Influence of stochastic gene expression on the cell survival rheostat after traumatic brain injury.

Experimental evidence suggests that random, spontaneous (stochastic) fluctuations in gene expression have important biological consequences, including determination of cell fate and phenotypic variation within isogenic populations. We propose that fluctuations in gene expression represent a valuable tool to explore therapeutic strategies for patients who have suffered traumatic brain injury (TBI), for which there is no effective drug therapy. We have studied the effects of TBI on the hippocampus because TBI survivors commonly suffer cognitive problems that are associated with hippocampal damage. In our previous studies we separated dying and surviving hippocampal neurons by laser capture microdissection and observed unexplainable variations in post-TBI gene expression, even though dying and surviving neurons were adjacent and morphologically identical. We hypothesized that, in hippocampal neurons that subsequently are subjected to TBI, randomly increased pre-TBI expression of genes that are associated with neuroprotection predisposes neurons to survival; conversely, randomly decreased expression of these genes predisposes neurons to death. Thus, to identify genes that are associated with endogenous neuroprotection, we performed a comparative, high-resolution transcriptome analysis of dying and surviving hippocampal neurons in rats subjected to TBI. We found that surviving hippocampal neurons express a distinct molecular signature--increased expression of networks of genes that are associated with regeneration, cellular reprogramming, development, and synaptic plasticity. In dying neurons we found decreased expression of genes in those networks. Based on these data, we propose a hypothetical model in which hippocampal neuronal survival is determined by a rheostat that adds injury-induced genomic signals to expression of pro-survival genes, which pre-TBI varies randomly and spontaneously from neuron to neuron. We suggest that pharmacotherapeutic strategies that co-activate multiple survival signals and enhance self-repair mechanisms have the potential to shift the cell survival rheostat to favor survival and therefore improve functional outcome after TBI.

Densitometría ósea y tamaño uterino: una relación de utilidad práctica en mujeres climatéricas / Bone mineral density and uterine size: a practical relationship for climacteric women

Background: Double beam bone densitometry allows to select climacteric women who will benefit from hormone replacement. However, it is not always affordable in clinical practice. Aim: To study possible alternative markers of bone mineral density. Patients and methods: A retrospective survey of climacteric women in whom bone mineral density was measured when hormone replacement therapy was started. Eighty one women were studied and in 27, uterine size index was obtained from pelvic ultrasound examinations. Women with and without uterine size index measurements were analyzed separately. Relationships of bone mineral density with age, lapse from menopause, body mass index and uterine size index were sought. Results: There was a significant regression between the lapse in years from menopause and lumbar bone mineral density in the group without uterine size index measurements (r2=0.228, ANOVA p=0.014). There was also a significant regression of lumbar bone mineral density with the uterine size index (r2=0.236, ANOVA p=0.01) in those women in whom this measurement was available. No other variables were associated with bone mineral density. Conclusion: In this group of patients, the lapse after menopause and uterine size index are predictors of lumbar bone mineral density

Etinil estradiol y acetato de medroxiprogesterona en mujeres climatéricas / Ethinyl-estradiol and medroxyprogesterone acetate in climateric women

A 150 pacientes climatéricas se les dio al menos tres meses de etinil estradiol (10 mcg) con acetato medroxiprogesterona periódico (10 mg durante 8 días en cada mes). En 114 de ellas se evaluaron los signos y síntomas vasomotores neurovegetativos del climaterio, observándose que desaparecen o mejoran en el 100% de los casos. El trofismo vulvovaginal se investigó en estas 114 climatéricas. Se encontró 62,2% de hipotrofismo genital antes del tratamiento, y sólo 22,8% usando la terapia. La estrogenización según el colpocitograma se analizó en 42 de las mujeres en estudio. Se vio que con este método 35 casos eran hipoestrogénicas (83,3%), y con el tratamiento 17 casos (40,4%) persistieron con algún déficit estrogénico. Se les efectuó biopsia de endometrio basal a 116 de las pacientes, encontrándose hiperplasia endometrial en 15,5% de ellas. A 38 de estas mujeres climatéricas se les tomó biopsia de endometrio durante el tratamiento. Antes del tratamiento, 20 casos (52,6) tenían endometrio atrófico o hipoestrogénico manifiesto, y 16 (42,1%) después del tratamiento. En este grupo estaban once de las 18 hiperplasias endometriales, a las cuales se les aplicó el esquema terapéutico de análisis después de habérseles tratado por tres ciclos con 10 mg diarios de acetato medroxiprogesterona. Los controles biópsicos demostraron la desaparición de las hiperplasias endometriales