Publications

OBJECTIVE

To determine whether actively using, methamphetamine (meth)-dependent men who have sex with men (msm) could be enrolled and retained in a pharmacologic intervention trial, and the degree to which participants would adhere to study procedures, including medication adherence. study design: phase ii randomized, double-blind trial of bupropion vs. placebo.

METHODS

Thirty meth-dependent, sexually active MSM were randomized to receive daily bupropion XL 300 mg or placebo for 12 weeks. Participants received weekly substance use counseling, provided weekly urine specimens, and completed monthly audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps (the number of distinct MEMS cap openings divided by the number of expected doses) and self-report.

RESULTS

Ninety percent completed the trial: 89% of monthly ACASIs were completed, 81% of study visits were attended, and 81% of urine samples were collected. Adherence by MEMS cap was 60% and by self-report was 81% and did not differ significantly by treatment assignment. The median number of positive urine samples was 5.5 out of a possible 11 (50%). Participants in both arms reported similar declines in the median number of sex partners (P = 0.52). No serious adverse events occurred and there were no significant differences in adverse events by treatment assignment (P = 0.11).

CONCLUSIONS

It is feasible to enroll and retain actively using, meth-dependent MSM in a pharmacologic intervention. Bupropion was well tolerated. Study participation and retention rates were high, however, study drug medication adherence was only moderate. Findings support a larger trial with improved adherence support to evaluate the efficacy of bupropion and other pharmacologic interventions for meth dependence in this population.

We have recently implicated mitochondrial mechanisms in models of neuropathic and inflammatory pain, in some of which a role of protein kinase Cepsilon (PKCepsilon) has also been implicated. Since mitochondria contain several proteins that are targets of PKCepsilon, we evaluated the role of mitochondrial mechanisms in mechanical hyperalgesia induced by proinflammatory cytokines that induce PKCepsilon-dependent nociceptor sensitization, and by a direct activator of PKCepsilon (psiepsilonRACK), in the rat. Prostaglandin E(2) (PGE(2))-induced hyperalgesia is short lived in naïve rats, while it is prolonged in psiepsilonRACK pre-treated rats, a phenomenon referred to as priming. Inhibitors of two closely related mitochondrial functions, electron transport (complexes I-V) and oxidative stress (reactive oxygen species), attenuated mechanical hyperalgesia induced by intradermal injection of psiepsilonRACK. In marked contrast, in a PKCepsilon-dependent form of mechanical hyperalgesia induced by prostaglandin E(2) (PGE(2)), inhibitors of mitochondrial function failed to attenuate hyperalgesia. These studies support the suggestion that at least two downstream signaling pathways can mediate the hyperalgesia induced by activating PKCepsilon.

BACKGROUND

A subset of HIV-infected patients, termed 'elite' viral controllers, maintain undetectable plasma HIV RNA levels in the absence of therapy. In this group, host-mediated viral control may be accompanied by chronic systemic inflammation. It is unknown whether either infection or chronic inflammation is present within the central nervous system of these individuals.

METHODS

Cross-sectional analysis compared cerebrospinal fluid (CSF) HIV RNA and biomarkers of intrathecal inflammation in eight controllers (plasma HIV RNA levels <50 copies/ml) with 26 HIV-uninfected individuals, 25 untreated individuals HIV-infected, viremic individuals, and 23 HIV-infected individuals with treatment-mediated viral suppression (plasma HIV RNA levels <50 copies/ml).

RESULTS

All controllers had CSF HIV RNA levels below 2.5 copies/ml. CSF white blood cell (WBC) counts and CSF: plasma albumin ratios in the controllers were similar to those in both HIV-uninfected individuals and antiretroviral therapy-suppressed HIV-infected individuals. CSF neopterin, MCP-1, and IP-10 concentrations were also not different in the controllers from either HIV-uninfected or treated HIV-infected individuals.

CONCLUSION

The character of CSF HIV infection and degree of immunoactivation in controllers is comparable to that of HIV-uninfected and antiretroviral therapy-suppressed HIV-infected individuals, but distinct from that of untreated, viremic HIV-infected individuals.

Autoimmune diseases such as type 1 diabetes are complex in their pathogenesis. One approach to improving our understanding of type 1 diabetes is the study of diseases that represent more extreme examples of autoimmunity. Autoimmune polyendocrine syndromes (APS) are relatively rare diseases that often include type 1 diabetes as part of the disease phenotype. Recently, there has been tremendous progress in unraveling some of the underlying mechanisms of APS. Here, we highlight the APS disorders with the perspective of the clues they can offer to the pathogenesis and treatment of type 1 diabetes.