Ethinylestradiol and estradiol have different effects on oxidative stress and nitric oxide synthesis in human endothelial cell cultures

Study objective: To compare the effects of ethinylestradiol (EE) and 17 beta-estradiol (E(2)) on nitric oxide (NO) production and protection against oxidative stress in human endothelial cell cultures. Design: Experimental study. Settings: Research laboratory. Material: Human ECV304 endothelial cell cultures. Intervention(s): The NO synthesis was determined by flow cytometry, and oxidative stress was determined by a cell viability assay, after exposure to hydrogen peroxide (H(2)O(2)) and stimulation of endothelial cells with EE at concentrations similar to those of a contraceptive containing 30 mu g EE. Main Outcome Measure(s): The effects of EE were compared with those of E(2) at concentrations similar to those occurring during the follicular phase. Result(s): Ethinylestradiol did not increase NO synthesis and did not protect cells against oxidative stress. The viability of the cells incubated with E(2) in combination with H(2)O(2) was greater than the viability obtained with H(2)O(2) only or with H(2)O(2) in combination with EE. The cells stimulated with E(2) presented a significant increase in NO production compared with control. Conclusion(s): In contrast to the effects of E(2), EE did not protect human ECV304 endothelial cells against oxidative stress and did not increase their production of NO. (Fertil Steril (R) 2010; 94: 1578-82. (C) 2010 by American Society for Reproductive Medicine.)

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background: The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (DC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women. Study Design: Eighty-eight women (23 +/- 2.1 years old) were divided into four groups active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min(-1) increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%. Results: The OC use effect for the variables relative and absolute oxygen uptake VO(2) mL kg(-1) min(-1); VO(2), L min(-1), respectively), carbon dioxide output (VCO(2), L min(-1)), ventilation (VE, L min(-1)), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables VO(2), VCO(2), VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4. Conclusions: Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests. (C) 2010 Elsevier Inc. All rights reserved.

Increased cell proliferation in experimentally induced endometriosis in rabbits

Objective: To characterize the pattern of cell proliferation and apoptosis of eutopic and ectopic endometrium in rabbits after endometrium implantation for the experimental induction of endometriosis. Design: Animal experimental study. Setting: Sector of experimental surgery. Animal(s): Twenty-female New Zealand rabbits. Intervention(s): All animals underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of 10 animals were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma determination. Main Outcome Measure(s): Cell proliferation and apoptosis were determined in the eutopic and ectopic endometrium, and the cell proliferation index (CPI) and apoptotic index (AI) were calculated as the number of labeled cells per 1,000 cells. The tissue homeostasis index was the CPI/AI ratio. Glands and stroma were analyzed separately. Result(s): The CPI for ectopic tissue was increased compared with eutopic tissue, but there was no difference in the ectopic lesions between 4 and 8 weeks of induction. Considering only the AI, eutopic and ectopic endometrium did not differ after 4 weeks, but differed significantly in glandular tissue after 8 weeks. The tissue homeostasis index revealed cell proliferation in these tissues, with a CPI/AI more than 1. Conclusion(s): Ectopic lesions seem to have a higher CPI than eutopic endometrium, with uncontrolled tissue growth occurring in induced endometriotic lesions. (Fertil Steril (R) 2010;93:1637-42. (C)2010 by American Society for Reproductive Medicine.)

Influence of third-generation oral contraceptives on the complexity analysis and symbolic dynamics of heart rate variability

Objective To evaluate the influence of oral contraceptives (OCs) containing 20 mu mu g ethinylestradiol (EE) and 150 mu mu g gestodene (GEST) on the autonomic modulation of heart rate (HR) in women. Methods One-hundred and fifty-five women aged 24 +/-+/- 2 years were divided into four groups according to their physical activity and the use or not of an OC: active-OC, active-non-OC (NOC), sedentary-OC, and sedentary-NOC. The heart rate was registered in real time based on the electrocardiogram signal for 15 minutes, in the supine-position. The heart rate variability (HRV) was analysed using Shannon`s entropy (SE), conditional entropy (complexity index [CInd] and normalised CInd [NCI]), and symbolic analysis (0V%, 1V%, 2LV%, and 2ULV%). For statistical analysis the Kruskal-Wallis test with Dunn post hoc and the Wilcoxon test (p < 0.05 was considered significant) were applied. Results Treatment with this COC caused no significant changes in SE, CInd, NCI, or symbolic analysis in either active or sedentary groups. Active groups presented higher values for SE and 2ULV%, and lower values for 0V% when compared to sedentary groups (p < 0.05). Conclusion HRV patterns differed depending on life style; the non-linear method applied was highly reliable for identifying these changes. The use of OCs containing 20 mu mu g EE and 150 mu mu g GEST does not influence HR autonomic modulation.

Variations of Jitter and Shimmer Among Women in Menacme and Postmenopausal Women

The objective of the study was to analyze comparatively the jitter and shimmer values of spoken voice among women in menacme and menopausal women using or not hormonal replacement therapy (HRT). Forty-five women were studied, divided into the following groups: Control Group (CG), 15 women aged 20-40 years with regular menstrual cycles who did not take hormonal contraceptives, Treated Group (TG), 15 women aged 45-60 years with at least 2 years of menopause, under continuous HRT with I mg estradiol valerate + 90 mu g norgestimate per day for at least 6 months; Untreated Group (UG), 15 women aged 45-60 years with at least 2 years of menopause who did not use HRT. Mean age was 30.3, 54.5, and 56.5 years for CG, TG, and UG, respectively. All subjects were submitted to acoustic analysis of jitter and shimmer for the sustained vowels /e/ and /i/. Mean jitter values were 0.56%, 0.64%, and 0.56% for the vowel /e/ and 0.88%, 0.79%, and 0.68% for the vowel /i/ for CG, TG, and UG, respectively. Mean shimmer values were 4.17%, 4.38%, and 4.77% for the vowel /e/ and 5.19%, 4.59%, and 5.37% for the vowel /i/ for CG, TG, and UG, respectively. There were no significant differences between the groups studied. The results obtained here by the methodology used suggest that there were no significant differences in jitter and shimmer when we assessed the sustained vowels /i/ and /e/ between menopausal women using or not HRT or between young and menopausal women treated or not.

Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome. Context To assess the presence of early CVD markers in young, nonobese women with PCOS. Patients Forty women with PCOS and 50 healthy women with regular menstrual cycles, matched for age and body mass index (BMI). Measurements The following CVD markers were assessed by ultrasonography: common carotid artery (CCA) stiffness index (beta), distensibility and intima-media thickness (IMT), and brachial artery flow-mediated dilatation (FMD). Inflammatory markers, including interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, homocysteine, C-reactive protein (CRP), glycaemia, lipid profile and insulin, were also assessed. Results CCA beta was higher in PCOS than in control women (3 center dot 72 +/- 0 center dot 96 vs. 3 center dot 36 +/- 0 center dot 96, P = 0 center dot 04) and CCA distensibility was lower (0 center dot 31 +/- 0 center dot 08 vs. 0 center dot 35 +/- 0 center dot 09 mmHg(-1), P = 0 center dot 02). Waist circumference, total testosterone and the Free Androgen Index (FAI) were higher in PCOS patients than in controls (78 center dot 2 +/- 10 center dot 0 vs. 71 center dot 5 +/- 7 center dot 2 cm, P = 0 center dot 001; 88 center dot 1 +/- 32 center dot 4 vs. 57 center dot 1 +/- 21 center dot 2 ng/dl, P < 0 center dot 01; 12 center dot 7 +/- 15 center dot 7%vs. 4 center dot 7 +/- 2 center dot 3%, P < 0 center dot 01, respectively), while SHBG was reduced (37 center dot 9 +/- 19 center dot 1 vs. 47 center dot 8 +/- 18 center dot 3 nmol/l, P = 0 center dot 01). The remaining variables did not differ between the groups. Conclusions Young women with PCOS exhibit changes in vascular elasticity even in the absence of classical risk factors for CVD, such as hypertension and obesity.

Glycodelin expression in the endometrium of healthy women and in the eutopic and ectopic endometrium of women with endometriosis

Objective: To analyze the expression of the glycodelin gene to better understand the molecular environment of endometriotic lesions and to elucidate the potential mechanisms that underlie the complex physiopathology of endometriosis. Design: Prospective laboratory study. Setting: University hospital. Patient(s): Eleven healthy fertile women and 17 patients with endometriosis in the early proliferative phase of the menstrual cycle. Intervention(s): Endometrial biopsy specimens were obtained from the endometrium of healthy women without endometriosis (controls) and from eutopic and ectopic endometrium tissues (pelvic and ovarian endometriotic implants) of endometriosis patients. Main Outcome Measure(s): The glycodelin relative expression level by real-time polymerase chain reaction (PCR) analysis. Result(s): The glycodelin down-regulation found in the endometriotic lesions was 332.26 and 123.17-fold lower, respectively, when compared with the eutopic tissue and the control endometrium. Conclusion(s): Glycodelin may be one of the molecules that contributes to the loss of cellular homeostasis in endometriotic lesions. (Fertil Steril (R) 2009;91:1676-80. (C)2009 by American Society for Reproductive Medicine.)

Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells

Calpains have been implicated in the regulation of apoptosis. Here, we identified Calpain5 as a target of HOXA10 transcriptional regulation in endometrial cells as well as its aberrant regulation in endometriosis. Histologically confirmed biopsies of endometriosis were obtained from 20 women. Eutopic endometrium was collected by endometrial biopsy from 30 controls and from the 20 subjects with endometriosis. First trimester decidual samples were obtained from five subjects at the time of pregnancy termination. Immunohistochemistry was used to identify Calpain5 expression. Calpain5 was expressed in endometrial stromal and glandular cells throughout the menstrual cycle and in decidua. Calpain5 protein expression was decreased in both stromal and glandular cells from women with endometriosis compared with that of fertile controls. Human endometrial stromal and epithelial cell lines were transfected with pcDNA/HOXA10, HOXA10 siRNA or respective controls. Quantitative real-time RT-PCR was performed to determine expression of HOXA10 and Calpain5 in each group. Transfection of HESC cells with an HOXA10 expression construct led to increased Calpain5 expression, whereas transfection with siRNA resulted in decreased expression. In conclusion, Calpain5 expression is regulated by HOXA10. Calpain5 expression was decreased in endometriosis likely as a result of decreased HOXA10 expression. Decreased apoptosis in endometrial cells may promote the development of endometriosis through a pathway involving HOXA10, Calpain5 and caspase.

Ovarian reserve evaluation: state of the art

Purpose Revise role of hormonal basal and dynamic tests, as well as ultrasonographic measures as ovarian reserve markers, in order to provide better counseling to subfertile couples. Methods Review of publications on the topic, with an emphasis on recent well designed articles. Results Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, even for premature ovarian senescence patients who do not present subfertility complaints. However, these markers occupy important place in initial approach to treatment of subfertile couples, predicting unsatisfactory results that could be improved by differentiated induction schemes and reducing excessive psychological and financial burdens, and adverse effects. Conclusions In order to remedy the limitations due to the scarcity of strong evidence about this topic, future studies should try to clarify predictive value of markers in groups of specific diseases-related subfertility and pay special attention to propaedeutic multivariate models including anti-Mullerian hormone and antral follicle count.

Osteopontin expression according to molecular profile of invasive breast cancer: a clinicopathological and immunohistochemical study

Osteopontin (OPN) is a secreted, calcium-binding phosphorylated glycoprotein involved in several physiological and pathological events such as angiogenesis, apoptosis, inflammation, wound healing, vascular remodeling, calcification of mineralized tissues, and induction of cell proteases. There is growing interest in the role of OPN in breast cancer. In an attempt to obtain new insight into the pathogenesis of OPN-associated breast carcinomas, an immunohistochemical panel with 17 primary antibodies including cytokeratins and key regulators of the cell cycle was performed in 100 formalin-fixed paraffin-embedded samples of invasive breast carcinomas. OPN was expressed in 65% of tumors and was negatively correlated with estrogen (p=0.0350) and progesterone (p=0.0069) receptors, but not with the other markers and clinicopathological features evaluated including age, menstrual status, pathological grading, tumor size, and metastasis. There was no correlation between OPN expression and carcinomas of the basal-like phenotype (p=0.1615); however, OPN correlated positively with c-erbB-2 status (p=0.0286) and negatively with carcinomas of the luminal subtype (p=0.0353). It is well known that carcinomas overexpressing c-erbB-2 protein have a worse prognosis than luminal tumors. Here, we hypothesize that the differential expression of OPN in the first subtype of carcinomas may contribute to their more aggressive behavior. (Int J Biol Markers 2008; 23: 154-60)

Tracking the Ovarian Cycle in Black-and-Gold Howlers (Alouatta caraya) by Measuring Fecal Steroids and Observing Vaginal Bleeding

A better understanding of a species` reproductive physiology can help conservation programs to manage primates in the wild and develop assisted reproductive technologies in captivity. We investigated whether measurements of fecal progestin and estrogen metabolites obtained by a radioimmunoassay could be used to monitor the ovarian cycle of Alouatta caraya. We also compared the occurrence of vaginal bleeding with the hormone profiles. We collected fecal samples from 3 adult and 1 subadult captive female over 5 mo and performed vaginal cytology for the adults. The interval between fecal progestin surges in the adult females was 19.11 +/- 2.14 d (n = 18 cycles). Fecal progestin concentrations remained at basal values for 9.83 +/- 2.21 d (n = 18) and rose to elevated values for 9.47 +/- 0.72 d (n = 19). The subadult female showed basal levels of fecal estrogen and progestin concentrations throughout the study, suggesting that our hormone measurements are valid to monitor the ovarian cycle. Bleeding periods coincided with basal levels of fecal estrogens and progestin at intervals of 19.8 +/- 0.9 d and lasted for 4.1 +/- 1.0 d. Although we obtained these data from only 3 individuals, the results indicate that this species likely has a menstrual-type ovarian cycle. These data provide the first endocrine profile for the Alouatta caraya ovarian cycle and are similar to results obtained for other howler species. This similarity is important for comparative studies of howlers, allowing for a better understanding of their reproductive physiology and contributing to a critical information base for managing Alouatta species.

Metformin and intervention in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is classically characterised by ovarian dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess (hirsutism and acne), obesity, and morphological abnormalities of the ovaries (cystic enlargement and stromal expansion). More, recently, insulin resistance has been found to be common in PCOS, along with an increased prevalence of other features of the metabolic syndrome, namely glucose intolerance, type 2 diabetes mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the disordered ovarian function and androgen excess of PCOS. Reducing insulin resistance by lifestyle modifications such as diet and exercise improves endocrine and menstrual function in PCOS. These lifestyle modifications are the best initial means of improving insulin resistance. Metformin, an oral hypoglycaemic agent that increases insulin sensitivity has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates. The effect of metformin alone on fertility rates is-unknown. Some studies suggest that metformin will reduce total body weight to a small extent, but with a predominant effect on visceral adipose reduction. The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the metabolic syndrome in PCOS. Further properly planned randomised controlled trials are required.

Relative importance of female-specific and non-female-specific effects on variation in iron stores between women

Women have lower iron stores than men because of iron loss during their reproductive years. However, variation between women could result from differences in iron loss, aspects of iron homeostasis common to men and women, or a combination of both. We compared the effects of age, menopause, menstrual blood loss and the number of pregnancies (sex-specific factors), and the effects of genetic variation, on markers of iron stores. We assessed how much the same genes or other familial factors influence iron status in both men and women. Data from 2039 female twins who participated in studies of reproductive health and iron status were used to estimate the proportions of variation that could be ascribed to genes, environment and measured factors. Significant effects of age, menopausal status and magnitude of menstrual blood loss were demonstrated, accounting for up to 18% of variance in serum ferritin in this sample, but number of children had no significant effect. Genetic effects were more than twice as great as sex-specific effects. The within-pair similarity of ferritin values in dizygotic female twin pairs was greater than for dizygotic opposite-sex pairs, but this difference was not quite significant, consistent with a minor role for sex-specific factors; and the opposite-sex within-pair differences did not diminish significantly with age. We conclude that the contribution of genetic differences between women to variation in iron stores outweighs the comparatively small effects of interindividual variation in iron loss through variation in menstruation and number of pregnancies.

O modelo organiza????es sociais: li????es e oportunidades de melhoria

As Organiza????es Sociais (OS) s??o organiza????es sem fins lucrativos, ???qualificadas??? para absorver atividades executadas por organiza????es p??blicas, nos termos e condi????es estabelecidas em contratos de gest??o firmados entre organiza????es e o governo. Este artigo relata os principais resultados do semin??rio ???O modelo OS: li????es e oportunidades de melhorias???, realizado em outubro de 2001, do qual participaram gestores e t??cnicos da Secretaria de Gest??o (SEGES), de OS, de ??rg??os supervisores dessas organiza????es, de ??rg??os intervenientes, e especialistas em gest??o p??blica. Com rela????o ??s OS analisadas, pode-se perceber que: a) h?? controv??rsias e ambig??idades quanto ?? sua natureza jur??dica e quanto ao processo de avalia????o dessas organiza????es; b) a gest??o de recursos humanos ?? afetada pela exist??ncia de grupos submetidos a distintos regimes de trabalho, isto ??, Estatuto dos Funcion??rios P??blicos e Consolida????o das Leis do Trabalho; c) a gest??o de recursos financeiros ?? marcada pela irregularidade no fluxo dos referidos recursos; e d) o controle dos bens p??blicos ocorre de forma fr??gil e o processo de compra est?? sendo realizado sem problemas. Com base nessas considera????es, o documento prop??e algumas sugest??es de aperfei??oamento do modelo OS.