento de hemodiálisis. .

Central nervous system stimulant actions of Alpinia galanga (L.) rhizome: A preliminary study.

Methanolic and ethyl acetate extract of A. galanga showed significant central nervous system (CNS) stimulant activity in mice using actophotometer and rotarod test. CNS stimulation at a dose of 500 mg/kg was comparable with standard drugs caffeine and amphetamine derivative modalart. The extracts did not shown any depressant effect in forced swim or tail suspension tests. It can be concluded that A. galanga rhizome may have stimulant activity in mice and the active constituents responsible for this effect is present both in crude methanolic extract as well as in ethyl acetate fraction of methanolic extract of this plant species.

Identification of morphine accumulation in the rat embryo central nervous system: a C14-morphine administration study

Previous studies have shown that morphine consumption during pregnancy may cause delay or defect of embryo development or abnormal nervous system function in the human and animal models. In the present study, the highest density of morphine accumulation in the central nervous system of rat embryos was evaluated using C14-morphine. Female Wistar rats [W 170-200 g] used and were crossed with male rats and coupling time was recorded [Embryonic day 0-E0]. Experimental groups received 0.05 mg/ml of C14-morphine in drinking water daily. On the 10[th] and 17[th] days of pregnancy, pregnant rats were anesthetized and the embryos with these uterus and placenta were surgically removed and were fixed in formalin 10% for 4 week. Then the embryos were processed, sectioned in 25 micro m and 5 micro m thicknesses, fixed on the glasses for further evaluations. The sectioned in 25, the glasses were fixed on the Blanc black and white film for 6 h. Then, the films were appeared and their negatives were prepared. The sectioned in five staining hematoxylin and eosin by light microscope and MOTIC software. Our results indicated that the highest C14-morphine accumulation was observed in the vesicles and the ventricular choroid plexus [CP] of [E17] embryos, whereas, in the [E10] embryos. Highest concentration was observed in the brain vesicles and the ventricular CP. In addition, this study showed the surface area of lateral, 3[rd] and 4[th] ventricular CP in the experimental groups were increased in compared to control groups. Our results indicated that effects of morphine on reduction of embryos brain development may be due to the highest accumulation of C14-morphine in the CP and brain vesicles

Tóxicos ambientales y su efecto sobre el neurodesarrollo / [Environmental toxic and its effect on neurodevelopment].

Neurodevelopmental disorders are the result of a disturbance of brain function. They are frequent, with varied symptomatology, manifest themselves at different times of life and tend to be persistent with impact at the individual, family and social level. The association of these disorders with genetic entities is low. Although the research supports a mode of genetic inheritance, epigenetic factors and environmental factors can play an important role. In recent years there was a striking increase of these disorders especially attention deficit hyperactivity disorders and pervasive development disorder. Environmental factors such as the intoxication of the fetus by especially heavy metals lead and mercury are to blame in some children, of these disorders. Other substances of wide use, little degradation and maintenance in the food chain as pesticides, polychlorinated biphenyls and now the recycling of electronic waste put especially infants and children at risk, and even more so in the developing countries.

Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

Hypertensive effects of the iv administration of picomoles of ouabain

Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na+ pump, inhibiting its activity. Inhibition of this pump increases intracellular Na+, which reduces the activity of the sarcolemmal Na+/Ca2+ exchanger and thereby reduces Ca2+ extrusion. Consequently, intracellular Ca2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.

[Effect of oral morphine consumption during pregnancy on the tongue development in the Wistar rat embryos]

Morphine consumption during pregnancy could lead to defect and delay in nervous system development in the embryos. In the present study, development of the tongue of embryos whom their mothers received oral morphine during pregnancy have been studied. Female Wistar rats [200-220 g] after pregnancy were divided randomly into the experimental and control groups. The control group received tap water whereas the experimental group received morphine [0.05 mg/ml] in their drinking waters. On the day 19, the pregnant rats were killed by chloroform overdose and the embryos were removed surgically and were fixed in formalin 10%. Simultaneously, the rats' bloods were collected for corticosterone measurement. Weight and length of the embryos were determined. Then the embryos' heads were removed for tissue processing, cutting and Hematoxylin- Eosin staining. The subjects were evaluated using light microscope and MOTIC software. Number of the cells also counted. Un-paired t-test applied for statistical analysis. Plasma corticosterone level, embryos' weight and length did not show any significant differences between control and experimental groups. The large diameter of the tongue of the experimental group was decreased but the small diameter in two groups did not differ. Tongue cells numbers in the experimental group were increased but their size decreased. Decrease in the large diameter of tongue, increase in the cell number and decrease in cell size indicate the influence of morphine consumption during pregnancy on tongue development in the embryos

[Opium dependency with histopathologic changes of brain in rats]

Central nervous system is one of the primary targets of the detrimental effects of narcotics. Although opiates are among the most drugs of abuse, little is known about their side effects on the brain structures. Most investigations in this field are about their biochemical or psychological side effects. In this study pathologic changes in morphine dependent rats have been investigated. In this experimental study, 48 male wistar rats were divided into 6 groups. The dependent groups received 0.4mg/ml morphine in drinking water for 7, 28 and 56 days. The control groups received a solution of saccharose in drinking water for the same periods and then the histological studies of the brain samples were done. Significant neuronal loss in frontal and parietal lobes and hippocampus was observed. Results also showed a significant relationship between the duration of morphine intake and neuronal loss. The results of this study, in line with the other studies in this field indicate that opiate drugs might induce neuronal damage after long term exposure. These changes could be more significant in chronic addiction. Since brain atrophy is the most common pathology in dementia, further investigations for finding probable relations between dementia and opiate dependency is suggested

Effect of intramuscular and intravenous lidocaine on propofol induction dose

Our purpose was to study whether or not intravenous [IV] administration of lidocaine reduces propofol dose requirement as intramuscular [IM] lidocaine in a placebo-controlled manner. Seventy-five adult patients with American Society of Anesthesiologists physical status I and II, aged 20-60 years who were scheduled for surgery under general anaesthesia were included in the study. The patients were randomly allocated to 3 groups: IM: intramuscular administration; IV: intravenous administration and C: control. There were 25 patients in each group. The patients in group IM received lidocaine 1.5 mg kg-1 administered into the deltoid muscle 10 min before anaesthesia induction. In group IV, the patients received IV lidocaine 1.5 mg kg-1, 2 min before anaesthesia induction. Group C patients served as control group who received only propofol injection. Hypnosis after propofol administration was measured with response to verbal commands. There were no statistical differences between group IM [100.8 +/- 26.1 mg] and group IV [110.8 +/- 30.1 mg] regarding the induction dose of propofol [p > 0.05]. In group C, the required propofol dose [151.2 +/- 27.4 mg] for anaesthesia induction was significantly higher than in the other groups [p < 0.001]. No side effect was observed in any patients. In this study, both IV and IM lidocaine administration were effective in reducing the hypnotic dose of propofol without any side effects. In addition, IV lidocaine may be more comfortable for awake patients

[CNS, cytotoxicity and antimicrobial activities of [+]-dihydroperfamine and its derivatives]

In this work [+]-dihydroperfamine was isolated from Haplophyllum tuberculatum and several derivatives, namely, anhydroperforine, dihydroperfaminole, haplophyllidine, [-]-perforine and [+]-perforine were prepared. Dihydroperfamine and its derivatives were investigated for prolongation of sleeping time of pentobarbitone. Their cytotoxic activity was performed using a mechanism-based bioassay utilizing genetically engineered mutants of the yeast Saccharomyces cerevisiae. In addition, their antimicrobial activity was also tested using agar dilution method. The results showed that dihydroperfamine and its derivatives except haplophyllidine prolonged the hypnotic duration of pentobarbital. Dihydroperfamine was the only compound that possessed cytotoxic activity against strain I. On the other hand, all compounds were antimicrobially inactive