Oxidative Folding and Preparation of ?-Conotoxins for Use in High-Throughput Structure-Activity Relationship Studies.

Oxidative folding and preparation of ?-conotoxins for use in high-throughput structure-activity relationship studies.

Filed under: Addiction Rehab

J Pept Sci. 2012 Nov 28;
Gyanda R, Banerjee J, Chang YP, Phillips AM, Toll L, Armishaw CJ

?-Conotoxins are peptide neurotoxins that selectively inhibit various subtypes of nicotinic acetylcholine receptors. They are important research tools for studying numerous pharmacological disorders, with profound potential for developing drug leads for treating pain, tobacco addiction, and other conditions. They are characterized by the presence of two disulfide bonds connected in a globular arrangement, which stabilizes a bioactive helical conformation. Despite extensive structure-activity relationship studies that have produced ?-conotoxin analogs with increased potency and selectivity towards specific nicotinic acetylcholine receptor subtypes, the efficient production of diversity-oriented ?-conotoxin combinatorial libraries has been limited by inefficient folding and purification procedures. We have investigated the optimized conditions for the reliable folding of ?-conotoxins using simplified oxidation procedures for use in the accelerated production of synthetic combinatorial libraries of ?-conotoxins. To this end, the effect of co-solvent, redox reagents, pH, and temperature on the proportion of disulfide bond isomers was determined for ?-conotoxins exhibiting commonly known Cys loop spacing frameworks. In addition, we have developed high-throughput ‘semi-purification’ methods for the quick and efficient parallel preparation of ?-conotoxin libraries for use in accelerated structure-activity relationship studies. Our simplified procedures represent an effective strategy for the preparation of large arrays of correctly folded ?-conotoxin analogs and permit the rapid identification of active hits directly from high-throughput pharmacological screening assays. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
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Web-based cognitive behavioral self-help intervention to reduce cocaine consumption in problematic cocaine users: randomized controlled trial.

Filed under: Addiction Rehab

J Med Internet Res. 2012; 14(6): e166
Schaub M, Sullivan R, Haug S, Stark L

Web-based self-help programs that reduce problematic substance use are able to reach hidden consumer groups in the general population. These programs are characterized by their low treatment threshold and nonrestrictive intervention settings. They are also cost effective, making them of interest to both low-income and high-income industrialized countries with ever-increasing health costs.To test the feasibility and effectiveness of an anonymous, fully automated, Web-based self-help intervention as an alternative to outpatient treatment services for cocaine users.A total of 196 cocaine-using participants were recruited through various online and offline media for a randomized controlled trial. Participants in the intervention group received interactive cognitive behavioral modules and a consumption diary to reduce cocaine use, whereas participants in the control group received online psychoeducative information modules. Web-based follow-up assessments were conducted after 4 weeks, 6 weeks, and 6 months. Treatment retention was examined and compared between the intervention and control groups. Severity of cocaine dependence was the main outcome measure. Secondary outcomes were cocaine craving, depression symptoms, and alcohol and other substance use.This Web-based intervention attracted older and more educated participants than existing outpatient treatment programs for which cocaine is the primary substance of abuse. Participants in the intervention group showed greater treatment retention compared with the control group (P = .04). Low response rates at the follow-up assessments restricted the explanatory power of the analyses. At the follow-up assessments, the severity of cocaine dependence did not differ between the intervention and control groups (P = .75). Furthermore, there were no differences in cocaine craving, depression, or alcohol and other substance use. Using the consumption diaries, the average number of cocaine-free days per week did not change significantly, whereas the weekly quantity of cocaine used decreased equally in both groups (P = .009).For cocaine users with low dependence severity, a fully automated Web-based cognitive behavioral self-help intervention is a feasible alternative with limited effectiveness in outpatient treatment services. However, this type of intervention may attract specific user groups that are rarely reached by existing outpatient treatment and may help them to control their cocaine consumption anonymously.ISRCTN93702927; http://www.controlled-trials.com/ISRCTN93702927 (Archived by WebCite at http://www.webcitation.org/6CTMM10MR).
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Application of Level of Care Utilization System for Psychiatric and Addiction Services (LOCUS) to Psychiatric Practice in Japan: A Preliminary Assessment of Validity and Sensitivity to Change.

Filed under: Addiction Rehab

Community Ment Health J. 2012 Nov 29;
Kimura T, Yagi F, Yoshizumi A

We applied an American medical necessity scale, Level of Care Utilization System for Psychiatric and Addiction Services (LOCUS), to psychiatric practice in Japan. This is an exploratory analysis of empirical data of 272 patients. We examined the relationships between levels of care of LOCUS and clinical variables, contribution of care levels on admission decision, and changes in care levels over time. Inpatients showed significantly higher levels of care than outpatients. Levels of care showed significant strong inverse correlations to Global Assessment Scale (GAS) scores, and significant moderate correlations to admission types, care environment, and diagnostic subgroups in almost all groups. Levels of care contributed as much to the admission decision as GAS scores. Levels of care significantly decreased from the time of admission to discharge. Our preliminary evidence indicates that LOCUS is valid and sensitive to change, and applicable for clinical use in Japan.
HubMed – addiction


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