Obstetric Cholestasis: Comparison of Maternal and Perinatal Outcome of Ursodeoxycholic Acid versus Placebo

Objectives: Objective: To compare the maternal and perinatal outcomes of ursodeoxycholic acid with placebo in obstetric cholestasis. Method: It was an open randomized parallel-group study with convenient sampling, conducted at Pakistan ordinance factories hospital (POF Hospital) Wah Cantt, from 1st June 2016-30th May 2019. Patients with obstetric cholestasis of pregnancy, diagnosed between 24-34 weeks of gestation, were randomized to receive either ursodeoxycholic acid 500mg twice daily or placebo one capsule twice daily for 4 weeks. The data was collected on a pre-designed proforma. The data of 84 patients, who full fill the inclusion criteria were analyzed using SPSS vs 19. Maternal outcomes measured were a relief in pruritus and a decrease in hepatic alanine aminotransferase levels (ALT) at the end of 2 weeks and 4 weeks of treatment. The mode of delivery was noted. Fetal outcomes measured were meconium staining of amniotic fluid and the need for neonatal intensive care unit (NICU) admission. Results: The results showed significant improvement in maternal itch score (P=0.001) and serum transaminases level (p=0.001) in patients using UDCA as compared to placebo. Although there were less number of caesarean sections (p=0.36), meconium-stained liquor (p=0.29) and NICU admissions (P=0.33) in the UDCA group the differences were not statistically significant. Conclusion: Treatment with UDCA in obstetric cholestasis improved maternal complaint of itching and decreased raised transaminases levels but did not affect significantly the mode of delivery, incidence of meconium-stained liquor and NICU admissions. Keywords: Obstetric cholestasis, Ursodeoxycholic acid, perinatal outcome, Pruritus.

Hydroxamic Acids Derivatives Induce γ Globin Gene Expression in Vivo.

We have previously shown that four hydroxamic acids: butyric and propionic hydroxamic acids, subericbishydroxamic acid (SBHA) and suberoylanilide hydroxamic acid (SAHA) are potent inhibitors of histone deacetylase and strong inducers of fetal hemoglobin expression in vitro (Exp Hematol.31:197, 2003). In the present study we tested their effect on fetal hemoglobin synthesis in vivo. Transgenic mice carrying the human μLCR Aγ construct continue to express the human γ gene in the adult stage of development ( γ/α mRNA ratio ~ 5%, Blood.77:1326, 1991). These mice were crossed to mice heterozygous for a thalassemia gene due to β globin gene deletion (PNAS.92:11608, 1995). The β thalassemia/μLCR Aγ mice represent an appropriate moderately anemic animal model for testing the effects of Hb F inducers. Compounds were administered subcutaneously with a mini-osmotic pump continuously for 7days in a high and a low concentration. Concentrations were: for butyric hydroxamic acid: 500mg/kg/day/100mg/kg/day; for propionic hydroxamic acid: 500mg/kg/day/100mg/kg/day; for SAHA: 100mg/kg/day/20mg/kg/day; and for SBHA: 200mg/kg/day/40mg/kg/day. Two test groups were studied. In group 1, 70μL mice blood was drawn every other day up to 20 days; in group 2, 70μL mice blood was drawn only on days 0 and 21. Reticulocytes and F reticulocytes were measured using flow cytometry, while γ globin gene expression was quantitated by RNase protection assay. Butyric and propionate hydroxamic acids increased reticulocytes by 70.52% (from 13.96% to 23.81%) and 172.52% (from 10.34% to 28.20%) respectively. There was only small increase in reticulocytes in the mice treated with SAHA (from 13.33% to 15.36%), SBHA (from 14.24% to 16.27%) and the PBS control (11.06% to 14.11%). All the compounds increased the level of γ mRNA: butyric hydroxamate by 53.07%; propionic hydroxamate by 40.05%; SAHA by 49.87%, and SBHA by 34.05%. These results suggest first that all the hydroxamic acid derivatives we used increase fetal hemoglobin in vivo in the thalassemia animal model; second butyric and propionic hydroxanic acids are in addition inducers of in vivo erythropoiesis.

Algitec: an illogical combination?

Algitec (SK&F) was introduced last year for use in gastro-oesophageal reflux. It is presented as a chewable tablet and as a suspension combining cimetidine 200mg with alginic acid 500mg and sodium bicarbonate, to be taken four times daily after food.