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2.  Genetic Association of GABA-A Receptor Alpha-2 and Mu Opioid Receptor with Cocaine Cue-Reactivity: Evidence for Inhibitory Synaptic Neurotransmission Involvement in Cocaine Dependence 
This pilot feasibility study examined the role of genetics in laboratory-induced cocaine craving.
Thirty-Four African American, cocaine-dependent male subjects underwent a baseline assessment, cue-exposure session and genetic analysis. Subjects were classified as either cue-reactive or non-reactive.
Among SNP markers in 13 candidate genes examined for association with cocaine cue-reactivity, two were statistically significant: GABRA2 (coding for GABA-A receptor alpha-2 subunit; rs11503014, nominal p = 0.001) and OPRM1 (coding for mu opioid receptor; rs2236256, nominal p = 0.03).
These pilot results suggest that cocaine craving shows variability among cocaine-dependent subjects, and that GABRA2 and OPRM1 polymorphisms have differential influences on cocaine cue-reactivity, warranting studies in future research.
PMCID: PMC3425941  PMID: 22882391
3.  Sertraline Delays Relapse in Recently Abstinent Cocaine-Dependent Patients with Depressive Symptoms1 
Addiction (Abingdon, England)  2011;107(1):131-141.
Whether the selective serotonin reuptake inhibitor sertraline at 200 mg/day delays relapse in recently abstinent cocaine dependent individuals
12-week, double blind, placebo-controlled clinical trial with 2-week residential stay followed by 10-wk outpatient participation
Veterans Affairs residential unit and outpatient treatment research program
Cocaine-dependent volunteers (N=86) with depressive symptoms (Hamilton score > 15), but otherwise no major psychiatric or medical disorder or contraindication to sertraline.
Participants were housed on a drug-free residential unit (wks 1–2) and randomized to receive sertraline or placebo. Participants then participated on an outpatient basis during weeks 3–12 while continuing to receive study medication. Patients participated in a day substance abuse day treatment program during weeks 1–3 and underwent weekly cognitive behavioral therapy during weeks 4–12. The primary outcome measure was thrice-weekly urine results and secondary measure was Hamilton Depression scores.
Pre hoc analyses were performed on those who participated beyond week 2. Generally no group differences in retention or baseline characteristics occurred. Sertraline patients showed a trend toward longer time before their first cocaine-positive urine (“lapse,” χ2=3.67, p=0.056), went significantly longer before having two consecutive urine samples positive for cocaine (“relapse,” χ2=4.03, p=0.04) and showed significantly more days to lapse (26.1±3.2±10.5; z = 2.89, p=0.004) and relapse (21.3±10.8 vs 32.3±14.9; z=2.25, p=0.02). Depression scores decreased over time (F=43.43, p<0.0001), but did not differ between groups (F =0.09, p = 0.77).
Sertraline delays time to relapse relative to placebo in cocaine dependent patients who initially achieve at least two weeks of abstinence.
PMCID: PMC3237722  PMID: 21707811
cocaine dependence; randomized clinical trial; placebo control; sertraline; relapse prevention; cognitive behavioral therapy
4.  Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae 
Transcriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes. Klebsiella pneumoniae is a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription of ramA is associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466–4467, 2012). Bioinformatic analyses of the available Klebsiella genome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded in K. pneumoniae, Enterobacter sp. 638, Serratia proteamaculans 568, and Enterobacter cloacae. We show that the overexpression of rarA results in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show that rarA (MGH 78578 KPN_02968) and its neighboring efflux pump operon oqxAB (KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest that rarA overexpression upregulates the oqxAB efflux pump. Additionally, it appears that oqxR, encoding a GntR-type regulator adjacent to the oqxAB operon, is able to downregulate the expression of the oqxAB efflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.
PMCID: PMC3421627  PMID: 22644028
5.  Intersection of chronic pain treatment and opioid analgesic misuse: causes, treatments, and policy strategies 
Treating chronic pain in the context of opioid misuse can be very challenging. This paper explores the epidemiology and potential treatments for chronic pain and opioid misuse and identifies educational and regulation changes that may reduce diversion of opioid analgesics. We cover the epidemiology of chronic pain and aberrant opioid behaviors, psychosocial influences on pain, pharmacological treatments, psychological treatments, and social treatments, as well as educational and regulatory efforts being made to reduce the diversion of prescription opioids. There are a number of ongoing challenges in treating chronic pain and opioid misuse, and more research is needed to provide strong, integrated, and empirically validated treatments to reduce opioid misuse in the context of chronic pain.
PMCID: PMC3846312  PMID: 24474854
addiction; dependence; diversion; comorbid; narcotic; treatment
6.  Preliminary Study of Buprenorphine and Bupropion for Opioid Dependent Smokers 
In this double-blind, placebo-controlled trial, bupropion (BUPRO, 300 mg/day) was compared to placebo (PBO) for concurrent treatment of opioid and tobacco addiction in 40 opioid-dependent smokers stabilized on buprenorphine (BUPRE, 24 mg/day). Participants received contingent, monetary reinforcement for abstinence from smoking, illicit opioids, and cocaine. Significant differences in treatment retention were observed (BUPRE+BUPRO, 58%; BUPRE+PBO, 90%). BUPRO treatment was not more effective than placebo for abstinence from tobacco, opioids, or cocaine in BUPRE stabilized patients. These preliminary findings do not support the efficacy of BUPRO, in combination with BUPRE, for concurrent treatment of opioid and tobacco addiction.
PMCID: PMC2588345  PMID: 18612883
opioid dependence; smoking cessation; bupropion; buprenorphine
7.  Validation of the String Test for the Recovery of Helicobacter pylori from Gastric Secretions and Correlation of Its Results with Urea Breath Test Results, Serology, and Gastric pH Levels 
Journal of Clinical Microbiology  2001;39(4):1650-1651.
The efficacy of the string culture test to isolate Helicobacter pylori from gastric secretions of 28 volunteers was studied. With the urea breath test (UBT) as the “gold standard,” the string culture test showed a sensitivity of 75% and a specificity of 100%. The results of string culture did not correlate with the UBT results, with serum antibody levels, or with the pH levels of gastric secretions.
PMCID: PMC87991  PMID: 11283108

Results 1-7 (7)