Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats.

When burning crack cocaine, the pyrolysis of cocaine generates anhydroecgonine methyl ester (AEME). AEME has been shown to be highly neurotoxic but its effects on cognitive function and oxidative stress are still unknown. Thus, this study investigated the effects of AEME on spatial working memory and on parameters of oxidative stress in the prefrontal cortex, hippocampus, and striatum. First, 18 well-trained rats in 8-arm radial maze (8-RM) procedures received acute intracerebroventricular (icv) administration of AEME at doses of 10, 32, or 100 µg or saline (SAL) in a counterbalanced order and were tested 5 min later in 1-h delayed tasks in the 8-RM. Secondly, separated animals received acute icv administration of AEME at doses of 10 (n = 5), 32 (n = 5), or 100 µg (n = 5) or SAL (n = 5) for analysis of advanced oxidation protein products, thiobarbituric acid, catalase, glutathione peroxidase, and superoxide dismutase. A higher number of errors were seen in the 1-h post-delay performance after AEME 32 µg and AEME 100 µg when compared to SAL. In the striatum, animals receiving AEME 100 µg icv showed increased advanced oxidation protein products levels when compared to 10 µg, and also showed increased activity of glutathione peroxidase enzyme when compared to SAL but also comparing to AEME 32 µg and AEME 10 µg. These results showed that AEME impairs long-term spatial working memory and also induces greater protein oxidation and increased levels of antioxidant enzymes in the striatum.

Simplified correction of a meningomyelocele-like defect in the ovine fetus.

PURPOSE: To develop a simplified technique for antenatal correction of a meningomyelocele -like defect in fetal sheep to allow direct skin closure. METHODS: A spinal defect was surgically created at 75 days of gestation in the fetuses of 36 pregnant sheep, 23 survived the surgery. At 102 days gestation, the defect was corrected in 14 cases (9 were left untreated). Skin surrounding the defect was dissected below the dermis to permit its edges to be approximated and sutured, without interposing any material to its edges. An interface material intended to protect the neural tissue from skin adhesion was used and the skin defect was completely closed over it. Pregnancy was allowed to continue up to 138 days gestation, the fetuses were submitted to macroscopic and microscopic analysis. RESULTS: The defect was successfully corrected in 90.9% in the experimental group, and spontaneous closure occurred in 22.3% in the control group (p < 0.05). The survival rate after the creation and correction of the defect was 63.4% and 78% respectively. CONCLUSION: This simplified technique was successful in the correction a meningomyelocele-like defect, in the fetal sheep.

Simplified correction of a meningomyelocele-like defect in the ovine fetus / Correção simplificada de um defeito semelhante à meningomielocele em fetos de ovelha

PURPOSE: To develop a simplified technique for antenatal correction of a meningomyelocele -like defect in fetal sheep to allow direct skin closure. METHODS: A spinal defect was surgically created at 75 days of gestation in the fetuses of 36 pregnant sheep, 23 survived the surgery. At 102 days gestation, the defect was corrected in 14 cases (9 were left untreated). Skin surrounding the defect was dissected below the dermis to permit its edges to be approximated and sutured, without interposing any material to its edges. An interface material intended to protect the neural tissue from skin adhesion was used and the skin defect was completely closed over it. Pregnancy was allowed to continue up to 138 days gestation, the fetuses were submitted to macroscopic and microscopic analysis. RESULTS: The defect was successfully corrected in 90.9 percent in the experimental group, and spontaneous closure occurred in 22.3 percent in the control group (p < 0.05). The survival rate after the creation and correction of the defect was 63.4 percent and 78 percent respectively. CONCLUSION: This simplified technique was successful in the correction a meningomyelocele-like defect, in the fetal sheep.

OBJETIVO: Desenvolver uma técnica simplificada de correção pré-natal de defeito semelhante à mielomeningocele em fetos de ovelha permitindo um fechamento direto da pele. MÉTODOS: Um defeito espinhal foi cirurgicamente criado com 75 dias de gestação, em 36 fetos de ovelha, 23 sobreviveram à cirurgia. Após 102 dias de gestação, o defeito foi corrigido em 14 casos (9 não foram tratados). A pele em volta do defeito foi dissecada abaixo da derme para permitir a aproximação direta das bordas através de sutura, sem a interposição de nenhum material entre a pele. Um material de interface foi colocado entre o tecido neural exposto e a pele, com o objetivo de evitar a adesão da medula à pele, que foi completamente fechada sobre o defeito. A gravidez foi mantida até 138 dias, os fetos foram submetidos a análises macroscópicas e microscópicas. RESULTADOS: O defeito foi corrigido em 90.9 por cento no grupo experimental, e o fechamento espontâneo ocorreu em 22.3 por cento no grupo controle (p < 0.05). A taxa de sobrevivência após a criação do defeito e posteriormente a sua correção foi de 63,4 por cento e 78 por cento, respectivamente. CONCLUSÃO: Esta técnica simplificada teve sucesso na correção do defeito semelhante à mielomeningocele em feto de ovelha.

Biosynthetic cellulose induces the formation of a neoduramater following pre-natal correction of meningomyelocele in fetal sheep.

PURPOSE: The aim of this study was to compare the effectiveness of two dura-mater substitutes, namely human acellular dermal matrix (HADM) and biosynthetic cellulose (BC), in repairing, in utero, surgically-induced meningomyelocele (MMC) in fetal sheep. METHODS: A neural tube defect was created at 74-77 days gestation in 36 fetal sheep. They were divided into 3 groups, the control group that did not receive pre-natal corrective surgery, and the other two groups that received corrective surgery using HADM (Group A) or BC (Group B). Both materials were used as a dura-mater substitutes between the neural tissue and the sutured skin. Correction was performed at gestation day 100 and the fetuses were maintained in utero until term. Sheep were sacrificed on gestation day 140. The fetal spine was submitted to macro and microscopic analysis. At microscopy, adherence of the material to the skin and neural tissue was analyzed. RESULTS: In the initial phase (pilot), experimentally-induced MMC was performed on 11 fetuses and 4 survived (37%). In the second phase (study), 25 fetuses received surgery and 17 survived (68%). In the study group, 6 fetuses did not undergo repair (control group), 11 cases were submitted to corrective surgery (experimental group) and one fetal loss occurred. Of the surviving cases in the experimental group, 4 constituted Group A and 6 in Group B. Macroscopically, skin and underlying tissues where easily displaced from the BC in all cases it was used; in contrast, HADM adhered to these tissues. To compare the adherence, 4 cases from Group A and 4 in Group B were studied. We observed adherence, host cell migration and vessel proliferation into the HADM all sections from Group A and this aspect was not present in any cases in Group B (p < 0.05). In Group B, we also observed that a new fibroblast layer formed around the BC thus protecting the medulla and constituting a "neoduramater". CONCLUSION: The use of BC seems to be more adequate as a dura-mater substitute to cover the damaged neural tissue than HADM. It seems promising for use in the in utero correction of MMC because to does not adhere to neural tissue of superficial and deep layers ("tethered spinal cord"). Thus, BC minimizes the mechanical and chemical intrauterine damage to the spinal medulla.

Validation of the ovine fetus as an experimental model for the human myelomeningocele defect.

PURPOSE: To produce a myelomeningocele-like human defect in the ovine fetus and validate this experimental model in our population. METHODS: A prospective study on 12 pregnant sheep of a crossed Hampshire/Down breed where a spinal defect was surgically created between Day 75 and Day 77 after conception. The technique consisted of a hysterotomy with exposure of fetal hind limbs and tail up to the mid spine. Fetal skin, paravertebral muscles, and 4 posterior spinal arches were excised, exposing the spinal cord. Duramater was opened and the medulla was incised until the medullar canal. Animals were euthanized at 139 days of gestation for fetal evaluation. The central nervous system was submitted to post-mortem magnetic resonance imaging (MRI) and the spine was submitted to pathological examination. RESULTS: The defect was created in 13 fetuses and 5 survived. Mean gestational age at necropsy was 121.6 days (varying from 93 to 145 days). Macroscopically, the defect was present in 4 cases. Microscopy revealed a flattened medulla with disappearance of the medullar canal and disruption of normal medullar architecture with neuronal apoptosis and/or fusion of the piamater and duramater. The MRI showed herniation of the cerebellum into the cervical canal and syringomyelia. CONCLUSIONS: The surgically produced defect mimics the defect found in the human fetus, including the Arnold-Chiari malformation. Post-mortem MRI was used for the first time in our study and proved an excellent alternative for demonstrating the cerebellar herniation. We standardized the technique for creating the defect in our population.

Validation of the ovine fetus as an experimental model for the human myelomeningocele defect

PURPOSE: To produce a myelomeningocele-like human defect in the ovine fetus and validate this experimental model in our population. METHODS: A prospective study on 12 pregnant sheep of a crossed Hampshire/Down breed where a spinal defect was surgically created between Day 75 and Day 77 after conception. The technique consisted of a hysterotomy with exposure of fetal hind limbs and tail up to the mid spine. Fetal skin, paravertebral muscles, and 4 posterior spinal arches were excised, exposing the spinal cord. Duramater was opened and the medulla was incised until the medullar canal. Animals were euthanized at 139 days of gestation for fetal evaluation. The central nervous system was submitted to post-mortem magnetic resonance imaging (MRI) and the spine was submitted to pathological examination. RESULTS: The defect was created in 13 fetuses and 5 survived. Mean gestational age at necropsy was 121.6 days (varying from 93 to 145 days). Macroscopically, the defect was present in 4 cases. Microscopy revealed a flattened medulla with disappearance of the medullar canal and disruption of normal medullar architecture with neuronal apoptosis and/or fusion of the piamater and duramater. The MRI showed herniation of the cerebellum into the cervical canal and syringomyelia. CONCLUSIONS: The surgically produced defect mimics the defect found in the human fetus, including the Arnold-Chiari malformation. Post-mortem MRI was used for the first time in our study and proved an excellent alternative for demonstrating the cerebellar herniation. We standardized the technique for creating the defect in our population.

OBJETIVO: Produzir um defeito semelhante a meningomielocele humana em feto de ovinos, validando este modelo experimental, em nosso meio. MÉTODOS: Estudo prospectivo com 12 ovelhas de cruzamento das raças Hampshire e Down, onde um defeito na coluna foi criado cirurgicamente com 75 a 77 dias de gestação. A técnica consistiu em histerotomia com exposição das patas traseiras e cauda até a metade da coluna fetal. Foram retirados pele, musculatura paravertebral e 4 arcos vertebrais posteriores, expondo a medula. A dura foi aberta e uma incisão até o canal medular foi realizada. O sacrifício foi realizado com 139 dias de gestação para avaliação fetal. O sistema nervoso central foi submetido a ressonância magnética (REMA) post-mortem e a coluna foi submetida a exame anátomo-patológico. RESULTADOS: O defeito foi criado em 13 fetos e 5 sobreviveram. A idade gestacional média da necropsia foi de 121,6 dias (variando de 93 a 145 dias). Macroscopicamente o defeito estava presente em 4 casos. A microscopia revelou achatamento da medula, com desaparecimento do canal medular e desarranjo da citoarquitetura medular com apoptose neuronal e/ou fusão da pia e dura-máter. A REMA demonstrou herniação do cerebelo para o canal cervical e siringomelia. CONCLUSÕES: O defeito produzido foi muito semelhante à meningomielocele em fetos humanos, levando inclusive à mal-formação de Arnold-Chiari. A REMA post-mortem, utilizada de forma inédita neste estudo, demonstrou ser uma excelente alternativa para demonstrar a presença da herniação do cerebelo. A técnica para produzir o defeito foi padronizada em nosso meio.

Biosynthetic cellulose induces the formation of a neoduramater following pre-natal correction of meningomyelocele in fetal sheep

PURPOSE: The aim of this study was to compare the effectiveness of two dura-mater substitutes, namely human acellular dermal matrix (HADM) and biosynthetic cellulose (BC), in repairing, in utero, surgically-induced meningomyelocele (MMC) in fetal sheep. METHODS: A neural tube defect was created at 74-77 days gestation in 36 fetal sheep. They were divided into 3 groups, the control group that did not receive pre-natal corrective surgery, and the other two groups that received corrective surgery using HADM (Group A) or BC (Group B). Both materials were used as a dura-mater substitutes between the neural tissue and the sutured skin. Correction was performed at gestation day 100 and the fetuses were maintained in utero until term. Sheep were sacrificed on gestation day 140. The fetal spine was submitted to macro and microscopic analysis. At microscopy, adherence of the material to the skin and neural tissue was analyzed. RESULTS: In the initial phase (pilot), experimentally-induced MMC was performed on 11 fetuses and 4 survived (37 percent). In the second phase (study), 25 fetuses received surgery and 17 survived (68 percent). In the study group, 6 fetuses did not undergo repair (control group), 11 cases were submitted to corrective surgery (experimental group) and one fetal loss occurred. Of the surviving cases in the experimental group, 4 constituted Group A and 6 in Group B. Macroscopically, skin and underlying tissues where easily displaced from the BC in all cases it was used; in contrast, HADM adhered to these tissues. To compare the adherence, 4 cases from Group A and 4 in Group B were studied. We observed adherence, host cell migration and vessel proliferation into the HADM all sections from Group A and this aspect was not present in any cases in Group B (p < 0.05). In Group B, we also observed that a new fibroblast layer formed around the BC thus protecting the medulla and constituting a "neoduramater". CONCLUSION: The use of BC...

OBJETIVO: Estudar os efeitos do emprego de dois materiais consideravelmente diferentes quanto à origem e custo na correção intra-uterina da meningomielocele criada experimentalmente em feto de ovino. MÉTODOS: Em 36 fetos de ovinos foi criado um defeito aberto de tubo neural, com 75 de dias de gestação. Os casos foram divididos em três grupos: o controle onde o defeito não foi corrigido, grupo corrigido A onde o material utilizado para cobrir a medula exposta foi a matriz dérmica humana acelular (MDHA) e o grupo corrigido B onde o material foi a celulose biossintética (CB). Após a correção realizada com 100 dias, os fetos eram mantidos intra-útero até o termo da gestação. Os sacrifícios foram realizados com 140 dias e a coluna fetal era submetida à análise macro e microscópica onde foi observada a aderência dos materiais à pele, medula ou tecido nervoso remanescente. RESULTADOS: Na fase inicial (piloto), 11 fetos foram operados e 4 sobreviveram (37 por cento). Na segunda fase (estudo) 25 fetos foram operados e 17 sobreviveram (68 por cento). No grupo de estudo, 6 fetos não foram submetidos à correção (grupo controle), 11 casos foram corrigidos e ocorreu 1 perda fetal. Do total de 10 casos, 4 constituíram o grupo A e 6, o grupo B. A macroscopia observou-se deslizamento da pele e tecidos subjacentes sobre a CB em todos os casos onde ela foi empregada e isto não ocorreu em nenhum dos casos onde a MDHA foi utilizada. Para comparar a aderência, foram considerados 4 casos do grupo A e 4 do grupo B. A aderência, caracterizada pela migração de células do hospedeiro e proliferação de vasos para dentro da MDHA, foi observada em 100 por cento dos casos do grupo A e em nenhum caso no grupo B (p < 0,05). No grupo B observou-se formação de uma camada de fibroblastos ao redor do material, protegendo a medula, caracterizando a formação de uma "neoduramater". CONCLUSÃO: A utilização da película de celulose biossintética parece ser mais adequada como substituto...

Validação do feto ovino como modelo experimental para o defeitomeningomielocele humana: estudo piloto / Validation of the ovine fetus as an experimental model for the human myelomeningocele defect: a pilot study

O objetivo deste trabalho foi produzir um defeito semelhante meningomielocele humanaem feto de ovinos, validando este modelo experimental, em nosso meio. Estudo prospectivo com 12 ovelhas de cruzamento das raças Hampshire e Down, onde um defeito na coluna foi criado cirurgicamente com 75 a 77 dias de gestação. A técnica consistiu emhisterotomia com exposição das patas traseiras e cauda até a metadeda coluna fetal. Foram retirados pele, musculatura paravertebral e quatro arcos vertebrais posteriores, expondo a medula. A dura foi aberta e uma incisão até o canal medular foi realizada. O sacrifício foi realizado com 139 dias de gestação para avaliação fetal. O sistemanervoso central foi submetido a ressonância magnética post-morteme a coluna foi submetida a exame anatomopatológico. O defeito foi criado em 13 fetos e 5 sobreviveram. A idade gestacional média da necropsia foi de 121,6 dias (variando de 93 a 145 dias).Macroscopicamente, o defeito estava presente em quatro casos. A microscopia revelou achatamento da medula, com desaparecimentodo canal medular e desarranjo da citoarquitetura medular com apoptose neuronal e/ou fusão da pia e dura-máter. A ressonância magnética demonstrou herniação do cerebelo para o canal cervical e siringomelia. Conclusões: O defeito produzido foi muito semelhante à meningomielocele em fetos humanos, levando inclusive àmalformação de Arnold-Chiari. A ressonância magnética postmortem,utilizada de forma inédita neste estudo, demonstrou ser uma excelente alternativa para demonstrar a presença da herniação do cerebelo. A técnica para produzir o defeito foi padronizada em nosso meio.

Prevalência de sintomas e doenças respiratórias em criançasna idade escolar, fumantes ou não-fumantes passivas / Prevalence of respiratory symptoms and disease in scholar-age children, passive smoking or passive non-smoking

Introdução: cerca de um terço da população brasileira faz uso do tabaco; deste total, dois terços residem em zonas urbanas. Pais fumantes que expõem seus filhos ao tabagismo aumentam, em até três vezes, a incidência de infecções respiratórias. Nosso objetivo é comparar a prevalência de sintomas de doenças respiratórias em crianças fumantes passivas ou não-fumantes passivas na idade escolar. Metodologia: avaliamos 217 crianças residentes em áreas urbanas, entre sete e dez anos, sendo 103 do sexo masculino. Para a coleta de dados, foi utilizado um questionário abrangendo os hábitos tabágicos do núcleo familiar e de pessoas que tivessem contato prolongado com as mesmas. Questões como presença de rinite, sibilância, dispnéia, coriza e cansaço também foram abordadas. Para identificação de doenças como asma, pneumonia e bronquite aguda, solicitamos diagnóstico médico para os pais. Para a análise dos dados, utilizou-se o teste do qui-quadrado com nível de significância <0,05. Resultados: verificou-se que 48,85% das crianças apresentavam história de hábito de fumar na família, 25,47% das crianças expostas ao fumo passivo tinham coriza e 24,52% rinite. O grupo não exposto ao fumo ambiental apresentou 9% de coriza e 3,6% rinite. Comparando os grupos, verificou-se maior prevalência de sintomas e doenças respiratórias no grupo exposto ao fumo passivo. Quando comparamos cada variável isoladamente, encontramos diferenças significativas apenas para a presença de coriza e rinite (p<0,05). Conclusão: os índices de doenças respiratórias nas escolas ainda são altos e, em grande parte, agravados ou até mesmo causados pela submissão de crianças ao tabagismo passivo.