No abstract

No abstract

ABSTRACT:The placenta plays an important role in modulating xenobiotic passage from mother to fetus. Studies in mice have demonstrated that placental ABCB1 and ABCG2 can affect the transfer of drugs across the placental barrier, suggesting a role for these transporters in protecting the fetus from environmental toxicants or drugs ingested by the mother during pregnancy. To assess the role of these transporters in the human placenta, studies were conducted to evaluate the expression and functional activity of placental ABCB1 and ABCG2. The effect of maternal smoking on these placental transporters was also assessed.

Antibiotic treatment during pregnancy was frequent in the study population, but was not associated with a significant risk of developing Candida vaginitis.

No abstract

ABSTRACT:CYP3A4, a cytochrome P450 (P450) isoform metabolizes estrogens, whereas CYP3A7, a fetal liver P450 isoform, is involved in estriol biosynthesis. The goal of this study was to evaluate expression of these enzymes in human uterine tissue during the proliferative and secretory phases of the menstrual cycle. Endometrium and cervix specimens were collected from women undergoing hysterectomy (n ‫؍‬ 36). Total mRNA was extracted, quantified, and reverse-transcription polymerase chain reaction (RT-PCR) was carried out using consensus primers for CYP3A. The 453 base pairs PCR product was hybridized with specific internal oligonucleotide probes for CYP3A4 or CYP3A7 end labeled with 32 P ␥-ATP. The relative intensity of hybridization was determined by autoradiography. Expression of CYP3A7 in endometrium was significantly greater (ϳ10-fold) in the proliferative phase compared with the secretory phase (p < 0.05). CYP3A4 expression was comparable between the two phases. Expression of both enzymes was minimal in the cervix. Fluorescence in situ hybridization of paraffinized sections indicated localized expression of CYP3A enzymes in the glandular epithelium as well as the stroma. Comparison of relative fluorescence intensity indicated differential expression of CYP3A7 in various phases of the menstrual cycle. These results suggest that CYP3A expression in the endometrium of premenopausal women may vary depending on the menstrual cycle phase. The P4501 enzymes are a family of hemeproteins that metabolize a number of exogenous and endogenous substrates including steroid hormones (Nelson et al., 1993;Sarkar et al., 1997). Of these, the CYP3A subfamily of enzymes has been established as the most abundant P450 in humans, representing about 30% of all hepatic P450 (Slaughter et al., 1995). So far three major isoforms have been identified in humans, CYP3A4, CYP3A5, and CYP3A7, of which CYP3A4 is the predominant hepatic isoform (Sarkar et al., 1997) and CYP3A7 is a human fetal liver form, first isolated as a 16-␣-dehydroepiandrosterone-sulfate (DHEA-s) hydroxylase (Kitada et al., 1987). The role of several P450 isoforms in catalyzing the hydroxylation of cortisol, testosterone, androstenedione, estradiol, and progesterone has been established (Berliner et al., 1956;Lipman et al., 1962;Tukey et al., 1985;Guengerich, 1988). However, it is not clear whether these reactions in the liver have any physiological importance, if any, or simply serve as accessory elimination pathways. Recent evidence from our lab has shown that the uterus, specifically endometrium and cervix, expressed differential levels of CYP1A1 and CYP1B1 mRNA (Satya et al., 1998). These observations suggest that extrahepatic P450 may participate in tissue-specific biotransformations, which might be of physiologic relevance.While several P450 isoforms have been indicated in estrogen biotransformation, CYP3A4 is probably one of the major isoforms involved in several pathways (Aoyama et al., 1990;Brian et al., 1990). CYP3A7 has been found to catalyze 16-␣-hydroxylati...

The virulence attributes of Candidaalbicans in cases of mucocutaneous disease have not been identified. Based on the recent finding that C. albicans is able to produce an immunosuppressive mycotoxin, gliotoxin, we analyzed vaginal samples of 3 women severely symptomatic for vaginal candidiasis and found that they contained significant levels of gliotoxin. Three control women who were not colonized with Calbicans showed no gliotoxin in vaginal samples. These findings raise the possibility that gliotoxin may play a role in the virulence of C. albicans.

No abstract