Increased pregnancy-associated plasma protein-A (PAPP-A) concentrations in peritoneal fluid of women with endometriosis

PROBLEM: Pregnancy-associated plasma protein-A (PAPP-A) belongs to a group of glycoproteins isolated from extracts of human placenta. Healthy ovarian and uterine tissues are also known to express PAPP-A. We hypothesized that PAPP-A levels might also be elevated in the peritoneal fluid (PF) of women with endometriosis, and examined variations in PF PAPP-A during the menstrual cycle and with the severity of the disease. METHOD OF STUDY: PF PAPP-A were measured in 60 women with endometriosis and 38 women without endometriosis using a high-sensitivity immunofluorometric assay. RESULTS: We found that the mean level of PAPP-A was higher in PF from patients with endometriosis than controls (p = 0.003). Furthermore, significant correlation was found between the stages of endometriosis and the levels of PAPP-A in these patients (r = 0.39, p = 0.009). The concentrations of PAPP-A in PF were significantly higher in the secretory phase than the proliferative phase of the menstrual cycle in both women with and without endometriosis (p = 0.009 and P = 0.002, respectively). Finally, among the controls, women undergoing tubal ligation had significantly lower mean PF levels of PAPP-A than women with infertility or pelvic pain (p = 0.001). CONCLUSION: We conclude that PF levels of PAPP-A vary during the menstrual cycle, and are highest in the secretory phase. We also find that PF PAPP-A levels are significantly increased in women with endometriosis, and that the degree of elevation corresponds to the extent of disease.     

Role of polymorphisms in Adamantiades-Behçet's disease

OBJECTIVE: We previously showed that Adamantiades-Beh?et's disease (A-BD) is associated with a lower incidence of malignancy compared with the general population. Transforming growth factor-beta (TGF-beta) has been shown to play a role in cartilage regeneration and is increased in patients with A-BD. We also found 2 functional polymorphisms of the TGF-beta pathway, TGFBR1*6A and TGFB1*CC, that are associated with risk of malignancy. We tested whether incidence of these polymorphisms would differ in patients with A-BD compared with healthy controls of similar age and geographic location. METHODS: We performed a case-control study including 139 cases and 128 controls from Greece. Cases and controls were genotyped for TGFBR1*6A and TGFB1*CC. RESULTS: We found that cases had lower incidence of TGFBR1*6A compared with controls (11.3% vs 13.3%, respectively). Also, the incidence of TGFB1*CC was lower in cases than controls (24.6% vs 27.0%, respectively). These differences were not statistically significant. CONCLUSION: Although there is a suggestion that the lower incidence of TGFBR1*6A in A-BD patients may play a protective role against development of malignancy, larger studies would be needed to fully evaluate the role of TGF-beta and its polymorphisms in A-BD.     

Intron 4 a/b polymorphism of the endothelial nitric oxide synthase gene is associated with both type 1 and type 2 diabetes in a genetically homogeneous population

Current classifications of diabetes distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D), however recent evidence highlights overlap between T1D and T2D. Earlier studies have suggested altered nitric oxide (NO) metabolism in both T1D and T2D. In the present case-control study, we investigated whether the endothelial NO synthase gene intron 4 a/b polymorphism is associated with T1D and T2D in the island of Crete, a well-defined area with genetically homogeneous population. Mutated allele "a" was more common in individuals with both T1D and T2D than in controls (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.06-2.77, p = 0.013; and OR = 1.50, 95% CI = 0.930-2.42, p = 0.047, respectively). Mutated genotype (a/a or a/b) was more common in individuals with T1D than in nondiabetic individuals (OR = 1.93, 95% CI = 1.12-3.32, p = 0.008); this increased frequency was also observed for T2D, although not at a significant level (OR = 1.38, 95% CI = 0.802-2.37). No difference was found in the frequency of mutated allele a or mutated genotype (a/a or a/b) between T1D and T2D populations. In conclusion, our results indicate that allele a of the intron 4 endothelial NO synthase gene is associated with susceptibility to both T1D and T2D and may represent a common genetic factor for diabetes.     

Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH

One of the most important factors influencing embryo viability is chromosome imbalance (aneuploidy). Embryos derived from aneuploid gametes have little potential for forming a viable pregnancy, but cannot be distinguished from normal embryos using standard morphological evaluation. For more than a decade, preimplantation genetic screening (PGS) has been used to assist in the identification of aneuploid embryos. However, current strategies, based upon cell biopsy followed by fluorescent in situhybridization, allow less than half of the chromosomes to be screened. In this review, we discuss methods that overcome the limitations of earlier PGS strategies and provide screening of the entire chromosome complement in oocytes and embryos. In recent months, there has been a rapid growth in the number of PGS cycles utilizing one such method, comparative genomic hybridization (CGH). Data from IVF cycles utilizing CGH must be considered preliminary, but appear to indicate a dramatic increase in embryo implantation following comprehensive chromosomal screening. It is expected that methods based upon microarrays will yield similar clinical results and may be sufficiently rapid to permit comprehensive screening without the need for embryo cryopreservation. Some microarray platforms also offer the advantage of embryo fingerprinting and the potential for combined aneuploidy and single gene disorder diagnosis. However, more data concerning accuracy and further reductions in the price of tests will be necessary before microarrays can be widely applied.     

Expression of urocortin in the extravillous human trophoblast at the implantation site

Urocortin (UCN) is a 40 amino acid peptide which is closely related to corticotropin-releasing hormone and binds with high affinity to both CRH type 1 and type 2 receptors. UCN is expressed in human reproductive tissues including endometrium, ovary, and placenta. This study was designed to investigate the cellular localization of UCN at the implantation site of the human blastocyst, as well as the regulation of the UCN promoter by two major intracellular signaling pathways, the cAMP/PKA and diacylglycerol/PKC pathways, in cells of placental origin. For this reason, immunohistochemistry was performed on tissue sections from paraffin-embedded human first trimester placentas and freshly isolated human invasive extravillous trophoblast cells (EVT) were analyzed for UCN expression using RT-PCR and immunofluorescence. Finally, UCN promoter activity was analyzed in the JEG3 human choriocarcinoma cell line. Immunohistochemistry revealed expression of UCN in the cytotrophoblast, the EVT and decidual cells. Both UCN mRNA and peptide were detectable in freshly isolated EVT. Finally, a human UCN promoter luciferase reporter construct transfected into JEG3 cells was significantly inducible by phorbol ester plus ionomycin, but not by phorbol ester alone or by forskolin. Collectively, the present study reports the expression of UCN in EVT and the activation of the UCN gene promoter by the diacylglycerol/PKC pathway. The functional significance of urocortin for the physiology of EVT requires further investigation.     

A randomized comparison between intravaginal misoprostol and prostaglandin E<Subscript>2</Subscript> for labor induction

Objective The aim of this randomized study was to compare the effectiveness, safety, and side effects of 6 h vaginal misoprostol versus vaginal prostaglandin E₂ (PGE₂) for labor induction. Study design Fifty microgram of misoprostol was given intravaginally in the misoprostol group (204 women), and 3 mg PGE₂ was given intravaginally in the PGE₂ group (211 women). In both groups, the dose was repeated every 6 h for a maximum of three doses, until active labor was achieved. Artificial rupture of membranes and oxytocin infusion was used during labor in both groups where it was indicated. Results The mean interval from the institution of labor induction to delivery was 11.3 ± 8.6 h for the misoprostol group, and 15.7 ± 9.3 h for PGE₂ group (P < 0.05). In the misoprostol group, oxytocin was used less frequently, but there was a higher prevalence of tachysystole. No statistically significant differences were observed between the two groups as regard abnormal patterns of fetal heart rate, the mode of delivery, and the need for neonatal intervention. Conclusion In conclusion, the intravaginal administration of 50 μg misoprostol at 6 h interval (maximum three doses) is comparable in safety, but more effective for induction of labor than 3 mg intravaginal PGE₂.     

SOLUBLE IL-6 RECEPTOR LEVELS IN THE SEMINAL PLASMA OF INFERTILE PATIENTS WITH ACCESSORY GLAND INFECTION

A technique was standardized to measure nuclear dihydrotestosterone receptors in human prostate. Normal, hyperplastic (BPH), and cancer tissues were homogenized and the homogenate centrifuged at 600 g × 10 min; the pellet was purified on sucrose density gradient. Purified nuclei were extracted with 0.4 M KC1. The nuclear extract was then incubated in the presence of [³H]dihydrotestosterone (DHT) at 4°C for 20 hr. Competition studies with different steroids indicated a high specificity of the receptor towards DHT and no affinity towards progesterone and 17β-estradiol. Isolation and purification of [³H]DHT after its incubation in the presence of the KC1 nuclear extract indicated that no significant degradation of the hormone occurred during incubation. The number of binding sites measured was 8.5 ± 0.77 fmol/mg protein(mean ± SEM) for normal, 38.6 ± 5.9 for BPH, and 79.9 ± 21.9for cancer. The possible clinical application of these results will require a long-term follow-up of the hormonal responsiveness of the prostatic-cancer patients investigated.