Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model / Ratas sem Status Epilepticus apresentam comportamento do tipo crise epiléptica na fase crônica do modelo experimental da Pilocarpina

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats / A serotonina endógena e exógena, mas não o sumatriptano, melhora as convulsões e a neuroinflamação no modelo de convulsão induzida por pentilenotetrazol em ratos

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice / Composição química do óleo essencial de Zhumeria majdae e seus efeitos na expressão da síndrome de abstinência de morfina e tolerância ao efeito anticonvulsivante da morfina em crises induzidas por pentilenotetrazol em camundongos

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

A case of epileptic seizure due to lidocaine local anesthesia

Lidocaine is an amide-structured local anesthetic commonly used in practice in anesthesiology. Because of its rapid onset, it is frequently used in topical and infiltration anesthesia, regional blocks, regional intravenous anesthesia (RIVA) and general anesthesia to suppress hemodynamic responses to intubation, as well as some cardiac arrhythmias and epileptic seizures. Here, we present a case with seizures and impaired consciousness following iv lidocaine treatment during sedoanalgesia without a history of epilepsy. A thirty-seven-year-old female patient, who was scheduled for a cervical biopsy operation in the Gynecology and Obstetrics clinic, developed a loss of consciousness due to lidocaine with tonic-clonic epileptic seizures during treatment with sedoanalgesia. The patient was intubated with 2 mg midazolam, 200 mg propofol and 50 mg rocuronium intravenously, while oxygen was provided by mask at 6 liters / min. Anesthesia was maintained with 4 lt / min 50% oxygen and 50% air mixture and 2% sevoflurane. There were signs of respiratory acidosis in the blood gas analysis. She was intubated for half an hour by a mechanical ventilator. The operation was canceled. In blood gas monitoring the values were within normal limits. Sugammadex was applied by the gynecology and obstetrics department. In all cases where local anesthetic is planned, necessary precautions should be taken to cope with rare complications

In silico screening and evaluation of the anticonvulsant activity of docosahexaenoic acid-like molecules in experimental models of seizures

Background: Resistance to antiepileptic drugs and the intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid [DHA] make it as a good candidate for designing and development of the new anticonvulsant medications

Methods: Ten DHA-based molecules were screened based on in silico screening of DHA-like molecules by root-mean-square deviation of atomic positions, the biological activity score of Professional Association for SQL Server, and structural requirements suggested by pharmacophore design. Anticonvulsant activity was tested against clonic seizures induced by pentylenetetrazole [PTZ, 60 mg/kg, i.p.] and tonic seizures induced by maximal electroshock [MES, 50 mA, 50 Hz, 1 ms duration] by intracerebroventricular [i.c.v.] injection of the screened compounds to mice

Results: Among screened compounds, 4-Phenylbutyric acid, 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in pentylenetetrazole test with ED[50] values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED[50] values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM

Conclusion: Common electrochemical features and three-dimensional spatial structures of the effective compounds suggest the involvement of the anticonvulsant mechanisms similar to the parent compound DHA

Seizure due to multiple drugs intoxication: a case report / Convulsão por causa de intoxicação por múltiplas drogas: relato de caso

Abstract The mechanism of the antidepressant effect of bupropion is not fully understood. Besides, using it in the treatment of depression, it is found to be effective in reducing withdrawal symptoms due to smoking cessation. A 28-year-old female patient with a history of depression was admitted to emergency department an hour after ingestion of bupropion, quetiapine, and levothyroxine in high doses to commit suicide. While accepting her into the Intensive Care Unit, she was awake, alert, disoriented and agitated. After 2 h, the patient had a generalized tonic-clonic seizure. The necessary treatment was given and 9 h later with hemodynamic improvement, the patients’ mental status improved. Bupropion may cause unusual behaviors such as delusions, paranoia, hallucinations, or confusion. The risk of seizure is strongly dose-dependent. We want to emphasize the importance of early gastric lavage and administration of activated charcoal.

Resumo O mecanismo do efeito antidepressivo de bupropiona ainda não está bem esclarecido. Contudo, seu uso no tratamento de depressão revelou ser eficaz para reduzir os sintomas de abstinência relacionados à cessação do tabagismo. Uma paciente do sexo feminino, 28 anos, com história de depressão, deu entrada no setor de emergência uma hora após a ingestão de bupropiona, quetiapina e levotiroxina em doses elevadas para cometer suicídio. Ao ser internada em unidade de terapia intensiva, estava acordada, alerta, desorientada e agitada. Após duas horas, apresentou uma crise tônico-clônica generalizada. O tratamento necessário foi administrado e nove horas mais tarde, com a estabilização hemodinâmica, o estado mental da paciente melhorou. Bupropiona pode causar comportamentos incomuns, incluindo delírios, paranoia, alucinações ou confusão mental. O risco de convulsão é altamente dependente da dose. Queremos enfatizar a importância da lavagem gástrica precoce e da administração de carvão ativado.

Montelukast reduces seizures in pentylenetetrazol-kindled mice

Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.

Absenteísmo-doença no serviço público municipal de Goiânia / Sickness absence in a municipal public service of Goiânia, Brazil

INTRODUÇÃO: O absenteísmo-doença, enquanto falta ao trabalho justificada por licença médica, é um importante indicador das condições de saúde dos trabalhadores. Em geral, características sociodemográficas e ocupacionais situam-se entre os principais fatores associados ao absenteísmo-doença. A administração pública é responsável por 21,8% dos empregos formais no Brasil. Esta população permite o estudo de uma grande variedade de categorias profissionais. OBJETIVO: Analisar o perfil e os indicadores de absenteísmo-doença entre servidores municipais de Goiânia, no Estado de Goiás, Brasil. Métodos: Estudo transversal das licenças certificadas para tratamento de saúde superiores a três dias, de todos os servidores, desde janeiro de 2005 a dezembro de 2010. Foram calculadas as prevalências, utilizando como critérios o número de indivíduos, os episódios e os dias de afastamento. RESULTADOS: Foram concedidas 40.578 licenças certificadas para tratamento de saúde a 13.408 servidores numa população média anual de 17.270 pessoas, o que resultou em 944.722 dias de absenteísmo. A prevalência acumulada de licença no período foi de 143,7%, com média anual de 39,2% e duração de 23 dias por episódio. A prevalência acumulada de absenteísmo-doença foi maior entre mulheres (52,0%) com idade superior a 40 anos (55,9%), com companheiro (49,9%), de baixa escolaridade (54,4%), profissionais de educação (54,7%), > 10 anos de serviço (61,9%) e múltiplos vínculos profissionais (53,7%). Os grupos de diagnósticos (CID-10) com as maiores prevalências acumuladas de licenças foram os do capítulo de transtornos mentais (26,5%), doenças osteomusculares (25,1%) e lesões (23,6%). CONCLUSÕES: Os indicadores de absenteísmo-doença expressam a magnitude desse fenômeno no serviço público e podem auxiliar no planejamento das ações de saúde do trabalhador, priorizando os grupos ocupacionais mais vulneráveis. .

BACKGROUND: Sickness absence, as work absenteeism justified by medical certificate, is an important health status indicator of the employees and, overall, sociodemographic and occupational characteristics are among the main factors associated with sickness absence. Public administration accounts for 21.8% of the formal job positions in Brazil. This population allows the study of a wide range of professional categories. OBJECTIVE: To assess the profile and indicators of sickness absence among public workers from the municipality of Goiania, in the State of Goiás, Brazil. METHODS: A cross-sectional study on certified sick leaves, lasting longer than three days, of all civil servants from January 2005 to December 2010. Prevalence rates were calculated using as main criteria the number of individuals, episodes and sick days. RESULTS: 40,578 certified sick leaves were granted for health treatment among 13,408 public workers, in an annual average population of 17,270 people, which resulted in 944,722 days of absenteeism. The cumulative prevalence of sick leave for the period was of 143.7%, with annual average of 39.2% and duration of 23 days per episode. The cumulative prevalence of sickness absence was higher among women (52.0%), older than 40 years old (55.9%), with a partner (49.9%), low schooling (54.4%), education professionals (54.7%), > 10 years of service (61.9%), and with multiple work contracts (53.7%). Diagnoses groups (ICD-10) with higher cumulative prevalence of sick leaves were those with mental disorders (26.5%), musculoskeletal diseases (25.1%), and injuries (23.6%). CONCLUSIONS: Indicators of sickness absence express the magnitude of this phenomenon in the public sector and can assist in planning health actions for the worker, prioritizing the most vulnerable occupational groups. .

Isolation of compound and CNS depressant activities of Mikania scandens Willd with special emphasis to brain biogenic amines in mice.

Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.

Evaluation of prenatal care in unit with family health strategy / Evaluación del cuidado prenatal en unidad con estrategia salud de la familia / Avaliação da assistência pré-natal em unidade com estratégia saúde da família

We analyzed prenatal care (PN) provided at a unit of the Family Health Strategy Service in São Paulo, according to the indicators of the Program for the Humanization of Prenatal and Birth (PHPB). We compared adequacy of PN in terms of sociodemographic variables, procedures, examinations and maternal and perinatal outcomes. Cross-sectional study with data from records of 308 pregnant women enrolled in 2011. We observed early initiation of PN (82.1%), conducting of a minimum of six consultations (84.1%), puerperal consultation (89.0%); to the extent that there is a sum of the actions, there is a significant drop in the proportion of adequacy. Prenatal care was adequate for 67.9%, with a significant difference between adequacy groups in relation to gestational age and birth weight. Prenatal care deficiencies exist, especially in regards to registration of procedures, exams and immunization. The difference between adequacy groups with respect to perinatal outcomes reinforces the importance of prenatal care that adheres to the parameters of the PHPB.
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Se evaluó el prenatal (PN) de un servicio de salud que cuenta con Estratégia Salud de la Familia, de la ciudad de São Paulo, conforme indicadores del Programa de Humanización del Prenatal y Nacimiento (PHPN) y se comparó la adecuación del PN con variables sociodemográficas, procedimientos, exámenes y los resultados maternos y perinatales. Estudio transversal con datos de los registros de 308 embarazadas inscritas en 2011. Se observó el inicio precoz de PN (82,1%), realización del mínimo de seis consultas (84,1%) y la consulta puerperal (89%) y, en la medida en que hay una suma de las acciones, hay una caída significativa en coeficiente de adecuación. El PN fue adecuado para el 67,9%, con una diferencia significativa entre los grupos de adecuación en relación a la edad gestacional y el peso al nacer. Hay deficiencias en el PN, especialmente en los registro de procedimientos, exámenes y vacunas. La diferencia entre los grupos en adecuación con respecto a los resultados perinatales refuerza la importancia de un PN conforme parámetros del PHPN.
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Analisou-se a assistência pré-natal (PN) de uma unidade com Estratégia Saúde da Família do Município de São Paulo, conforme os indicadores do Programa de Humanização do Pré-Natal e Nascimento (PHPN), e comparou-se adequação do PN com variáveis sociodemográficas, procedimentos, exames e desfechos maternos e perinatais. Estudo transversal com dados de registros de 308 gestantes inscritas em 2011. Observou-se início precoce do PN (82,1%), realização do mínimo de seis consultas (84,1%), consulta puerperal (89,0%) e, à medida que há um somatório das ações, há uma queda importante na proporção de adequação. O PN foi adequado para 67,9%, com diferença significante entre os grupos de adequação em relação à idade gestacional e peso ao nascer. No PN existem deficiências, especialmente no registro de procedimentos, exames e imunização. A diferença nos grupos de adequação com relação aos desfechos perinatais reforça a importância de um PN, conforme os parâmetros do PHPN.

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Intoxicação espontânea e experimental por frutos de Eugenia uvalha Cambess (Myrtaceae) em ovinos / Spontaneous and experimental poisoning by fruits of Eugenia uvalha Cambess (Myrtaceae) in sheep

Descrevem-se os dados epidemiológicos, sinais clínicos e lesões de uma enfermidade de ovinos caracterizada por apatia, sialorréia, ranger de dentes, andar em círculos, cegueira, incoordenação motora, opistótono e convulsões, geralmente seguidos de morte. A doença ocorreu nos meses de fevereiro e março de 2009 a 2013, nas regiões Oeste e Planalto do Estado de Santa Catarina e está associada à queda dos frutos da "uvaieira" (Eugenia uvalha Cambess). Nas propriedades onde ocorreram os surtos havia grande quantidade de frutos caídos ao chão e os ovinos os consumiam avidamente. Os que sobreviveram permaneceram com convulsões intermitentes. Não foram observadas alterações macroscópicas ou histológicas. No entanto, foram encontrados frutos inteiros ou fragmentados, misturados ao conteúdo dos pré-estômagos e intestinos. A doença foi reproduzida a partir do fornecimento de frutos maduros de uvaia à três ovinos, nas doses diárias de 45,45g/kg, 68,18g/kg e 82,35g/kg por até seis dias. A principal forma de diagnóstico de intoxicação por "uvaia" é a observação do quadro clínico e epidemiológico, associado à presença de frutos e sementes no trato gastrointestinal.

We describe the epidemiological, clinical signs and lesions of a disease of sheep characterized by apathy, sialorrhoea, teeth grinding, circling, blindness, incoordination, seizures and opisthotonos usually followed by death. The disease occurred in February and March 2009 of 2013, in the West highlands and mountanous regions of Santa Catarina State and was associated with the falling fruits of "uvaieira" (Eugenia uvalha Cambess). In farms where outbreaks occurred had loads of fruit fallen to the ground and the sheep ate them hungrily. Those who survived remained with intermittent seizures. No gross or histological changes were observed. However, the whole fruits or their fragments mixed in the content of the pre-stomachs and bowels were found. The disease was reproduced providing the uvaia ripe fruits to three sheep, in daily doses of 45,45 g/kg, 68,18 g/kg and 82,35 g/kg each, for until six days. The main way to diagnose the uvaia poisoning is the observation of the clinical and epidemiological data, associated with the presence of fruits and seeds in the gastrointestinal tract.

Antiepileptic potential of Anisomeles indica (Linn.) Kuntze aerial parts in pentylenetetrazole-induced experimental convulsions in Wistar rats.

The chloroform (4.20% w/w), ethyl acetate (4.23% w/w) and aqueous decoction (12.11% w/w) extracts of the aerial parts of A. indica were screened for the antiepileptic activity against maximal electroshock (MES) model and pentylenetetrazole (PTZ) models at  doses of 200, 400 mg/kg, po once. Phenytoin and diazepam (25 and 2 mg/kg, ip) were used as standard drugs in MES and PTZ model, respectively. Further, ethyl acetate extract (active extract) was fractionated into flavonoid and tannin fraction, which were subsequently evaluated for the antiepileptic potential against both MES and PTZ models at a dose of 50 mg/kg, po. Pretreatment with ethyl acetate extract 200, 400 mg/kg, po, for 1 week showed significant antiepileptic activity against PTZ induced convulsions only. Isolated flavonoid fraction showed more potent antiepileptic activity as compared to ethyl acetate extract, without any neurotoxic effect. However, tannin fraction did not produce antiepileptic activity against PTZ induced convulsions. It may be concluded that the flavonoids fraction of ethyl acetate extract of aerial parts of A. indica, but not the aqueous decoction has antiepileptic potential, without producing neurotoxic effects.

[Comparison of the effects of chronic administration of morphine and tramadol in infancy on acute pentylenetetrazol-induced seizure in prepubertal rats]

It is demonstrated that morphine and tramadol affects seizure but the mode of action of these drugs on seizure has not been compared yet with increasing of age. The aim of this study was to compare the impact of exposure to these drugs on Pentylenetetrazol-induced seizure in immature rat. Male neonate rats were randomly chosen and divided into three groups namely Saline [n=21], Morphine [n=12] and Tramadol [n=13]. On postnatal days 8-14, Saline group received normal saline and two other groups received morphine and tramadol with additive doses, respectively. On postnatal days 22-28, the saline treated rats divided into three subgroups and received saline [n=8], morphine [n=8] or tramadol [n=5]. Morphine treated rats received saline or morphine [each n=6], and tramadol treated rats received saline [n=7] or tramadol [n=6]. At postnatal day 29, they were evaluated for PTZ-induced seizure. Number of tonic-clonic seizure was increased in all groups compared with control and tramadol+saline groups [P<0.05]. Duration of tonic-clonic seizure was decreased in tramadol+saline group compared with other tramadol groups [P<0.05]. Latency of tonic-clonic seizurewas decreased in tramadol+saline group compared with control rats [P<0.05], But it was increased in saline+tramadol group compared with other groups except to saline group [P<0.05]. Latency of myoclonic contractions in saline+morphine and saline+tramadol groups was lower than in control rats [P<0.05]. Similar age-related changes may occur inchronic exposure to morphine and tramadol in the neonatal period which leads to an increase in severity of seizures in rats on postnatal days 22-28. The effect of morphine and tramadol does not show any significant difference