RESUMO
Human and murine succinic semialdehyde dehydrogenase (SSADH; gamma-hydroxybutyric (GHB) aciduria) deficiency represents an epileptic disorder associated with hyperGABA- and hyperGHB-ergic states. Despite significant neurotransmitters alterations, well-defined single-cell electrophysiological studies, aimed to provide insight into regional neuropathology, have been lacking. In this study, we characterized the effect of residual SSADH enzyme function/increased GABA levels on single-cell hippocampal electrophysiology in SSADH+/+ (wild-type; WT), SSADH+/- (heterozygous; HET), and SSADH-/- (knock-out; KO) mice. Tonic extrasynaptic GABAA receptor (GABAAR)-mediated currents were elevated in HET and KO mice, whereas phasic synaptic GABAAR currents were unaltered in dentate gyrus granule cells. Similarly, tonic GABAAR-mediated currents were increased in dentate gyrus interneurons of KO animals, while phasic GABAergic neurotransmission was unaffected in the same cells. Our results indicate global disruption of cortical networks in SSADH KO mice, affecting both excitatory and inhibitory neurons. Our findings provide new clues concerning seizure evolution in the murine model (absence-->tonic-clonic-->status epilepticus), and extend pathophysiological insight into human SSADH deficiency.
Assuntos
Dosagem de Genes/genética , Hipocampo/patologia , Potenciais da Membrana/genética , Neurônios/fisiologia , Convulsões , Succinato-Semialdeído Desidrogenase/deficiência , Animais , Animais Recém-Nascidos , Biofísica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estimulação Elétrica/métodos , Feminino , Antagonistas GABAérgicos/farmacologia , Humanos , Técnicas In Vitro , Modelos Lineares , Lisina/análogos & derivados , Masculino , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Camundongos Knockout , Neurônios/classificação , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp/métodos , Piridazinas/farmacologia , Convulsões/genética , Convulsões/patologia , Convulsões/fisiopatologia , Ácido gama-Aminobutírico/metabolismoRESUMO
High-value trees, such as those located in residential, recreational, or administrative sites, are particularly susceptible to bark beetle (Coleoptera: Curculionidae: Scolytinae) attack as a result of increased amounts of stress associated with drought, soil compaction, mechanical injury, or vandalism. Tree losses in these unique environments generally have a substantial impact. The value of these individual trees, cost of removal, and loss of esthetics may justify protection until the main thrust of a bark beetle infestation subsides. This situation emphasizes the need for ensuring that effective insecticides are available for individual tree protection. In this study, we assess the efficacy of bifenthrin (Onyx) and carbaryl (Sevin SL) for protecting: ponderosa pine, Pinus ponderosa Dougl. ex. Laws., from western pine beetle, Dendroctonus brevicomis LeConte, in California; mountain pine beetle, Dendroctonus ponderosae Hopkins in South Dakota; and Ips spp. in Arizona; lodgepole pine, Pinus contorta Dougl. ex Loud., from D. ponderosae in Montana; pinyon, Pinus edulis Engelm. in Colorado and Pinus monophylla Torr. and Frem. in Nevada from pinyon ips, Ips confusus (LeConte); and Engelmann spruce, Picea engelmannii Parry ex. Engelm. from spruce beetle, Dendroctonus rufipennis (Kirby) in Utah. Few trees were attacked by Ips spp. in Arizona and that study was discontinued. Sevin SL (2.0%) was effective for protecting P. ponderosa, P. contorta, and P. monophylla for two field seasons. Estimates of efficacy could not be made during the second field season in P. edulis and P. engelmannii due to insufficient mortality in untreated, baited control trees. Two field seasons of efficacy was demonstrated in P. ponderosa/D. brevicomis and P. monophylla for 0.06% Onyx. We conclude that Onyx is an effective individual tree protection tool, but repeated annual applications may be required in some systems if multiyear control is desired.
Assuntos
Carbaril , Besouros , Inseticidas , Pinus/parasitologia , Piretrinas , Animais , Montana , South Dakota , Sudoeste dos Estados UnidosRESUMO
Type I diabetes mellitus is an autoimmune disease characterized by the selective destruction of the insulin-secreting beta-cell found in pancreatic islets of Langerhans. Cytokines such as interleukin-1 (IL-1), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) mediate beta-cell dysfunction and islet degeneration, in part, through the induction of the inducible isoform of nitric-oxide synthase and the production of nitric oxide by beta-cells. Cytokines also stimulate the expression of the inducible isoform of cyclooxygenase, COX-2, and the production of prostaglandin E(2) (PGE(2)) by rat and human islets; however, the role of increased COX-2 expression and PGE(2) production in mediating cytokine-induced inhibition of islet metabolic function and viability has been incompletely characterized. In this study, we have shown that treatment of rat islets with IL-1beta or human islets with a cytokine mixture containing IL-1beta + IFN-gamma +/- TNF-alpha stimulates COX-2 expression and PGE(2) formation in a time-dependent manner. Co-incubation of rat and human islets with selective COX-2 inhibitors SC-58236 and Celecoxib, respectively, attenuated cytokine-induced PGE(2) formation. However, these inhibitors failed to prevent cytokine-mediated inhibition of insulin secretion or islet degeneration. These findings indicate that selective inhibition of COX-2 activity does not protect rat and human islets from cytokine-induced beta-cell dysfunction and islet degeneration and, furthermore, that islet production of PGE(2) does not mediate these inhibitory and destructive effects.
Assuntos
Citocinas/metabolismo , Ilhotas Pancreáticas/enzimologia , Ilhotas Pancreáticas/patologia , Isoenzimas/fisiologia , Prostaglandina-Endoperóxido Sintases/fisiologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Western Blotting , Celecoxib , Células Cultivadas , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Citocinas/biossíntese , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Glucose/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Interferon gama/metabolismo , Interleucina-1/metabolismo , Ilhotas Pancreáticas/citologia , Proteínas de Membrana , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Nitritos/metabolismo , Isoformas de Proteínas , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Fatores de TempoRESUMO
3-Methylglutaconic-aciduria type I (MGA1, OMIM 250950) resulting from 3-Methylglutaconyl-coenzyme A hydratase deficiency is a rare inherited metabolic disorder of l-leucine catabolism. We diagnosed this condition in a 4-year-old German male with generalized fever-associated seizures from the age of 12 months and normal psychomotor development. First he was considered to suffer from uncomplicated febrile seizures. After his eighth seizure, laboratory investigations were performed to exclude inborn errors of metabolism. Analysis of organic acids in urine indicated highly elevated concentrations of 3-methylglutaconic and 3-hydroxyisovaleric acids. 3-Methylglutaconyl-coenzyme A hydratase activity was markedly decreased in skin fibroblasts. Mutation analysis in the AUH gene revealed homozygosity for a novel splice site mutation IVS9-2A>G. We conclude that MGA1 may be associated with fever-associated seizures even in children without delayed psychomotor development.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Enoil-CoA Hidratase/genética , Glutaratos/urina , Hidroliases/deficiência , Proteínas de Ligação a RNA/genética , Convulsões Febris/genética , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Diferencial , Fibroblastos/enzimologia , Seguimentos , Heterozigoto , Homozigoto , Humanos , Hidroliases/genética , Íntrons/genética , Masculino , Fenótipo , Sítios de Splice de RNA/genética , Recidiva , Convulsões Febris/enzimologia , Valeratos/urinaRESUMO
The antiaggregation pheromone 3-methylcyclohex-2-en-1-one (MCH) is highly effective in preventing the infestation of high-risk trees by Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins. A large portion of the cost of an MCH treatment is related to the time applicators spend walking through an area dispersing the formulated pheromone. Application of fewer MCH dispensers eluting at a higher rate than those currently registered for operational use could potentially reduce treatment costs. Two higher elution rates, 6 and 18 mg/d per dispenser, were compared with the current standard of 2 mg/d per dispenser and an untreated control on 1-ha circular plots. Dispensers were spaced 5,15, and 44 m apart around the plot perimeters eluting 2, 6, and 18 mg/d, respectively. The nominal dose of MCH was 144 mg/ha/d on all plots. Percentages of Douglas-fir trees > or = 20 cm diameter at breast height mass attacked by Douglas-fir beetle were significantly lower on plots treated with dispensers eluting 2 and 6 mg/d and spaced 5 and 15 m apart, respectively, compared with the untreated control. Infestation rate on plots treated with dispensers eluting 18 mg/d and spaced 44 m apart was not significantly different from the control. Douglas-fir beetle abundance and host tree availability were similar on all plots. These results indicate that MCH dispensers eluting 6 mg/d (three times the current standard rate) and spaced 15 m apart (three times existing standard distance) can effectively prevent Douglas-fir beetle infestations.
Assuntos
Besouros , Controle Biológico de Vetores , Pseudotsuga , Atrativos Sexuais , Animais , Masculino , Controle Biológico de Vetores/métodos , Estações do AnoRESUMO
Evaluamos 23 historias médicas con diagnóstico de fiebre tifoidea, de pacientes provenientes del Reten de Catia durante el período Diciembre 1991 -Septiembre 1992. Conseguimos edad, sexo, ocurrencia estacional, motivo de consulta, sintomas, signos complicaciones, paraclínicos y mortalidad. Todos los pacientes fueron varones con edad promedio de 25-78 años. El mayor número de casos ocurrió en Mayo 1992, el tiempo de convalescencia fue de 41-57 días. Los hallazgos más frecuenttes fueron: como motivos de consulta y datos de la enfermedad actual, fiebre, disminución de peso, diarrea, dolor abdominal, taquicardia, hipotensión taquipnea al examen físico y perforación intestinal y sepsis como complicaciones Serología y cultivos fuerron positivos en un 69.57 por ciento y 43.48 por ciento respectivamente. Encontramos elevado porcentaje de complicaciones y alta mortalidad debido al traslado tardio de los pacientes al hospital (entre la tercera y cuarta semana). Sugerimos medidas preventivas
Assuntos
Humanos , Masculino , Surtos de Doenças/prevenção & controle , Métodos Epidemiológicos , Febre Tifoide/complicações , Febre Tifoide/epidemiologia , Febre Tifoide/mortalidade , Vacinas Tíficas-Paratíficas/administração & dosagem , Vacinas Tíficas-Paratíficas/uso terapêutico , Infecções por Salmonella/diagnósticoRESUMO
Se hace la descripción de un neonato con antecedentes familiares importantes de epilepsia, incluyendo a la madre, la cual recibió tratamiento con fenobarbital y difenilhidantonia, durante la gestación, sin obtenerse control de su cuadro convulsivo. Se describen múltiples malformaciones congénitas representativas del síndrome. Se realiza una breve revisión de la literatura mundial, a partir del primer reporte de esta entidad, por Meadow (Inglaterra) en 1968. Se puntualizan los probables factores etiopatogénicos: genético-hereditario, acción específica de la o las drogas anticonvulsivantes, y convulsiones durante el embarazo. Se trata del primer caso en la literatura pediátrica venezolana, altamente representativo por sus manifestaciones clínicas. Se plantea un plan de trabajo sistematizado, para lograr el diagnóstico, que dado a la característica multifactorial de su etiología, es por descarte. Finalmente, se exponen tanto el riesgo genético, como recomendaciones obstétricas y pediátricas, para el manejo de esta situación clínica
