Sex, drugs and STDs: Preliminary findings from the Belfast Youth Development Study

Young people's participation in sexual risk behaviours is commonly linked with participation in a range of other risky behaviours, and in particular with substance use behaviours. This cross-sectional analysis of the sixth sweep of the Belfast Youth Development Study aimed to examine associations between substance use and sexual activity and related risks among 17-19-year olds in Northern Ireland. Being sexual activity and participating in sexual risk behaviours was associated with the use of a range of licit and illicit substances particularly alcohol and ecstasy. Additionally, females were more likely to have been tested for a sexually transmitted disease (STD). The findings add to the existing research body suggesting that substance misuse and sexual risk behaviours tend to co-occur in adolescence and highlight a need to develop appropriate interventions and initiatives for school aged young people.

Comparison of three adjuvants used to produce polyclonal antibodies to veterinary drugs

Two commercially available adjuvants, Gerbu LQ 3000 and Montanide ISA 50V, were assessed as potential replacements for Freund's adjuvant by evaluating their efficacy in the production of polyclonal antibodies to veterinary drugs in rabbits. The aim was to find an adjuvant that could produce a similar (or enhanced) immune response in the host animal without the undesirable side effects associated with Freund's complete and incomplete adjuvant. The assessment involved the examination of each injection site and the characterisation of the resultant antibodies with regards to antibody titre and sensitivity. It was found that the rabbits immunised with Gerbu adjuvant produced some of the most sensitive antibodies. However, titres were relatively low and adverse effects at injection sites were relatively common. Montanide adjuvant produced no adverse effects and the related antibodies were found to be of adequate sensitivity when compared to those from rabbits immunised with Freund's. It was concluded that Montanide ISA 50V could be considered as a suitable replacement to Freund's for the production of polyclonal antibodies, to low molecular weight compounds in rabbits. (C) 2007 Elsevier B.V. All rights reserved.

Use of antigen mimics to produce specific antibodies to anti-coccidial drugs

A range of polyclonal antibodies was successfully produced to the coccidiostatic drugs diclazuril and robenidine. Initial attempts to make immunogenic complexes of both drugs were ineffective due to difficulties encountered while trying to couple the compounds to large carrier proteins. Structural mimics, which could act as haptens for each drug, were sought and identified. The compounds identified were more open to chemical manipulation and were conjugated to carrier proteins to produce effective immunogens. The most sensitive antisera produced displayed IC(50)s of 1.5 ng/ml and 13 ng/ml for diclazuril and robenidine respectively. The antibody for diclazuril was shown to be specific, cross-reacting only with clazuril by 15%. The robenidine antibody displayed a low cross-reactivity of 1.2% to the compound used to produce the antibody. (C) 2007 Elsevier B.V. All rights reserved.

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register

Objective: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs).

Influence of drugs, demographics and medical history on hospital readmission of elderly patients - A predictive model

Objective: To investigate factors that influence hospital readmissions of elderly patients and to construct a robust hospital readmissions predictive model.

Malignant pleural mesothelioma: current treatments and emerging drugs

Background: Malignant pleural mesothelioma (MPM) is an uncommon disease whose incidence is increasing worldwide over the past 30 years. Surgical resection and radiotherapy represent the standard treatment in patient with resectable MPM. Chemotherapy is also necessary to reduce incidence of distant metastases, but the optimal setting of treatment (neoadjuvant, adjuvant and intrapleural) is not clarified. For the patients with unresectable MPM, the combination cisplatin and pemetrexed or ralitrexed is the standard treatment as supported by a Phase III study. Better understanding of molecular pathways involved in MPM has enabled inclusion of new drugs targeted against pathways responsible for proliferation, cell survival and angiogenesis. Objective: This review discusses the current treatment option, the specific signal pathways activated in MPM and the novel agents under evaluation in clinical trials. Methods: We use for this article abstracts, papers, oral presentations from ASCO and the website http://www.clinical-trials.gov. Results/conclusion: This review summarizes the activity of chemotherapy and of new agents under evaluation in clinical trials. The better understanding of molecular pathways activated in MPM will hopefully provide new therapeutic options for these patients in the future.

A Preference for Mephedrone: Drug Markets, Drugs of Choice, and the Emerging “Legal High” Scene

This study focuses on individuals' preferences for mephedrone, a new psychoactive substance that has emerged in several countries. We examine the reasons for mephedrone preferences, and describe the positive and negative effects of the drug experience, route of administration and consumers' views about the legality of mephedrone. Data were collected through semi-structured interviews with 45 adults who had used mephedrone since January 2010. Respondents resided in one of two jurisdictions that were characterized by different legislative controls over mephedrone. The findings suggest the importance of macro-level drug market factors that shaped people's preferences for mephedrone. Additionally, respondents' preferences were guided by pharmacological properties that helped them conceal the effects of mephedrone in public and semi-public spaces. Respondents were not deterred by the (impending) change from legal to illicit drug. The findings have implications for the study of localized drug markets, and in particular, legislative controls over emerging legal highs.

Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases

Current therapeutics and prophylactics for malaria are under severe challenge as a result of the rapid emergence of drug-resistant parasites. The human malaria parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and PfA-M17, which function in regulating the intracellular pool of amino acids required for growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. We previously reported the x-ray crystal structure of the monomeric PfA-M1 and proposed a mechanism for substrate entry and free amino acid release from the active site. Here, we present the x-ray crystal structure of the hexameric leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with antimalarial activity. The six active sites of the PfA-M17 hexamer are arranged in a disc-like fashion so that they are orientated inwards to form a central catalytic cavity; flexible loops that sit at each of the six entrances to the catalytic cavern function to regulate substrate access. In stark contrast to PfA-M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which accounts for its highly restricted substrate specificity. We also explicate the essential roles for the metal-binding centers in these enzymes (two in PfA-M17 and one in PfA-M1) in both substrate and drug binding. Our detailed understanding of the PfA-M1 and PfA- M17 active sites now permits a rational approach in the development of a unique class of two-target and/or combination antimalarial therapy.