Obstinação terapêutica sob o referencial bioético da vulnerabilidade na prática da enfermagem / Willfulness therapeutic under reference bioethical vulnerability the practice nursing

A tecnologia desencadeia dilemas bioéticos, entre eles a obstinação terapêutica. E frente a esses dilemas enfermeiros priorizam avanços tecnológicos aos saberes reflexivos. O objetivo da presente pesquisa foi o de compreender a percepção do enfermeiro de UTI sobre obstinação terapêutica, à luz do referencial bioético da vulnerabilidade. Como método, utilizou-se a pesquisa descritiva, análise do conteúdo de Bardin, com quatorze estudantes pós-graduandos do Curso de Especialização de uma instituição de ensino superior privada que atuavam em UTI, há mais de um ano, após aprovação do Comitê de Ética em Pesquisa e dos entrevistados. Como resultados obteve-se duas categorias: desconhecimento do conceito; posicionamento, com cinco subcategorias: passividade diante da decisão médica, dificuldade de enfrentar a terminalidade; percebendo negativamente a obstinação terapêutica, sentimentos em relação a terminalidade do jovem e criança, reconhecendo o papel do enfermeiro em relação a terminalidade. Desconhecimento sobre obstinação terapêutica influencia na vulnerabilidade do enfermeiro ao vivenciar tal situação, provavelmente não foi preparado durante a graduação e pós-graduação, principalmente quando os envolvidos são jovens ou crianças. Também estão despreparados a reconhecer quando a recuperação do paciente está em detrimento à tecnologia, necessitando consenso multiprofissional. Enfermeiros reconhecem a necessidade de controle da dor, diminuição do sofrimento e promoção da dignidade. Por fim, evidenciou-se a necessidade de inclusão dos aspectos bioéticos na formação do enfermeiro, pois identifica-se que estes não conhecem o conceito de obstinação terapêutica, porém reconhecem o prolongamento do processo de morte como negativo, principalmente quando estão envolvidos jovens, ainda sim, reconhecem seu papel na terminalidade. Preparar o enfermeiro desde a graduação, para lidar com situações de terminalidade possibilitará uma assistência de enfermagem mais adequada e com menor sofrimento dos envolvidos.

The technology triggers bioethical dilemmas, including the therapeutic obstinacy, and face these dilemmas, nurses prioritize technological advances to reflective knowledge. The aim of this research was to understand the perception of the ICU nurse about therapeutic obstinacy in the light of bioethical term vulnerability. As a method, we used the descriptive research, analysis of Bardin content, with fourteen graduate students of the Specialization Course of a private institution of higher education who worked in the ICU for more than a year after approval by the Ethics Committee research and interviewed. As a result, there was obtained two categories: lack concept; positioning, with five subcategories: passivity in the face of medical decision, difficulty facing the terminal illness; negatively realizing the therapeutic obstinacy, feelings towards the terminally young child, recognizing the role of the nurse in relation to terminally. Ignorance of therapeutic obstinacy influences the vulnerability of nurses to experience such a situation probably was not prepared for the undergraduate and graduate levels, especially when those involved are young people or children. They are also unprepared to recognize when the patient's recovery is rather to technology, requiring multidisciplinary consensus. Nurses recognize the need for pain control, reduced suffering and promote dignity. Finally, evidence of the need for inclusion of bioethical issues in nursing education, it identifies that these do not know the concept of therapeutic obstinacy, but recognize the prolongation of the dying process as negative, especially when they are involved young, still yes, they recognize their role in terminally. Prepare the nurse since graduation, to handle terminal situations will enable a more adequate nursing care, with less suffering of those involved.

O ensino da bioética e a tomada de decisões: impacto em estudantes de medicina / The teaching of bioethics and decision making: impacts on medical students

Com a evolução da Bioética e sua consolidação após 4 décadas de desenvolvimento e expansão pelo mundo inteiro,concomitante ao desenvolvimento biotecnológico e à complexização das relações humanas, passou-se a questionar os limites do início e fim da vida humana diante dos avanços possibilitados pela tecnologia e até mesmo os limites do conceito de humanidade. Consolida-se, assim, em uma nova ciência, que passa a ser replicada e ensinada. Todavia, qual a efetividade do ensino da Bioética? Em seu atual estágio de desenvolvimento epistemológico, o ensino da Bioética tem contribuído na formação dos profissionais que conviverão diariamente com os dilemas bioéticos? Neste contexto, o presente artigo procura compreender os impactos do ensino da Bioética em estudantes de Medicina, analisados no 1.º, 6.º e9.º semestres do curso de graduação, para avaliar o impacto que a matéria de Bioética causa em suas opiniões diante de diversos casos concretos apresentados que envolvam conflitos de distintos princípios. Os resultados estatísticos coletados e apresentados nesta pesquisa demonstram que, a despeito do grande desenvolvimento e divulgação da Bioética, o seu impacto na formação da nova geração de médicos ainda é baixo, de modo que, na relação de formação interdisciplinar desta ciência, a influência epistemológica ainda é um caminho de mão única, ou seja, ainda que a Medicina contribua com a formulação da Bioética, a Bioética pouco está contribuindo com a formulação da Medicina contemporânea, como se pode observar pelos dados que demonstram forte corporativismo entre os alunos. Ressaltam-se, todavia, resultados que comprovam instabilidade nos posicionamentos e que permitem a conclusão de que a Bioética possibilita a manutenção da dúvida, evitando a formação de dogmas e decisões pré-formuladas em situação de dilema ético.

The evolution and consolidation of Bioethics as a discipline after four decades of development and expansion throughout the world along with the development of Biotechnology and the increasingly complex human relationships that started to question the limits of the beginning and the end of life in relation to technologic advances, and even the limits of the concept of Humankind. Thus, a new Science is consolidated which may be replicated and taught. However, how effective the teaching of Bioethics is? In its current epistemological state of development, has the teaching of Bioethics been contributing to the training of professionals that will be dealing with bioethical dilemmas in a daily basis? Within this context,this paper seeks to understand the impacts that the teaching of bioethics has over medical students, by means of an analysis in the 1st, 6th an 9th semesters of the undergraduate course. The statistical results obtained and presented in this paper show that, despite the great development and dissemination of Bioethics, its impact over the training of the new generation of doctors seems to be low, so that the interdisciplinary relationship specific to the discipline and its epistemological influence are still a one-way route, meaning that even if Medicine contributes to the formulation of Bioethics, Bioethics seems to be of little relevance as regards contributing to the profile of modern medicine, as observed in data that show astrong corporatism among students. It should be noted, however, that there are results showing instability in the opinions that allow affirming that Bioethics may contribute for doubts to emerge, for avoiding dogmas and pre-conceived decisions to be formulated in an ethical dilemma situation.

Malnutrition in infancy as a susceptibility factor for temporal lobe epilepsy in adulthood induced by the pilocarpine experimental model.

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.

[Nurses' autonomy and vulnerability in the Nursing Assistance Systematization practice]. / Autonomia e vulnerabilidade do enfermeiro na prática da Sistematização da Assistência de Enfermagem.

The objective of this study was to recognize the autonomy and vulnerability of nurses in the implementation of the Sistema da Assistência de Enfermagem (SAE) Nursing Care System through an integrative literature review, using content analysis. A survey was conducted, and 40 articles published between 1998 and 2008 were selected based on their relevance. Results showed two main categories of meaning: Benefits associated to the SAE practice (to patients, to the profession and to the institution) and Determinants for the Implementation of SAE (nurse's competence, training and education, record-instruments, infrastructure and collective sharing-construction). From the integration of the two categories, the highlights were the autonomy in acting with freedom and responsibility, science-based decision-making, and being valued for their social work, as well as the vulnerability expressed by interpersonal relationships, the wear generated by professional stress and the risk inherent to the service.

Autonomia e vulnerabilidade do enfermeiro na prática da Sistematização da Assistência de Enfermagem / Nurses' autonomy and vulnerability in the Nursing Assistance Systematization practice / Autonomía y vulnerabilidad del enfermero en la práctica de la Sistematización de la Atención de Enfermería

O estudo objetivou reconhecer a autonomia e a vulnerabilidade do enfermeiro no processo de implantação e implementação da Sistematização da Assistência de Enfermagem (SAE), através de revisão bibliográfica integrativa, mediante análise de conteúdo. Dentre os artigos pesquisados, selecionaram-se 40 em conformidade com o foco, publicados entre 1998 e 2008. Os resultados apresentaram duas categorias de significados principais: Benéficos Associados à Prática da SAE (ao paciente, para a profissão e para a instituição) e Fatores Determinantes para a Implantação/Implementação da SAE (competência do enfermeiro, formação e ensino, registro-instrumentos, infra-estrutura e compartilhamento-construção coletivos). Na integração de ambas, destacou-se a autonomia no agir com liberdade e responsabilidade, na tomada de decisão com base científica e na conquista do valor de seu trabalho social, bem como a vulnerabilidade expressa pelas relações interpessoais, no desgaste gerado pelo estresse profissional e no risco inerente à assistência.

The objective of this study was to recognize the autonomy and vulnerability of nurses in the implementation of the Sistema da Assistência de Enfermagem (SAE) Nursing Care System through an integrative literature review, using content analysis. A survey was conducted, and 40 articles published between 1998 and 2008 were selected based on their relevance. Results showed two main categories of meaning: Benefits associated to the SAE practice (to patients, to the profession and to the institution) and Determinants for the Implementation of SAE (nurse's competence, training and education, record-instruments, infrastructure and collective sharing-construction). From the integration of the two categories, the highlights were the autonomy in acting with freedom and responsibility, science-based decision-making, and being valued for their social work, as well as the vulnerability expressed by interpersonal relationships, the wear generated by professional stress and the risk inherent to the service.

El estudio objetivó reconocer autonomía y vulnerabilidad del enfermero en el proceso de implantación e implementación de Sistematización de Atención de Enfermería (SAE), mediante revisión bibliográfica integradora, usándose análisis de contenido. Entre los artículos investigados, fechados de 1998 a 2008, se seleccionaron 40 en conformidad con el foco. Los resultados presentan dos categorías principales de significados: Beneficios Asociados a la Práctica del SAE (al paciente, para la profesión y para la institución) y Factores Determinantes para la Implantación/Implementación de SAE (competencia del enfermero, formación y enseñanza, registro-instrumentos, infraestructura y compartido-construcción colectiva). En integración de ambas, se destacó la autonomía en el accionar con libertad y responsabilidad, en la toma de decisiones con base científica y en la conquista del valor de su trabajo social, así como la vulnerabilidad expresada por relaciones interpersonales, en desgaste generado por estrés profesional y en riesgo inherente a la atención.

Ácidos graxos ômega 3 e tratamento da esquizofrenia: [revisão] / Omega 3 fatty acid and schizophrenia treatment: [review]

CONTEXTO: A esquizofrenia é uma desordem psiquiátrica complexa e debilitante cujo tratamento de base é realizado com medicamentos antipsicóticos. No entanto, evidências sugerem que a suplementação dietética com ácidos graxos ômega 3 (n-3) pode ser benéfica em diversas desordens psiquiátricas. OBJETIVO: Revisar a eficácia do n-3 como coadjuvante no tratamento farmacológico da esquizofrenia. MÉTODOS: Realizou-se uma pesquisa nas bases de dados eletrônicas Medline, Lilacs e SciELO. A estratégia de busca também incluiu a busca em árvore. Todos os estudos randomizados e controlados relevantes foram incluídos nesta revisão, independentemente do ano de publicação. RESULTADOS: Até o momento, foram divulgados seis estudos randomizados, duplo-cegos placebo controlados; cinco deles apresentaram resultados positivos na melhora dos sintomas da esquizofrenia, assinalando, ainda, superioridade do ácido graxo eicosapentaenoico (EPA) em relação ao ácido graxo docosaexaenoico. Em geral, o consumo de 2 g/dia de EPA conjuntamente com a medicação antipsicótica usual parece reduzir a sintomatologia da esquizofrenia, particularmente os sintomas positivos. CONCLUSÃO: A terapia nutricional com EPA mostrou-se útil como coadjuvante no tratamento da esquizofrenia. Por conseguinte, sugere-se que os pacientes esquizofrênicos sejam encorajados a consumir refeições balanceadas e saudáveis ricas em EPA e, caso a quantidade ideal não seja atingida pela dieta, a suplementação pode ser benéfica.

BACKGROUND: Schizophrenia is a complex and debilitating psychiatric disorder, whose primary pharmacological intervention is the use of antipsychotics. There is, however, growing evidence that dietary supplementation with omega 3 fatty acids (n-3) may be beneficial in several psychiatric conditions. OBJECTIVE: To review the efficacy of n-3 as a treatment for schizophrenia. METHODS: Electronic searches of the following databases were performed: Medline, Lilacs e SciELO. The search strategy also included cited reference searching. All relevant randomized controlled trials were included in the review. RESULTS: To date, five out of six randomized, double-blind, and placebo controlled studies obtained improvement in the symptoms of the psychosis. Besides, an advantage in the intake of eicosapentaenoic fatty acid (EPA) in relation to docosahexaenoic fatty acid was designated. Essentially, the intake of 2 g/day of EPA in addition to the standard medication was effective in decreasing the symptoms of schizophrenia. DISCUSSION: The nutritional therapy with EPA revealed to be useful as coadjutant in the treatment of schizophrenia. Therefore, we suggest that the schizophrenic patients should be encouraged to consume balanced and healthy meals rich in EPA and, if the ideal amount is not reached by the diet, the supplementation is likely to be beneficial.

O conceito de vulnerabilidade no contexto das pesquisas envolvendo seres humanos / The concept of vulnerability in the context of reserarch involving human beings

Os inúmeros abusos observados nas pesquisas biomédicas no século XX culminaram no reconhecimento de indivíduos vulneráveis que, além de terem seus direitos desrespeitados, eram colocados em situação de risco. As diversas regulamentações das pesquisas envolvendo seres humanos têm indicado desde então situações de vulnerabilidade a que estão expostos os participantes. Incluem desde a redução da capacidade em consentir de maneira livre e esclarecida, bem como situações de coerção e exploração por vulnerabilidade social ou econômica, com aumento de exposição ao dano e distribuição desigual dos benefícios e ônus da pesquisa, comprometendo assim o princípio da justiça. A questão da vulnerabilidade, além de fundamentar o princípio da autonomia, remete-nos à questão da dignidade humana, no reconhecimento do outro como humano, o qual não deve ser utilizado como meio e sim ser protegido em suas fragilidades.

The abuses observed in biomedical research during 20th century have culminated in the recognition of vulnerable individuals that had their rights disrespected, as well as were placed in situations of risk. The various regulations of research involving human beings have indicated since then situations of vulnerability, that include the reduction of the capacity in free consent and also situations of coercion and exploration of social or economic vulnerability, with increase exposition to the damage and unequal distribution of benefits and burdens, compromising the principle of justice. The question of the vulnerability more than establishing the principle of autonomy emphasizes the matter of human dignity and the recognition of another human being, which should not be used, but protected in its fragilities.

Neurogenesis induced by seizures in the dentate gyrus is not related to mossy fiber sprouting but is age dependent in developing rats.

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.

Neurogenesis induced by seizures in the dentate gyrus is not related to mossy fiber sprouting but is age dependent in developing rats / A neurogênese induzida por crises no giro denteado não está relacionada ao brotamento de fibras musgosas, mas é dependente da idade, em ratos durante o desenvolvimento

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.

A neurogênese no giro dentado tem atraído atenção já que ela ocorre na mesma região do hipocampo que o brotamento das fibras musgosas, na epilepsia do lobo temporal. Assim, submetemos ratos em desenvolvimento ao status epilepticus induzido (SE) por pilocarpine. Grupos foram submetidos em I-P9, II-P7, P8, P9; III-P17 e IV-P21. A neurogênese foi observada usando o protocolo do BrdU e confirmada por dupla marcação com pentraxina neuronal. Outros animais foram monitorados até P120 e seus cérebros analisados (Nissl e Timm). A neurogênese nos grupos P17 (p=0,007) e P21 (p=0,006) aumentaram. Entretanto, o P21 apresentou crises espontâneas e brotamento de fibras musgosas, na mesma região onde ocorreu a neurogênese, enquanto o grupo P17 apresentou somente aumento na neurogênese. Assim, nossos resultados sugerem que o fenômeno da neurogênese não está relacionado com o brotamento de fibras musgosas nem com o aparecimento de crises espontâneas e recorrentes no modelo da pilocarpina.

Neuromodulatory effect of creatine on extracellular action potentials in rat hippocampus: role of NMDA receptors.

The creatine (Cr) and phosphocreatine (PCr) system is essential for the buffering and transport of high-energy phosphates. Although achievements made over the last years have highlighted the important role of creatine in several neurological diseases, the adaptive processes elicited by this guanidino compound in hippocampus are poorly understood. In the present study, we showed that creatine (0.5-25mM) gradually increases the amplitude of first population spike (PS) and elicits secondary PS in stratum radiatum of the CA1 region, in hippocampal slices. Creatine also decreased the intensity of the stimulus to induce PS, when compared with hippocampal slices perfused with artificial cerebrospinal fluid (ACSF). The competitive NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP5; 100microM) attenuated creatine-induced increase of amplitude of PS and appearance of secondary PS, providing pharmacological evidence of the involvement of NMDA receptors in the electrophysiological effects of creatine. Accordingly, creatine (0.01-1mM) increased [3H]MK-801 binding to hippocampal membranes by 55%, further indicating that this compound modulates NMDA receptor function. These results implicate the NMDA receptor in amplitude and population spike increase elicited by creatine in hippocampus. Furthermore, these data suggest that this guanidino compound may also play a putative role as a neuromodulator in the brain, and that at least some of its effects may be mediated by an increase in glutamatergic function.

Bioética: humanização em saúde, vulnerabilidade, tecnociência e ética na pesquisa / Bioethics: humanization in health, vulnerability, techno science and ethics in research

Com a presente edição monográfica sobre bioética — reflexões: humanização em saúde, vulnerabilidade, tecnociênciae ética na pesquisa, já são cinco edições inteiramente devotadas às discussão de temas de bioética. Registrando o caminho percorrido temos: a) 1999 — Bioética (v. 23, n. 5, set./out.); b) 2002 — Bioética: uma perspectiva brasileira (v. 26, n. 1, na./mar.); c) 2004 — Bioética, cuidar e saúde (v. 28, n. 3, jul./set.); d) 2005 — Bioética: intuições pioneiras, fundamentos e experiências educacionais brasileiras (v. 29, n.3, jul./set.)...

Avaliação eletrofisiológica in vitro de drogas antiepilépticas em fatias hipocampais humanas provenientes de pacientes portadores de epilepsia do lobo temporal refratária ao tratamento medicamentoso / In vitro electrophysiological assessment of antiepileptic drugs in human hippocampal slices originating from patients with refractory temporal lobe epilepsy

The absence of a satisfactory response to antiepileptic drug (AED) therapy, is an unresolved problem in a significant number of epileptic patients. Mechanisms of intractability are not well understood but may include a combination of poor penetration of AED across a functionally altered blood-brain barrier owing to increased expression of multiple drug resistance transporters. Therefore, the aim of this work was to assess the in vitro efficacy of antiepileptic drugs through human hippocampal slices originating from patients with refractory temporal lobe epilepsy submitted to corticoamygdalohippocampectomy. Slices was prepared from a 1 cm3 block of the hippocampus body 30 min after resection. Briefly, hippocampal slices of 400 µM thickness was cut coronally. Extracellular field potentials was recorded from the st. Granulosum of the dentate gyrus. The antiepileptic drugs added in the bath were Carbamazepine, Topiramate and Phenytoin. The phenytoin was effective reducing the hyperexcitability (polispikes) in 60% of the experiments (n = 5). On the other hand, the carbamazepine promoted a decrease in evoked epileptiform activity in 37,5% of the cases (n = 8). The application of topiramate in the bath reduced in 30% the number of polispikes (n = 10). Our results showed that the phenytoin application resulted in a significant reduction in neuronal excitability, however, the carbamazepine and topiramate were not able to control of the hiperexcitability, suggesting that local neuronal alterations, as well changes in blood brain barrier, could be responsible for such behaviors.

Dysmorphic neurons in patients with temporal lobe epilepsy.

We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients with medically intractable TLE and compare histological, clinical, and imaging features with ten TLE patients with classical hippocampal sclerosis without abnormal cells. Such dysmorphic neurons were observed in the hilus of the dentate gyrus and were characterized by giant or misshapen cells with abnormal cytoskeletal structure and atypical dendritic processes that resembled the dysmorphic neurons from cortical dysplasias. Specimens with dysmorphic cells also contained other cytoarchitectural abnormalities including bilamination of the dentate granular cell layer (four out seven cases), and the presence of Cajal-Retzius cells in the dentate gyrus or Ammon's horn (five out seven cases). There were no statistically significant differences regarding the age at onset, duration of epilepsy, and hippocampal asymmetry ratio between patients with or without dysmorphic cells. Nevertheless, it is interesting to note that a higher proportion of patients with dysmorphic neurons continued to present auras after surgery, when compared with patients without those cells.

Effects of pinealectomy and the treatment with melatonin on the temporal lobe epilepsy in rats.

The aim of the present work was to analyze the effects of pinealectomy in the development of the epilepsy model induced by pilocarpine in adult male rats. Group I: Wistar male adult rats were submitted to pinealectomy, and 7 days after surgery, these animals received pilocarpine (350 mg/kg, i.p.) to induce three distinct behavioral phases: status epilepticus, seizure-free, and chronic phases. This late, as well as all control groups were continuously video-recorded for 60 days, to study behavior parameters. These animals were killed and the brain sections were processed for Nissl and neo-Timm. Group II: Another group, also submitted to pinealectomy, received several injections of melatonin (2.5 mg/kg): 20 min before, concomitantly with pilocarpine, 30 min, 1 h, and 2 h after pilocarpine administration. Some animals from group I and all from group II were sacrificed 48 h following status epilepticus onset to perform TUNEL assay. The latency for status epilepticus onset, status epilepticus length as well as mortality rate during status epilepticus were similar for pinealectomized and control groups. On the other hand, pinealectomized rats presented minor duration of the silent period, a higher number of spontaneous seizures during the chronic phase, increased number of TUNEL-positive cells (acute phase), increased neuronal loss, and marked supragranullar mossy fibers sprouting (chronic phase) in the hippocampal formation, when compared with control groups. Our data show that the pinealectomy facilitates the epileptogenic process that follows the long-lasting status epilepticus. This facilitation can be partially reverted by the simultaneous administration of melatonin.

Gap junctions in human hippocampal sclerosis

Um grande número de portadores de epilepsia do lobo temporal não obtém controle de suas crises com os medicamentos antiepilépticos atualmente disponíveis. Nesses casos de epilepsia fármaco-resistente uma possibilidade terapêutica é a ressecção cirúrgica do foco epiléptico. Estudos em preparações de fatias hipocampais de tecido epileptogênico proveniente da cirurgia de epilepsia tem mostrado a ocorrência de junções comunicantes (gap junctions) o que poderia estar relacionada com o hipersincronismo observado no foco epiléptico. Neste trabalho, nós mostramos estudos eletrofisiológicos in vitro feitos na formação hipocampal obtida de um paciente após uma cirurgia de epilepsia. População de espículas (Population spikes) de pequena amplitude foram registradas sugerindo uma lesão neuronal significante. As propriedades intrínsicas de membranas obtidas desses neurônios mostraram-se normais. A presença das junções comunicantes nas células granulares do giro dentado também foram observadas. Nossos achados sugerem que a presença de junções comunicantes no tecido epiléptico pode ter um papel importante na geração de descargas epileptiformes

The effects of alcohol intake and withdrawal on the seizures frequency and hippocampal morphology in rats with epilepsy.

The aim of our study, using the pilocarpine model of epilepsy, was to investigate the effects of alcohol administration and withdrawal on the spontaneous recurrent seizures (SRSs). Four groups of adult, male Wistar rats were studied: (A). control rats (n=10), received neither pilocarpine nor alcohol, (B). alcohol-treated rats (n=10), received a daily dose of 3.0 g x kg(-1) of a 30% alcohol solution via an oesophagic probe for 30 days, (C). rats with epilepsy (n=10), (D). rats with epilepsy with alcohol intake (n=10). SRSs were induced by a single dose of pilocarpine (i.p.) and the basal frequency of SRSs was video monitored (24h per day) for 30 days. Following this period, the animals of group D received a daily dose of alcohol solution as described above and at the end of this period, alcohol administration was stopped and the seizure frequency was assessed for more 30 days. The basal seizure frequency observed in groups C and D during the first 30 days was 2.2+/-1.8 seizures per week per animal. In group D, it was observed an increase to 12.2+/-5.8 during the first 2 weeks of alcohol administration. During the last 2 weeks of alcohol administration, the number of SRSs returned to the previous basal level. During alcohol withdrawal the seizure frequency increased to 14.3+/-7.4 seizures per week per animal for the first 2 weeks, and returned to the basal level in the remaining period of observation. The Neo-Timm and Nissl staining of hippocampal formation and of the dentate gyrus in rats with epilepsy showed a cell loss in the hippocampal subfield CA1 and in the hillus of dentate gyrus. In rats with epilepsy with alcohol intake, we observed a cell loss in hippocampal subfields CA3 and hillus of the dentate gyrus, with significant neuronal death in subfield CA1, when compared with control animals. The alcohol withdrawal syndrome is a crucial event for the development of functional and neuropathological alterations associated with epilepsy.

Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study.

Status epilepticus (SE) is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG) procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO) using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%), caudate-putamen (+30.6%), frontoparietal cortex (+32.2%), amygdala (+31.7%), entorrinal cortex (+28.2%), thalamic nucleus (+93.5%), pre-tectal area (+50.1%) and substantia nigra (+50.3%) when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

Status epilepticus (SE) is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG) procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO) using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6 percent), caudate-putamen (+30.6 percent), frontoparietal cortex (+32.2 percent), amygdala (+31.7 percent), entorrinal cortex (+28.2 percent), thalamic nucleus (+93.5 percent), pre-tectal area (+50.1 percent) and substantia nigra (+50.3 percent) when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus