927 resultados para Endocrine-disrupting chemicals
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Endocrine disruptors (EDs) are widespread in the environment, especially aquatic systems, and cause dangerous effects on wildlife and humans. This work was aimed to assess the capacity of radish (Raphanus sativus L.) and ryegrass (Lolium perenne L.) seedlings to tolerate and remove two combinations of EDs containing bisphenol A (BPA), 17α-ethynilestradiol (EE2), and linuron from four aqueous media: distilled water, a solution of natural organic matter (NOM), a lake water and a river water. Seeds of the two species were germinated in each contaminated medium and, at the end of germination, the seedling growth was evaluated by biometric measurements and residual EDs were quantified by chromatographic analysis. Biometric measurements revealed that the phytotoxicity of the two combinations of EDs depended on the medium used. Radish showed a discrete tolerance in distilled water and lake water but was inhibited in the solution of NOM and river water. Ryegrass was negatively affected mainly in river water. The concentration of each ED appeared significantly reduced in all media in the presence of seedlings of both species, but not in the blanks without plants. In 5 days, radish removed up to 88% of BPA, 100% of EE2 and 42% of linuron, and in 6 days ryegrass removed up to 92% of BPA, 74% of EE2 and 16% of linuron. The considerable removal capacity of radish and ryegrass in all media tested encourages the use of phytoremediation to remove EDs from waters. © 2013 Copyright Taylor and Francis Group, LLC.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Ipomoea carnea is a toxic plant in Brazil and other tropical countries that often poisons livestock; its primary toxin is swainsonine. Some substances that interact with the endocrine system have been called endocrine disruptors (EDs). Considering swainsonine's mode of action, it is feasible to hypothesize that this compound could act as an ED. Bisphenol A (BPA), an estrogen-mimic, is considered a classical ED in rodents. This study aimed to evaluate the possible ED actions of I. cameo and BPA in male goats. Seventeen adult male goats were divided into three homogeneous groups: control (C, n = 5); IC (n = 6, received 5.0 g/kg body weight of freshly harvested I. cornea per day), and BPA (n = 6, received 25.0 mg/kg body weight of BPA per day). The experimental period was 120 days. During the experiment, blood samples were collected at 0, 30, 60, 90 and 120 days for biochemical and hormonal evaluations. On the same days, semen samples were collected for andrological evaluation, and scrotal circumference and testicular consistency were determined. The males were castrated on day 121, and fragments of testicle and epididymis were collected for histopathological evaluation. A decrease in serum T3 and T4 was observed in the IC group as well as an increase in the number of sperm with morphological alterations. In the BPA group, reduced serum 14 and a decreased percentage of sperm with plasma membrane integrates were observed. A histopathological examination revealed the vacuolar degeneration of Sertoli cells and areas of laminar patterns of calcium deposits in the IC group and vacuolar degeneration in the rete testis in the BPA group. These results indicate that both I. cameo and BPA are potential EDs in goats. This study emphasized the susceptibility of livestock to ED actions. We also demonstrated the action of I. cameo acting as EDs in the endocrine and reproductive systems. (C) 2014 Elsevier B.V. All rights reserved.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Spermatogonial stem cells (SSCs) either self-renew or differentiate into spermatogonia that further develop into spermatozoa. Self-renewal occurs when residing in a specific micro-environment (niche) while displacement from the niche would tip the signalling balance towards differentiation. Considering the cystic type of spermatogenesis in fish, the SSC candidates are single type A undifferentiated (A(und)) spermatogonia, enveloped by mostly one niche-forming Sertoli cell. When going through a self-renewal cell cycle, the resulting new single type Aund spermatogonium would have to recruit another Sertoli cell to expand the niche space, while a differentiating germ cell cyle would result in a pair of spermatogonia that remain in contact with their cyst-forming Sertoli cells. In zebrafish, thyroid hormone stimulates the proliferation of Sertoli cells and of type Aund spermatogonia, involving Igf3, a new member of the Igf family. In cystic spermatogenesis, type Aund spermatogonia usually do not leave the niche, so that supposedly the signalling in the niche changes when switching from self-renewal to differentiation. and rzAmh inhibited differentiation of type A(und) spermatogonia as well as Fsh-stimulated steroidogenesis. Thus, for Fsh to efficiently stimulate testis functions, Amh bioactivity should be dampened. We also discovered that Fsh increased Sertoli cell Igf3 gene and protein expression; rzIgf3 stimulated spermatogonial proliferation and Fsh-stimulated spermatogenesis was significantly impaired by inhibiting Igf receptor signaling. We propose that in zebrafish, Fsh is the major regulator of testis functions and, supported by other endocrine systems (e.g. thyroid hormone), regulates Leydig cell steroidogenesis as well as Sertoli cell number and growth factor production to promote spermatogenesis.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Stress hormones in Rocky Mountain bighorn sheep (Ovis canadensis canadensis), produced in response to environmental changes, road development, or high population density, may impact their immune systems to a threshold level that predisposes them to periodic, large-scale mortality. We compared the stress response to a novel environmental situation and repeated handling between bighorn sheep born and raised in captivity (CR) and bighorn sheep born in the wild (WC) and brought into captivity. We measured plasma epinephrine, norepinephrine, cortisol, and fecal glucocorticoid metabolites (FGM). Three weeks after each group’s arrival we used a one-time drop-net event to elicit an acute stress response, and we collected blood samples from each sheep over 35 minutes, as well as one fecal sample. We collected blood and fecal samples from both groups on 7 other occasions over the subsequent 6 months. We also collected fecal samples from the pen at approximately 24-hour intervals for 3 days following every handling event to monitor the stress response to handling. We found that CR sheep had a stronger autonomic nervous system response than WC sheep, as measured by epinephrine and norepinephrine levels, but we found a very similar hypothalamic–pituitary–adrenal axis (HPA) response, measured by cortisol levels, to the acute stress event of a drop-net restraint. We also found that once the WC sheep had acclimated, as indicated by the return to the initial baseline FGM levels within 12 weeks, the CR and WC groups’ HPA responses to sampling events were not significantly different from one another. Fecal samples can provide a noninvasive mechanism for managers to monitor baseline FGM for a given herd. Using long-term monitoring of FGM rather than values from a single point in time may allow managers to correlate these levels to outside influences on the herd and better understand the impacts of management changes, population density, or increased human developments on the health of the sheep population.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer. Core biopsies at baseline, week 4, and surgery were assessed for biomarker changes. Primary endpoint: change in Ki67 labeling index (LI) from baseline to week 4 determined by automated computer imaging system (ACIS). Secondary endpoints: ER protein expression and function; progesterone receptor (PgR) expression; tumor response; tolerability. ER and PgR were examined retrospectively using the H score method. A total of 211 patients were randomized (fulvestrant 500 mg: n = 109; 250 mg: n = 102). At week 4, fulvestrant 500 mg resulted in greater reduction of Ki67 LI and ER expression versus 250 mg (-78.8 vs. -47.4% [p < 0.0001] and -25.0 vs. -13.5% [p = 0.0002], respectively [ACIS]); PgR suppression was not significantly different (-22.7 vs. -17.6; p = 0.5677). However, H score detected even greater suppression of ER (-50.3 vs. -13.7%; p < 0.0001) and greater PgR suppression (-80.5 vs. -46.3%; p = 0.0018) for fulvestrant 500 versus 250 mg. At week 16, tumor response rates were 22.9 and 20.6% for fulvestrant 500 and 250 mg, respectively, with considerable decline in all markers by both ACIS and H score. No detrimental effects on endometrial thickness or bone markers and no new safety concerns were identified. This provides the first evidence of greater biological activity for fulvestrant 500 versus 250 mg in depleting ER expression, function, and growth.