LOS ASPECTOS DEL FACTOR MASCULINO EN LA ESTERILIDAD

This study are describe the diverse genetic causes of masculine infertility, the cromossomic and molecular alteration that may happen in patients with oligo or azoospermia. Its also pretends to revise the tecniques of pre-implantational diagnosis avaliable nowadays. The study is centered in genetic aspects of the masculine factor in the couples infertility. The importance of this study is in the ethic duty of analysing case by case, when to opt for intra-citoplasmatic injection of spermatozoons (ICIS), it because a significative fraction of person with idiopatic oligo or azoospermia have genetic alterations in their spermatozoons or spermatogonias, and there is a great probability of the child to have a genetic disease. This way, the (ICIS) is not a good way to the coupler wich face this problem.Describe las causas genéticas diversas de la esterilidad masculina, las alteraciones cromosómicas y moleculares que pueden pasar en pacientes con oligo o azoospermia. Además proyecta tambiém una revisión de las tecnicas de diagnóstico pre-implantacional disponible actualmente. El estudio se centra en aspectos genéticos del factor masculino en la esterilidad de las parejas. La importancia de este estudio consiste en un deber ético de analizar caso por caso, cuándo optar para la inyección del intra-citoplasmatic de espermatozoos (ICIS), él porque una fracción significativa de individuos con oligo o azoospermia tiene alteraciones genéticas en su espermatozoos o spermatogonias y hay una gran probabilidad del niño para tener una enfermedad genética. De esta manera, el (ICIS) no es una manera buena para que las parejas enfrenten este problema.Descreve diversas causas genéticas de infertilidade masculina, as alterações cromossômicas e moleculares que podem estar presentes em pacientes com oligo ou azoospermia idiopática. Faz, também, uma revisão das técnicas de diagnóstico pré-implantacional disponíveis atualmente. O estudo está centrado nos aspectos genéticos do fator masculino da infertilidade de casais. Sua importância consiste no dever ético de se analisar caso a caso, quando se opta por técnicas de injeção intra-citoplasmática de espermatozóides (ICSI), porque uma significativa fração dos indivíduos com oligo ou azoospermia idiopática, apresentam alterações genéticas em seus espermatozóides ou outras células do epitélio germinativo. A probabilidade da criança apresentar doença genética é grande. Deste modo, a ICSI não é a opção mais indicada para casais que enfrentam este problema

Juvenile GM2 Gangliosidosis: A Model for Investigation of Small-molecule Therapies for Lysosomal Storage Diseases

Juvenile GM2 gangliosidosis (jGM2) is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase A (Hex A) resulting in GM2 ganglioside accumulation in brain. Like many other lysosomal storage diseases (LSDs), no specific treatment currently exists. In order to establish clinical outcomes for the investigation of potential therapies for jGM2, I collected comprehensive information on the natural history of the condition by studying retrospective and prospectively a cohort of 21 patients with the disease, and reviewing previously published reports of 134 patients. Several symptoms at disease onset, symptom latencies, and the survival curve were described. Genotype-phenotype correlations and neuroradiological findings were also studied. Based on pre-clinical results in animal models, we studied substrate reduction therapy (SRT), with miglustat, in a phase I/II clinical trial to assess its pharmacokinetics (PK), safety, tolerability in infantile and jGM2. Miglustat showed a PK profile similar to the one found in adult patients. The drug was found to be safe and well-tolerated in patients with jGM2, with diarrhea and weight loss being the most common drug-related adverse events. The analysis of efficacy showed that SRT was unable to arrest the full neurological progression of the condition; however, relative stabilization of cognitive function was noted, which was consistent with brain MRI findings. Because of the limited efficacy obtained with SRT, enzyme-enhancement therapy was considered to be an attractive alternative therapy for the late onset forms of GM2 gangliosidosis. Screening of a FDA-approved library of approved therapeutic compounds resulted in the identification of pyrimethamine, as a potential pharmacological chaperone for mutant forms of Hex A. Relative enhancements of enzyme activity and protein levels were observed in patient cells treated with therapeutic concentrations of drug. Applying the same principles, ambroxol was identified as a potential PC for mutant glucocerebrosidase (GCC), the lysosomal enzyme that when deficient causes Gaucher disease (GD). Significant increases of residual mutant GCC were observed in cultured patients cells with type 1 GD. In conclusion, principles developed in the course of studies on jGM2 were shown to be useful for the investigation of novel small-molecule therapies for LSDs, associated with significant neurodegeneration.Ph

Ossificação do ligamento longitudinal posterior na coluna cervical: relato de caso Ossification of the posterior longitudinal ligament in the cervical spine: case report

A ossificação do ligamento longitudinal posterior (OLLP) é causa incomum de mielopatia compressiva na população caucasiana. É relatado o caso de um paciente do sexo masculino com um quadro de paraparesia espástica, cuja investigação radiológica mostrou OLLP. O raio-X de coluna cervical mostrou imagem laminar, vertical, com densidade óssea, posterior aos corpos vertebrais, que se estendia de C2 a T1. A tomografia computadorizada (TC) e a mielotomografia mostravam OLLP causando compressão medular ântero-posterior no segmento descrito. Na ressonância magnética, observou-se área de hiperintensidade em T2 no segmento C7-T1, compatível com mielomalácia. O paciente foi submetido a laminoplastia tipo "open-door", com melhora do quadro parético dos membros inferiores. A OLLP deve entrar no diagnóstico diferencial das mielopatias cervicais, sendo facilmente diagnosticada através de radiografias e TC da coluna cervical. São revisados os aspectos clínicos e radiológicos e o tratamento da OLLP.<br>Ossification of the posterior longitudinal ligament (OPLL) is an uncommon cause of compressive myelopathy in the Caucasian population. A case of spastic paraparesis in a Caucasian man whose radiological investigation showed OPLL is presented. The radiographs of the cervical spine showed a strip of bony density posterior to the vertebral bodies, extending from C2 to T1. Computerized tomography (CT) and CT myelography showed OPLL at the same level. Magnetic resonance showed an area of increased signal on T2-weighted sequences at C7-T1 level suggestive of myelomalacia. The patient underwent an open-door laminoplasty (C2 to C7) with improvement of the paraparesis. OPLL should be included in the differential diagnosis of cervical myelopathy. It can be easily detected by plain radiographs and CT of the cervical spine. A review of the clinical and radiological features and the treatment of OPLL is presented