Comparison of different regimes of misoprostol for the termination of early pregnancy failure

Background

Nearly 20% of all confirmed pregnancies end in spontaneous abortion. Misoprostol''s use in early pregnancy failure is varied and dose and route are not well established. The aim of this study was to compare the efficacy and the side effects of different regimes of misoprostol in causing expulsion of products of conception in early pregnancy failure.

Method

Women patients with an ultrasound diagnosis of early pregnancy failure, less than 12 weeks gestation were divided into two, Group-A: tab. Misoprostol 800 mcg 6 hourly vaginally, upto 3 doses. Group-B tablet misoprostol 600 mcg 6 hourly, sublingually for 3 doses. All observations were noted and statistical analyzed.

Results

Mean gestational age was 7.93 weeks. Mean induction abortion interval 18.183 h. Women patients with less than six weeks gestational age had least mean induction-abortion interval time, 15.75 ± 2.82 h in vaginal group but was highest in sublingual group 22 ± 2 h and 18.43 h in overall (P = 0.02). Though after 8 weeks, both routes were equally effective. Mean dose required in group-A was 20044 mcg and in group-B was 1564 mcg (P < 0.001). Efficacy of protocol was 88.89% in group-A and 92.85% in group-B.

Conclusion

Both regimes had comparable efficacy, acceptability (90%) and side effects. In women patients less than six weeks period of gestation, the vaginal (800 mcg) route was distinctly superior, in women patients with 6–8 weeks the sublingual (600 mcg) route was more advantageous. The correct dose must be used for the route chosen. The route of administration should be decided in accordance with the preference of the patient and the clinical situation.     

Lysosomal destabilization and cathepsin B contributes for cytochrome c release and caspase activation in embelin‐induced apoptosis

XIAP is an important antiapoptotic protein capable of conferring resistance to cancer cells. Embelin, the small molecular inhibitor of XIAP, possesses wide spectrum of biological activities with strong inhibition of nuclear factor kappa B and downstream antiapoptotic genes. However, the mechanism of its cell death induction is not known. Our studies using colon cancer cells lacking p53 and Bax suggest that both lysosomes and mitochondria are prominent targets of embelin‐induced cell death. Embelin induced cell‐cycle arrest in G₁ phase through p21, downstream of p53. In the absence of p21, the cells are sensitized to death in a Bax‐dependent manner. The loss of mitochondrial membrane potential induced by embelin was independent of Bax and p53, but lysosomal integrity loss was strongly influenced by the presence of p53 but not by Bax. Lysosomal role was further substantiated by enhanced cathepsin B activity noticed in embelin‐treated cells. p53‐dependent lysosomal destabilization and cathepsin B activation contribute for increased sensitivity of p21‐deficient cells to embelin with enhanced caspase 9 and caspase 3 activation. Cathepsin B inhibitor reduced cell death and cytochrome c release in embelin‐treated cells indicating lysosomal pathway as the upstream of mitochondrial death signaling. Deficiency of cell‐cycle arrest machinery renders cells more sensitive to embelin with enhanced lysosomal destabilization and caspase processing emphasizing its potential therapeutic importance to address clinical drug resistance. © 2009 Wiley‐Liss, Inc.     

Comparison of different regimes of misoprostol for the termination of early pregnancy failure

Background

Nearly 20% of all confirmed pregnancies end in spontaneous abortion. Misoprostol's use in early pregnancy failure is varied and dose and route are not well established. The aim of this study was to compare the efficacy and the side effects of different regimes of misoprostol in causing expulsion of products of conception in early pregnancy failure.

Method

Women patients with an ultrasound diagnosis of early pregnancy failure, less than 12 weeks gestation were divided into two, Group-A: tab. Misoprostol 800 mcg 6 hourly vaginally, upto 3 doses. Group-B tablet misoprostol 600 mcg 6 hourly, sublingually for 3 doses. All observations were noted and statistical analyzed.

Results

Mean gestational age was 7.93 weeks. Mean induction abortion interval 18.183 h. Women patients with less than six weeks gestational age had least mean induction-abortion interval time, 15.75 ± 2.82 h in vaginal group but was highest in sublingual group 22 ± 2 h and 18.43 h in overall (P = 0.02). Though after 8 weeks, both routes were equally effective. Mean dose required in group-A was 20044 mcg and in group-B was 1564 mcg (P < 0.001). Efficacy of protocol was 88.89% in group-A and 92.85% in group-B.

Conclusion

Both regimes had comparable efficacy, acceptability (90%) and side effects. In women patients less than six weeks period of gestation, the vaginal (800 mcg) route was distinctly superior, in women patients with 6–8 weeks the sublingual (600 mcg) route was more advantageous. The correct dose must be used for the route chosen. The route of administration should be decided in accordance with the preference of the patient and the clinical situation.     

Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform

Current cancer therapeutics are identified based on initial tumor regression screens that mostly kill differentiated tumor cells, sparing the rare cancer stem cells (CSCs). Being rare and difficult to characterize, it remains a challenge to identify compounds active against them. Side population (SP) cells identified in multiple cancer cell line panels expressing mitochondrial Cytochrome C-EGFP were evaluated for identifying possible drug candidates utilizing high-throughput imaging. We identified heat shock protein 90 inhibitors as potential agents to sensitize SP cells to anticancer drugs. Hsp90 inhibitors induced down regulation of Akt leading to proteasomal degradation of survivin and consequent mitochondrial apoptosis. A successful screening platform for identifying compounds targeting drug resistant side population cells was developed.