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Ayorinde Adehin,1,2 Martin Alexander Kennedy,3 Julius Olugbenga Soyinka,1 Olusegun Isaac Alatise,4 Olalekan Olasehinde,4 Oluseye Oladotun Bolaji1 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria; 2Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, People’s Republic of China; 3Department of Pathology and Biomedical Science; Carney Centre of Pharmacogenomics, University of Otago, Christchurch, New Zealand; 4Department of Surgery, Faculty of Clinical Sciences, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, NigeriaCorrespondence: Ayorinde Adehin Department of Pharmaceutical Chemistry, Faculty of PharmacyObafemi Awolowo University, Ile-Ife, NigeriaTel +234 8022013470Email aadehin@oauife.edu.ngAbstract: Estrogen-receptor positivity in tumour, often requiring long-term tamoxifen therapy, is thought to characterise between 43% and 65% of breast cancer cases in Nigeria. The patient population is further marked by late-stage diagnosis which significantly heightens the tendency for tumour relapse in the course of tamoxifen therapy. Despite tamoxifen being considered a reliable chemopreventive in high-risk individuals and an effective adjuvant therapy for hormone-sensitive tumours, mortality has remained high among breast cancer patients in the West African region where Nigeria belongs. The Nigerian breast cancer population, like other similar patient-populations in the West African region, provides a mix of intrinsic genome-diversity and perhaps unique tumour biology and evolution. These peculiarities suggest the need for a rational approach to tumour management and a personalised delivery of therapy in Nigeria’s dominant estrogen-receptor-positive patient population. Herein, critical indices of tamoxifen-therapy success are discussed in the context of the Nigerian breast cancer population with emphasis on salient aspects of tamoxifen-biotransformation, host- and tumour-genomics, and epigenetics.Keywords: breast cancer, estrogen receptor, tamoxifen, Nigeria, epigenetics, genomics

The last decade has seen an increase in the trend of HMG-CoA reductase inhibitor (statin) usage in the Western world, which does not come as a surprise noting that the latest American Heart Association heart and stroke statistics indicate an alarming prevalence of 80  million Americans (one in three) with one or more forms of diagnosed cardiovascular disease (CVD). Meta-analysis of several large-scale, randomized clinical trials has demonstrated statins to be efficacious in significantly reducing CVD-associated mortality in both primary and secondary prevention. Despite their proven efficacy, statins have also gained attention with respect to adverse drug reactions (ADRs) of muscle myopathy, derangements in hepatic function and even ADRs classified as psychiatric in nature. The depletion of cholesterol within the myocyte cell wall and/or the depletion of key intermediates within the cholesterol synthesis pathway are hypothesized as possible mechanisms of statin-associated ADRs. However, pharmacogenetic variability may also be a risk factor for ADRs and can include, for example, enzymes, transporters, cell membrane receptors, intracellular receptors or components of ion channels that contribute to the pharmacokinetics or pharmacodynamics of response to a particular drug. The cytochrome P450 (CYP) enzymatic pathways that comprise the polymorphic genes, CYP2D6, CYP3A4 and CYP3A5, and also a hepatic transporter, solute carrier organic anion transporter (SLCO1B1), which is a single nucleotide polymorphism discovered to be associated with statin-induced myopathy through a genome-wide association study, are discussed with respect to their effect on altering the pharmacokinetic profile of statin metabolism. Variants of the Apolipoprotein E (APO-E) gene, polymorphisms in the cholesteryl ester transfer protein (CETP) gene, the HMG-CoA reductase gene and other proteins are discussed with respect to altering the pharmacodynamic profile of statins. Pharmacogenetics and its application in medicine to individualize drug therapy has been previously shown to be clinically and economically beneficial through quality-adjusted life-year assessment. Therefore, polymorphisms affecting the pharmacokinetic and pharmacodynamic profiles of statins, which are widely used in therapy, with their potential application in the personalized prescribing of statin therapy, need further research. In this review, we update the recent literature with respect to genetic polymorphisms that may influence the pharmacokinetics and pharmacodynamics of statin therapy, and consider the relevance of these findings to the efficacy of treatment, prevention of ADRs and what this may mean for patient tolerance and compliance. [ABSTRACT FROM AUTHOR]

Over the past several decades, more and more research has been published demonstrating the health benefits of physical activity. The benefits have been far ranging-from reducing premature death from all causes of mortality to reducing depression in older adults. This past year, Secretary Michael Leavitt from the US Health and Human Services convened a panel of experts to carefully review all of the scientific evidence for the benefits of physical activity. A 13-member committee was brought together to form the Physical Activity Guidelines Advisory Committee. In June of 2008, the Committee submitted their comprehensive 683-page report to Secretary Leavitt. The technical report was used by the US Department of Health and Human Services to develop the 2008 Physical Activity Guideline for Americans. The inaugural set of Physical Activity Guidelines for Americans was released on October 7, 2008. This article summarizes the events that led up to the development of those Guidelines and provides a brief overview of their key recommendations. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Ile164 variant of the β2-adrenoceptor has been shown to alter cardiovascular phenotypes and adversely affect survival in heart failure patients. Aims: We aimed to replicate this observation by genotyping a cohort of 451 heart failure patients for the Ile164 polymorphism. Methods: Patient outcome was recorded over a median follow-up period of 3.09 years, and genotypes were derived by multiplex amplification refractory mutation system PCR. Results: Genotypes were obtained for 443 patients, and 3.2% of these (14 patients) were heterozygous for the Ile164 SNP. Demographic data, cardiac function and neurohormonal profiles did not differ between genotype groups. Ile164 genotype did not significantly affect survival in this cohort (Thr164 homozygotes 48.9%, Ile164 heterozygous 42.9%, p =0.66), although multivariate analysis suggested that β-blocker treatment may negatively impact survival in the heterozygote group. Conclusion: This study suggests that the Ile164 polymorphism of the β2-adrenoceptor does not have a major impact on outcome in individuals with heart failure, although it''s potential interaction with β-blockers requires further examination. [Copyright &y& Elsevier]

Much of the research on prostitution to date has focused on the risks of working on the streets. However, no research has described the recruitment process for street prostitution. This exploratory study describes some of the main techniques that pimps use to recruit children and women into the trade, including the pretense of love, threats of indebtedness, drug addiction, manipulation, and violence. In addition, social situations that leave women feeling that they have few alternatives to working on the streets are described. [ABSTRACT FROM AUTHOR]

Background. Borderline personality disorder (BPD) is often co-morbid with major depression and may complicate its treatment. We were interested in differences in genetic and developmental risk factors between depressed patients with or without a co-morbid BPD.Method. Out-patients with major depressive disorder were recruited for two treatment trials. Assessment of depressed patients included the assessment of personality disorders, developmental risk factors and DNA samples for genetic analyses.Results. In each study there was a significant association between the 9-repeat allele of the dopamine transporter (DAT1) and BPD, with odds ratios (OR) >3 and p/=35 years (OR 9.31, p=0.005).Conclusion. This replicated association in depressed patients between the 9-repeat allele of DAT1 and BPD may provide clues to understanding the neurobiology of BPD. The finding that the association is larger in the older depressed patients, suggests that the 9-repeat allele may be associated with a poorer prognosis BPD, rather than a young adult limited variant of BPD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported. METHOD: A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline. RESULTS: Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic anti-depressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter. CONCLUSIONS: These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing. [ABSTRACT FROM AUTHOR]

Research investigating trauma's ensuing psychological sequels has flourished in recent years. Unfortunately, no direct research has focused on disentangling the relative severity of PTSD symptoms across divergent types of traumatic experiences. The present study was undertaken for such a purpose. As part of a larger study investigating the impact of trauma on eyewitness memory, 36 prostitutes were interviewed regarding past autobiographical traumatic experiences (both sexual and non-sexual traumas). The participants' self-reported PTSD symptoms for each type of trauma were elicited and compared indicating significantly higher total, avoidance, and intrusion symptoms for sexual traumas than for non-sexual traumas. Implications for the assessment and treatment of trauma victims are discussed. [ABSTRACT FROM AUTHOR]