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    Effects of estradiol and medroxyprogesterone-acetate treatment on erythrocyte antioxidant enzyme activities and malondialdehyde plasma levels in amenorrhoic women

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    Plasma levels of 17 beta-estradiol (E2) and malondialdehyde and erythrocyte antioxidant enzyme [superoxide dismutase, catalase, and glutathione-peroxidase (GSH-Px)] activities were evaluated in 20 healthy eumenorrhoic women (EW) on day 7 of the menstrual cycle and in 48 secondary hypothalamic amenorrhea patients (AP) (time 0). The AP were randomly divided into four subgroups of 12 subjects and treated with transdermal E2 for 30 days (subgroup A), oral medroxyprogesterone-acetate for 30 days (subgroup B), and transdermal E2 plus medroxyprogesterone-acetate for 30 days (subgroup C). The fourth subgroup acted as control. E2 and malondialdehyde plasma levels and superoxide dismutase, catalase, and GSH-Px activities were evaluated in subgroups A, B, and C on day 30 of therapy and in the control subgroup. GSH-Px activity was significantly higher in EW than in AP at time 0. A statistically significant increase in E2 plasma levels and GSH-Px activity was observed in subgroups A and C on day 30 of treatment, and there was a significant positive correlation between E2 plasma levels and GSH-Px activity in both subgroups. After a month of treatment, erythrocyte GSH-Px activity in subgroups A and C was not significantly different from that observed in EW. After a month of treatment, no significant variation was found in subgroup B nor in the control group. These results strongly suggest that when plasma E2 is restored to physiological levels in AP, it stimulates erythrocyte GSH-Px activity. Progesterone therapy did not induce significant modifications

    Changes in the erythrocyte antioxidant enzyme system during transdermal estradiol therapy for secondary amenorrhea

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    Twenty-two hypothalamic amenorrheic patients, who were non-smokers and of normal weight, received replacement therapy for 1 month with transdermal patches containing 8 mg estradiol. No other drugs were prescribed or taken during the study. Before treatment (time 0) and 1 month after its start, blood samples were taken for assay of plasma estradiol levels, the erythrocyte antioxidant enzyme activities of superoxide dismutase, catalase, glutathione peroxidase (GSH-Px), and an age-dependent erythrocyte enzyme activity, pyruvate kinase. Plasma malondialdehyde levels, as an index of lipoperoxidation products, were also detected. The results showed no significant variations in superoxide dismutase, catalase, pyruvate kinase erythrocyte enzyme activities or plasma malondialdehyde levels. A significant increase in plasma estradiol levels (time 0, 17.33 +/- 4.12 pg/ml; 1 month, 81.25 +/- 10.45 pg/ml; means +/- SD; p < 0.0001) and in GSH-Px erythrocyte activity (time 0, 11.97 +/- 2.31 IU/g hemoglobin; 1 month, 16.88 +/- 4.38 IU/g hemoglobin; p < 0.004) was found. Plasma estradiol levels correlated significantly with GSH-Px erythrocyte activity 1 month after therapy was begun (r = 0.776, p < 0.003). We suggest that estrogens restored to physiological plasma levels, stimulate erythrocyte antioxidant GSH-Px activity, improving the antioxidant power of amenorrheic patients

    The behavioral and neuronal effects induced by repetitive nociceptive stimulation are affected by gonadal hormones in male rats

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    The role of gonadal hormones in inducing long-term modifications in response to transient nociceptive stimuli was investigated in adult male rats. Three weeks after gonadectomy or sham surgery, animals were randomly divided into groups to be exposed to sham (only a prick in the dorsal hind paw) or formalin treatment (50 microl, 5% s.c. in the dorsal hind paw) once a week for the following 3 weeks. In gonadectomized animals the formalin-induced responses (licking, flexing and jerking of the injected paw) did not differ from those of intact animals after the first formalin injection. However, their levels were higher after the second or third injections. Indeed, in intact animals the formalin-induced responses progressively decreased, being significantly lower after the third injection than after the first; in gonadectomized animals, the formalin-induced responses did not change with repetition of the formalin treatment. In intact rats, c-Fos expression in the paraventricular nucleus of the thalamus and arcuate nucleus of the hypothalamus remained at control levels or decreased in animals injected two or three times with formalin; in gonadectomized rats, c-Fos expression increased with repetition of the noxious stimulation, reaching the highest levels in animals injected three times with formalin. These results show that male gonadal hormones have an inhibitory, adaptive effect on the behavioral and neuronal responses to repeated nociceptive stimulation

    Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle

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    OBJECTIVE: Antioxidant enzymes are an important part of the defence mechanisms against free radical damage. Little is known, however, about the relationship between sex steroid hormones and cellular antioxidant systems. We have investigated the effect of physiological sex steroid changes on the erythrocyte antioxidant glutathione peroxidase (GSH-Px) activity during the menstrual cycle in a population of healthy normomenorrhoic women. DESIGN: Prospective, controlled. PATIENTS: Ten normally cycling women (age range: 19-28 years; mean: 23.3 years) were recruited for alternate-day blood sampling from the first day of one menstrual bleed until the first day of the subsequent menstrual phase. MEASUREMENTS: Plasma was analysed for LH, FSH, oestradiol (E2) and progesterone (P4) concentrations. Erythrocyte GSH-Px activity was evaluated on the same days in all subjects. Pyruvate-kinase (PK) activity, as an index of red blood cell population age, was also determined. RESULTS: All the women examined had a normal ovulatory cycle, as indicated by the hormone plasma pattern. Cycle length was standardized on the basis of the preovulatory E2 peak. Significant cycle phase-related changes in GSH-Px (P < 0.03) were observed, with higher GSH-Px activity levels being found from the later follicular to early luteal phase as compared to early follicular phase (chi 2 = 8.53, P < 0.001 and chi 2 = 5.54, P < 0.002, respectively). A significant positive correlation was observed between mean E2 and GSH-Px cycle-related changes (r = 0.78, P = 0.001). Conversely, no significant cycle phase-dependent variations were detected in PK. CONCLUSIONS: The findings support the hypothesis that physiological ovarian E2 production during the menstrual cycle may play an important role in regulating erythrocyte glutathione peroxidase activity

    Impaired pregnenolone secretion after combined cyproterone acetate and ethynyl estradiol therapy in hirsute patients.

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    6 women affected by hirsutism, either of idiopathic origin or due to polycystic ovary syndrome, have been treated with cyproterone acetate and ethynyl estradiol in combined therapy using, respectively, 100 mg and 50 micrograms/day, from the 5th to the 25th day of the cycle. The adrenal function was assessed before treatment and at the end of the 4th month of therapy, evaluating the peripheral plasma concentrations of pregnenolone (delta 5P), progesterone, 17-OH-progesterone, dehydro-epiandrosterone sulfate, androstenedione, testosterone, and cortisol in basal conditions and after dexamethasone suppression and an adrenocorticotropic hormone (ACTH) stimulation test. A group of healthy, untreated females were examined in the early follicular phase, as controls, Before therapy, the hirsute patient showed testosterone and androstenedione plasma levels, which were significantly higher than in the controls, and a significant reduction in pregnenolone response to ACTH. After 4 months of therapy with cyproterone acetate plus ethynyl estradiol, a significant decrease was found in testosterone and androstenedione plasma levels, and pregnenolone basal plasma levels, dexamethasone suppressibility, and response to ACTH were also markedly reduced, showing a significant difference versus the same patients before therapy and versus the control group. The existence of an impairment in adrenal function after cyproterone acetate plus ethynyl estradiol therapy at the given dose seems to be evident only in the case of directly ACTH-dependent adrenal enzymatic activities responsible for cholesterol cleavage to pregnenolone

    Repeated nociceptive stimulation induces different behavioral and neuronal responses in intact and gonadectomized female rats

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    Tissue damage induces acute pain but also long-term central modifications that can affect the behavioral and neuronal responses to a second painful stimulus. To study the effects of female gonadal hormones on the responses to repetition of a nociceptive stimulus, we subjected adult female rats to the formalin test. Three weeks after gonadectomy (GDX) or sham-surgery (INT), animals were randomly divided into groups to be left in the home cage as controls (HC) or to be exposed to Sham (S) or Formalin (F) stimuli (s.c. formalin injection, 50 microl, 5%, in the dorsal hind paw) in the subsequent 2 weeks (Trial 1; Trial 2). The resulting groups were: INT or GDX SS (Sham-Sham), SF (Sham-Form) and FF (Form-Form). During Trial 1, licking duration was longer in the INT-FF group than in GDX-FF; during Trial 2, there was no difference between the two groups due to the decrease in INT-FF alone. c-Fos expression, determined in the arcuate nucleus of the hypothalamus in the same animals 1 week after the last formalin test, was higher in GDX than INT animals; moreover, while in INT rats, c-Fos was higher in the formalin-injected animals (SF and FF) than in HC, in GDX, it did not differ among groups. These results show that female gonadal hormones affect the behavioral and neuronal responses to repeated nociceptive stimulation, indicating a possible role of ovarian hormones in determining sex differences in pain

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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