A Study of the androgen receptor gene polymorphism and the level of expression of the androgen receptor in androgenetic alopecia among Egyptians

Background: Androgenetic alopecia (AGA) occurs in men and women. Thenature of the genetic predisposition to androgenetic alopecia is still unresolved. The aim of the work is to study the genotype of the androgen receptor gene (StuI polymorphism) and its relationship to AGA in a case control study and to determine the level of androgen receptor expression (AR) in the balding scalp relative to the non-balding scalp area.Subjects and Methods: This study was conducted on one hundred individuals; 60 cases with AGA (36 males and 24 females) and 40 age and sex matched control patients (20 males and 20 females). StuI restriction fragment length polymorphism(RFLP) of exon 1 was detected by PCR based assay using genomic DNA of subjects with AGA and controls. Immunohistochemical detection of the androgen receptor (AR) using antihuman AR antibody was implemented to compare its level in the balding scalp and in the non-balding area in individuals having AGA.Results: Analysis of StuI restriction fragment length polymorphism in exon 1 of the androgen receptor (AR) gene revealed a relatively commoner incidence of the cut allele in males with AGA relative to age and sex matched controls (the association was of border line signifi cance p=0.07. Interestingly, all persons who had maternal uncles suffering from AGA had the Stu1 cut variant of AR gene (p= 0.03 using Chi square test). Semiquantitative immunohistochemical analysis of AR in the bold scalp biopsies showed higher expression in the level of AR than the non bold bioposies within the same individual.Conclusion: To the best of our knowledge this is the fi rst study of AR gene polymorphism and AR expression in AGA amongst Egyptians. This study contributes in the understanding of the molecular pathogenesis of AGA which could help in fi nding better therapeutic alternatives for such trait in the future.Keywords: Androgenetic alopecia, androgen receptor, StuI polymorphism, immunohistochemical expression

Ovarian cysts in women receiving tamoxifen for breast cancer

Tamoxifen is a nonsteroidal anti-oestrogen with gynaecological side-effects. Only recently, ovarian cyst formation during tamoxifen treatment has been reported. The present study aimed to evaluate patient-related parameters that determine ovarian cyst formation in women using tamoxifen for breast cancer. A cross-sectional study was performed in 142 breast cancer patients using tamoxifen. Forty-five patients were also examined prior to tamoxifen treatment. Gynaecological assessment, transvaginal ultrasonography (TVU) and serum oestradiol (E2) and follicle stimulating hormone (FSH) analysis were performed. Follow-up assessments were performed twice a year. Uni- or bilateral ovarian cysts were detected by TVU in 24 tamoxifen-using patients and in one patient before tamoxifen treatment. Multiple regression analysis showed that cyst development is related (multiple R = 0.73) to high E2 (P < 0.001), younger age (P < 0.001) and absence of high-dose chemotherapy (P = 0.007). Patients with ovarian cysts had higher serum E2 levels compared to patients without cysts (1.95 vs 0.05 nmol l−1; P < 0.001). All patients after high-dose chemotherapy or older than 50 years had E2 < 0.10 nmol l−1 and/or amenorrhoea > 1 year and did not develop ovarian cysts. Patients still having a menstrual cycle during tamoxifen had a high chance (81%) of developing ovarian cysts. Breast cancer patients receiving tamoxifen only develop ovarian cysts if their ovaries are able to respond to FSH stimulation as shown by E2 production. © 1999 Cancer Research Campaig

Partial Inhibition of Estrogen-Induced Mammary Carcinogenesis in Rats by Tamoxifen: Balance between Oxidant Stress and Estrogen Responsiveness

Epidemiological and experimental evidences strongly support the role of estrogens in breast tumor development. Both estrogen receptor (ER)-dependent and ER-independent mechanisms are implicated in estrogen-induced breast carcinogenesis. Tamoxifen, a selective estrogen receptor modulator is widely used as chemoprotectant in human breast cancer. It binds to ERs and interferes with normal binding of estrogen to ERs. In the present study, we examined the effect of long-term tamoxifen treatment in the prevention of estrogen-induced breast cancer. Female ACI rats were treated with 17β-estradiol (E2), tamoxifen or with a combination of E2 and tamoxifen for eight months. Tissue levels of oxidative stress markers 8-iso-Prostane F2α (8-isoPGF2α), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) were quantified in the mammary tissues of all the treatment groups and compared with age-matched controls. Levels of tamoxifen metabolizing enzymes cytochrome P450s as well as estrogen responsive genes were also quantified. At necropsy, breast tumors were detected in 44% of rats co-treated with tamoxifen+E2. No tumors were detected in the sham or tamoxifen only treatment groups whereas in the E2 only treatment group, the tumor incidence was 82%. Co-treatment with tamoxifen decreased GPx and catalase levels; did not completely inhibit E2-mediated oxidative DNA damage and estrogen-responsive genes monoamine oxygenase B1 (MaoB1) and cell death inducing DFF45 like effector C (Cidec) but differentially affected the levels of tamoxifen metabolizing enzymes. In summary, our studies suggest that although tamoxifen treatment inhibits estrogen-induced breast tumor development and increases the latency of tumor development, it does not completely abrogate breast tumor development in a rat model of estrogen-induced breast cancer. The inability of tamoxifen to completely inhibit E2-induced breast carcinogenesis may be because of increased estrogen-mediated oxidant burden

Women's Education Level, Maternal Health Facilities, Abortion Legislation and Maternal Deaths: A Natural Experiment in Chile from 1957 to 2007

The aim of this study was to assess the main factors related to maternal mortality reduction in large time series available in Chile in context of the United Nations' Millennium Development Goals (MDGs).Time series of maternal mortality ratio (MMR) from official data (National Institute of Statistics, 1957-2007) along with parallel time series of education years, income per capita, fertility rate (TFR), birth order, clean water, sanitary sewer, and delivery by skilled attendants were analysed using autoregressive models (ARIMA). Historical changes on the mortality trend including the effect of different educational and maternal health policies implemented in 1965, and legislation that prohibited abortion in 1989 were assessed utilizing segmented regression techniques.During the 50-year study period, the MMR decreased from 293.7 to 18.2/100,000 live births, a decrease of 93.8%. Women's education level modulated the effects of TFR, birth order, delivery by skilled attendants, clean water, and sanitary sewer access. In the fully adjusted model, for every additional year of maternal education there was a corresponding decrease in the MMR of 29.3/100,000 live births. A rapid phase of decline between 1965 and 1981 (-13.29/100,000 live births each year) and a slow phase between 1981 and 2007 (-1.59/100,000 live births each year) were identified. After abortion was prohibited, the MMR decreased from 41.3 to 12.7 per 100,000 live births (-69.2%). The slope of the MMR did not appear to be altered by the change in abortion law.Increasing education level appears to favourably impact the downward trend in the MMR, modulating other key factors such as access and utilization of maternal health facilities, changes in women's reproductive behaviour and improvements of the sanitary system. Consequently, different MDGs can act synergistically to improve maternal health. The reduction in the MMR is not related to the legal status of abortion

Maintenance Optimization and Inspection Planning of Wind Energy Assets: Models, Methods and Strategies

Designing cost-effective inspection and maintenance programmes for wind energy farms is a complex task involving a high degree of uncertainty due to diversity of assets and their corresponding damage mechanisms and failure modes, weather-dependent transport conditions, unpredictable spare parts demand, insufficient space or poor accessibility for maintenance and repair, limited availability of resources in terms of equipment and skilled manpower, etc. In recent years, maintenance optimization has attracted the attention of many researchers and practitioners from various sectors of the wind energy industry, including manufacturers, component suppliers, maintenance contractors and others. In this paper, we propose a conceptual classification framework for the available literature on maintenance policy optimization and inspection planning of wind energy systems and structures (turbines, foundations, power cables and electrical substations). The developed framework addresses a wide range of theoretical and practical issues, including the models, methods, and the strategies employed to optimise maintenance decisions and inspection procedures in wind farms. The literature published to date on the subject of this article is critically reviewed and several research gaps are identified. Moreover, the available studies are systematically classified using different criteria and some research directions of potential interest to operational researchers are highlighted