Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.524
Filtrar
1.
Am J Physiol Heart Circ Physiol ; 320(4): H1712-H1723, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33666502

RESUMO

Uterine spiral artery remodeling (UAR) is essential for placental perfusion and fetal development. A defect in UAR underpins placental ischemia disorders, e.g., preeclampsia, that result in maternal systemic vascular endothelial dysfunction and hypertension. We have established a model of impaired UAR by prematurely elevating maternal serum estradiol levels during the first trimester of baboon pregnancy. However, it is unknown whether this experimental paradigm is associated with maternal vascular endothelial dysfunction. Therefore, in the present study baboons were administered estradiol on days 25-59 of gestation to suppress UAR and maternal vascular function determined on day 165 (term = 184 days) peripherally and in skeletal muscle, which accounts for over 40% of body mass and 25% of resting systemic vascular resistance. Maternal serum sFlt-1 levels were 2.5-fold higher (P < 0.05), and skeletal muscle arteriolar endothelial nitric oxide synthase (eNOS) protein expression and luminal area, and skeletal muscle capillary density were 30-50% lower (P < 0.05) in UAR suppressed baboons. Coinciding with these changes in eNOS expression, luminal area, and capillary density, maternal brachial artery flow-mediated dilation and volume flow were 70% and 55% lower (P < 0.05), respectively, and mean arterial blood pressure 29% higher (P < 0.01) in UAR defective baboons. In summary, maternal vascular function was disrupted in a baboon model of impaired UAR. These results highlight the translational impact of this primate model and relevance to adverse conditions of human pregnancy underpinned by improper uterine artery transformation.NEW & NOTEWORTHY Maternal vascular dysfunction is a hallmark of abnormal human pregnancy, particularly early-onset preeclampsia, elicited by impaired UAR. The present study makes the novel discovery that maternal systemic vascular dysfunction was induced in a baboon experimental model of impaired UAR. This study highlights the translational relevance of this nonhuman primate model to adverse conditions of human pregnancy underpinned by defective UAR.


Assuntos
Pressão Arterial , Artéria Braquial/fisiopatologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Microvasos/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Artéria Uterina/fisiopatologia , Remodelação Vascular , Vasodilatação , Animais , Artéria Braquial/metabolismo , Modelos Animais de Doenças , Estradiol/análogos & derivados , Feminino , Idade Gestacional , Hipertensão Induzida pela Gravidez/induzido quimicamente , Hipertensão Induzida pela Gravidez/metabolismo , Microvasos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Papio anubis , Gravidez , Primeiro Trimestre da Gravidez , Artéria Uterina/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
2.
Toxicol Mech Methods ; 31(1): 43-52, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32967526

RESUMO

Early detection and treatment of endometrial hyperplasia (EH) is mandatory for endometrial cancer prevention. Several bioactive agents of plant origin have been shown to elicit their chemotherapeutic effect against tumors and cancer via induction of mitochondrial permeability transition(mPT) pore opening. This research was therefore aimed at evaluating the potential chemopreventive effect of methyl palmitate (MP), on estradiol benzoate(EB)-induced EH, looking at the mitochondrial-mediated pathway and other possible mechanisms of action. Mitochondria were isolated using differential centrifugation. The mPT pore, mitochondrial ATPase (mATPase) activity, lipid peroxidation and cytochrome c release were determined by standard methods using spectrophotometer. Uterine interleukin 1b, MDA levels and SOD, GSH activities, were determined using commercially available kits. The uterine histological and immunohistochemical assessment of estrogen receptor (ERα), IL-1b and caspas-3 were carried out. The fibroblast cell count density was determined using histomorphometry. At all the concentrations of MP used, there was no significant induction of mPT pore opening, neither any enhancement of mATPase activity nor release of cytochrome c when compared to the control. Similar pattern of results were recorded for the in vivo study. However, there was marked increase in the uterine MDA and interleukin 1b levels, with concurrent decrease in SOD and GSH activities, in the EB-treated group, which was significantly reversed by MP co-administration. Endometrial Hyperplasia observed in the EB-treated group was ameliorated by MP co-administration. The immunoexpression of ERα and IL-1b in the EB-treated group was reversed by MP co-administration. This study suggests anti-inflammatory, antioxidant and anti-proliferative potential of MP against EB-induced EH.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Hiperplasia Endometrial/prevenção & controle , Endométrio/efeitos dos fármacos , Estradiol/análogos & derivados , Mitocôndrias/efeitos dos fármacos , Palmitatos/farmacologia , Animais , Citocromos c/metabolismo , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Endométrio/metabolismo , Endométrio/patologia , Estradiol/toxicidade , Receptor alfa de Estrogênio/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais
3.
Medicine (Baltimore) ; 99(37): e22178, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925788

RESUMO

INTRODUCTION: Postmenopausal osteoporosis (PMOP), which is a common and frequently occurring age-related metabolic bone disease in perimenopausal women, severely affects patients living quality. Modern medicine therapies for PMOP have several problems such as side reactions, low compliance, and high costs. Thus, nonpharmacological modality is urgently needed. Although acupoint thread embedding treatment is widely used in clinical practice, there is no persuasive evidence of its effect on increasing bone mass for PMOP. This experiment aims to investigate the efficacy and safety of acupoint thread embedding on PMOP and elucidate the correlations among brain neural activation, bone mineral density (BMD), and clinical outcomes with magnetic resonance evidence, thus to explore its neural mechanism. METHODS: This parallel designed, exploratory randomized, controlled, assessor-statistician-blinded, positive medicine clinical trial will include 70 participants with PMOP recruited from 2 traditional Chinese Medicine hospitals. These participants will be randomly allocated to a treatment group (Group Embedding) and a control group (Group Medication) in a 1:1 ratio. Participants in the treatment group will receive acupoint thread embedding treatment once 2 weeks in the following predefined acupoints: Shenshu (BL23), Sanyinjiao (SP6), Guanyuan (RN4), Ganshu (BL18), Dazhu (BL11), Xuanzhong (GB39), Zusanli (ST36), and Pishu (BL20). Meanwhile, the participants in the control group will take 0.3 mg Climen tablet orally, 1 tablet/day; every month has a schedule of the 21-day-continuous-taking-medicine period, and 7-day tablet-free period. There is a study period of 3 months and a follow-up period of 1 month for each group. The primary outcomes will be the following therapeutic indexed: Short-Form of McGill Pain Questionnaire (SF-MPQ), Osteoporosis Symptom Score during the observation period and follow-up period. The secondary outcomes will be Osteoporosis Quality of Life Scale (OQOLS), 16-item Assessment of Health-Related Quality of Life in Osteoporosis. In addition, functional magnetic resonance imaging (fMRI) scans and bone density test will be done before and after the observation period to show cranial neuroimaging changes. All the outcomes will be evaluated before and after treatment. The safety of interventions will be assessed at every visit. DISCUSSION: We present study design and rationale to explore the effectiveness and neural mechanism of acupoint thread embedding for PMOP through these outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-17011491.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Categute , Osteoporose Pós-Menopausa/terapia , Idoso , Biomarcadores , Densidade Óssea , Acetato de Ciproterona/uso terapêutico , Combinação de Medicamentos , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Qualidade de Vida , Método Simples-Cego
4.
J Toxicol Sci ; 45(8): 435-447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741896

RESUMO

The imbalance of testosterone to estradiol ratio has been related to the development of prostate diseases. Although rat models of prostate diseases induced by endocrine-disrupting chemicals (EDCs) and/or hormone exposure are commonly used to analyze gene expression profiles in the prostate, most studies utilize a single endpoint. In this study, microarray analysis was used for gene expression profiling in rat prostate tissue after exposure to EDCs and sex hormones over multiple time points (prepubertal through adulthood). We used dorsolateral prostate tissues from Sprague-Dawley rats (male offspring) and postnatally administered estradiol benzoate (EB) on postnatal days (PNDs) 1, 3, and 5, followed by treatment with additional hormones [estradiol (E) and testosterone (T)] on PNDs 90-200, as described by Ho et al. Microarray analysis was performed for gene expression profiling in the dorsolateral prostate, and the results were validated via qRT-PCR. The genes in cytokine-cytokine receptor interaction, cell adhesion molecules, and chemokines were upregulated in the EB+T+E group on PNDs 145 and 200. Moreover, early-stage downregulation of anti-inflammatory gene: bone morphogenetic protein 7 gene was observed. These findings suggest that exposure to EB, T, and E activates multiple pathways and simultaneously downregulates anti-inflammatory genes. Interestingly, these genes are reportedly expressed in prostate cancer tissues/cell lines. Further studies are required to elucidate the mechanism, including analyses using human prostate tissues.


Assuntos
Disruptores Endócrinos/toxicidade , Estradiol/análogos & derivados , Estradiol/toxicidade , Perfilação da Expressão Gênica/métodos , Expressão Gênica , Próstata/metabolismo , Puberdade , Testosterona/toxicidade , Transcriptoma , Fatores Etários , Animais , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Disruptores Endócrinos/efeitos adversos , Estradiol/efeitos adversos , Inflamação/genética , Masculino , Análise em Microsséries , Ratos Sprague-Dawley , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Testosterona/efeitos adversos
5.
Clin Nucl Med ; 45(9): e403-e405, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32657871

RESUMO

Radiation pneumonitis (RP) can be an adverse complication of radiotherapy and usually occurs as an acute reaction from 6 to 12 weeks after radiotherapy. FDG PET is described as an early and adequate barometer for RP diagnosis. Only 1 case of fluoroestradiol uptake contemporary of metabolic FDG changes attributed to RP is reported. We report a case of a breast cancer patient with asymptomatic RP, who at 1 year later, at sequelar stage on CT, showed long-term memory of RP by F-fluoroestradiol PET imaging with nonmetabolic FDG PET.


Assuntos
Estradiol/análogos & derivados , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Pneumonite por Radiação/diagnóstico por imagem , Doenças Assintomáticas , Neoplasias da Mama/radioterapia , Feminino , Humanos
6.
Phytomedicine ; 68: 153151, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32058234

RESUMO

BACKGROUND AND PURPOSE: Primary dysmenorrhea is the most common gynaecologic problem in menstruating women and is characterized by spasmodic uterine contraction and pain symptoms associated with inflammatory disturbances. Paeonol is an active phytochemical component that has shown anti-inflammatory and analgesic effects in several animal models. The aim of this study was to explore whether paeonol is effective against dysmenorrhea and to investigate the potential mechanism of cannabinoid receptor signalling. EXPERIMENTAL APPROACH: Dysmenorrhea was established by injecting oestradiol benzoate into female mice. The effects of paeonol on writhing time and latency, uterine pathology and inflammatory mediators were explored. Isolated uterine smooth muscle was used to evaluate the direct effect of paeonol on uterine contraction. KEY RESULTS: The oral administration of paeonol reduced dysmenorrhea pain and PGE2 and TNF-α expression in the uterine tissues of mice, and paeonol was found to be distributed in lesions of the uterus. Paeonol almost completely inhibited oxytocin-, high potassium- and Ca2+-induced contractions in isolated uteri. Antagonists of CB2R (AM630) and the MAPK pathway (U0126), but not of CB1R (AM251), reversed the inhibitory effect of paeonol on uterine contraction. Paeonol significantly blocked L-type Ca2+ channels and calcium influx in uterine smooth muscle cells via CB2R. Molecular docking results showed that paeonol fits well with the binding site of CB2R. CONCLUSIONS AND IMPLICATIONS: Paeonol partially acts through CB2R to restrain calcium influx and uterine contraction to alleviate dysmenorrhea in mice. These results suggest that paeonol has therapeutic potential for the treatment of dysmenorrhea.


Assuntos
Acetofenonas/farmacologia , Dismenorreia/tratamento farmacológico , Receptor CB2 de Canabinoide/metabolismo , Útero/efeitos dos fármacos , Acetofenonas/química , Animais , Cálcio/metabolismo , Dinoprostona/metabolismo , Dismenorreia/induzido quimicamente , Dismenorreia/metabolismo , Estradiol/análogos & derivados , Estradiol/toxicidade , Feminino , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Miócitos de Músculo Liso , Miométrio/efeitos dos fármacos , Miométrio/metabolismo , Ocitocina/farmacologia , Receptor CB2 de Canabinoide/química , Fator de Necrose Tumoral alfa/metabolismo , Contração Uterina/efeitos dos fármacos , Útero/metabolismo
8.
9.
Theriogenology ; 141: 197-201, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563861

RESUMO

To minimize costs and labor for short-term ovulation synchronization protocol, we developed one wherein each treatment-drug administration and timed artificial insemination (TAI)-was performed 24 h apart. The objective of the present study was to evaluate this short-term ovulation synchronization protocol in lactating dairy cows. Data were derived from 133 inseminations performed in 120 cows (32 primiparous and 88 multiparous), and the ovaries of these cows were scanned using ultrasound. The cows detected to have a functional corpus luteum (CL) received prostaglandin F2α (PGF) as a luteolytic agent. The cows were randomly assigned to two treatment groups: (1) treatment with estradiol benzoate (EB) 24 h after PGF treatment, and TAI 24-28 h after EB treatment (EB group); and (2) treatment with gonadotropin-releasing hormone agonist (GnRH) 56 h after PGF treatment, and TAI 16-20 h after GnRH treatment (GnRH group). As a luteolytic agent, either dinoprost (DP; 25 mg) or D-cloprostenol (DCLP; 0.15 mg) was administered intramuscularly in each treatment group. Pregnancy per AI (P/AI) was significantly higher in the DP- or DCLP-treated cows in the EB group when compared with their counterparts in the GnRH group (64.5% vs. 33.3%, P = 0.03 in the DP-treated cows and 51.1% vs. 27.3%, P = 0.04 in the DCLP-treated cows, respectively). Regarding parity, multiparous cows had greater P/AI in the EB group than in the GnRH group (52.8% vs. 26.7%, P = 0.01), whereas primiparous cows showed no significant intergroup difference (65.2% vs. 41.7%, P = 0.28). To conclude, the use of a convenient synchronization protocol comprising the administration of PGF and EB 24 h apart, rather than PGF and GnRH 56 h apart, has greater potential to improve pregnancy rates after TAI in lactating dairy cows given that a functional CL was accurately detected. This beneficial effect of the protocol using EB was clearly demonstrated in multiparous cows.


Assuntos
Dinoprosta/farmacologia , Estradiol/análogos & derivados , Sincronização do Estro/efeitos dos fármacos , Inseminação Artificial/veterinária , Animais , Bovinos , Dinoprosta/administração & dosagem , Estradiol/administração & dosagem , Estradiol/farmacologia , Sincronização do Estro/métodos , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Inseminação Artificial/métodos , Paridade , Gravidez , Estações do Ano
10.
Toxicol Lett ; 318: 99-103, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669098

RESUMO

Fluorination preventing metabolic hydroxylation of 17ß-estradiol (E2) was applied to investigate the mechanisms underlying estrogen-induced carcinogenesis. Either 2-fluoro-17ß-estradiol (2-FE2) or 4-fluoro-17ß-estradiol (4-FE2) was administered subcutaneously for 52 weeks to August Copenhagen Irish (ACI) rats, the preferred animal model for human breast cancer. 4-FE2 induced frequent mammary tumors whereas 2-FE2 did not. The cumulative incidence of mammary tumors in rats treated with 4-FE2 was comparable to that observed with E2. The carcinogenic results were supported by histological examination of mammary glands of fluorinated estrogen-treated ACI rats. To evaluate the estrogenic potential of the fluorinated estrogens, 2-FE2 or 4-FE2 was administrated subcutaneously to ovariectomized rats. Both 4-FE2 and 2-FE2 showed high uterotrophic potency. Our results indicate that estrogenic potential may not be the sole factor driving mammary tumorigenesis. Since fluorination inhibits metabolic hydroxylation of E2 at the substituted position, the carcinogenic effect may occur through the metabolic activation of 2-hydroxylated E2, in combination with the compound's estrogenic potency.


Assuntos
Neoplasias da Mama/induzido quimicamente , Transformação Celular Neoplásica/induzido quimicamente , Estradiol/análogos & derivados , Animais , Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Estradiol/toxicidade , Feminino , Tamanho do Órgão/efeitos dos fármacos , Ratos Endogâmicos ACI , Medição de Risco , Útero/efeitos dos fármacos , Útero/patologia
11.
Biomed Res Int ; 2019: 1850462, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886177

RESUMO

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 µM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 µM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 µM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proteínas de Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Fatores de Transcrição/genética , Antimitóticos/farmacologia , Antineoplásicos , Apoptose/efeitos dos fármacos , Azepinas/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/antagonistas & inibidores , Estradiol/análogos & derivados , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Mitose/efeitos dos fármacos , Metástase Neoplásica , Proteínas Nucleares/genética , Sulfonamidas/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Triazóis/farmacologia
12.
Rev Bras Ginecol Obstet ; 41(12): 703-709, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31856289

RESUMO

OBJECTIVE: To investigate the action of testosterone (T), isolated or associated with estradiol benzoate (EB), on the proliferation markers and apoptosis of breasts of ovariectomized rats. METHODS: A total of 48 castrated female Wistar rats were divided into 6 groups, and each of them were submitted to one of the following treatments for 5 weeks: 1) control; 2) EB 50 mcg/day + T 50 mcg/day; 3) T 50mcg/day; 4) EB 50 mcg + T 300 mcg/day; 5) T 300 mcg/day; and 6) EB 50 mcg/day. After the treatment, the mammary tissue was submitted to a histological analysis and immunoexpression evaluation of proliferation markers (proliferating cell nuclear antigen, PCNA) and apoptosis (caspase-3). RESULTS: There was a statistically significant difference among the groups regarding microcalcifications and secretory activity, with higher prevalence in the groups treated with EB. There was no difference among the groups regarding atrophy, but a higher prevalence of atrophy was found in the groups that received T versus those that received EB + T. There was a difference among the groups regarding the PCNA (p = 0.028), with higher expression in the group submitted to EB + T 300 mcg/day. Regarding caspase-3, there was no difference among the groups; however, in the group submitted to EB + T 300 mcg/day, the expression was higher than in the isolated T group. CONCLUSION: Isolated T did not have a proliferative effect on the mammary tissue, contrary to EB. Testosterone in combination with EB may or may not decrease the proliferation, depending on the dose of T.


Assuntos
Apoptose/efeitos dos fármacos , Mama/citologia , Proliferação de Células/efeitos dos fármacos , Testosterona/farmacologia , Animais , Biomarcadores/análise , Mama/patologia , Calcinose/patologia , Caspase 3/análise , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Ovariectomia , Antígeno Nuclear de Célula em Proliferação/análise , Ratos Wistar
13.
Anim Reprod Sci ; 211: 106234, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31785632

RESUMO

Two experiments evaluated the effects of injectable trace minerals (ITM) administered 11 d before artificial insemination (AI) on body weight (BW), body condition score (BCS), ovarian structures, pregnancy rate, and antioxidant response of Nellore cows. In Experiment 1, 20 multiparous cows were assigned to one of two treatments: subcutaneous injection (6 mL/cow; 11 d before AI) of saline solution or ITM (60, 10, 5, and 15 mg/mL of Zn, Mn, Se and Cu, respectively) and BW, BCS, ovarian structures and blood were evaluated. In Experiment 2, 1,144 multiparous cows were assigned to same treatments described in Experiment 1 and pregnancy rate on d 30 was evaluated. In Experiment 1, ITM did not affect (P ≥  0.23) BW, dominant follicle size, ovulation rate, and plasma concentrations of haptoglobin, ceruloplasmin and progesterone (P4). The ITM treatment tended to increase (P =  0.06) cow BCS and reduce (P ≤  0.06) corpus luteum (CL) diameter and volume. Furthermore, ITM treatment tended to increase (P =  0.06) plasma concentrations of SOD and increased (P =  0.007) GSH-Px compared with saline injection. In Experiment 2, ITM treatment tended (P =  0.06) to increase pregnancy rate of cows with BCS ≤ 5.0 but not cows with BCS > 5.0 (P =  0.99). The ITM treatment did not alter BW, plasma P4, and acute phase response, but enhanced plasma concentrations of antioxidant enzymes, and tended to enhance BCS and pregnancy rates to AI of cows with BCS ≤ 5.0, even though there was a smaller corpus luteum size.


Assuntos
Bovinos , Inseminação Artificial/veterinária , Oligoelementos/administração & dosagem , Animais , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/farmacologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Gravidez , Progesterona/administração & dosagem , Progesterona/farmacologia , Reprodução/efeitos dos fármacos , Substâncias para o Controle da Reprodução/administração & dosagem , Substâncias para o Controle da Reprodução/farmacologia
14.
Anim Sci J ; 90(12): 1523-1529, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646735

RESUMO

We aimed to define whether embryo collection carried out after pseudopregnancy was of similar outcome and quality as after artificial abortion. To induce pseudopregnancy, 30 gilts or sows were given 20 mg intramuscular estradiol dipropionate (EDP) 10-11 days after the onset of estrus. Ten additional pigs were inseminated artificially at natural estrus as a control group. Prostaglandin F2α (PGF2α ) was administered twice with a 24 hr interval beginning 15, 20, or 25 days after EDP-treatment (n = 10 per group) or between 23 and 39 days after artificial insemination in control pigs. Following this, all pigs were given 1,000 IU equine chorionic gonadotropin and 500 IU human chorionic gonadotropin (hCG) and then inseminated. Embryos were recovered 6 or 7 days after hCG treatment and outcome was recorded. There was no significant difference in the number of normal embryos collected from the pigs with PGF2α initiated at different time points or from the control group. Embryonic developmental stages 7 days after hCG treatment also did not differ among groups. These results indicate that the use of EDP to induce pseudopregnancy, followed by PGF2α administration to synchronize estrus for subsequent embryo harvest, is a suitable alternative to the artificial abortion method.


Assuntos
Estradiol/análogos & derivados , Estro/efeitos dos fármacos , Pseudogravidez , Criação de Embriões para Pesquisa/métodos , Sus scrofa , Animais , Gonadotropina Coriônica/administração & dosagem , Embrião de Mamíferos , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Prostaglandinas F/administração & dosagem , Prostaglandinas F/farmacocinética
15.
J Anim Physiol Anim Nutr (Berl) ; 103(6): 1885-1894, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31483545

RESUMO

The objective of this study was to evaluate the effects of zearalenone (ZEA) and estradiol benzoate (EB) on stress injury and uterine development in post-weaning gilts. Thirty healthy post-weaning female gilts (Duroc × Landrace × Large White) aged 28-32 days were randomly allocated to three treatments as follows: (a) basal diet (Control), (b) basal diet plus 1.0 mg/kg purified ZEA (ZEA) and (c) basal diet plus 0.75 ml (1.5 mg) EB per pig at 3-days intervals by intramuscular injection (EB). The serum estradiol (E2 ), the final and the increased vulvar area, uterine index, thickness of the myometrium and endometrium, and protein expression of heat shock protein 70 (HSP70) in ZEA group were higher than those in the control group (p < .05), but lower than those in the EB group (p < .05). The serum luteinizing hormone in ZEA group was lower than that of the control group (p < .05), but higher than that in the EB group (p < .05). Higher serum follicle-stimulating hormone and progesterone were observed in the ZEA and control groups than those in the EB group (p < .05). The serum glutathione peroxidase activity in the ZEA group was lower than that in the control and EB groups (p < .001), and the malondialdehyde in the ZEA group was higher than that in the control and EB groups (p < .001). Moreover, the relative mRNA and protein expression of growth hormone receptor (GHR) and relative mRNA expression of HSP70 in the ZEA and EB groups were higher than those in the control group (p < .05). In conclusion, both ZEA (1.0 mg/kg) and EB (1.5 mg at 3 days intervals by intramuscular injection) stimulated vulvar swelling and uterine hypertrophy by disordering serum hormones and up-regulating GHR expression, and induced stress by different mechanisms in this study. Furthermore, the observed up-regulating HSP70 expression challenged by ZEA or EB may be part of the mechanism to resist stress injury.


Assuntos
Estradiol/análogos & derivados , Maturidade Sexual/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Suínos/crescimento & desenvolvimento , Zearalenona/toxicidade , Ração Animal/análise , Animais , Dieta/veterinária , Estradiol/toxicidade , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Vulva/anatomia & histologia , Vulva/efeitos dos fármacos
16.
Neurosci Lett ; 712: 134474, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31479724

RESUMO

Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17ß-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERß or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -ß (ERß) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERß, while activation of ERα, -ß and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance.


Assuntos
Adenosina Trifosfatases/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Hipocampo/metabolismo , Pirofosfatases/metabolismo , Sinaptossomos/metabolismo , Animais , Estradiol/análogos & derivados , Estradiol/farmacologia , Receptor alfa de Estrogênio/agonistas , Receptor beta de Estrogênio/agonistas , Fulvestranto/farmacologia , Ginsenosídeos/farmacologia , Masculino , Nitrilas/farmacologia , Ratos , Sapogeninas/farmacologia , Sinaptossomos/efeitos dos fármacos
17.
Clin Chem ; 65(10): 1276-1286, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31492715

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor with variable prognosis even within the same tumor stage. Cancer-related sex hormones and their sulfated metabolites in body fluids can be used as tumor markers. The role of steroid sulfation in ACC has not yet been studied. MALDI mass spectrometry imaging (MALDI-MSI) is a novel tool for tissue-based chemical phenotyping. METHODS: We performed phenotyping of formalin-fixed, paraffin-embedded tissue samples from 72 ACC by MALDI-MSI at a metabolomics level. RESULTS: Tumoral steroid hormone metabolites-estradiol sulfate [hazard ratio (HR) 0.26; 95% CI, 0.10-0.69; P = 0.005] and estrone 3-sulfate (HR 0.22; 95% CI, 0.07-0.63; P = 0.003)-were significantly associated with prognosis in Kaplan-Meier analyses and after multivariable adjustment for age, tumor stage, and sex (HR 0.29; 95% CI, 0.11-0.79; P = 0.015 and HR 0.30; 95% CI, 0.10-0.91; P = 0.033, respectively). Expression of sulfotransferase SULT2A1 was associated with prognosis to a similar extent and was validated to be a prognostic factor in two published data sets. We discovered the presence of estradiol-17ß 3,17-disulfate (E2S2) in a subset of tumors with particularly poor overall survival. Electron microscopy revealed novel membrane-delimited organelles in only these tumors. By applying cluster analyses of metabolomic data, 3 sulfation-related phenotypes exhibited specific metabolic features unrelated to steroid metabolism. CONCLUSIONS: MALDI-MSI provides novel insights into the pathophysiology of ACC. Steroid hormone sulfation may be used for prognostication and treatment stratification. Sulfation-related metabolic reprogramming may be of relevance also in conditions beyond the rare ACC and can be directly investigated by the use of MALDI-MSI.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/mortalidade , Biomarcadores Tumorais/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Esteroides/análise , Adolescente , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Criança , Estradiol/análogos & derivados , Estradiol/análise , Estradiol/metabolismo , Estrona/análogos & derivados , Estrona/análise , Estrona/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Esteroides/metabolismo , Sulfotransferases/metabolismo , Adulto Jovem
18.
Clin Oncol (R Coll Radiol) ; 31(11): e1-e9, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31543301

RESUMO

Although surgery and radiotherapy remain the most commonly used treatments for non-melanoma skin cancer, there are a variety of alternatives. Here we discuss the use of electrochemotherapy and ablative treatments and examine the evidence for their effectiveness against a number of non-melanoma skin cancers.


Assuntos
Eletroquimioterapia/métodos , Estradiol/análogos & derivados , Noretindrona/uso terapêutico , Neoplasias Cutâneas/terapia , Testosterona/análogos & derivados , Combinação de Medicamentos , Estradiol/farmacologia , Estradiol/uso terapêutico , Humanos , Noretindrona/farmacologia , Testosterona/farmacologia , Testosterona/uso terapêutico
19.
J Anim Sci ; 97(11): 4371-4385, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31541251

RESUMO

Predominately Angus steers (n = 24; initial BW = 435 ± 28.3 kg) were used to evaluate non-coated (NC) and coated implants (CI) containing equal amounts of trenbolone acetate (TBA; 200 mg) and estradiol benzoate (EB; 28 mg) in finishing steers on sera metabolite responses, gene expression, and immunohistochemical analyses of the Longissimus muscle (LM). Performance data were analyzed as a randomized complete block design, and all other data were analyzed as repeated measures for a completely randomized design. Treatments were no implant (NI), NC (Synovex-PLUS; Zoetis, Parsippany, NJ), and CI (Synovex-One Feedlot) implant. There were 2 pen replicates per treatment (n = 4 steers/pen). LM biopsies, blood, and BW were collected before feeding on days 0, 14, 28, 56, 84, 112, and 133, with final BW being captured on day 140. Genes of interest were determined by RT-qPCR using two housekeeping genes. Sera was analyzed for estradiol-17ß (E2),17ß-trenbolone (TbOH), insulin-like growth factor 1 (IGF-I), NEFA, and urea-N (SUN). An α of 0.10 determined significance for performance and sera data; α of 0.05 was used for gene and histology data. No performance differences (P ≥ 0.10) were detected. An implant × day interaction (P ≤ 0.10) for E2, IGF-I, and SUN was detected; implants elevated (P ≤ 0.10) E2, 17ß-TbOH, and IGF-I; and decreased SUN across day of the study, meaning sera metabolites are not altered with time on feed. An implant × day interaction was detected for myogenic factor 5 (MYF-5) positive cells and proportions of MHCIIX. In LM, CI had greater (P < 0.10) IGF-I in LM over NI. CI increased (P < 0.05) G protein-coupled estrogen receptor 1 (GPER1) expression, as well as, GPER1 semi-quantitative scores over NI and NC. An implant × day interaction (P ≤ 0.05) for estrogen and androgen receptor-positive nuclei was detected; implants had increased (P ≤ 0.05) estrogen and androgen receptor-positive nuclei compared to NI. CIs increase genes associated with muscle tissue growth.


Assuntos
Anabolizantes/administração & dosagem , Bovinos/fisiologia , Estradiol/análogos & derivados , Esteroides/administração & dosagem , Acetato de Trembolona/administração & dosagem , Anabolizantes/sangue , Ração Animal , Animais , Bovinos/sangue , Dieta/veterinária , Implantes de Medicamento/administração & dosagem , Ingestão de Alimentos , Estradiol/administração & dosagem , Estradiol/sangue , Imuno-Histoquímica/veterinária , Fator de Crescimento Insulin-Like I/análise , Masculino , Músculo Esquelético/metabolismo , Distribuição Aleatória , Carne Vermelha/análise , Acetato de Trembolona/sangue
20.
Anim Reprod Sci ; 209: 106141, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31514931

RESUMO

This study aimed to minimize the number of times cattle need to be confined during protocols for TAI in beef cows treated for induction of ovulation with EB at the time of P4 device removal (P4r). In Experiment 1, cows were treated with P4 plus EB (Day 0; AM) and were allocated to one of three groups at P4r: EB8.5, EB at P4r on Day 8.5 (PM; three confinements); EB9, EB 24 h after P4r on Day 8 (AM; four confinements) and EC8, EC at P4r on Day 8 (AM; positive control; three confinements). At P4r, cows were treated with PGF2a plus eCG. Ultrasonography was performed from D8 to D12. The interval from P4r to ovulation was less in the EB8.5 compared to EB9 and EC8 group. There was no difference in the ovulation rate between groups. The variability of ovulation was greater in the EB8.5 and EC8 compared to EB9 group. In Experiment 2, cows of EC8 and EB9 groups were submitted to TAI 48 to 52 h (AM) or 54 to 58 h (PM) after P4r (D10). Cows of the EB8.5 group were submitted to TAI 38 to 42 h (AM) or 44 to 48 h (PM) after P4r (D10). There was no interaction between treatments and timing of AI and no treatment effect and timing of AI on P/AI. In conclusion, the delay compared to what typically occurs by 10 h of P4r concomitant with EB administration (Day 8.5) reduced the frequency of animal confinement for the TAI protocol without affecting the reproductive efficiency and the flexibility to perform the TAI in suckled beef cows.


Assuntos
Bovinos , Remoção de Dispositivo , Estradiol/análogos & derivados , Inseminação Artificial , Dispositivos Intrauterinos Medicados , Indução da Ovulação , Animais , Remoção de Dispositivo/veterinária , Estradiol/farmacologia , Sincronização do Estro/métodos , Feminino , Fertilidade/efeitos dos fármacos , Inseminação Artificial/veterinária , Dispositivos Intrauterinos Medicados/veterinária , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Indução da Ovulação/métodos , Indução da Ovulação/veterinária , Gravidez , Progesterona/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...