Teresa Imelda Fortoul van der Goes

Protective effect of systemic l-kynurenine and probenecid administration on behavioural and morphological alterations induced by toxic soluble amyloid beta (25–35) in rat hippocampus

Amyloid beta (Abeta) peptide exerts different toxic effects at a cellular level, including over-activation of N-methyl-D-aspartate receptor (NMDAr) and excitotoxicity, synaptic dysfunction and neuronal death. Kynurenic acid (KYNA) is an endogenous antagonist of NMDAr and alpha7 nicotinic receptors. Systemic administrations of both the immediate metabolic precursor of KYNA, L-kynurenine (L-KYN), and a proved inhibitor of KYNAs brain transport, probenecid (PROB), have shown to produce neuroprotective effects in a considerable number of experimental toxic conditions; however, this strategy has not been tested in the toxic model Abeta peptide so far. In this study we evaluated the effects of systemic administration of PROB (50 mg/kg/day for 7 days), L-KYN (75 mg/kg/day for 7 days) and their combination, on behavioural (locomotor activity and spatial memory) and morphological alterations induced by an intrahippocampal infusion of Abeta 25-35 to rats. An additional group was administered with the potent NMDAr antagonist dizocilpine (MK-801, 0.8 mg/kg/day for 7 days) for comparative purposes. A significant improvement of spatial memory was evident in Abeta-lesioned rats since post-lesion day 21 with all treatments tested and this effect was correlated with a reduction of cell damage and a decrease in reactive gliosis in hippocampal CA1 area. Neither L-KYN, nor PROB, or their combination, produced major alterations in motor function when given alone to rats. These results suggest that modulation of NMDAr activity by mean of therapeutic strategies designed to enhance KYNA in the brain may help to counteract neurodegenerative events coursing with Abeta toxicity and excitotoxic patterns.

Cytoplasmic calcium mediates oxidative damage in an excitotoxic /energetic deficit synergic model in rats

Excessive calcium is responsible for triggering different potentially fatal metabolic pathways during neurodegeneration. In this study, we evaluated the role of calcium on the oxidative damage produced in an in vitro combined model of excitotoxicity/energy deficit produced by the co‐administration of quinolinate and 3‐nitropropionate to brain synaptosomal membranes. Synaptosomal fractions were incubated in the presence of subtoxic concentrations of these agents (21 and 166 µm, respectively). In order further to characterize possible toxic mechanisms involved in oxidative damage in this experimental paradigm, agents with different properties – dizocilpine, acetyl l‐carnitine, iron porphyrinate and S‐allylcysteine – were tested at increasing concentrations (10–1000 µm). Lipid peroxidation was assessed by the formation of thiobarbituric acid‐reactive substances. For confirmatory purposes, additional fractions were incubated in parallel in the presence of the intracellular calcium chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester (BAPTA‐AM). Under physiological conditions of extracellular calcium availability, synaptomes exposed to both toxins displayed an increased lipoperoxidation (76% above controls), and this effect was partially attenuated by the tested agents as follows: dizocilpine = iron porphyrinate > acetyl l‐carnitine > S‐allylcysteine. When the incubation medium was deprived of calcium, the lipoperoxidative effect achieved in this experimental paradigm was still high (49% above the control), and the order of attenuation was: iron porphyrinate > S‐allylcysteine > acetyl l‐carnitine > dizocilpine. BAPTA‐AM was effective in preventing the pro‐oxidant action of both toxins, promoting even lower peroxidative levels than those quantified under basal conditions. Our results suggest that the lipid peroxidation induced in synaptosomal fractions by quinolinate plus 3‐nitropropionate is largely dependent on the cytoplasmic concentrations of calcium.

Correlación entre la evaluación diagnóstica y el rendimiento académico de los estudiantes de medicina

Resumen Introduccion El rendimiento academico de los estudiantes esta asociado con una gran variedad de factores, uno de ellos corresponde a los conocimientos previos de ingreso a la licenciatura de medico cirujano, por lo que, describir las calificaciones en los examenes departamentales a partir de dichos conocimientos, en la fase inicial de la licenciatura, permitira identificar aquellos en riesgo academico e implementar las medidas remediales pertinentes. Objetivo Determinar la relacion entre los resultados en el examen diagnostico y en los examenes departamentales de las asignaturas de primer ano en estudiantes de nuevo ingreso a la licenciatura de Medico Cirujano. Metodo Se realizo un estudio de correlacion y comparacion que incluyo los datos de un total de 6 590 estudiantes. En particular se calcularon correlaciones de forma separada para seis generaciones (2007 a 2012), para tres tipos de bachillerato de procedencia y para seis asignaturas del primer ano entre, por un lado, el examen diagnostico de conocimientos generales y por otro la calificacion promedio de los examenes departamentales. Resultados Se encontraron diferencias en los resultados de la evaluacion diagnostica entre estudiantes que provienen de los sistemas NO UNAM, ENP y CCH. Los estudiantes que provienen del bachillerato NO UNAM presentaron correlaciones mayores en las seis asignaturas y seis ciclos escolares estudiados, con respecto a los estudiantes de la ENP y CCH. Por asignatura Bioquimica presento los mayores valores de correlacion: para estudiantes de la ENP vario entre 0.38 y 0.55, CCH entre 0.42 y 0.58 y NO UNAM entre 0.63 y 0.82: por otro lado Salud Publica presento las correlaciones menores, la ENP entre 0.26 y 0.42, CCH entre 0.36 y 0.47 y NO UNAM entre 0.51 y 0.70 Conclusiones Estos resultados muestran una correlacion entre el promedio de los examenes departamentales de las asignaturas de primer ano y el examen diagnostico de conocimientos generales, lo cual en una investigacion futura se puede aprovechar para realizar predicciones y proponer medidas remediales tempranas para los estudiantes que puedan detectarse.