Excitotoxicity, defined as cell death resulting from the toxic actions of excitatory amino acids, is actually considered as a major factor contributing to the early stage of ischemic cell death in stroke. In stroke, once vessel occlusion is produced, the disruptions to the blood flow in the affected areas decrease the delivery of oxygen and metabolic substrates to neurons. Consequently, the lack of oxygen interrupts oxidative phosphorylation by the mitochondria and drastically reduces cellular ATP production, which results in a rapid decline in cellular ATP. After several minutes, inhibition of the Na + /K +-ATPase function causes a profound loss of ionic gradients and depolarization of regulated neurons, which leads to excessive release of excitatory amino acids-particularly glutamate-to the extracellular compartment. The presence of excessive amounts of glutamate into the synapses and extrasynaptic sites can lead eventually to neuronal death. Excitotoxicity leads to a number of deleterious consequences, including impairment of cellular calcium homeostasis, generation of free radicals and oxidative stress, mitochondrial damage, and activation of several transcription factors and their genes expression. All these mechanisms' acting synergy can cause neuron death by apoptosis. Oxidative stress induced by excitotoxicity is considered to be the main event leading to brain damage after stroke. On the basis of experimental models, there is ample evidence of the role of oxidative stress in ischemic brain damage.
In order to examine the possible role of rat brain glutathione depletion by diethyl maleate (DEM) in the potentiation of 6-hydroxydopamine (6-OHDA) neurotoxicity, the relationships between both effects were evaluated using the circling behavior test (CBT), and determining striatal glutathione S-transferase (GST)-specific activity. There were significant differences between the two studied groups: 6-OHDA and DEM + 6-OHDA lesioned animals in striatal glutathione (GSH) concentration at the moment of the lesion with 6-OHDA and also at the end of the experiment (30 d after 6-OHDA lesion). The circling behavior test following the administration of amphetamine was qualitatively different between both groups of simple- and double-damaged animals. In accordance with our results, DEM injury makes the animals more susceptible to brain-oxidative damage by 6-OHDA, which can indicate that in the double-damaged animal group, DEM could induce potentiation of the toxicity through striatal glutathione depletion.
Colistin is used as a last-line antibiotic for the treatment of Gram-negative multiresistant bacteria. Due to its high nephrotoxicity, Therapeutic Drug Monitoring (TDM) is recommended for dose adjustment. We aimed to evaluate the available evidence of TDM in patients given colistin to treat Gram-negative infections. In this paper, we offer an overview, using an electronic search of the literature (published up to June 2019, without language restrictions) that compares the clinical outcomes and measurements of colistin TDM. Ultimately, the Therapeutic Drug Monitoring (TDM) of colistin in Plasma could prevent nephrotoxicity risk.
Multidrug resistance-associated proteins (MRP) 1 and 2 belong to the ABC (ATP-Binding Cassette) transporters. These transport proteins are involved in the removal of various drugs and xenobiotics, as well as in multiple physiological, pathological, and pharmacological processes. There is a strong correlation between different polymorphisms and their clinical implication in resistance to antiepileptic drugs, anticancer, and anti-infective agents. In our study, we evaluated exon regions of MRP1 (ABCC1)/MRP2 (ABCC2) in a Colombian cohort of healthy subjects to determine single nucleotide polymorphisms (SNPs) and to determine the allelic and genomic frequency. Results showed there are SNPs in our population that have been previously reported for both MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) and MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). Additionally, 13 new SNPs were identified. Evidence also shows a significant clinical correlation for polymorphisms rs3740066 and rs2273697 in the transport of multiple drugs, which suggests a genetic variability in regards to that reported in other populations.
La hemoptisis es una condición seria y potencialmente fatal debido a su curso poco previsible. Es por ello, que el clínico debe investigar todas las causas y sitio del sangrado para realizar un tratamiento oportuno que evite el aumento de la morbilidad y mortalidad del paciente. Existen muchos reportes de hemoptisis causadas por cuerpos extraños al intentar retirarlos, pero pocos donde el cuerpo extraño genere los episodios de hemoptisis, de tal manera que en los algoritmos diagnósticos se considera como causa remota. Se presenta un caso de un paciente joven previamente sano con episodios intermitentes de hemoptisis cuya causa correspondió a una rama vegetal de 6 cm aproximadamente.
Introducción. El tratamiento antirretroviral de la infección por el virus de la inmunodeficiencia humana (HIV) se ha relacionado con diversos problemas de los medicamentos que causan o pueden causar la aparición de resultados negativos. En este contexto, es importante determinar su incidencia, caracterizarlos y clasificarlos para diseñar estrategias que minimicen su impacto.Objetivo. Estimar la incidencia global y de cada uno de los problemas relacionados con los medicamentos antirretrovirales utilizados en el tratamiento del HIV en una cohorte de pacientes hospitalizados en una institución de tercer nivel de Bogotá.Materiales y métodos. Se hizo un estudio descriptivo y retrospectivo de cohorte en pacientes de 18 años o más de edad con diagnóstico de infección por el HIV y en tratamiento antirretroviral, hospitalizados entre el 1° enero de 2015 y el 31 de diciembre de 2016 en el Hospital Santa Clara de Bogotá.Resultados. La incidencia global de los problemas relacionados con los medicamentos antirretrovirales fue de 0,90 (IC95% 0,85-0,93). La incidencia de las interacciones medicamentosas fue de 0,85 (IC95% 0,80-0,90), la de las reacciones adversas de 0,28 (IC95% 0,22-0,35) y la del error de prescripción de 0,12 (IC95% 0,08-0,17).Conclusión. Los problemas relacionados con los medicamentos deben estudiarse, diagnosticarse, prevenirse y tratarse para que el personal de salud pueda anticiparse a su aparición, disminuir su incidencia, implementar planes de manejo del riesgo y optimizar el cumplimiento del tratamiento antirretroviral.
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