Active Drug-Using Women Use Female-Initiated Barrier Methods to Reduce HIV/STI Risk: Results from a Randomized Trial

Background. We tested an original, woman-focused intervention, based on body empowerment, and female-initiated barrier methods, including the female condom (FC) and cervical barriers. Methods. Eligible women were \u3e= 18 years of age, HIV seronegative, and active drug users, reporting 30% or greater unprotected sex acts. Both controls (C) and intervention (I) participants received enhanced HIV/STI harm reduction counseling. I participants underwent 5 additional weekly group sessions. We compared change in frequency of unprotected vaginal intercourse across arms at 12 months. Results. Among 198 enrolled women, over 95% completed followup. Two-thirds were African-American; most of them used crack, had a primary partner, and reported sex exchange. In paired t-tests from baseline to followup, the frequency of unprotected vaginal sex dropped significantly for I (primary P \u3c 0.00, nonprimary P \u3c 0.002) and C (primary P \u3c 0.008, nonprimary P \u3c 0.000) arms with all partners. The difference in change across arms was of borderline significance for primary partner (P = 0.075); no difference was seen for nonprimary partner (P = 0.8). Use of male condom and FC increased with both partner types over time, but more consistently among I women. Conclusion: The ?value-added? impact of the intervention was observed mainly with primary partners. Body knowledge with routine FC counseling should be incorporated into interventions for drug-using women

IGF-I Activation of the AKT Pathway Is Impaired in Visceral But Not Subcutaneous Preadipocytes from Obese Subjects

Obesity morbidity is associated with excess visceral adiposity, whereas sc adipose tissue is much less metabolically hazardous. Human abdominal sc preadipocytes have greater capacity for proliferation, differentiation, and survival than omental preadipocytes. IGF-I is a critical mediator of preadipocyte proliferation, differentiation, and survival through multiple signaling pathways. We investigated IGF-I action in primary cultures of human preadipocytes isolated from sc and omental adipose tissue of obese subjects. IGF-I-stimulated DNA synthesis was significantly lower in omental compared with sc preadipocytes. IGF-I phosphorylation of the IGF-I receptor and the ERK pathway was comparable in sc and omental cells. However, omental preadipocytes had decreased insulin receptor substrate (IRS)-1 protein associated with increased IRS-1-serine636/639 phosphorylation and degradation. IGF-I-stimulated phosphorylation of AKT on serine473 but not threonine308 was decreased in omental cells, and activation of downstream targets, including S6Kinase, glycogen synthase kinase-3, and Forkhead box O1 was also impaired. CyclinD1 abundance was decreased in omental cells due to increased degradation. Over-expression of IRS-1 by lentivirus in omental preadipocytes increased IGF-I-stimulated AKT-serine473 phosphorylation. The mammalian target of rapamycin (mTOR)-Rictor complex regulates phosphorylation of AKT-serine473 in 3T3-L1 adipocytes, but knockdown of Rictor by lentivirus-delivered short hairpin RNA in sc preadipocytes did not affect AKT-serine473 phosphorylation by IGF-I. These data reveal an intrinsic defect in IGF-I activation of the AKT pathway in omental preadipocytes from obese subjects that involves IRS-1 but probably not mTOR-Rictor complex. We conclude that impaired cell cycle regulation by AKT contributes to the distinct growth phenotype of preadipocytes in visceral fat of obese subjects

Extended-release naltrexone to prevent relapse among opioid dependent, criminal justice system involved adults: rationale and design of a randomized controlled effectiveness trial.

BACKGROUND: Extended-release naltrexone (XR-NTX, Vivitrol; Alkermes Inc.) is an injectable monthly sustained-release mu opioid receptor antagonist. XR-NTX is a potentially effective intervention for opioid use disorders and as relapse prevention among criminal justice system (CJS) populations. METHODS: This 5-site open-label randomized controlled effectiveness trial examines whether XR-NTX reduces opioid relapse compared with treatment as usual (TAU) among community dwelling, non-incarcerated volunteers with current or recent CJS involvement. The XR-NTX arm receives 6 monthly XR-NTX injections at Medical Management visits; the TAU group receives referrals to available community treatment options. Assessments occur every 2 weeks during a 24-week treatment phase and at 12- and 18-month follow-ups. The primary outcome is a relapse event, defined as either self-report or urine toxicology evidence of \u3e/=10 days of opioid use in a 28-day (4 week) period, with a positive or missing urine test counted as 5 days of opioid use. RESULTS: We describe the rationale, specific aims, and design of the study. Alternative design considerations and extensive secondary aims and outcomes are discussed. CONCLUSIONS: XR-NTX is a potentially important treatment and relapse prevention option among persons with opioid dependence and CJS involvement. ClinicalTrials.gov: NCT00781898

A multisite pilot study of extended-release injectable naltrexone treatment for previously opioid-dependent parolees and probationers.

A feasibility study was conducted to pilot test the ability of 5 sites to recruit, treat, and retain opioid-dependent offenders in a trial of extended-release injectable naltrexone (XR-NTX). The participants, 61 previously opioid-dependent individuals under legal supervision in the community, received up to 6 monthly injections of Depotrex brand naltrexone and completed a 6-month follow-up interview. Six-month outcomes showed that those who completed treatment had significantly fewer opioid-positive urines and were less likely to have been incarcerated than those who had not completed treatment. The findings indicate that XR-NTX holds promise as a feasible, effective treatment option for opioid-dependent offenders