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1.
Ann Agric Environ Med ; 27(3): 394-400, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955221

RESUMO

INTRODUCTION: Overweight and obesity, as well as a gonadal function, are pivotal factors influencing bone tissue metabolism. MATERIAL AND METHODS: The aim of the study was to determine the effect of dietary induced obesity (DIO) on bone tissue metabolism in sham-operated (SHO) or ovariectomized (OVX) adult female Wistar rats. Additionally, the influence of DIO in SHO or OVX on the concentration of sclerostin in the blood serum was analyzed. After SHO or OVX, the rats were placed in groups (n=8) and either received a standard diet (11.5 MJ/kg) (SHO-CON; OVX-CON) or a high-energy diet (17.6 MJ/kg) (SHO-FAT; OVX-FAT). The experiment lasted for 90 days and allowed for the establishment of osteopenia in OVX females and obesity in the rats that had received the high-energy diet. RESULTS: The results of the study demonstrate that obesity or/and ovariectomy increases the resorption of femora and tibiae, hence decreasing the densitometric and mechanical parameters affecting the bone structure in adult females rats. The strongest osteodegenerative effect was seen in the OVX-FAT females. Interestingly, the degree of bone tissue degradation caused exclusively by ovariectomy was similar to that found in the obese sham-operated rats. CONCLUSIONS: Bone losses invoked by DIO seem to be independent from the Wnt/ß-catenin pathway inhibition induced by sclerostin. While further study is necessary, the obtained results suggest that the usage of sclerostin anti-body in the treatment of osteoporosis can be ineffective, and in obese patients the undertaking of such therapy should be reassessed.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Osso e Ossos/metabolismo , Dieta/efeitos adversos , Obesidade/complicações , Ovariectomia/efeitos adversos , Via de Sinalização Wnt , Animais , Reabsorção Óssea , Feminino , Marcadores Genéticos , Humanos , Obesidade/etiologia , Ratos , Ratos Wistar
2.
Rev Assoc Med Bras (1992) ; 66(8): 1134-1138, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32935810

RESUMO

Women with mutations in the BRCA 1 and 2 genes are at increased risk for ovarian and breast cancer and therefore candidates for risk-reducing surgery, including salpingo-oophorectomy and mastectomy. Risk-reducing salpingo-oophorectomy (RRSO) is considered the most effective prophylactic measure for ovarian cancer prevention in this group of patients. This procedure involves loss of ovarian function and induced menopause. Estrogen therapy is the most effective treatment for controlling vasomotor symptoms and improving the quality of life of climacteric women. However, the potential hormonal stimulation of these tumors and the risk of breast cancer are a concern regarding the safety of hormone replacement therapy (HRT) in this population. This article aims to review the current evidence regarding the potential benefits and safety of HRT after RRSO.


Assuntos
Neoplasias da Mama , Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama/terapia , Feminino , Humanos , Mastectomia , Mutação , Neoplasias Ovarianas , Ovariectomia , Qualidade de Vida , Fatores de Risco , Salpingo-Ooforectomia
3.
Life Sci ; 258: 118030, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739470

RESUMO

The risk of atherosclerosis (AS) ascends among post-menopausal women, while current hormone replacement therapy exerts several adverse effects. Alisol B 23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, was reported to show multiple physiological activities, including regulating lipid metabolism. According to molecular docking analysis, it was predicted to bind with estrogen receptor α (ERα). In this study, we aimed to observe the effect of AB23A on preventing post-menopausal AS and explore whether the mechanism was mediated by ERα. In vitro, free fatty acid (FFA) was applied to induce the abnormal lipid metabolism of L02 cells. In vivo, the ApoE-/- mice were ovariectomized to mimic the cessation of estrogen. The high-fat diet was also given to induce post-menopausal AS. We demonstrated AB23A attenuated the accumulation of total cholesterol and triglyceride induced by free fatty acids in hepatocytes. In high-fat diet-ovariectomy-treated ApoE-/- mice, AB23A eliminated lipids in blood and liver. AB23A not only reduced the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) through sterol-regulatory element binding proteins (SREBPs) but also suppressed the secretion of PCSK9 through silent information regulator 1 (SIRT1). Notably, AB23A promoted the expression of ERα in vivo and in vitro. The both ERα inhibitor and ERα siRNA were also applied in confirming whether the hepatic protective effect of AB23A was mediated by ERα. We found that AB23A significantly promoted the expression of ERα. AB23A could inhibit the synthesis and secretion of PCSK9 through ERα, lower the accumulation of triglyceride and cholesterol, and prevent post-menopausal AS.


Assuntos
Aterosclerose/patologia , Colestenonas/farmacologia , Receptor alfa de Estrogênio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Animais , Aterosclerose/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colestenonas/química , Dieta Hiperlipídica , Ácidos Graxos/metabolismo , Feminino , Lipoproteínas LDL/metabolismo , Camundongos , Ovariectomia , Regiões Promotoras Genéticas/genética , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Sirtuína 1/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Regulação para Cima/efeitos dos fármacos
4.
Breast Cancer Res Treat ; 184(1): 249-254, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32772225

RESUMO

PURPOSE: The coronavirus disease (COVID-19) pandemic has had a profound impact on cancer care in the US Guidelines focused on the management of COVID-19, rather than healthcare needs of breast cancer patients requiring access to crucial services. This US survey of breast cancer survivors characterizes treatment delays early period in the pandemic. METHODS: We developed a survey and administered it to 609 adult breast cancer survivors in the US. We used snowball sampling with invitations distributed via social media. We used logistic regression to select a model of delay from a pool of independent variables including race, cancer stage, site of care, health insurance, and age. We used descriptive statistics to characterize delay types. RESULTS: Forty-four percent of participants reported cancer care treatment delays during the pandemic. Delays in all aspects of cancer care and treatment were reported. The only variable which had a significant effect was age (97 (.95, 99), p < 0.001) with younger respondents (M = 45.94, SD = 10.31) reporting a higher incidence of delays than older respondents (M = 48.98, SD = 11.10). There was no significant effect for race, insurance, site of care, or cancer stage. CONCLUSIONS: Our findings reveal a pervasive impact of COVID-19 on breast cancer care and a gap in disaster preparedness that leaves cancer survivors at risk for poor outcomes. Delays are critical to capture and characterize to help cancer providers and healthcare systems develop effective and patient-tailored processes and strategies to manage cases during the current pandemic wave, subsequent waves, and future disasters.


Assuntos
Neoplasias da Mama/terapia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Betacoronavirus , Neoplasias da Mama/diagnóstico por imagem , Assistência à Saúde , Diagnóstico por Imagem/estatística & dados numéricos , Feminino , Aconselhamento Genético/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Mamoplastia/estatística & dados numéricos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Ovariectomia/estatística & dados numéricos , Radioterapia/estatística & dados numéricos , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
5.
BMJ ; 370: m2614, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732303

RESUMO

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.


Assuntos
Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Modelos Logísticos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Calibragem , Tratamento Conservador , Neoplasias das Tubas Uterinas/terapia , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Ovariectomia , Estudos Prospectivos , Medição de Risco/métodos , Ultrassonografia , Adulto Jovem
6.
Nat Commun ; 11(1): 4278, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855388

RESUMO

Activation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell Akt signaling in those OPCs. Two lead compounds are discovered, YLL3 and YLL8, both of which increase osteoprogenitor osteogenic differentiation in vitro. When given to normal or osteopenic mice, the compounds increase mineral apposition rate, bone formation, bone mass, and bone strength, as well as expedite fracture repair through stimulated endogenous osteogenesis. When covalently conjugated to alendronate, YLLs acquire an additional function resulting in a "tri-functional" compound that: (i) binds to OPCs, (ii) targets bone, and (iii) induces "pro-survival" signal. These bone-targeted, osteogenic peptides are well suited for current tissue-specific therapeutic paradigms to augment the endogenous osteogenic cells for bone regeneration and the treatment of bone loss.


Assuntos
Anabolizantes/farmacologia , Fraturas Ósseas/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Peptídeos/farmacologia , Células-Tronco/efeitos dos fármacos , Anabolizantes/química , Animais , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Fraturas Ósseas/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Orquiectomia , Osteogênese/fisiologia , Ovariectomia , Peptídeos/química , Peptídeos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Técnicas de Síntese em Fase Sólida , Células-Tronco/citologia
7.
PLoS One ; 15(7): e0232507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645007

RESUMO

Sex-related differences in cardiovascular diseases are highly complex in humans and model-dependent in experimental laboratory animals. The objective of this work was to comprehensively investigate key sex differences in the response to acute and prolonged adrenergic stimulation in C57Bl/6NCrl mice. Cardiac function was assessed by trans-thoracic echocardiography before and after acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg) in 15 weeks old male and female C57Bl/6NCrl mice. Thereafter, prolonged adrenergic stimulation was achieved by sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days in male and female mice. Cardiac function and morphometry were assessed by trans-thoracic echocardiography on the 15th day. Thereafter, the mice were euthanized, and the hearts were collected. Histopathological analysis of myocardial tissue was performed after staining with hematoxylin & eosin, Masson's trichrome and MAC-2 antibody. Gene expression of remodeling and fibrotic markers was assessed by real-time PCR. Cardiac function and morphometry were also measured before and after isoproterenol 10 mg/kg/day for 14 days in groups of gonadectomized male and female mice and sham-operated controls. In the current work, there were no statistically significant differences in the positive inotropic and chronotropic effects of isoproterenol between male and female C57Bl/6NCrl. After prolonged adrenergic stimulation, there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, prolonged isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. The current work demonstrated lack of significant sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6NCrl mice. This study suggests that female sex may not be sufficient to protect the heart in this model of isoproterenol-induced cardiac dysfunction and underscores the notion that sexual dimorphism in cardiovascular diseases is highly model-dependent.


Assuntos
Cardiopatias/fisiopatologia , Caracteres Sexuais , Animais , Biomarcadores/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Isoproterenol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia
8.
Arterioscler Thromb Vasc Biol ; 40(9): 2143-2158, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640903

RESUMO

OBJECTIVE: ERα (estrogen receptor alpha) exerts nuclear genomic actions and also rapid membrane-initiated steroid signaling. The mutation of the cysteine 451 into alanine in vivo has recently revealed the key role of this ERα palmitoylation site on some vasculoprotective actions of 17ß-estradiol (E2) and fertility. Here, we studied the in vivo role of the arginine 260 of ERα which has also been described to be involved in its E2-induced rapid signaling with PI-3K (phosphoinositide 3-kinase) as well as G protein in cultured cell lines. Approach and Results: We generated a mouse model harboring a point mutation of the murine counterpart of this arginine into alanine (R264A-ERα). In contrast to the C451A-ERα, the R264A-ERα females are fertile with standard hormonal serum levels and normal control of hypothalamus-pituitary ovarian axis. Although R264A-ERα protein abundance was normal, the well-described membrane ERα-dependent actions of estradiol, such as the rapid dilation of mesenteric arteries and the acceleration of endothelial repair of carotid, were abrogated in R264A-ERα mice. In striking contrast, E2-regulated gene expression was highly preserved in the uterus and the aorta, revealing intact nuclear/genomic actions in response to E2. Consistently, 2 recognized nuclear ERα-dependent actions of E2, namely atheroma prevention and flow-mediated arterial remodeling were totally preserved. CONCLUSIONS: These data underline the exquisite role of arginine 264 of ERα for endothelial membrane-initiated steroid signaling effects of E2 but not for nuclear/genomic actions. This provides the first model of fertile mouse with no overt endocrine abnormalities with specific loss-of-function of rapid ERα signaling in vascular functions.


Assuntos
Lesões das Artérias Carótidas/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Estradiol/farmacologia , Receptor alfa de Estrogênio/agonistas , Terapia de Reposição de Estrogênios , Estrogênios/farmacologia , Fertilidade/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Mutação Puntual , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Ativação Enzimática , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismo , Ovariectomia , Reepitelização/efeitos dos fármacos , Transdução de Sinais , Fatores de Tempo , Útero/efeitos dos fármacos , Útero/metabolismo , Remodelação Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
9.
Life Sci ; 257: 118138, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712298

RESUMO

AIMS: Hypertension is a relevant sex and sex hormones-dependent risk factor where the cardiovascular and renal health of the population are concerned. Men experience greater losses of renal function (RF) than women, but the mechanisms remain somewhat unclear. Our goal was to evaluate the relationship between oxidative stress (OS), angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activities and RF in male and female SHR. MAIN METHODS: Twelve-week-old spontaneously hypertensive rats (SHR) were submitted to either castration or SHAM surgery and divided into 4 groups, SHAM or Castrated (CAST) males or females. After 51 days we evaluated RF (inulin and sodium para-aminohippurate), ACE and ACE2 activities (fluorimetry), OS (flow cytometry), collagen deposition (picrosirius red) and protein expression (western blot). KEY FINDINGS: Males presented lower RF than females and castration impaired this parameter in both groups. Sexual dimorphism was not observed regarding OS and inflammation; however, castration increased this parameter more severely in males than in females. SHAM males exhibited higher collagen deposition than females, though castration increased it in both sexes, eliminating the difference. We found sexual dimorphism regarding renal ACE and ACE2 activities, which were lower in males than in females. Although castration did not alter ACE activity, it reduced ACE2 activity in females and increased it in males. SIGNIFICANCE: These results indicate that sex hormones affect RF in SHR. As alterations in the oxidative system were capable of promoting podocyte injury, inflammation, and collagen deposition, we put forward that these effects are differently modulated by ACE and ACE2.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Nefropatias/etiologia , Estresse Oxidativo , Peptidil Dipeptidase A/metabolismo , Ratos Endogâmicos SHR/metabolismo , Animais , Western Blotting , Colágeno/metabolismo , Feminino , Rim/enzimologia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Orquiectomia , Ovariectomia , Estresse Oxidativo/fisiologia , Ratos , Ratos Endogâmicos SHR/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fatores Sexuais
10.
Surg Today ; 50(10): 1206-1212, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32656700

RESUMO

PURPOSE: Rectovaginal fistula (RVF) is a complicated and troublesome complication of low anterior resection (LAR) for rectal cancer. We aimed to investigate the risk factors for post-LAR RVF and develop a predictive nomogram. METHODS: We performed a retrospective analysis of 821 female patients with rectal cancer who underwent LAR between October 2010 and October 2018. Logistic regression was performed to identify risk factors. A nomogram was developed to predict RVF. RESULTS: The incidence of post-LAR RVF was 3.4% (28/821). A multivariate analysis showed that the preoperative serum hemoglobin level (OR 2.449, 95% CI 1.144-5.239), the distance between the tumor and anal verge (OR 4.158, 95% CI 1.392-12.418), surgical procedure (OR 2.369, 95% CI 1.117-5.027), hysterectomy (OR 2.996, 95% CI 1.106-8.833), and bilateral oophorectomy (OR 5.823, 95% CI 1.639-20.689) were significantly associated with the development of RVF. A nomogram was developed, which showed a C-index of 0.824 (95% CI 0.730-0.918) and an adjusted C-index of 0.790. CONCLUSION: This study identified the preoperative serum hemoglobin level, the distance between the tumor and the anal verge, the type of surgical procedure, hysterectomy, and bilateral oophorectomy as predictors of post-LAR RVF. A nomogram was successfully developed. It could aid in the prediction of RVF in patients undergoing LAR.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Nomogramas , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Fístula Retovaginal/epidemiologia , Idoso , Canal Anal/patologia , Feminino , Hemoglobinas , Humanos , Histerectomia , Modelos Logísticos , Pessoa de Meia-Idade , Ovariectomia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Fístula Retovaginal/etiologia , Estudos Retrospectivos , Fatores de Risco
11.
Medicine (Baltimore) ; 99(29): e21127, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702865

RESUMO

RATIONALE: Advanced stage ovarian cancer is rarely encountered in pregnant women, due to the high number of ultrasound imagistic studies performed during this period. The clinical course of patients diagnosed with advanced stage ovarian cancer is similar in pregnant and nonpregnant women. PATIENT CONCERNS: We present the case of a 27-year-old woman initially submitted to emergency surgery for ovarian cyst torsion in the ninth week of gestation, at that moment ovarian cystectomy being performed. DIAGNOSES: The histopathological studies demonstrated the presence of a moderately differentiated epithelial ovarian cancer. INTERVENTIONS: Although the interdisciplinary team decided for staging surgery followed by platinum-based chemotherapy beginning from the second trimester of pregnancy, both the patient and her family refused this strategy and opined for total hysterectomy en bloc with bilateral adnexectomy. Surprisingly, intraoperatively both ovaries had a tumoral aspect, whereas peritoneal carcinomatosis nodules were found in the Douglas pouch. Therefore, the neoplastic process was staged as a IIIC epithelial ovarian cancer, a total hysterectomy with bilateral adnexectomy, Douglas pouch peritonectomy, omentectomy, pelvic and para-aortic lymph node dissection being performed. OUTCOMES: The patient was discharged in the sixth postoperative day and was confined to the oncology service in order to be submitted to the standard taxanes and platinum based chemotherapy. LESSONS: Although ovarian cancer has been rarely reported during pregnancy, this diagnostic should be taken in consideration whenever persistent adnexal masses are encountered.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Ovarianas/cirurgia , Adulto , Feminino , Humanos , Histerectomia/métodos , Linfonodos/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Ovariectomia/métodos , Ovário/patologia , Gravidez , Segundo Trimestre da Gravidez , Romênia
12.
Int. j. morphol ; 38(3): 683-688, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098307

RESUMO

The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.


El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.


Assuntos
Animais , Feminino , Ratos , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Alendronato/administração & dosagem , Gengiva/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/complicações , Ovariectomia , Ratos Wistar , Difosfonatos/administração & dosagem
13.
Am J Orthod Dentofacial Orthop ; 158(2): 247-263.e1, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32507529

RESUMO

INTRODUCTION: This study aimed to investigate the effects of estrogen on root repair after orthodontically induced root resorption. METHODS: Seventy-two 6-week-old female Wistar rats were randomly divided into 3 groups: ovariectomy only (OVX), ovariectomy plus estradiol injection (OVX + E2), and sham operation (control). E2 was administrated to all the experimental animals after the establishment of the root repair model. One-way analysis of variance with the Tukey post-hoc test was used to analyze the experimental results. RESULTS: Micro-computed tomography and hematoxylin and eosin staining showed that the total volumes of resorption lacunae were significantly smaller in the control and OVX + E2 groups than those in the OVX group. Alkaline phosphatase and tartrate-resistant acid phosphatase stainings suggested that the cementoblastic activities and the amount of new cementum formation were inhibited while the activities of osteoclasts were obvious in the OVX group. The immunohistochemistry stainings revealed that the osteoprotegerin to receptor activator of nuclear factor-кB ligand ratio and the phosphorylated extracellular signal-regulated kinases to extracellular signal-regulated kinases ratio of the control and OVX + E2 groups were significantly greater than those of the OVX group. CONCLUSIONS: These findings demonstrated that estrogen administration might be a solution to reduce orthodontically induced root resorption through the activation of extracellular signal-regulated kinase-1/2 pathway and enhancement of cementogenesis.


Assuntos
Reabsorção da Raiz , Animais , Estrogênios , Feminino , Osteoclastos , Ovariectomia , Ratos , Ratos Wistar , Microtomografia por Raio-X
14.
Life Sci ; 256: 117975, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32565251

RESUMO

Our goal is to understand how loss of circulating estrogens and estrogen replacement affect brain physiology and function, particularly in brain regions involved in cognitive processes. We recently conducted a large metabolomics study characterizing the effects of rodent models of menopause and treatment with estrogen receptor (ER) agonists on neurochemical targets in hippocampus, frontal cortex, and striatum. Here we characterize effects on levels of several key enzymes involved in glucose utilization and energy production, specifically phosphofructokinase, glyceraldehyde 3-phosphate dehydrogenase, and pyruvate dehydrogenase. We also evaluated effects on levels of ß-actin and α-tubulin, choline acetyltransferase (ChAT) activity, and levels of ATP citrate lyase. All experiments were conducted in young adult rats. Experiment 1 compared the effects of ovariectomy (OVX), a model of surgical menopause, and 4-vinylcyclohexene diepoxide (VCD)-treatments, a model of transitional menopause, with tissues collected at proestrus and at diestrus. Experiment 2 used a separate cohort of rats to evaluate the same targets in OVX and VCD-treated rats treated with estradiol or with selective ER agonists. Differences in the expression of metabolic enzymes between cycling animals and models of surgical and transitional menopause were detected. These differences were model-, region- and time- dependent, and were modulated by selective ER agonists. Collectively, the findings demonstrate that loss of ovarian function and ER agonist treatments have differing effects in OVX vs. VCD-treated rats. Differences may help to explain differences in the effects of estrogen treatments on brain function and cognition in women who have experienced surgical vs. transitional menopause.


Assuntos
Acetilcoenzima A/metabolismo , Encéfalo/metabolismo , Colina O-Acetiltransferase/metabolismo , Estrogênios/farmacologia , Menopausa/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Cicloexenos/toxicidade , Estradiol/sangue , Feminino , Menopausa/efeitos dos fármacos , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Compostos de Vinila/toxicidade
15.
Life Sci ; 256: 118012, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593710

RESUMO

AIMS: Bisphenol (BP)-A exposure can impair glucose and lipid metabolism. However, it is unclear whether this endocrine disruptor (ED) modulates these processes in postmenopause, a period with organic changes that increase the risk for metabolic diseases. Herein, we evaluated the effects of BPA exposure on adiposity, glucose homeostasis and hepatic steatosis in ovariectomized (OVX) mice fed on a high-fat diet (HFD). MAIN METHODS: Adult Swiss female mice were OVX and submitted to a normolipidic diet or HFD and drinking water without [control (OVX CTL) and OVX HFD groups, respectively] or with 1 µg/mL BPA (OVX CBPA and OVX HBPA groups, respectively), for 3 months. KEY FINDINGS: OVX HFD females displayed increased adiposity, glucose intolerance, insulin resistance and moderate hepatic steatosis. This effect was associated with a high hepatic expression of genes involved in lipogenesis (Srebf1 and Scd1), ß-oxidation (Cpt1a) and endoplasmic reticulum (ER) stress (Hspa5 and Hyou1). BPA did not alter adiposity or glucose homeostasis disruptions induced by HFD. However, this ED triggered severe steatosis, exacerbating hepatic fat and collagen depositions in OVX HBPA, in association with a reduction in Mttp mRNA, and up-regulation of genes involved in ß-oxidation (Acox1 and Acadvl), mitochondrial uncoupling (Ucp2), ER stress (Hyou1 and Atf6) and chronic liver injury (Tgfb1and Casp8). Furthermore, BPA caused mild steatosis in OVX CBPA females, increasing the hepatic total lipids and mRNAs for Srebf1, Scd1, Hspa5, Hyou1 and Atf6. SIGNIFICANCE: BPA aggravated hepatic steatosis in OVX mice. Especially when combined with a HFD, BPA caused NAFLD progression, which was partly mediated by chronic ER stress and the TGF-ß1 pathway.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Fenóis/toxicidade , Adiposidade/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Progressão da Doença , Feminino , Glucose/metabolismo , Resistência à Insulina , Lipogênese/efeitos dos fármacos , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Ovariectomia
16.
Ann Agric Environ Med ; 27(2): 219-224, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32588596

RESUMO

INTRODUCTION: Osteoporosis, the "quiet epidemic", is one of the most serious threats to public health. It is known that estrogen plays a significant role in the regulation of bone turnover, and its loss at menopause causes osteoporosis. Added to this, insufficient calcium intake accelerates bone mass loss, increasing the risk of fractures. OBJECTIVE: The study aimed to answer the question whether a fructan-enriched diet could be helpful in preventing from disturbances in bone turnover caused by calcium restriction combined with ovariectomy-induced estrogen deficiency. The differences related to the kind of fructan and 'matrix effect' of fructan action (form of addition) were also evaluated. MATERIAL AND METHODS: The study was conducted using sham-operated (control groups) or ovariectomized (OVX) rats fed a calcium restricted diet. The treatment diets contained one of three fructan sources - Jerusalem artichoke, yacon and Beneo Orafti Synergy1 - added alone or as an ingredient of strawberry sorbet, all in the amount providing 8% fructans. Analyses of biological material included: serum Ca, Mg and P concentrations, alkaline phosphatase activity (ALP), osteocalcin (OC) and C-telopeptide degradation products from type I collagen (CTX). Densitometric parameters of femora were also assayed. RESULTS: Among markers of bone turnover, the ALP activity depended both on the kind of fructan and the form of addition. The highest value was shown in the OVX group fed a low-calcium diet, whereas administration of diet enriched with Jerusalem artichoke led to an almost 50% decrease in the value of this parameter. Dietary fructans also lowered the OC level. Feeding rats with diet containing sorbet enriched in yacon or Jerusalem artichoke resulted in a decrease of CTX, compared to the diet containing yacon alone or fructan formulation in both forms No significant differences were observed in densitometric parameters between treatment groups. CONCLUSIONS: The obtained findings suggest that fructan administration with a calcium-restricted diet might exert a positive effect on bone turnover parameters. Regarding the form of their addition, it is possible that other constituents of sorbets contributed to the fructan action. It remains open whether this impact would be significant over a longer period of time.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Cálcio/deficiência , Fêmur/efeitos dos fármacos , Frutanos/metabolismo , Osteoporose/prevenção & controle , Ovariectomia , Ração Animal/análise , Animais , Cálcio/administração & dosagem , Cálcio na Dieta/administração & dosagem , Dieta , Suplementos Nutricionais/análise , Feminino , Frutanos/administração & dosagem , Ratos , Ratos Wistar
17.
Ceska Gynekol ; 85(1): 49-58, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32414285

RESUMO

INTRODUCTION: An ovarian cancer prevention program must encourage the application of factors associated with decreased risk that include both surgical and non-surgical approaches. Non-surgical preventive approaches include oral contraceptives, parity, multiparity and breastfeeding. In addition, approaches that decrease inflammation and oxidative stress such as regular exercise and a healthy diet are also important. Surgical approaches include tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy. OBJECTIVE: To highlight protective approaches for the prevention of ovarian cancer in order to increase awareness among women of the general population and too find out whether or not these approaches are enough to prevent the disease. DESIGN: Review article. SETTING: Department of Chemical Pathology, NHLS, Tygerberg Hospital and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. METHODS: Literary sources related to the topic were used. Articles were selected primarily based on PubMed and Google searches. CONCLUSION: Ovarian cancer cannot be prevented completely, however the application of preventive approaches may decrease the risk significantly. Although, multiparity followed by long periods of breastfeeding may not seem feasible for most today women, it is the most pronounced preventive approach for women in the general population. Tubal ligation, hysterectomy also reduce the risk significantly. Opportunistic salpingectomy may provide better prevention for women at average risk, while women at high risk (BRCA mutation and family with history of ovarian cancer) are advised to undergo risk-reducing salpingo-oophorectomy. Highlighting these approaches may increase women's awareness towards decreasing risk and decrease the incidence of ovarian cancer and potentially increase the five-year survival rate.


Assuntos
Carcinoma Epitelial do Ovário/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , Ovariectomia , Procedimentos Cirúrgicos Profiláticos/métodos , Salpingo-Ooforectomia , Feminino , Humanos , Gravidez , Salpingectomia
18.
Rev Assoc Med Bras (1992) ; 66(2): 174-179, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428152

RESUMO

OBJECTIVE: Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS: Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17ß-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS: We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS: Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.


Assuntos
Colo do Útero/efeitos dos fármacos , Estrogênios/farmacologia , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Colo do Útero/patologia , Epitélio/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Antígeno Ki-67/análise , Membrana Mucosa/efeitos dos fármacos , Ovariectomia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/análise
19.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 57(2): e162109, mai. 2020. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1122173

RESUMO

This survey evaluated mombin leaves (Spondias mombin L.) decoction efficiency as an antiseptic during post-surgery period on cats submitted to orchiectomy and ovariosalpingohisterectomy. For this purpose, 45 castrated mongrels cats were divided into three groups, the first group as a positive control using 0.5% chlorhexidine-alcohol solution, the second a negative control group using sterile distilled water and, finally, the test group using mombin leaves decocted with a concentration of 100 mg/mL. All animals, independent of age and sex, had visibly healed in most cases in a similar time. Animals treated with mombin leaves decoction presented a significant reduction of bacterial growth. In addition, the animals treated in the test group had better surgical wound healing. All isolated bacterial strains presented inhibition halo for chlorhexidine and for Spondias mombin L. Thus, the decoction of Spondias mombin L. leaves proved antiseptic efficacy in the surgical wounds of cats submitted to orchiectomy and ovariosalpingohisterectomy.(AU)


Foi avaliada a eficiência do decocto das folhas de cajá (Spondias mombin L.) como antisséptico no pós-cirúrgico de gatos submetidos à orquiectomia e ovariosalpingohisterectomia. Para tal, foram submetidos à castração 45 gatos sem raça definida, divididos em três grupos. O primeiro grupo como controle positivo com Solução Alcoólica de Clorexidine a 0,5%; segundo grupo controle negativo com água destilada estéril; e o grupo teste com o decocto de cajá à concentração de 100 mg/mL. Todos os animais, independentemente da idade e sexo, tiveram cicatrização visível em tempo similar. Animais tratados com o decocto apresentaram uma redução significativa do crescimento bacteriano. Além disso, observou-se uma melhor cicatrização das feridas cirúrgicas dos animais tratados no grupo teste. Todas as estirpes bacterianas isoladas apresentaram halo de inibição para clorexidine e para Spondias mombin L. Portanto, o decocto das folhas da Spondias mombin L. apresentou eficácia antisséptica nas feridas cirúrgicas de gatos submetidos à orquiectomia e ovariosalpingohisterectomia.(AU)


Assuntos
Animais , Gatos , Castração/veterinária , Anacardiaceae , Anti-Infecciosos Locais/uso terapêutico , Plantas Medicinais , Infecção da Ferida Cirúrgica/prevenção & controle , Orquiectomia/veterinária , Ovariectomia/veterinária , Histerectomia/veterinária
20.
J Bone Miner Metab ; 38(5): 648-657, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350616

RESUMO

INTRODUCTION: Lactoferrin has recently been reported for its potent bone growth effects. However, the effects of lactoferrin on the healing process of fragility fracture have not yet been studied, so the purpose of this study is to investigate whether oral administration of lactoferrin can promote the fracture healing in an OVX animal model. MATERIALS AND METHODS: Three months after bilateral ovariectomy, all rats underwent unilateral tibial osteotomy and were then randomly divided into control group and bovine lactoferrin (bLF) group. At 4 and 8 weeks post-fracture, animals were sacrificed, and the fractured tibiae and serum samples were collected for evaluation. RESULTS: Our results showed that bLF treatment not only accelerated the bone growth at an early stage of OPF healing but also shortened the remolding process of OPF healing. When compared to control group, bLF treatment induced a significant rise in callus BMD (by 35.0% at 4 weeks and by 39.7% at 8 weeks; both p < 0.05) consistent with enhanced biomechanical strength of the callus, with ultimate force increased by 3.39-fold at 4 weeks (p < 0.05) and 1.95-fold at 8 weeks (p < 0.05). Besides, bLF administration resulted in a substantial increase in serum levels of BALP and a significant decrease in serum levels of TRAP 5b and TNF-α. Moreover, both the RANKL/OPG mRNA ratio and the expression of TNF-α in the callus of bLF-treated group were markedly lower than those in the control group. CONCLUSIONS: At a dose of 85mg/kg/day orally administrated bLF potently promoted the bone healing following tibial fracture in OVX rats.


Assuntos
Consolidação da Fratura/efeitos dos fármacos , Lactoferrina/administração & dosagem , Lactoferrina/farmacologia , Ovariectomia , Absorciometria de Fóton , Administração Oral , Fosfatase Alcalina/sangue , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologia , Feminino , Humanos , Lactoferrina/sangue , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a Tartarato/sangue , Tíbia/efeitos dos fármacos , Tíbia/patologia , Fator de Necrose Tumoral alfa/sangue , Microtomografia por Raio-X
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