Placental transfer of sulindac, sulindac sulfide, and indomethacin in a human placental perfusion model.

OBJECTIVE: Evaluation of the transplacental transfer and placental metabolism of sulindac, its active sulfide metabolite, and indomethacin, drugs used as tocolytic agents, in dual recirculating human placental perfusion. STUDY DESIGN: Term placentas were obtained with maternal consent immediately after delivery. Drugs were added to the maternal reservoir, together with antipyrine as a reference compound, and disappearance from the maternal circulation and appearance in the fetal circulation were followed up for 2 hours in 4 experiments for each compound. Drug concentrations were analyzed by high-performance liquid chromatography. RESULTS: The fetal/maternal concentration ratios after 2-hour perfusions were 0. 34 +/- 0.19 (mean +/- SD, sulindac), 0.54 +/- 0.17 (sulfide), and 0. 45 +/- 0.16 (indomethacin), and the fetal-maternal transfer percentages at 2 hours were 11.6 +/- 5.9 (sulindac), 18.2 +/- 5.2 (sulfide), and 15.3 +/- 4.5 (indomethacin). No metabolism of sulindac or indomethacin was detected. CONCLUSION: Sulindac sulfide, formed through hepatic metabolism, reaches the fetus in higher concentrations than does sulindac or indomethacin. Neither sulindac nor indomethacin is metabolized by the human placenta.

Autonomic influence on pregnancy outcome in IDDM.

We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy.

Sera from multiparous women contain antibodies mediating cytotoxicity against breast carcinoma cells.

We have searched for immunological mechanisms contributing to the epidemiologically established phenomenon of lower incidence of breast carcinoma among multiparous women and women with pregnancy at early age. Sera collected from 55 clinically healthy multiparous women were tested for the ability to mediate cytotoxicity in an antibody-dependent cell-mediated (ADCC) assay with normal blood leucocytes against three different mammary carcinoma cell lines (MDA-MB 157, MDA-MB 231, and MDA-MB 436). Sera from 12 women (22%) mediated significant cytolysis against all three cell lines. Three additional sera were positive against MDA-MB 231 and 10 more against MDA-MB 436 (total 42%). Cross-adsorptions revealed that the ADCC-active sera contained antibodies that recognized the same antigen(s) on the different mammary carcinoma-derived cell lines. The sera from multiparous women contained no detectable ADCC-active antibodies against a colon carcinoma cell line (SW 1116) or a neuroblastoma cell line (SH-SY5Y). ADCC-active antibodies were found neither in sera from 35 nulliparous women nor in sera from 20 men. The ADCC-active antibodies against mammary carcinoma cells could not be removed by adsorption with lymphoblastoid cells established from the respective husbands of the multiparous women. This observation and the fact that the mammary carcinoma cell lines were established from different patients argue against an impact of HLA-related antigens. The ADCC-active antibodies reported here might result from autoimmunization against some proliferation/differentiation antigen(s) of breast epithelium which is (are) expressed during pregnancy and lactation.