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A protein with NAD-dependent 11-hydroxythromboxane B2 dehydrogenase activity was purified to apparent homogeneity from porcine kidney using a relatively simple purification procedure, involving precipitation, anion-exchange chromatography (diethylaminoethyl-cellulose), affinity chromatography (5′-AMP-Sepharose) and gel-filtration chromatography (Protein Pak 125). The dehydrogenase was found to have a molecular mass of 50–55 kDa as determined by comparison with standards on SDS/PAGE. The molecular mass on gel-filtration chromatography was dependent on the ionic strength of the buffer. The apparent Km and Vmax values for thromboxane B2 were also dependent of the ionic strength with a Vmax of 214 nmol min-1 mg-1 using 250 Tris/HC1, pH 8.0, and a corresponding Km of 2.9 mM. The enzyme was NAD dependent and was clearly separated from the proteins with 15-hydroxyprostaglandin dehydrogenase activity also present in the kidney. Furthermore, it was found that 11-hydroxythromboxane B2 dehydrogenase did not utilize prostaglandin D2, prostaglandin E2, prostaglandin F2α or cholic acid as substrate, and that the enzyme did not catalyse the reverse reaction, conversion of 11-dehydrothromboxane B2 to thromboxane B2. [ABSTRACT FROM AUTHOR]

The antiprogestin RU 486 (mifepristone) is highly effective in inducing early abortion in women only if the compound is combined with a prostaglandin analogue. A new related antiprogestin, ZK 98, 734, has been reported in animal studies to be much more potent as an abortifacient than mifepristone, concomitant with less antiglucocorticoid activity. The aim of the present two-centre study was to explore the abortifacient efficacy and plasma concentrations of ZK 98, 734 in women seeking abortion. A total of 96 pregnant women with amenorrhoea of <49 days were treated with oral doses of 12.5, 25, 50 or 100 mg ZK 98, 734 twice daily for 4 days. The overall rate of complete abortion and continuing live pregnancies was 68 and 20% respectively, i.e. results comparable with treatment with mifepristone alone. No dose-response relationship was noted. In patients with complete abortion, signs of luteal sysfunction in terms of oestradiol and progesterone production were evident on the fourth treatment day, in contrast to patients with failures. Increased amounts of cortisol and prolactin were found during treatment both in successfully treated patients and failures, whereas aldosterone values remained unaffected. The effect on cortisol may indicate some antiglucocorticoid activity in the human. The concentrations of ZK 98, 734 in peripheral blood after 25, 50 and 100 mg twice daily for 4 days were similar. The values were slightly above 0.5μmol/l on the second day of treatment. Maximal concentrations of 0.7 μmol/l were seen on treatment day 4. Plasma concentrations of ZK 98, 734 did not differ in cases of complete abortion and failures. In conclusion, the abortifacient efficacy in relation to dose of the new antigestaged ZK 98, 734 does not essentially differ from that of mifepristone treatment alone. [ABSTRACT FROM PUBLISHER]

Objective: To identify the distribution of the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A(2) (cPLA(2)) in the human ovary and endometrium.Design: Prospective clinical study.Setting: Hospital-based unit for reproductive health and research laboratories.Patient(s): Twenty-nine healthy fertile women with normal menstrual cycles.Intervention(s): Endometrial and ovarian biopsy samples were obtained from healthy, fertile women in the luteal phase of the menstrual cycle or during caesarean section.Main Outcome Measure(s): Pinopode formation and immunohistochemical staining of cPLA(2), COX-1, and COX-2.Result(s): In the endometrium, the immunostaining of cPLA(2) was most intense in the luminal epithelium when pinopodes were present. The staining of both COX-1 and COX-2 was most intense in the epithelial cells, with the stroma staining positive only for COX-2. The endometrial vessels expressed COX-2 but not COX-1. The staining of COX-1 and COX-2 was intense on the surface epithelial cells on the outer lining of the ovary.Conclusion(s): This study details the distribution of these prostaglandin synthase enzymes and emphasizes their importance for the functions of both the endometrium and the ovary. [ABSTRACT FROM AUTHOR]