A case report of obstetrical management of a pregnancy with hypermobile Ehlers-Danlos syndrome and literature review.

We present a case report of a successful pregnancy outcome in a woman diagnosed with Ehlers-Danlos syndrome (EDS) hypermobility type or type III. EDS is a group of connective tissue disorders that has a common genotypic defect, but heterogeneous phenotypic presentations. The variation in EDS manifestations can result in moderate to severe effects on life-expectancy for some types. A number of studies and a review of the literature indicate that generally in pregnant women with EDS, maternal and neonatal outcomes are favourable. However, in EDS type IV, pregnancy can be associated with serious maternal complications. Therefore, obstetrical management should be individualized. This paper discusses the obstetric management of a patient with EDS hypermobility type and compares it to other studies in the literature.

Differential recovery of prostacyclin synthesis in cultured vascular endothelial vs. smooth muscle cells after inactivation of cyclooxygenase with aspirin.

Conflicting findings from clinical trials on the use of aspirin in preventing myocardial infarction emphasize the importance of understanding the effects of aspirin on vascular cells. Cultured vascular endothelial cells and smooth muscle cells of human, rat and bovine origin synthesized prostacyclin, a key component in vascular homeostasis, when superfused with 14C arachidonic acid. Prostacyclin synthesis was inactivated following brief treatment with aspirin, which irreversibly acetylates cyclooxygenase. Marked differences were observed between endothelial and smooth muscle cells in the recovery of cyclooxygenase after aspirin treatment. Smooth muscle cells recovered within 3 hours by a process that required serum factors replaceable by epidermal growth factor (EGF) and TGF-beta. Recovery in both smooth muscle and endothelial cells was blocked by cycloheximide but not by actinomycin-D. Endothelial cell recovery occurred much more slowly, requiring up to 24 hours and was not dependent on serum factors or EGF. Furthermore, it was suppressed by growth inducing agents such as endothelial cell growth factor (ECGF) and was enhanced by conditions favoring growth arrest and cellular differentiation. Regulation of expression and recovery of cyclooxygenase following inactivation by aspirin thus differs considerably in the endothelial and smooth muscle compartments of the vasculature.

Reconstituted U1 small nuclear ribonucleoprotein complex restores 5' splice site cleavage activity.

Functional reconstitution of U1 small nuclear ribonucleoprotein particle (U1 snRNP) was performed using in vitro transcribed U1 snRNA. Hela cell nuclear extract was depleted of its constituent snRNPs by centrifugation at 100,000 X g. The supernatant was devoid of snRNAs and lacked cleavage activity in splicing reactions using in vitro transcribed beta-globin pre-mRNA as substrate. The resulting pellet which contained the snRNAs, retained 5' splice site cleavage activity in a similar splicing reaction. Supplementation of the inactive supernatant fraction with in vitro transcribed U1 snRNA, partially restored 5' splice site cleavage activity thereby demonstrating the specific requirement of U1 snRNP in the initial stage of pre-mRNA splicing.

Recovery of prostacyclin synthesis in human vascular endothelial cells following intermittent or continuous exposure to indomethacin.

Indomethacin is a potent prostaglandin synthesis inhibitor, which is widely used in treating arthritis and other inflammatory conditions. This study investigated the effect of physiological levels of indomethacin on synthesis of the antiplatelet substance prostacyclin, by human vascular endothelial cells in culture. The nature of the inhibition and its reversibility following removal of indomethacin were characterized. Almost complete inhibition of prostacyclin synthesis was obtained at concentrations of 5.6 microM indomethacin, which were within physiological blood levels (1.4-16.8 microM) attained during routine indomethacin therapy. Inhibition was essentially irreversible for all exposure periods in excess of one minute. Following inactivation by brief (5 minute) exposure to indomethacin, partial recovery of prostacyclin synthesis to between 45% and 60% of control values was attained 24 hours after indomethacin removal. Prolonged (24 hours) exposure of cells to indomethacin did not further impair subsequent recovery of prostacyclin synthesis and did not affect cell viability. Recovery of enzyme was much more rapid in confluent quiescent monolayers of endothelial cells than in dividing cultures. The results indicate that continuous or intermittent exposure to indomethacin may significantly impair vascular prostacyclin synthesis in vascular endothelium, but that substantial recovery may occur within 24 hours of drug removal.