Spinocerebellar Ataxia Type 23: A Genetic Update

The spinocerebellar ataxia type 23 locus was identified in 2004 based on linkage analysis in a large, two-generation Dutch family. The age of onset ranged 43–56 years and the phenotype was characterized by a slowly progressive, isolated ataxia. Neuropathological examination revealed neuronal loss in the Purkinje cell layer, dentate nuclei, and inferior olives. Ubiquitin-positive intranuclear inclusions were found in nigral neurons, but were considered to be Marinesco bodies. The disease locus on chromosome 20p13-12.3 was found to span a region of approximately 6 Mb of genomic DNA, containing 97 known or predicted genes. To date, no other families have been described that also map to this SCA locus. Direct sequencing of the coding regions of 21 prioritized candidate genes did not reveal any disease-causing mutation. Apparently, the SCA23 gene is a disease gene with a different function than the genes that have been associated with other known SCA types. Work to elucidate the chromosomal organization of the SCA23 locus will eventually discover the responsible disease gene

Low molecular weight heparin in obstetric care: a review of the literature

Low molecular weight heparins (LMWHs) are widely used during pregnancy since several randomized controlled trials have demonstrated their important role in preventing not only thromboembolic disease but also pregnancy complications associated with thrombophilia: recurrent pregnancy loss (RPL), fetal growth restriction (FGR), preeclampsia (PE), abruptio placentae and intrauterine fetal death (IUFD). LMWHs have revealed their effectiveness in reducing the recurrence of negative obstetrics events even in patients without known trombophilias, despite the mechanisms whereby LMWHs operate remain still unclear. However, in order to confirm the suggested benefits, adequately powered and properly controlled trials are needed in this area. Such trials are currently underway and their results will be important to inform evidence-based practice in this area. In our review we report the results of the most relevant trials performed to assess the efficacy of LMWHs in preventing pregnancy complications associated or not with maternal thrombophilia. This review was conducted based on a MEDLINE search for relevant articles between January 2000 and August 2010 and using the following search terms: heparin, low molecular weight heparin, thrombophilia, pregnancy complications, preeclampsia, recurrent pregnancy loss, abruptio placentae, fetal growth restrictio

Thrombin Regulates Soluble fms-Like Tyrosine Kinase-1 (sFlt-1) Expression in First Trimester Decidua : Implications for Preeclampsia

The primary placental defect in preeclampsia is shallow trophoblast invasion of the decidua leading to incomplete vascular transformation and inadequate uteroplacental perfusion. Soluble fms-like tyrosine kinase-1 (sFlt-1) seems to interfere with these events by inhibiting local angiogenesis and/or by impeding trophoblast invasion. Preeclampsia is also associated with maternal thrombophilias and decidual hemorrhage, which form thrombin from decidual cell-expressed tissue factor. Although sFlt-1 is highly expressed by trophoblasts, sFlt-1 expression has not been studied in decidual cells, which are the predominant cell type encountered by invading trophoblasts. Here, we demonstrate that isolated decidual cells express sFlt-1 mRNA, suggesting that they can synthesize sFlt-1. Moreover, in first trimester decidual cells, thrombin enhanced sFlt-1 mRNA levels, as measured by quantitative reverse transcriptase-polymerase chain reaction, and levels of secreted sFlt-1 protein, as measured by enzyme-linked immunosorbent assay. The thrombin antagonist hirudin blocked this effect, demonstrating that active thrombin is required. Emphasizing the specificity of the thrombin response, neither interleukin-1β nor tumor necrosis factor-α affected sFlt-1 expression in the decidual cells. In contrast to first trimester decidual cells, thrombin did not affect sFlt-1 levels in cultured term decidual cells. In early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote pre-eclampsia by interfering with local vascular transformation