Severe rhabdomyolysis after allogeneic transplantation of facial structures: a case report.

We present a patient with panfacial neurofibromatosis type 1 who underwent allogeneic transplantation of facial structures, which was complicated by severe rhabdomyolysis and temporary oligoanuria. Because of his underlying disease, this 35 year-old man, weighing 68 kg and with a body mass index (BMI) of 27, had undergone 17 operations for resection modeling of hypertrophied tissues, either alone or combined with static suspension techniques. He finally underwent allogeneic transplantation of facial structures. In the early hours of the postoperative period, in the context of a systemic inflammatory response syndrome, he experienced severe rhabdomyolysis, with elevation of the muscle enzyme creatine kinase producing a minor impact on kidney function. The patient was discharged home at 12 weeks after the transplantation.

Polymorphisms in the promoter regions of FAS and FASL genes as candidate genetic factors conferring susceptibility to endometriosis.

Although the pathophysiological mechanisms leading to endometriosis remain unknown, several hypothesis have been proposed, including a dysregulation of the normal apoptotic process which takes place in the endometrium. One of the apoptotic pathways playing a crucial role in the programmed cell death within the endometrium is the Fas-FasL system. In this study we have performed a case-control analysis in order to evaluate three polymorphisms located within FAS (-1377G>A and -670A>G) and FASL (-843C>T) genes, as susceptibility factors for endometriosis. We have analysed a series of women with endometriosis compared respectively to a group of women without symptoms of the disease, and to a group of confirmed unaffected women. The genotyping of the three variants was carried out by Fluorescence Resonance Energy Transfer (FRET) technology, and statistical analysis was performed using chi2 test with Yates correction. Our results show that the differences in the distribution of the polymorphic variants were not statistically significant when the group of patients was compared to the other groups. Thus, it seems to indicate that the variants here analysed are not involved in the pathogenesis of the disease in our population. However this does not let us to completely exclude such genes as potential candidates for the disease. A complete genetic analysis of the genes involved in the intricate regulatory system of the apoptosis may lead to the identification of susceptibility factors for the disease and a better understanding of its etiology.

Analysis of the involvement of CCR5-Delta32 and CCR2-V64I variants in the development of endometriosis.

Several arguments support the proposal that the cytokine network plays a critical role in the aetiology of endometriosis. Among various chemokines, regulated-on-activation, normal-T-cell-expressed and -secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) concentrations have been shown to be increased in the peritoneal fluid of women with endometriosis. Some studies have demonstrated that, in the context of endometriosis, these chemokines are involved in apoptosis, angiogenesis and/or chemotaxis. Since the chemokines exert their effects by binding to their receptors, it would be plausible that factors affecting such interactions might play a role in the pathogenesis of endometriosis. Thus we postulated that the genes encoding CCR5 and CCR2, which are the receptors for RANTES and MCP-1 respectively, could be good candidate genes for the disease. We have used real-time PCR and FRET technologies to genotype and evaluate the variants CCR5-Delta32 and CCR2-V64I, as susceptibility factors in a cohort of Spanish women with endometriosis. No differences have been found in the frequencies of the two polymorphisms nor in the haplotype/genotype distribution between cases and controls. These data would suggest the lack of association between these polymorphisms and endometriosis in our population, although they do not permit us to discard completely a possible role of other variants within CCR5 and CCR2 genes in this pathology.

Evaluation of germline sequence variants within the promoter region of RANTES gene in a cohort of women with endometriosis from Spain.

The RANTES (regulated upon activation normal T cells expressed and secreted) chemokine, is known to be expressed in endometriotic lesions in a concentration correlating with the severity of endometriosis. Since it has been widely demonstrated that endometriosis has a genetic basis, we postulated that the gene encoding RANTES could be a good candidate gene for the disease. We have used fluorescence resonance energy transfer (FRET) technology to genotype and evaluate the role of the variants -403G-->A and -28C-->G, located within the promoter region of the gene, as susceptibility factors in a cohort of Spanish women with endometriosis. No differences have been found in the allelic frequencies of both variants nor in the haplotype/ genotype distribution between patients and controls. These data are consistent with the lack of association between these polymorphisms and endometriosis in our population. They do not exclude completely a possible role of other variants within RANTES gene in this pathology.

Morphological bases for a role of nitric oxide in adult neurogenesis.

The subventricular zone (SVZ) of the adult mouse brain retains the capacity to generate new neurons from stem cells. The neuronal precursors migrate tangentially along the rostral migratory stream (RMS) towards the olfactory bulb, where they differentiate as periglomerular and granular interneurons. In this study, we have investigated whether nitric oxide (NO), a signaling molecule in the nervous system with a role in embryonic neurogenesis, may be produced in the proximity of the progenitor cells in the adult brain, as a prerequisite to proposing a functional role for NO in adult neurogenesis. Proliferating and immature precursor cells were identified by immunohistochemistry for bromo-deoxyuridine (BrdU) and PSA-NCAM, respectively, and nitrergic neurons by either NADPH-diaphorase staining or immunohistochemical detection of neuronal NO synthase (NOS I). Nitrergic neurons with long varicose processes were found in the SVZ, intermingled with chains of cells expressing PSA-NCAM or containing BrdU. Neurons with similar characteristics surrounded the RMS all along its caudo-rostral extension as far as the core of the olfactory bulb. No expression of NOS I by precursor cells was detected either in the proliferation or in the migration zones. Within the olfactory bulb, many small cells in the granular layer and around the glomeruli expressed either PSA-NCAM or NOS I and, in some cases, both markers. Colocalization was also found in a few isolated cells at a certain distance from the neurogenesis areas. The anatomical disposition shown indicates that NO may be released close enough to the neuronal progenitors to allow a functional influence of this messenger in adult neurogenesis.