Evaluation of trappin-2 in cervicovaginal secretions as predictor of spontaneous preterm birth in asymptomatic high-risk women: Nested case-control study.

OBJECTIVE: To evaluate trappin-2 levels in cervicovaginal secretions for prediction of spontaneous preterm birth (sPTB) and compare it with transvaginal sonography (TVS) cervical length in asymptomatic women at risk of PTB. METHODS: Trappin-2 levels assessed in cervicovaginal secretions collected from 80 asymptomatic pregnant women at high risk for preterm delivery and cervical length measured by TVS, first at 14-20 weeks of pregnancy and repeated 8 weeks later. On the basis of delivery outcomes, participants were divided into cases (delivery <37 weeks) and controls (delivery at 37-41 weeks). RESULTS: The mean value of cervicovaginal trappin-2 was significantly higher in women who delivered preterm (n = 40), compared with the term group (n = 40: P < 0.001) both at 14-20 weeks and at 22-28 weeks. The critical cut-off value for cervicovaginal trappin-2 at 14-20 weeks was 4620 pg/mL, above which participants delivered prematurely with sensitivity, specificity, and positive and negative predictive values of 82.5%, 71.0%, 78.5%, and 81.5% respectively, whereas TVS cervical length in this window period was not significantly associated with preterm birth. At 22-28 weeks a trappin-2 value of 6900 pg/mL had similar predictive accuracy. CONCLUSION: Raised cervicovaginal trappin-2 levels can be used as an early tool for prediction of PTB as early as 14-20 weeks (earlier than TVS) in asymptomatic high-risk women.

Gene environment interaction in urinary bladder cancer with special reference to organochlorine pesticide: a case control study.

Urinary bladder cancer (UBC) is a common disease worldwide with a higher incidence rate in developed countries. Organochlorine pesticides (OCPs), potent endocrine disrupters, are found to be associated with several cancers such as prostate, breast, bladder, etc. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous environmental toxins including OCPs. The present study was carried out in UBC subjects (n=50) and healthy control subjects (n=50) with an aim to determine the role of GSTM1 and GSTT1 polymorphism and its implication on the OCP detoxification or bioaccumulation which may increase the risk of UBC in humans. This study was also designed to identify the "gene-environment interaction" specifically between gene polymorphism in xenobiotic metabolizing genetic enzyme(s) and blood OCP levels. GSTM1/GSTT1 gene polymorphism was analysed by using multiplex PCR. OCPs levels in whole blood were estimated by Gas chromatography equipped with electron capture detector. The results demonstrated a significant (p< 0.05) increase in frequency of GSTM1^{-}/GSTT1^{-} (null) genotype in UBC cases without interfering the distribution of other GSTT1/GSTM1 genotypes. The blood levels of alpha (α), Beta (ß), Gamma (γ), total - Hexachlorcyclohexane (HCH) and para-para - dichlorodiphenyltrichloroetane (p,p'-DDT) were found to be significantly (p< 0.05) high in UBC cases as compared to controls. Multiple regression analysis revealed a significant interaction between ß-HCH and GSTM1^{-} genotype (p< 0.05) as well as in ß-HCH and GSTT1^{-} genotype (p< 0.05) respectively. These findings indicate that "gene-environment interaction" may play a key role in increasing the risk for UBC in individuals who are genetically more susceptible due to presence of GSTM1/GSTT1 null deletion during their routine encounter with or exposure to OCPs.

Nephrotoxicity and its prevention by taurine in tamoxifen induced oxidative stress in mice.

Tamoxifen (TAM) is an anti-neoplastic drug used for the treatment of breast cancer. It decreases the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in cells leading to tissue injury. The present study was undertaken to investigate modulatory effects of taurine on the nephrotoxicity of TAM with special reference to protection against disruption of nonenzymatic and enzymatic antioxidants. Oxidative stress was measured by renal lipid peroxidation (LPO) level, protein carbonyl (PC) content, reduced glutathione (GSH), activities of phase I and II drug metabolizing and antioxidant enzymes. TAM treatment resulted in a significant (P < 0.001) increase in LPO in kidney tissues as compared to control, while taurine pretreatment showed a significant decrease (P < 0.01) in the LPO in kidneys when compared with the TAM-treated group. Taurine + TAM group animals showed restoration in the level of cytochrome P450 content, activities of glutathione metabolizing enzymes viz., glutathione-S-transferase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase. Pretreatment of animals with taurine markedly attenuated, PC content, restored the depleted nonenzymatic and enzymatic antioxidants. These results clearly demonstrate the role of oxidative stress, and suggest a protective effect of taurine on TAM-induced nephrotoxicity in mice.