Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment.

Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum (S/R = 1.4) and brain compartments (S/R = l.0-1.1). These findings may have clinical relevance for the safety of venlafaxine in chronic hepatic encephalopathy.

Iowa 2008 Medicare Part D Stand-Alone Prescription Drug Plans, 2008

Medicare Deductible, co-insurance and premiuns form, and rescription drugs plans.

Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study.

OBJECTIVES: We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS: A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART.

A member of the PLEIOTROPIC DRUG RESISTANCE family of ATP binding cassette transporters is required for the formation of a functional cuticle in Arabidopsis.

Although the multilayered structure of the plant cuticle was discovered many years ago, the molecular basis of its formation and the functional relevance of the layers are not understood. Here, we present the permeable cuticle1 (pec1) mutant of Arabidopsis thaliana, which displays features associated with a highly permeable cuticle in several organs. In pec1 flowers, typical cutin monomers, such as ω-hydroxylated fatty acids and 10,16-dihydroxypalmitate, are reduced to 40% of wild-type levels and are accompanied by the appearance of lipidic inclusions within the epidermal cell. The cuticular layer of the cell wall, rather than the cuticle proper, is structurally altered in pec1 petals. Therefore, a significant role for the formation of the diffusion barrier in petals can be attributed to this layer. Thus, pec1 defines a new class of mutants. The phenotypes of the pec1 mutant are caused by the knockout of ATP BINDING CASSETTEG32 (ABCG32), an ABC transporter from the PLEIOTROPIC DRUG RESISTANCE family that is localized at the plasma membrane of epidermal cells in a polar manner toward the surface of the organs. Our results suggest that ABCG32 is involved in the formation of the cuticular layer of the cell wall, most likely by exporting particular cutin precursors from the epidermal cell.

Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study.

OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients were included who had genotypic resistance tests performed on plasma samples collected while antiretroviral therapy naive. TDR was defined as at least one resistance mutation from a list proposed for genotypic TDR surveillance. Multivariable logistic regression was used to analyze factors associated with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients with resistance and consequently low power.

Drug use and suicide attempts: the role of personality factors.

This study on suicide attempts is part of a large research project on dependent behavior in adolescents and young adults. 228 subjects aged 14-25 (107 "drug abusers," 121 controls) from the French speaking part of Switzerland were evaluated on the basis of a semi-structured interview (Mini International Neuropsychiatric Interview), enabling a DSM-IV diagnosis, and self-reports (SSS by Zuckermann, MMPI-2, IDI by Hirschfeld). 31.5% of "drug abuser" males and 41.2% of "drug abuser" females committed one or more suicide attempts. The results of a logistic regression show that the significant factor explaining suicide attempts in drug users is emotional reliance for males and experience-seeking for females.

Current trends in illegal drug use and drug related health problems in Switzerland.

As part of the evaluation of the Confederation's measures to reduce drug related problems, a review of available data on drug use and drug related problems in Switzerland has been conducted. Source of data included: population surveys (adults and teenagers), surveys among drug users, health statistics (drug related and AIDS related deaths, HIV case reporting, drug treatments) police statistics (denunciations for consumption). The aims of reducing the number of dependent hard drug users have been achieved where heroin is concerned. In particular, there seems to have been a decrease in the number of people becoming addicted to this substance. For all other illegal substances, especially cannabis, the trend is towards an increased use, as in many European countries. As regards dependent drug users, especially injecting drug users, progress has been made in the area of harm reduction and treatment coverage. This epidemiological assessment can be used in the discussions currently engaged about the revision of the Law governing narcotics and will be a baseline for future follow up of the situation.

Drug utilization studies and data registries in primary care

This article reviews the methodology of the studies on drug utilization with particular emphasis on primary care. Population based studies of drug inappropriateness can be done with microdata from Health Electronic Records and e-prescriptions. Multilevel models estimate the influence of factors affecting the appropriateness of drug prescription at different hierarchical levels: patient, doctor, health care organization and regulatory environment.Work by the GIUMAP suggest that patient characteristics are the most important factor in the appropriateness of prescriptions with significant effects at the general practicioner level.

Iowa’s Drug Control Strategy, November 1, 2007

The attached annual report is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialists, law enforcement officers, a prevention specialist, a judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy were in developed in consultation with the DPAC.

Drug innovation, prices and health

This article tries to reconcile economic-industrial policy with health policy when dealing with biomedical innovation and welfare state sustainability. Better health accounts for an increasingly large proportion of welfare improvements. Explanation is given to the welfare losses coming from the fact than industrial and health policy tend to ignore each other. Drug s prices reflecting their relative relative effectiveness send the right signal to the industry rewarding innovation with impact on quantity and quality of life- and to the buyers of health care services.The level of drug s public reimbursement indicates the social willingness to pay of the different national health systems, not only by means of inclusion, or rejection, in the basket of services covered, but especially establishing the proportion of the price that is going to be financed publicly.Reference pricing for therapeutic equivalents as the upper limit of the social willingness to pay- and two-tiered co-payments for users (avoidable and inversely related with the incremental effectiveness of de drug) are deemed appropriate for those countries concerned at the same time with increasing their productivity and maintaining its welfare state. Profits drive R&D but not its location. There is no intrinsic contradiction between high productivity and a consolidated National Health Service (welfare state) as the European Nordic Countries are telling us every day.

Governor’s Office of Drug Control Policy Performance Plan, FY 2009

Agency Performance Plan, Governor’s Office of Drug Control Policy

Governor's Office of Drug Control Policy, Strategic Plan, 2003-2008

This report outlines the strategic plan for Governor's Office of Drug Control Policy, goals and mission.

Iowa's Drug Control Strategy, 2009

The 2009 Iowa Drug Control Strategy is the annual report and Drug Control Strategy for the State of Iowa, produced in accordance with Iowa law, by the Governor's Office of Drug Control Policy, in cooperation with the Drug Policy Advisory Council.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.