Hormonal and reproductive factors in relation to melanoma in women: current review and meta-analysis

A number of studies have focused on possible relationships between characteristics of female endocrine status and melanoma (CM) risk; however, the link between melanoma, oral contraceptive (OC) and hormonal replacement therapy (HRT) use, and reproductive factors remains controversial. A comprehensive, systematic bibliographic search of the medical literature was conducted to identify relevant studies. Random effects models were used to summarise results. Subgroup, meta-regression and sensitivity analyses have been carried out to explore sources of between-study variation and bias. We included thirty-six observational studies published in the last 30 years. Summarising a total of 5626 melanoma cases, we did not find any significant melanoma risk associated with OC and HRT use. Several reproductive factors were also investigated, summarising data on 16787 melanoma cases. We found a significantly increased melanoma risk for late age at first birth, and women with more than one child may be at a lower risk for melanoma; however, socio-economic confounders were found to play a significant role in explaining this association. This study confirmed no increased risk of CM with the use of oral contraceptives and hormone replacement therapy: exogenous female hormones do not contribute to an increased risk of CM. In contrast, significant associations of CM with parity and age at first pregnancy were observed in this meta-analysis finds and warrant further research.     

Diagnosis of Congenital Hypothyroidism from Human Anagen Scalp Hair by Infrared Microspectroscopy

A highly efficient Fourier transform infrared (FT-IR) microscopy was used to determine the biophysical structure of anagen scalp hair roots of neonates suffering from congenital hypothyroidism (CH) due to ectopic thyroid. The present results indicate that the lower composition near 1,053 cm- 1 (also assigned to the aromatic iodide stretching band) in the infrared (IR) spectra of the hair roots for CH patients was directly associated with the lower serum level of T 4 and fT 4, and the elevated TSH levels determined by RIA method. This strongly implies the lower evidence of the aromatic iodide stretching band in the IR spectra of hair roots. These findings suggest that FT-IR microscopy has the potential to become a good diagnostic tool and that hair can be useful as a genetic marker.     

Late-life consequences of short-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood in female mice

Di(2-ethylhexyl) phthalate (DEHP) is a known endocrine disruptor and diisononyl phthalate (DiNP) is a common DEHP replacement chemical. However, little is known about late-life consequences due to DEHP or DiNP exposure during adulthood. Thus, this study tested the hypothesis that adult exposure to DEHP or DiNP affects female reproductive parameters during late-life in female mice. Female CD-1 mice (age 39–40 days) were dosed with either vehicle control, DEHP (20 μg/kg/day–200 mg/kg/day), or DiNP (20 μg/kg/day–200 mg/kg/day) for 10 days and breeding trials were conducted at 12 and 15 months post-dosing. Further, ovaries and sera were collected at 12, 15, and 18 months post-dosing. DEHP and DiNP disrupted estrous cyclicity, increased pregnancy loss, decreased fertility, altered the sex ratio of pups, altered ovarian follicle populations, and disrupted hormone levels. Collectively, these data show that short-term exposure to DEHP or DiNP during adulthood has long-term consequences in late-life.     

A comprehensive review of regulatory test methods for endocrine adverse health effects

Development of new endocrine disruption-relevant test methods has been the subject of intensive research efforts for the past several decades, prompted in part by mandates in the 1996 Food Quality Protection Act (FQPA). While scientific understanding and test methods have advanced, questions remain on whether current scientific methods are capable of adequately addressing the complexities of the endocrine system for regulatory health and ecological risk assessments. The specific objective of this article is to perform a comprehensive, detailed evaluation of the adequacy of current test methods to inform regulatory risk assessments of whether a substance has the potential to perturb endocrine-related pathways resulting in human adverse effects. To that end,??approximately 42 existing test guidelines (TGs) were considered in the evaluation of coverage for endocrine-related adverse effects. In addition to evaluations of whether test methods are adequate to capture endocrine-related effects, considerations of further enhancements to current test methods, along with the need to develop novel test methods to address existing test method gaps are described. From this specific evaluation, up to 35 test methods are capable of informing whether a chemical substance perturbs known endocrine related biological pathways. Based on these findings, it can be concluded that current validated test methods are adequate to discern substances that may perturb the endocrine system, resulting in an adverse health effect. Together, these test methods predominantly form the core data requirements of a typical food-use pesticide registration submission. It is recognized, however, that the current state of science is rapidly advancing and there is a need to update current test methods to include added enhancements to ensure continued coverage and public health and environmental protection.     

连苏止呕胶囊对化疗呕吐家鸽胃肠激素影响的实验研究

目的　对连苏止呕胶囊抗化疗呕吐的内在机制加以探讨。方法　采用家鸽腹腔注射顺铂法制造模型 ,用放免试剂盒检测胃肠激素。结果　连苏止呕胶囊高剂量组能明显升高外周血中表皮生长因子 (EGF)的含量 (P <0 0 5 ) ,连苏止呕胶囊低剂量组、高剂量组能明显降低外周血中胃泌素(Gas)的含量 (P <0 0 5 ,P <0 0 1) ,连苏止呕胶囊高剂量组能明显降低外周血中血管活性肠肽(VIP)的含量 (P <0 0 5 )。结论　连苏止呕胶囊对胃肠粘膜起到了一定保护作用 ,对胃肠运动具有改善作用 ,这可能是该药抗化疗呕吐尤其是迟发性呕吐的机制所在     

Adrenergic effects on adrenocortical cortisol response to incremental exercise to exhaustion

This study evaluated the influence of adrenergic factors on the cortisol response to maximal exercise in endurance-trained men. This was achieved by testing healthy young men during exercise while varying both the condition of β-adrenergic blockage and the presence of a well-controlled simulated competitive environment to simulate activity of the sympatho-adrenal systems. Subjects (n = 10) performed maximal exercise (running) to exhaustion on a treadmill during four conditions: (1) placebo non-competitive [PNon] (2) after administration of 80 mg propranolol non-competitive [βNon] (3) in a simulated competition after a placebo intake [PCom], and (4) in a simulated competition after propranolol intake [βCom]. Blood samples were obtained before (pre-) and 3 min after (post-) exercise and assayed for cortisol (C). The data were analyzed with a multi-factorial repeated measures ANCOVA procedure. Statistical analysis revealed a significant three-way interaction for the drug versus competition versus sampling time effects (P < 0.05). Post-hoc tests revealed that the pre-exercise cortisol values did not differ significantly among the conditions. Cortisol did increase from pre- to post-exercise in all experimental conditions (P < 0.01), and the magnitudes of increase in the PCom, βNon and βCom conditions were greater than that of the PNon condition. Furthermore, the cortisol increases for both β-blockage conditions post-exercise (βNon, βCom) did not differ from one another (P > 0.05). The findings suggest β-adrenergic blockage and competitive conditions enhance the exercise cortisol response. In combination, however, these conditions do not act in an additive fashion. This suggests that perhaps there may be two separate influences or mechanisms (i.e., excitatory, inhibitory) on the adrenergic control of adrenocortical function, or a sympathetic compensation for β-blockage during exhaustive maximal exercise. Furthermore, the data suggests a possible “ceiling” on the hypothalamic-pituitary-adrenal axis response to exercise in endurance-trained men.     

不同免疫抑制剂及甲泼尼龙对小鼠肺间质纤维化的疗效对比

目的比较环磷酰胺、来氟米特和甲泼尼龙对博来霉素诱导的肺间质纤维化小鼠模型的疗效。方法将75只C57BL/6小鼠随机分成空白组、模型组、环磷酰胺组、来氟米特组及甲泼尼龙组(n=15)。空白组气管内注入0.9%氯化钠注射溶液0.2 m L,其余5组气管内注入博来霉素(5 mg/kg)建立肺纤维化模型,24 h后分别对空白组、模型组每日用0.2 m L 0.9%氯化钠注射溶液灌胃,药物组每日分别用环磷酰胺(50 mg/kg)、来氟米特(4 mg/kg)和甲泼尼龙灌胃(10 mg/kg)。并于造模后第7、14、28天分批处死小鼠,取小鼠肺脏评估肺泡炎程度及纤维化的程度。结果 (1)博来霉素诱导组小鼠体质量较对照组减轻(P<0.05),环磷酰胺、来氟米特组和甲泼尼龙组小鼠在第7、14、28天小鼠体质量较模型组均明显增加(P<0.05)。(2)与模型组相比,环磷酰胺组与甲泼尼龙组小鼠7天、14天时肺泡炎评分降低(P<0.05);第7天、14天、28天时纤维化评分明显降低(P<0.05)。而来氟米特组小鼠肺泡炎及纤维化评分较模型组差异无统计学意义。结论环磷酰胺和甲泼尼龙能显著降低博来霉素诱导的小鼠肺间质纤维化,减轻肺组织肺泡炎及肺纤维化程度,但来氟米特没有类似作用。