N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 μg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Interleukin-5 and interleukin-10 are major cytokines in cerebrospinal fluid from patients with active neurocysticercosis

Neurocysticercosis (NCC) is a common neurological disorder especially in developing countries, caused by infection of the brain with encysted larvae of the tapeworm Taenia solium. Seizures are a common finding associated with this disease. The objective of the present study was to evaluate the correlation between the levels of various cytokines present in the cerebrospinal fluid (CSF) of patients with NCC and the severity of the disease. The levels of the cytokines IL-1î, TNF-alpha, IL-5, IL-10 and IFN-gamma were determined in the CSF of 22 patients with active NCC, 13 patients with inactive NCC and 15 control subjects. CSF from patients with active NCC presented significantly higher IL-5 levels compared to control subjects. IL-5 and IL-10 levels in CSF from NCC patients with inflammatory CSF were significantly higher than those detected in non-inflammatory CSF. These results show a predominant Th2 lymphocyte activation in human NCC and also indicate the possible use of cytokines in the CSF as a marker for the differential diagnosis between inactive disease and the active form of NCC

Bloqueio atrioventricular total por trauma cardíaco fechado / Complete heart block due to non-penetrating thoracic trauma

Os autores relatam o caso de uma paciente de 57 anos que passou a apresentar bloqueio atrioventricular total (BAVT) em conseqüência de um coice desferido por cavalo (trauma cardíaco fechado). O impacto de coice do animal foi de tal intensidade que arremessou a paciente a vários metros, fraturando-lhe uma costela e provocando o transtorno de conduçäo atrioventricular. Realizado com sucesso o implante de marcapasso provisório, a paciente mostrou boa evoluçäo. O ritmo sinusal com conduçäo AV 1:1 foi restabelecido no dia seguinte ao traumatismo e avaliaçöes posteriores confirmaram o desaparecimento do transtorno.

Marcapasso endocárdico em recém-nascido / Endocardial pacemakerin small children

Os autores relatam o caso em que uma criança de 48 horas de vida, portadora de bloqueio atrioventricular (BAV) de grau avançado, bradicardia acentuada e insuficiência cardíaca importante foi submetida com sucesso a um implante de marcapasso endocárdico. Como via de acesso foi utilizada a veia jugular interna, o cabo-eletrodo de fixaçäo passiva foi posicionado no ventrículo direito e uma alça foi efetuada no interior do átrio direito. Com o crescimento da criança, observou-se o progressivo desenrolar do cabo-eletrodo. A freqüência inicial do marcapasso com que se obteve melhor débito cardíaco foi de 120 ppm, valor definido através de ecocardiograma bidimensional. Após 28 meses a criança vem apresentando ótima evoluçäo clínica. O marcapasso atualmente demonstra bom funcionamento, tanto no comando como na sensibilidade, e o cabo-eletrodo apresenta desenrolar suave, acompanhando o crescimento da criança.