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[en] The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC50 of 0.01 ng mL-1 and 0.16 ng mL-1 respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally active compounds the combination of biological and physio-chemical techniques is optimal.
[en] Objective: To assess the impact of androgenetic alopecia on quality of life in our patients using DLQI. Design: Observational study. Place and Duration of Study: The study was carried out in Outpatient Department of Dermatology, KEMU/ Mayo Hospital, Lahore, for six months from (15-04-2010 to 14-10-2010). Material and Methods: A total of 125 patients suffering from androgenetic alopecia, of any severity, with age 18 years or above, belonging to either sex, who themselves were able to understand and complete the DLQI questionnaire in English or Urdu version, were enrolled in the study. Patients were asked to indicate how there life has been affected over the preceding week. The data was analyzed after compiling the results. The higher the DLQI score, the poorer is the QoL. Results: The mean DLQI score in 125 patients (53 males and 72 females) was 12.80 +- 3.76. The findings indicate several areas in which androgenetic alopecia had an impact on individual's QoL, particularly in relation to symptoms and feelings and personal relationships. Women reported poorer QoL compared to men. Mean DLQI score was 11.87 +- 3.35 in males and 13.49 +- 3.91 in females. Conclusion: It was noted that in patients of androgenetic alopecia, there were significant psychosocial limitations resulting from reactions of close relatives and friends. (author)
[en] The products are prepared by action of a magnesian tritiated methyl halide on 3,3(1,2 ethanediyl bis (oxy)-estra 4,9, 11-trien-17-one to give, after acid hydrolysis, (17β)-17-hydroxy-17-methyl-3H3-estra-4,9, 11-trien-3-one; the free hydroxyl function of this product may be etherified or esterified as the case may be. The magnesian tritiated methyl halide used is the iodide and the reaction takes place in anhydrous ether at room temperature; the acid hydrolysis agent is hydrochloric acid. The free hydroxyl function is etherified by an agent such as an alcoyl or aryl halide or a dialcoyl sulphate; this function is esterified by means of a functional acid derivative such as chloride or anhydride. These products, especially (17β)-17-hydroxy-17-methyl-3H3-estra-4,9, 11-trien-3-one, show a strong affinity for androgen receptors and great metabolic stability, allowing the location, determination and study of these receptors in the cells of androgen target tissues, such as the prostate, sebaceous gland and androgen-dependent tumours, in both animals and man. Since moreover they are not fixed by plasma proteins binding the androgen proteins present in certain animal species and in man these products are especially useful for the study of androgen receptors in human tissues, avoiding interference due to contamination of the tissue preparations by plasma proteins
[fr]Procede de preparation des produits caracterise en ce que l'on fait agir sur le 3,3(1,2 ethanediyl bis (oxy)-estra 4,9, 11-trien-17-one un halogenure de methyl tritie magnesien et obtient apres hydrolyse acide (17β)-17-hydroxy-17-methyl-3H3-estra-4,9, 11-trien-3-one, dont on peut le cas echeant etherifier ou esterifier la fonction hydroxyle libre; l'halogenure de methyle tritie magnesien est l'iodure et l'on opere dans l'ether anhydre a temperature ambiante; l'agent d'hydrolyse acide est l'acide chlorhydrique. On etherifie la fonction hydroxyle libre au moyen d'un agent d'etherification, tel qu'un halogene d'alcoyle ou d'aryle, ou un dialcoyle sulfate; et on esterifie la fonction hydroxyle libre au moyen d'un derive fonctionnel d'acide, tel que le chlorure ou l'anhydride. Ces produits et notamment le (17β)-17-hydroxy-17-methyl-3H3-estra-4,9, 11-trien-3-one presentant une haute affinite pour les recepteurs androgenes et une grande stabilite metabolique, permettent la localisation, le dosage et l'etude de ces recepteurs dans les cellules des tissus cibles des androgenes, comme la prostate, la glande sebacee et les tumeurs androgenodependantes, aussi bien chez l'animal que chez l'homme. Par ailleurs, comme ils ne se fixent pas sur les proteines plasmatiques liant les androgenes -proteines presentes chez certaines especes animales et chez l'homme- ces produits sont particulierement utiles pour l'etude des recepteurs androgenes dans les tissus humains car ils evitent l'interference de la contamination des preparations tissulaires par les proteines plasmatiques
[en] Highlights: • Ternary classification models based on known hormonal activities’ chemicals were developed. • Both of the optimum models for AR and TR was support vector machines (SVM). • A system for identifying different hormone activities was constituted. Endocrine disrupting chemicals (EDCs) can exhibit adverse effects by increasing or blocking hormonal activities as agonists or antagonists through nuclear receptors. Computational toxicology research provides a fast and automated screening tool for determining the potential effects of EDCs. Here, we collected a large dataset of known hormonal activities to develop ternary classification models of androgen receptor (AR) and thyroid hormone receptor (TR), in combination linear discriminant analysis (LDA), classification and regression trees (CART), and support vector machines (SVM). The optimum model for classifying AR and TR activities was SVM. These newly developed models constitute a rapidly systematic early-warning technical system for identifying different hormone activities.
[en] Graphical abstract: Both the known AR antagonist nilutamide and the pyrethroid insecticide cypermethrin inhibited DHT-induced AR N/C interaction in the mammalian two-hybrid assay. However, cypermethrin was a weaker androgen antagonist than nilutamide. Highlights: ► We have developed the mammalian two-hybrid assay. ► The assay displayed appropriate response to DHT and nilutamide. ► The N/C interaction was induced by DHT in a dose-dependent manner. ► Nilutamide inhibited DHT-induced AR N/C interaction. ► Cypermethrin exhibits inhibitory effects on DHT-induced AR N/C interaction. -- Abstract: The pyrethroid insecticide, cypermethrin has been demonstrated to be an environmental anti-androgen in the androgen receptor (AR) reporter gene assay. The amino- and carboxyl-terminal (N/C) interaction is required for transcription potential of the AR. In order to characterize the anti-androgen effects of cypermethrin involved in the N/C interaction of AR, the mammalian two-hybrid assay has been developed in the study. The fusion vectors pVP16-ARNTD, pM-ARLBD and the pG5CAT Reporter Vector were cotransfected into the CV-1 cells. The assay displayed appropriate response to the potent, classical AR agonist 5α-dihydrotestosterone (DHT) and known AR antagonist nilutamide. The N/C interaction was induced by DHT from 10−11 M to 10−5 M in a dose-dependent manner. Nilutamide did not activate N/C interaction, while inhibited DHT-induced AR N/C interaction at the concentrations from 10−7 M to 10−5 M. Treatment of CV-1 cells with cypermethrin alone did not activate the reporter CAT. Cypermethrin significantly decreased the DHT-induced reporter CAT expression at the higher concentration of 10−5 M. The mammalian two-hybrid assay provides a promising tool both for defining mechanism involved in AR N/C interaction of EDCs and for screening of chemicals with androgen agonistic and antagonistic activities. Cypermethrin exhibits inhibitory effects on the DHT-induced AR N/C interaction, while the potency is weaker than that of nilutamide.
[en] Highlights: • BPA, BPA alternatives, and parabens were detected in maternal and cord plasma. • BPA was significantly higher in mixed cord than in maternal plasma (p=0.0455). • Parabens were negatively associated with testosterone in mixed cord plasma. • Main hormonal steroids and selected neurosteroids were determined in both fluids. The harmful effects of endocrine disrupting compounds (EDCs) on human health are generally well-known, and exposure during fetal development may have lasting effects. Fetal exposure to bisphenol A (BPA) has been recently relatively well-studied; however, less is known about alternatives such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF), which have started to appear in consumer products. Parabens are another widespread group of EDCs, with confirmed transplacental passage. The usage of many cosmetic, pharmaceutical and consumer products during the pregnancy that may contain parabens and bisphenols has led to the need for investigation.
[en] LncRNAs were altered in several cancers and played a crucial role in various biological activities and progressions of different diseases, including proliferation, chemical resistance, and metastasis. In the present study, we revealed that prostrate androgen-regulated transcript-1 (PART-1) was highly expressed in colorectal cancer cells and tissues, and knockdown of PART-1 suppressed cell proliferation and metastasis, both in vitro and in vivo. In addition, PART-1 functioned as a ceRNA of DNMT3A, by sponging miR-143. Finally,PART-1 induced tumor progression by regulating DNMT3A. - Highlights: • Prostrate androgen-regulated transcript-1 (PART-1) was highly expressed in colorectal cancer cells and tissues. • Knockdown of PART-1 suppressed cell proliferation and metastasis, both in vitro and in vivo. • PART-1 functioned as a ceRNA of DNMT3A, by sponging miR-143. • PART-1 induced tumor progression by regulating DNMT3A.