PP169. Management of fetal and maternal prognosis during severe toxemia.

INTRODUCTION: Severe gravidic toxemia gives heavy maternal and fetal morbidity and mortality. OBJECTIVES: The purpose of our data is to identify bad maternal and fetal factors during severe toxemia and the outcome of pregnancy. METHODS: It is a retrospective and comparative study about 200 cases of severe toxemia reported during 8 years 2004-2011 among 25,000 deliveries (control group). Toxemia is considered severe when blood pressure⩾160/100mHg, proteinuria ⩾2g/l, bad neurosensorial signs, hemostasis disorders, kidney and liver failure, some fetal tests: delay intra-uterine growth acute fetal suffering, fetal death. RESULTS: Frequency of severe toxemia 8‰, primiparous 58% vs. 35% control, gestational diabetes 12% vs. 10% control, oedema 87% vs. 45% control. Maternal morbidity is dominated by hemostasis disorders: low platelet count<80,000 23% vs. 8%, hypofibrinogenemia <4g/l 13% vs. 2%, HELLP syndrome eight cases vs. 0. We raised eight cases of eclampsia crises, 22 cases of retroplacental hematoma vs. 10 control. Blood transfusion 15% vs. 10% control, inhibitors of VII factor administered in two cases vs. 0. We do not deplore any maternal mortality. Fetal prognosis is very compromised ,the delay intra uterine growth 44% vs. 18% control, prematurity 66% vs. 15% control, perinatal mortality 60‰ vs 12‰ control CONCLUSION: More toxemia appears early during pregnancy more maternal and especially fetal prognosis is compromised. New drugs, predictive tests and preventives measurements improve maternal outcome better than fetals' one.

Development of substituted Benzo[c]quinolizinium compounds as novel activators of the cystic fibrosis chloride channel.

Chloride channels play an important role in the physiology and pathophysiology of epithelia, but their pharmacology is still poorly developed. We have chemically synthesized a series of substituted benzo[c]quinolizinium (MPB) compounds. Among them, 6-hydroxy-7-chlorobenzo[c]quinolizinium (MPB-27) and 6-hydroxy-10-chlorobenzo[c]quinolizinium (MPB-07), which we show to be potent and selective activators of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. We examined the effect of MPB compounds on the activity of CFTR channels in a variety of established epithelial and nonepithelial cell systems. Using the iodide efflux technique, we show that MPB compounds activate CFTR chloride channels in Chinese hamster ovary (CHO) cells stably expressing CFTR but not in CHO cells lacking CFTR. Single and whole cell patch clamp recordings from CHO cells confirm that CFTR is the only channel activated by the drugs. Ussing chamber experiments reveal that the apical addition of MPB to human nasal epithelial cells produces a large increase of the short circuit current. This current can be totally inhibited by glibenclamide. Whole cell experiments performed on native respiratory cells isolated from wild type and CF null mice also show that MPB compounds specifically activate CFTR channels. The activation of CFTR by MPB compounds was glibenclamide-sensitive and 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid-insensitive. In the human tracheal gland cell line MM39, MPB drugs activate CFTR channels and stimulate the secretion of the antibacterial secretory leukoproteinase inhibitor. In submandibular acinar cells, MPB compounds slightly stimulate CFTR-mediated submandibular mucin secretion without changing intracellular cAMP and ATP levels. Similarly, in CHO cells MPB compounds have no effect on the intracellular levels of cAMP and ATP or on the activity of various protein phosphatases (PP1, PP2A, PP2C, or alkaline phosphatase). Our results provide evidence that substituted benzo[c]quinolizinium compounds are a novel family of activators of CFTR and of CFTR-mediated protein secretion and therefore represent a new tool to study CFTR-mediated chloride and secretory functions in epithelial tissues.