E-selectin S128R polymorphism and severe coronary artery disease in Arabs

Background  

The E-selectin p. S128R (g. A561C) polymorphism has been associated with the presence of angiographic coronary artery disease (CAD) in some populations, but no data is currently available on its association with CAD in Arabs.     

Characterization of lymphocyte beta 2-adrenoceptor signalling in patients with left ventricular volume overload disease

1. Studies using animal experimental models have suggested that the beta2-adrenoceptor is uncoupled in association with alterations in the expression of G-protein-coupled receptor kinases (GRK) 2/3 in heart failure. However, the functional expression of the components of this pathway in human disease has not been fully elucidated yet. In the present study, we evaluated the possibility that the regulation of beta2-adrenoceptor signalling components in patients with left ventricular volume overload (VOL) depends on the severity of the overload. 2. We characterized the lymphocyte GRK 2-6, beta-arrestins 1 and 2, beta2-adrenoceptor expression at the mRNA and protein levels, as well as the activity of adenylyl cyclase, protein kinases (PK) A and PKC in patients with VOL using healthy blood donors as controls. 3. In the patient group, GRK2 mRNA was increased by 61% (P < 0.001), GRK3 was increased by 54% (P < 0.005), GRK5 was increased fivefold (P < 0.001) and the beta-arrestin 2 mRNA was increased by 40% (P < 0.05). These increases were paralleled with a sixfold increase in GRK2, a twofold increase in GRK3 and a 1.3-fold increase in GRK5 protein levels. These changes were associated with a significant decrease in beta2-adrenoceptor mRNA, the basal, catalytic and receptor-mediated activity of adenylyl cyclase and sensitization of the forskolin-stimulated activity towards augmented inhibition by guanylimidodiphosphate. In general, the increase in GRK2 and 5 mRNA exhibited a positive correlation with the gravity of the haemodynamic load, as determined by changes in left ventricular fractional shortening. 4. The results suggest that VOL induces an increase in the expression of lymphocyte beta2-adrenoceptor-specific GRK and beta-arrestin 2 in association with an attenuation in beta2-adrenoceptor levels. It can be speculated that the cardiac circulatory system adapts itself to altered haemodynamic functional demands partly by altering beta2-adrenoceptor signalling.     

T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking

Background  

The association of the deletion in GSTT1 and GSTM1 genes with coronary artery disease (CAD) among smokers is controversial. In addition, no such investigation has previously been conducted among Arabs.     

Factors associated with HIV sero-status in young rural South African women: connections between intimate partner violence and HIV

BACKGROUND: This paper aims to describe factors associated with HIV sero-status in young, rural South African women and the relationship between intimate partner violence (IPV) and HIV. METHODS: A total of 1295 sexually active female volunteers, aged 15-26, from 70 villages were recruited to participate in a cluster randomized controlled trial of an HIV behavioural intervention. The main measures were HIV sero-status, and IPV and sexual practices measured using a questionnaire administered during baseline interviews. RESULTS: About 12.4% of women had HIV and 26.6% had experienced more than one episode of physical or sexual IPV. After adjusting for age, HIV infection was associated with having three or more past year partners [odds ratio (OR) 2.39; 95% confidence interval (95% CI) 1.48-3.85], sex in past 3 months (OR 3.33; 95% CI 1.87-5.94), a partner three or more years older (OR 1.69; 95% CI 1.16-2.48), and a more educated partner (OR 1.91; 95% CI 1.30-2.78). IPV was associated with HIV in two-way analyses (OR 1.56; 95% CI 1.08-2.23), but the effect was non-significant after adjusting for HIV risk behaviours. The experience of IPV was strongly associated with past year partner numbers, time of last sex, and partner's education; it was also marginally associated with partner age difference. Adverse experiences in childhood, including sexual abuse, increased the likelihood of having more past year partners (OR 1.43; 95% CI 1.21-1.69). CONCLUSIONS: IPV was strongly associated with most of the identified HIV risk factors. Our findings provide further evidence of links between IPV and HIV among women and the importance of joint prevention.     

Preferential existence of death-inducing proteins in the human cardiomyopathic left ventricle

INTRODUCTION: Idiopathic or acquired dilated cardiomyopathy (DCM) is a leading health threat resulting in considerable mortality and serious long-term disability with a substantial economic healthcare expenditure. The purpose of this study was to investigate the modulation of apoptotic signaling genes in human cardiomyopathy. METHODS: Cardiac tissue was obtained from six heart transplant recipients (age = 43 +/- 7 y) with DCM. Equivalent control specimens were taken from six healthy heart donors (age = 33 +/- 4 y). The mRNA expression of death-inducing proteins, the death (DRs) and decoy receptors (DcRs), in the four cardiac chambers was quantified using real time polymerase chain reaction LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). Immunodetectable receptor protein expression was quantified densitometrically. Data were analyzed by analysis of variance and unpaired Student's t-test. RESULTS: In DCM tissues, DR1 mRNA was elevated by 42.7% (P < 0.01) in the left ventricle (LV) and 56.4% (P < 0.001) in the left atrium (LA), while DR2 increased by 112.5% (P < 0.00001) in LV and 45.8% (P < 0.05) in LA. Increase in DR4 was 29.6% (P < 0.01) in LV, 82.5% (P < 0.01) in the right ventricle (RV), 210.8% (P < 0.01) in LA, and 99.1% (P < 0.01) in the right atrium (RA). DR5 was elevated by 66.7% (P < 0.01) in LV, 181.8% (P < 0.005) in LA, and 90.2% (P < 0.05) in RA. DcR1 decreased by 30.8% in LV, 44% (P < 0.05) in LA, and 12.5% in RA; DcR3 by 67.1% (P < 0.0001) in LV, 82.4% (P < 0.0001) in RV, 85.1% (P < 0.0001) in LA, and 84.6% (P < 0.0001) in RA. The trends in mRNA expression were comparable to the changes in protein expression. CONCLUSIONS: Left heart-sided increase of death-inducing proteins in human cardiomyopathy is suggestive of their potential modulatory roles in death-related signaling in the pathogenesis of end-stage myocardial failure.     

Responding to Her Question: A Review of the Influence of Pregnancy on HIV Disease Progression in the Context of Expanded Access to HAART in Sub-Saharan Africa

In 2007, sub-Saharan Africa was home to over half of all women living with HIV. The vast majority of these women are of reproductive age, which raises concerns about the high incidence of pregnancy. As access to antiretroviral treatment is rapidly scaled up, two important questions must be answered: (1) Does pregnancy impact HIV disease progression?; (2) Does pregnancy modify the highly active antiretroviral therapy (HAART) response on HIV disease progression? A systematic review of the biomedical literature was conducted and seven relevant studies were identified. To date, it appears that there is no effect of pregnancy on HIV disease progression. Furthermore, initial studies in high-income countries suggest that pregnancy may positively modify the HAART response. These findings, however, must be interpreted with caution as it remains unclear how other factors, such as adherence, may influence the relationship between pregnancy, HIV disease progression, and HAART.     

Women Living with HIV in South Africa and Their Concerns About Fertility

Health and quality of life benefits accrued from the availability of highly active antiretroviral therapy (HAART) are commendable, but the social milieu continues to pose challenges for women’s decision making around having children. This paper qualitatively explored women’s questions and concerns around living with HIV, being on HAART and pregnancy. Women of reproductive age were recruited from Eastern Cape and Gauteng Provinces, South Africa. Information on women’s fertility desires and pregnancy planning was collected through participatory workshop, focus groups, and one-on-one interviews. Three main themes emerged. Women living with HIV require information on the impact of HIV on pregnancy outcomes and vice versa. Women who are young, lost a child, not consistently using contraception or who have not been seriously ill have positive reproductive aspirations. Ambivalent attitudes of health care workers towards pregnancy impacts women’s fertility aspirations. Unbiased pre-conceptual communication should form part of HIV treatment and care services, despite expressed pregnancy intentions.     

Early adolescent pregnancy increases risk of incident HIV infection in the Eastern Cape,South Africa: a longitudinal study

Introduction

Adolescents having unprotected heterosexual intercourse are at risk of HIV infection and unwanted pregnancy. However, there is little evidence to indicate whether pregnancy in early adolescence increases the risk of subsequent HIV infection. In this paper, we tested the hypothesis that adolescent pregnancy (aged 15 or younger) increases the risk of incident HIV infection in young South African women.

Methods

We assessed 1099 HIV-negative women, aged 15–26 years, who were volunteer participants in a cluster-randomized, controlled HIV prevention trial in the predominantly rural Eastern Cape province of South Africa. All of these young women had at least one additional HIV test over two years of follow-up. Outcomes were HIV incidence rates per 100 person years and HIV incidence rate ratios (IRRs) estimated by Poisson multivariate models. Three pregnancy categories were created for the Poisson model: early adolescent pregnancy (a first pregnancy at age 15 years or younger); later adolescent pregnancy (a first pregnancy at age 16 to 19 years); and women who did not report an adolescent pregnancy. Models were adjusted for study design, age, education, time since first sexual experience, socio-economic status, childhood trauma and herpes simplex virus type 2 infection.

Results

HIV incidence rates were 6.0 per 100 person years over two years of follow-up. The adjusted IRR was 3.02 (95% CI 1.50–6.09) for a pregnancy occurring at age 15 or younger. Women with pregnancies occurring between 16 and 19 years of age did not have a higher incidence of HIV (IRR 1.08; 95% CI 0.64–1.84). Early adolescent pregnancies were associated with higher partner numbers and a greater age difference with partners.

Conclusions

Early adolescent pregnancies increase the incidence of HIV among South African women. The higher risk is associated with sexual risk behaviours such as higher partner numbers and a greater age difference with partners rather than a biological explanation of hormonal changes during pregnancy.     

Motivations for,and perceptions and experiences of participating in,a cluster randomised controlled trial of a HIV-behavioural intervention in rural South Africa

Empirical research on ethical issues in HIV-prevention and gender-based violence research, critical for honing ethical and safety guidelines, is limited. In this paper we describe South African young people's motivations for participating in randomised controlled trial, the prevalence of negative occurrences, participation regrets and associated factors. This trial partly followed, but also deviated from, the WHO safety guidelines for research on violence against women. A total of 1085 women and 985 men provided information two years after the trial start. Most participated for HIV testing and to help their community. Fewer reported motivation by the financial incentive. Minor adverse events included upset from questions on childhood experiences and arguments at home with siblings. Just under 1 in 10 (8.1% women, 9.8% men) regretted participation. Factors were associated with this were keeping some questions secret from their partners, feeling sad about questions on childhood, quarrelling at home and, for women, being motivated by the incentive. Men who had been physically violent to a partner were twice as likely to regret participation. There were no recorded adverse effects from the deviations from the ethical guidelines. Participation regrets mostly stemmed from problems in participants’ families preceding the research. There was no evidence that the research had been unsafe.