Effects of some naturally occurring prostanoids and some cyclooxygenase inhibitors on the contractility of the human lower uterine segment in vitro.

The contractility of strips of human lower segment myometrium obtained from elective cesarean section performed at term of pregnancy was studied in vitro. The effects of indomethacin and tiaprofen upon spontaneous contractile activity were examined. Concentration-effect curves for PGD2, PGE2, PGF2 alpha, 6-keto-PGE1, and 6-keto-PGF1 alpha were constructed in the presence of indomethacin. Neither indomethacin nor tiaprofen in concentrations up to 100 mumol/L had any effect upon spontaneous activity. Contractions were induced by the prostanoids with the following mean EC50 values: PGE2, 13 nM; PGF2 alpha, 250 nM; PGD2, 790 nM; both 6-keto-PGF1 alpha and 6-keto-PGE1 were without effect in concentrations up to 30 mumol/L. In some tissues PGE2 inhibited spontaneous activity with a mean IC50 of 100 nM. No other prostanoid tested caused inhibition under any circumstance. The marked potency differences between the natural prostanoids is an important parameter to consider when assessing their relative contributions to the process of parturition and the design of new therapeutic agents for the management of preterm labour.

Lack of evidence of neurotoxicity following 8 weeks of treatment with tripotassium dicitrato bismuthate.

OBJECTIVE: To search for evidence of subclinical neurotoxicity in patients treated with tripotassium dicitrato bismuthate. DESIGN: Prospective, controlled, triplicate study using urinary bismuth concentration, magnetic resonance imaging (MRI), nerve conduction studies, visual evoked response and a battery of 10 neuropsychological screening tests. SETTING: Out-patient clinics, Walsgrave Hospital, Coventry, UK. SUBJECTS: Fourteen dyspeptic patients; 8 (treatment group) treated with tripotassium dicitrato bismuthate one tablet q.d.s and 6 (control group) treated with ranitidine 150 mg b.d. for 8 weeks. MAIN OUTCOME MEASURES: Changes in urinary bismuth, MRI, nerve conduction studies, visual evoked response, and neuropsychological tests performed before, immediately after and 8 weeks after the cessation of treatment. RESULTS: In the treatment group the median (range) urinary bismuth concentration was 1 (1-12) ng/ml before treatment, increased to 560 (140-1300) immediately after treatment (P < 0.01, Wilcoxon Rank Sum test) and was still significantly elevated (23 (7-53) ng/ml) 8 weeks after the cessation of treatment. In the patient who recorded the highest urinary bismuth, a high intensity signal appeared in the globus pallidus immediately after treatment and was still present (though diminished in intensity) 8 weeks after the cessation of treatment. This isolated MRI finding was not associated with evidence of subclinical neurotoxicity. No changes in the MRI, nerve conduction studies, visual evoked response and neuropsychological tests were observed among the other patients studied. CONCLUSIONS: Bismuth accumulation occurs in patients receiving a conventional course of treatment with tripotassium dicitrato bismuthate but this is not associated with significant changes in the nervous system.

Fibronectin binding by Salmonella strains: evaluation of a particle agglutination assay.

Thirty-five Salmonella strains isolated from human cases of salmonellosis were tested and compared for their fibronectin (fn) binding capacities by using two fn-particle agglutination assays (fn-PAAs) prepared by coating with human fn either (i) latex beads (Difco; 0.81-micron diameter) (L-fn-PAA) or (ii) heat-killed formalin-treated Staphylococcus aureus Cowan 1 cells (C-fn-PAA). Six S. aureus strains were also included in this study as controls. The strains were cultured on colonization factor antigen agar and blood agar and in tryptic soy broth and brain heart infusion broth. The Salmonella and S. aureus strains were cultured at 33 and 37 degrees C, respectively, for optimal expression of fn-binding proteins. Bacterial cells (approximately 10(10) cells per ml) harvested from growth in various culture media and suspended in 0.02 M potassium phosphate buffer (pH 6.8) agglutinated the fn-PAA reagents. These reactions were scored semiquantitatively from + to + depending on the speed or intensity of the reactions within 2 min. Maximum agglutination in fn-PAA systems was observed when the cells were grown in brain heart infusion broth, while tryptic soy broth proved to be least suitable media for culturing cells for fn-PAAS. Although a statistically highly significant correlation was obtained between results of assays of radiolabeled fn and 29-kDa fragment binding, no significant correlation was observed (i) between the results of strains cultured in different media or (ii) when semiquantitative score results of the two fn-PAA systems were compared with those of the conventional radiolabeled fn assay. To enhance the efficiency of the test system, the C-fn-PAA reagent was stained with methylene blue (2% in 0.17 M glycine-NaOH buffer [pH 6.8]). This facilitated easy interpretation of results, which could be performed on hydrophobic paper instead of glass slides. The results obtained with both unstained C-fn-PAA and stained C-fn-PAA were comparable to each other and reproducible. Although the fn-PAAs are simple and easy to perform, the results did not differentiate between negative, low, moderate, and high binding abilities when Salmonella strains were evaluated for fn binding, and the results were not comparable to those obtained by the conventional radiolabeling method.

The effects of some synthetic prostanoids on the contractility of the human lower uterine segment in vitro.

We have investigated the ability of three synthetic prostanoids to directly influence uterine contractility by studying the effects in vitro. Strips of lower uterine segment smooth muscle were obtained from women undergoing elective cesarean section at term. The ability of these strips to develop tension in the presence of cumulative additions of prostanoids or oxytocin was assessed. Spontaneous contractions were inhibited by ZK 96.480, a stable synthetic analog of prostaglandin I2, with a 50th percentile effective concentration (EC50) of 8 nmol/L. Both sulprostone, an analog with selectivity for some of the actions of prostaglandin E2, and U-44069, a stable thromboxane A2 mimetic, caused excitation with EC50s of 20 and 16 nmol/L, respectively. The EC50 for oxytocin was 6 nmol/L. There were no significant differences in the maximal tensions developed in response to the excitatory prostanoids or oxytocin.

Abortifacient activity of a medicinal plant "moringa oleifera" in rats.

Dried powder of leaf extract of common Indian plant Moringa Oleifera of Moringaceae family was tested experimentally in albino rats in our laboratory for its antifertility activity. Cant per cent abortifacient activity was found when administered orally in aqueous solution at dose of 175 mg/kg body weight daily to Charles foster strain albino rats from days 5-10 post mated.