Characterization of placental efflux transporters

s / Drug and Alcohol Dependence 140 (2014) e169–e251 e171 Conclusions: In addition to the previously known effects of lead on development, the results of this study suggest that exposure to lead in childhood acts as a risk factor to tobacco use in adolescence. Financial support: No financial support. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.479 Transactional sex among an emergency department sample: Exploring gender, substance abuse and HIV risk Rikki Patton1,2, F.C. Blow2, Amy S. Bohnert2, Erin E. Bonar2, K.L. Barry2, M.A. Walton2 1 Substance Abuse Research Center, University of Michigan, Ann Arbor, MI, United States 2 Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States Aims:Men andwomen involved in transactional sex (TS) report increased rates ofHIV risk behaviors and substance abuse problems as compared to the general population.When people engaged in TS seek healthcare, they may be more likely to utilize the emergency department (ED) rather than primary care services. Our goal was to examine the prevalence and correlates of TS involvement among an emergency department (ED) sample of men and women. Methods: Adults ages 18–60 were recruited from an urban ED, as part of a larger randomized control trial. Participants (n=3699; 2428 women, 1271 men) self-administered a screening survey that assessed both substance use and HIV risk behaviors, including transactional sex (i.e. being paid for the exchange of a sexual behavior for money, drugs, or other needs). Results: Of the sample, 13.6% reported TS involvement within the past three months (62% were female). Bivariate analysis showed TS involvement was positively associated with alcohol use (OR=1.02), drug use (OR=1.83) and HIV risk behaviors, including inconsistent condom use (OR=5.63) and multiple partners (OR=1.37). These variables remained significantly positively associated in a multi-variate regression analysis. Gender findings were non-significant. Conclusions: The prevalence rates of both men and women in the ED who report recent TS involvement are substantial. These individuals were more likely to report higher rates of alcohol/drug useandother risky sexual behaviors. As such, theEDmaybeaprime target location to engage both men and women who are involved in TS into substance use interventions. Financial support: This investigation was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32 DA007267 and NIDA #026029. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.480 Characterization of placental efflux transporters Jonathan A. Paul, S.L. Patrikeeva, X. Wang, G.D. Hankins, T.N. Nanovskaya, Mahmoud S. Ahmed Obstetrics and Gynecology, University of Texas Medical Brance, Galveston, TX, United States Aims: P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), and several Multidrug Resistance Proteins (MRP’s) are expressed in the human placenta. The major function of placental efflux transporters is to decrease fetal exposure to xenobiotics including medications used for treatment of the pregnant patients e.g. opiates and bupropion. The aim of this investigation is to characterize the activity of P-gp and BCRP using their respective prototypic substrates [3H]-Paclitaxel, Taxol & [3H]Estrone-3-Sulfate, E1S. Methods: Inside-out brush-border membrane vesicles (IOV) were prepared from termplacentas (n=10). ATP dependent uptake of E1S and Taxol by IOV was calculated as the difference in uptake of each substrate in the presence and absence of ATP. The chemical inhibitors to P-gp (verapamil, haloperidol), BCRP (Ko143, fumitremorgin C), and MRPs (indomethacin, pravastatin, bromosulfalein)were used to identify the efflux transporters contributing to placental vesicular uptake of E1S and Taxol. Results: The kinetic parameters determined for ATP dependent uptake of E1S and Taxol by IOV revealed the following apparent Kt values; 670±200nM and 66±38nM and Vmax values of 0.8±0.2pmolmg protein−1 min−1 and 4.5±0.5pmolmg protein−1 min−1, respectively. The ATP-dependent uptake of Taxol was significantly reduced in the presence of P-gp (50–70%) and MRPs (60–70%) inhibitors while ATP-dependent uptake of E1S was 40–60% reduced by MRPs and 20% by BCRP inhibitors. Conclusions: Previously Taxol and E1S were characterized as prototypic substrates of P-gp and BCRP using P-gp and BCRP vesicles prepared from recombinant baculovirus-infected insect cells. The data obtained in this investigation revealed that ATPdependent uptake of these substrates by placental IOV are mediated by more than one transporter. These data suggest that most likely multiple transporters are involved in the in vivo efflux of different substrates/medications. Financial support: NIDA R01DA13431 (MSA), NIDA R01DA030998 (TN), NICHD T32HD55163. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.481 Is primary care accessible to general population adults who use drugs? Brittany Payne1, Y. Khodneva1, X. Wang1, M. Pletcher3, M. Stafford1, J. Richman1, Stefan Kertesz1,2 1 University of Alabama at Birmingham, Birmingham, AL, United States 2 VA Medical Center, Birmingham, AL, United States 3 University of California, San Francisco, San Francisco, CA, United States Aims: Illicit drug use is common in adults; however, data regarding the impact of drug use on health service utilization is scarce outside of clinical addiction populations. The Coronary Artery RiskDevelopment in YoungAdults study (CARDIA)was used to study whether the longitudinal trajectories of both marijuana andnon-marijuanadrugusewere associatedwith reducedprimary care (PC) access at 18-year follow-up. Methods: A cohort of 4300 healthy young adults was repeatedly queried about drug use from 1987–1988 to 2005–2006. We compared self-report of having a usual PC provider at end followup (ages 38–50) among trajectories (using SAS PROC TRAJ) for non-marijuana drug use (cocaine, opioids, amphetamines) and marijuana use. Models were adjusted for demographics, insurance, health status, tobacco and alcohol. Results: For non-marijuana drugs, there were 160 (3.7%) Persistent Occasional users, 110 (2.6%) Early Frequent/Late Occasional users, 340 (7.9%) Early Occasional users and 3690 (86%) non-users. Persons with continuing drug use were more likely to lack PC at follow-up (42%, 26%, 20%, 15% for the 4 groups, respectively, p< .001). Adjusting for covariates, the association was significant