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1.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479877

RESUMO

To discuss (1) the significance of seropositivity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and (2) clinical decision making in oophorectomy resistant disease. Patient A (a 35-year-old woman) had high CSF and serum anti-NMDA antibody titres, a complicated hospital course, little improvement with first and second-line therapies, and remained with high CSF and serum antibody titres despite unilateral oophorectomy, requiring a nearly 13-month long hospitalisation. Conversely, patient B (a 29-year-old woman) had low CSF titres, seronegative disease and quickly recovered to her baseline with first line therapies and oophorectomy. Anti-NMDAR antibodies are themselves pathological, causing signalling dysfunction and internalisation of the NMDAR. Seropositivity with anti-NMDAR antibodies likely reflects leakage from the blood-brain barrier, with high serum titres being a downstream effect of high CSF titres. Empiric bilateral oophorectomies is controversial but appropriate on a case-by-case basis in extremely treatment-resistant NMDAR encephalitis given the possibility of antigenic microteratomas, which may not be detected on imaging or even bilateral ovarian biopsies.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Adulto , Autoanticorpos , Diagnóstico por Imagem , Feminino , Humanos , Ovariectomia , Receptores de N-Metil-D-Aspartato
2.
Nat Commun ; 12(1): 4974, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404802

RESUMO

Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important 'signaling node' in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. Our transcriptomic analyses coupled with CRISPR/Cas9 genetic deletion identify Elmo1 associated regulators of osteoclast function, including cathepsin G and myeloperoxidase. Further, we define the 'ELMO1 interactome' in osteoclasts via proteomics and reveal proteins required for bone degradation. ELMO1 also contributes to osteoclast sealing zone on bone-like surfaces and distribution of osteoclast-specific proteases. Finally, a 3D structure-based ELMO1 inhibitory peptide reduces bone resorption in wild type osteoclasts. Collectively, we identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to osteoporosis and arthritis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doenças Ósseas Metabólicas/metabolismo , Osteoclastos/metabolismo , Osteoporose/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Animais , Artrite/patologia , Reabsorção Óssea/metabolismo , Sistemas CRISPR-Cas , Feminino , Camundongos , Camundongos Knockout , Osteoprotegerina/deficiência , Ovariectomia , Transcriptoma , Microtomografia por Raio-X
3.
Ned Tijdschr Geneeskd ; 1652021 06 29.
Artigo em Holandês | MEDLINE | ID: mdl-34346601

RESUMO

Prophylactic salpingo-oophorectomy (PSO) can be offered to all patients suffering from colorectal cancer to prevent ovarian metastasis (OM). Arguments to offer PSO are given for discussion: 1. PSO for colorectal cancer is mentioned in various guidelines, 2. Other disciplines such as gynecology and urology, offer or routinely perform PSO during abdominal surgery, 3. A better prognosis could be achieved, 4. It has been shown that systemic therapy has limited effects on OM, since ovaria are considered to be 'sanctuary sites', 5. In postmenopausal women negative side effects of PSO are expected to be very low, 6. PSO for prevention of OM is thought to be a cost effective oncological procedure, 7. Reducing the risk of the occurrence of primary ovarian cancer could be a positive side effect, and 8. It is part of 'shared decision making'.


Assuntos
Neoplasias Colorretais , Neoplasias Ovarianas , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Neoplasias Ovarianas/prevenção & controle , Ovariectomia , Salpingo-Ooforectomia
4.
Nutrients ; 13(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34371845

RESUMO

Because the world's population is deficient in dietary calcium, it is important to search for new sources of this essential mineral for the bones and the entire body. One of the innovative foods that could act as such a source is pumpkin enriched with calcium lactate by means of osmotic dehydration. Providing the body with easily absorbable calcium may have beneficial effects on the reconstruction of bone tissue. Postmenopausal osteoporosis is associated with body weight and fat mass gain, and the aim of the present study was to evaluate the effect of consuming enriched pumpkin on the levels of adipokines and cytokines produced by the adipose tissue. This study was conducted on 12-month-old female Wistar rats that received nutritional intervention for 12 weeks. After termination of the rats, the levels of leptin, adiponectin, interleukin 31 and interleukin 33 in serum and adipose tissue were determined, and the femurs were examined histopathologically. It was demonstrated that calcium-enriched pumpkin reduced bone marrow femoral adipocytes and also markedly decreased serum leptin levels in groups of rats after ovariectomy, which was associated with a decrease of fat content. Additionally, it seems that calcium-enriched pumpkin may reduce body weight gain often observed after menopause.


Assuntos
Cálcio na Dieta/administração & dosagem , Cucurbita , Alimentos Fortificados , Leptina/sangue , Osteoporose Pós-Menopausa/dietoterapia , Adiponectina/sangue , Tecido Adiposo/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Interleucinas/sangue , Osteoporose Pós-Menopausa/sangue , Ovariectomia , Ratos , Ratos Wistar
5.
Artigo em Inglês | MEDLINE | ID: mdl-34444432

RESUMO

Postmenopausal women represent a vulnerable population towards endocrine disruptors due to hormonal deficit. We previously demonstrated that chronic exposure of ovariectomized C57Bl6/J mice fed a high-fat, high-sucrose diet to a low-dose mixture of chemicals with one dioxin, one polychlorobiphenyl, one phthalate, and bisphenol A triggered metabolic alterations in the liver but the intestine was not explored. Yet, the gastrointestinal tract is the main route by which pollutants enter the body. In the present study, we investigated the metabolic consequences of ovarian withdrawal and E2 replacement on the various gut segments along with investigating the impact of the mixture of pollutants. We showed that genes encoding estrogen receptors (Esr1, Gper1 not Esr2), xenobiotic processing genes (e.g., Cyp3a11, Cyp2b10), and genes related to gut homeostasis in the jejunum (e.g., Cd36, Got2, Mmp7) and to bile acid biosynthesis in the gut (e.g., Fgf15, Slc10a2) and liver (e.g., Abcb11, Slc10a1) were under estrogen regulation. Exposure to pollutants mimicked some of the effects of E2 replacement, particularly in the ileum (e.g., Esr1, Nr1c1) suggesting that the mixture had estrogen-mimetic activities. The present findings have important implications for the understanding of estrogen-dependent metabolic alterations with regards to situations of loss of estrogens as observed after menopause.


Assuntos
Poluentes Ambientais , Animais , Dieta Hiperlipídica , Poluentes Ambientais/toxicidade , Estradiol , Estrogênios , Feminino , Humanos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 332-336, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374249

RESUMO

Objective: To investigate the effects of estrogen receptor α (ERα) gene overexpression on bone metabolism and calcium and phosphorus metabolism in ovariectomized osteoporosis mice, and to provide experimental basis for targeted gene therapy of osteoporosis. Methods: Thirty SPF female mice were randomly divided into sham operation group, model group and ERα overexpression group with 10 mice in each group. After the model was established, the ERα overexpression group was transfected with recombinant adenovirus vector carrying mouse ERα gene by intraspinal injection. The model group was transfected with empty virus, and the sham operation group was not treated. The expression of ERα gene in bone tissue of mice was detected by quantitative Real-time PCR (qRT-PCR). Bone mineral density (BMD) of mouse femur was measured after modeling. Trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular segregation (Tb.Sp), bone volume fraction (BV/TV) and biomechanical strength of femur were measured by micro-CT scanning. Serum levels of calcium (Ca), phosphorus (P), osteocalcin (BGP) and alkaline phosphatase (ALP) were measured by automatic biochemical analyzer. The expressions of tissue inhibitor of metalloproteinases 1 (TIMP-1) and monocyte chemotactic protein 1 (MCP-1) in bone homogenate were detected by Immunohistochemistry. Results: Compared with sham operation group, the expression level of ERα gene in bone tissue of model group was decreased significantly, the levels of BMD, BV/TV, Tb. Th, maximum load, rigidity coefficient, Ca and P were decreased, while the levels of Tb. Sp, BGP and ALP were increased significantly (P<0.05). Compared with the sham operation group, the expression level of TIMP-1 protein in the bone tissue of the model group was significantly decreased, while that of MCP-1 protein was increased, while that of the ERα overexpression group was increased while that of MCP-1 was decreased (P<0.05).The levels of ERα gene expression, BMD, BV/TV, TB. Th, maximum load, rigidity coefficient, Ca and P in the ERα overexpression group were significantly higher than those in the model group, while Tb. Sp, BGP and ALP were significantly lower (P<0.05). Compared with the sham operation group, mean optical density of TIMP-1 in the bone tissue of the model group was significantly decreased, while that of MCP-1 was significantly increased, and that of the ERα overexpression group was significantly increased while that of MCP-1 was significantly decreased (P<0.05). Conclusion: ERα gene overexpression can improve osteoporosis by regulating bone mineral density, bone parameters, bone metabolism, calcium and phosphorus metabolic indicators and the expression levels of TIMP-1 and MCP-1 in tissues.


Assuntos
Densidade Óssea , Osteoporose , Animais , Cálcio , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Camundongos , Ovariectomia , Fósforo , Ratos , Ratos Sprague-Dawley
7.
Artigo em Inglês | MEDLINE | ID: mdl-34360338

RESUMO

The purpose of this study was to evaluate the association between female medical history and thyroid cancer. Methods: Data from the Korean Genome and Epidemiology Study were collected from 2004 to 2016. Among a total of 1303 participants with thyroid cancer and 106,602 control (non-thyroid cancer) participants, the odds ratios (ORs) with 95% confidence intervals (CIs) of hysterectomy, oophorectomy, use of oral contraceptives, and number of children were evaluated. Results: The adjusted OR of hysterectomy for thyroid cancer was 1.73 (95% CI = 1.48-2.01, p < 0.001) in the minimally adjusted model. The adjusted ORs for thyroid cancer were 1.89 (95% CI = 1.06-3.37, p = 0.031), 0.89 (95% CI = 0.83-0.94, p < 0.001), and 0.85 (95% CI = 0.73-0.99, p = 0.040) for bilateral oophorectomy, number of children, and use of oral contraceptives, respectively, in the fully adjusted model. In the subgroup analysis, the adjusted ORs of bilateral oophorectomy were significant in the younger age (OR = 3.62, 95% CI = 1.45-9.03, p = 0.006), while the number of children was significant in the older age (OR = 0.86, 95% CI = 0.80-0.93, p < 0.001). Conclusions: The ORs of hysterectomy and bilateral oophorectomy were significantly higher in the thyroid cancer group in the younger age group. The adjusted ORs of the number of children were significantly low in the older age group.


Assuntos
Histerectomia , Neoplasias da Glândula Tireoide , Idoso , Criança , Estudos Transversais , Feminino , Humanos , Ovariectomia , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologia
8.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361069

RESUMO

Postmenopausal osteoporosis is closely associated with excessive osteoclast formation and function, resulting in the loss of bone mass. Osteoclast-targeting agents have been developed to manage this disease. We examined the effects of ciclopirox on osteoclast differentiation and bone resorption in vitro and in vivo. Ciclopirox significantly inhibited osteoclast formation from primary murine bone marrow macrophages (BMMs) in response to receptor activator of nuclear factor kappa B ligand (RANKL), and the expression of genes associated with osteoclastogenesis and function was decreased. The formation of actin rings and resorption pits was suppressed by ciclopirox. Analysis of RANKL-mediated early signaling events in BMMs revealed that ciclopirox attenuates IκBα phosphorylation without affecting mitogen-activated protein kinase activation. Furthermore, the administration of ciclopirox suppressed osteoclast formation and bone loss in ovariectomy-induced osteoporosis in mice and reduced serum levels of osteocalcin and C-terminal telopeptide fragment of type I collagen C-terminus. These results indicate that ciclopirox exhibits antiosteoclastogenic activity both in vitro and in vivo and represents a new candidate compound for protection against osteoporosis and other osteoclast-related bone diseases.


Assuntos
Antifúngicos/farmacologia , Reabsorção Óssea/tratamento farmacológico , Ciclopirox/farmacologia , Osteoclastos/citologia , Osteogênese , Ovariectomia/efeitos adversos , Substâncias Protetoras/farmacologia , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/patologia , Diferenciação Celular , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Ligante RANK/genética , Ligante RANK/metabolismo
9.
Medicina (Kaunas) ; 57(7)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34356961

RESUMO

Background and Objectives: To introduce a new technique for fast leakage-proof, intraumbilical, single-incision laparoscopic ovarian cystectomy for huge ovarian masses (>10 cm) Materials and Methods: Seven consecutive, reproductive-aged women, including three adolescents, with huge ovarian masses (mature cystic teratoma, n = 4; endometrioma, n = 2; and mucinous cystadenoma, n = 1) who underwent transumbilical single-incision ovarian cystectomy with the new "hybrid cystectomy and reimplantation" method were included. The procedure was: (1) trans-umbilical single-incision laparoscopy; (2) inspection of the pelvic cavity and placing the mass in a laparoscopic endo-bag for cystic content leakage prevention; (3) in-bag resection using cold scissors and minimal cauterization of the cystectomy site; (4) in-bag tissue extraction; (5) rapid extracorporeal cystectomy with traction without electrocautery; (6) re-insertion of the retrieved ovarian cortex intracorporeally through the single port, and (7) intracorporeal suture of the retrieved tissue to the in situ ovary. Results: The mean patient age was 24.71 ± 6.56 (range 17-37) years and the mean maximal diameter of the masses was 17.71 ± 2.86 (range 13-22) cm. There was no case of unintended intracorporeal cyst rupture and no need for copious irrigation for washing and suctioning the leaked mass content. The mean total operating time was 76.42 ± 6.39 (range 65-85) min, the total volume of saline used for irrigation was 814.28 ± 331.35 (range 500-1500) mL, and the estimated blood loss was 107.14 ± 47.72 (range 50-200) mL. There were no perioperative complications. All patients except the two endometriosis patients had regular, normal menstruation. Conclusions: Our preliminary findings were encouraging in terms of the safety and efficiency of the new method. Future trials need to elucidate the benefits of this method in terms of fertility preservation.


Assuntos
Laparoscopia , Neoplasias Ovarianas , Adolescente , Adulto , Cistectomia , Feminino , Humanos , Neoplasias Ovarianas/cirurgia , Ovariectomia , Reimplante , Adulto Jovem
10.
Eur J Neurosci ; 54(4): 5293-5309, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34302304

RESUMO

Menopause, natural or surgical, might facilitate the onset of psychiatric pathologies. Some reports suggest that their severity could increase if the decline of ovarian hormones occurs abruptly and before natural endocrine senescence. Therefore, we compared the effects of ovariectomy on microglia's morphological alterations, the complexity of newborn neurons, and the animal's ability to cope with stress. Young adult (3 months) and middle-aged (15 months) female Wistar rats were subjected to an ovariectomy (OVX) or were sham-operated. After 3 weeks, animals were assigned to one of the following independent groups: (1) young adult OVX + no stress; (2) young adult sham + no stress; (3) young adult OVX + stress; (4) young adult sham + stress; (5) middle-aged OVX + no stress; (6) middle-aged sham + no stress; (7) middle-aged OVX + stress; (8) middle-aged sham + stress. Acute stress was induced by forced swimming test (FST) exposure. Immobility behavior was scored during FST and 30 min after; animals were euthanized, their brains collected and prepared for immunohistochemical detection of Iba-1 to analyze morphological alterations in microglia, and doublecortin (DCX) detection to evaluate the dendrite complexity of newborn neurons. OVX increased immobility behavior, induced microglia morphological alterations, and reduced dendrite complexity of newborn neurons in young adult rats. FST further increased this effect. In middle-aged rats, the main effects were related to the aging process without OVX or stress exposure. In conclusion, surgical menopause favors in young adult rats, but not in middle-aged, the vulnerability to develop immobility behavior, retracted morphology of microglial cells, and decreased dendrite complexity of newborn neurons.


Assuntos
Microglia , Estresse Psicológico , Animais , Dendritos , Feminino , Humanos , Proteínas Associadas aos Microtúbulos , Neurônios , Neuropeptídeos , Ovariectomia , Ratos , Ratos Wistar
11.
JSLS ; 25(2)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248340

RESUMO

Background: Minimally invasive surgery is currently a preferred treatment for symptomatic ovarian cyst(s), with single-site techniques, such as transumbilical laparoendoscopic single-site surgery (TU-LESS) and transvaginal laparoendoscopic single-site surgery (TV-LESS), gaining increasing popularity. Although both methods have delivered positive outcomes, there is currently limited literature directly comparing TU-LESS and TV-LESS. Objectives: This study had two primary objectives: (1) to evaluate the safety and feasibility of TV-LESS and TU-LESS for the treatment of ovarian cysts and (2) to compare the surgical and postoperative outcomes of the two procedures. Method: This was a prospective observational clinical analysis of 81 patients with a diagnosis of benign ovarian cyst with indication for TV-LESS or TU-LESS. Surgeries were performed at a tertiary hospital between February 1, 2018 and January 31, 2020. Patients were divided into TV-LESS (n = 40) and TU-LESS groups (n = 40), with one excluded due to severe pelvic adhesive disease. Demographics, operation outcomes, and follow-up details were compared. Results: All 80 patients underwent uncomplicated procedures. The two groups were demographically matched (except age), with no difference in operation time, intra-operative blood loss, hemoglobin loss, and hospitalization costs (P > 0.05). However, TV-LESS patients had significantly faster time to ambulation (P < 0.001), faster time to return of bowel function (P < 0.001), less postoperative pain level (P < 0.001), and shorter length of hospital stay (P < 0.001). The cosmetic scores at 1, 4, and 24 weeks after surgery were also higher for the TV-LESS group. Conclusion: Our preliminary experience suggested that TU-LESS and TV-LESS are both feasible and safe for ovarian cystectomy and salpingo-oophorectomy. However, TV-LESS may provide three main advantages including: (1) fewer postoperative complications (i.e. incisional hernia); (2) less postoperative pain; and (3) improved cosmetic satisfaction.


Assuntos
Laparoscopia/métodos , Cistos Ovarianos/cirurgia , Ovariectomia/métodos , Umbigo/cirurgia , Vagina/cirurgia , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Resultado do Tratamento
12.
Int J Mol Sci ; 22(13)2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34281260

RESUMO

Males have a higher risk for cardiovascular diseases (CVDs) than females. Ambient fine particulate matter (PM) exposure increases CVD risk with increased reactive oxygen species (ROS) production and oxidative stress. Endothelial progenitor cells (EPCs) are important to vascular structure and function and can contribute to the development of CVDs. The aims of the present study were to determine if sex differences exist in the effect of PM exposure on circulating EPCs in mice and, if so, whether oxidative stress plays a role. Male and female C57BL/6 mice (8-10 weeks old) were exposed to PM or a vehicle control for six weeks. ELISA analysis showed that PM exposure substantially increased the serum levels of IL-6 and IL-1ß in both males and females, but the concentrations were significantly higher in males. PM exposure only increased the serum levels of TNF-α in males. Flow cytometry analysis demonstrated that ROS production was significantly increased by PM treatment in males but not in females. Similarly, the level of circulating EPCs (CD34+/CD133+ and Sca-1+/Flk-1+) was significantly decreased by PM treatment in males but not in females. Antioxidants N-acetylcysteine (NAC) effectively prevented PM exposure-induced ROS and inflammatory cytokine production and restored circulating EPC levels in male mice. In sharp contrast, circulating EPC levels remained unchanged in female mice with PM exposure, an effect that was not altered by ovariectomy. In conclusion, PM exposure selectively decreased the circulating EPC population in male mice via increased oxidative stress without a significant impact on circulating EPCs in females independent of estrogen.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Material Particulado/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Citocinas/sangue , Células Progenitoras Endoteliais/patologia , Estrogênios/metabolismo , Feminino , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fatores Sexuais
13.
Maturitas ; 150: 22-29, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34274072

RESUMO

OBJECTIVES: While it has been reported that women with uterine fibroids or endometriosis are commonly overweight and hypertensive, the association between non-malignant gynecological diseases and the risk of hypertension has been little studied prospectively. The aim of this study was to investigate in a large French cohort of women whether a history of hysterectomy, uterine fibroids, or endometriosis was prospectively related to an increased risk of incident hypertension. STUDY DESIGN: We analyzed 50,286 women from the E3N cohort who were free of hypertension at baseline, with a median follow-up of 16.4 years. MAIN OUTCOME MEASURES: Gynecological diseases were based on self-report. Cox proportional hazards models with age as the timescale were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates included smoking status, body mass index (BMI), physical activity, and hormonal factors. RESULTS: A total of 12,073 women (24%) developed hypertension during follow-up. Women with a history of hysterectomy had an increased risk of incident hypertension, which persisted after adjustment for potential confounding factors (adjusted HR=1.18, 95% CI 1.12-1.24). Risk was similar in women with hysterectomy with or without oophorectomy. Risk of hypertension was higher in women with a history of endometriosis (HRendometriosis 1.19, 95%CI 1.11-1.22) or uterine fibroids (HRfibroids 1.18, 95%CI 1.13-1.22), irrespective of hysterectomy. Associations were similar after further adjustment for BMI. CONCLUSIONS: Hysterectomy and non-malignant gynecological diseases were associated with an increased risk of hypertension in this large prospective study. Women with these conditions may benefit from blood pressure monitoring. ClinicalTrials.gov identifier: NCT03285230.


Assuntos
Índice de Massa Corporal , Doenças dos Genitais Femininos/cirurgia , Hipertensão/etiologia , Histerectomia/efeitos adversos , Ovariectomia/efeitos adversos , Adulto , Idoso , Feminino , França/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
14.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198932

RESUMO

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17ß-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17ß-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1ß, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Hipocampo/metabolismo , Ovariectomia/efeitos adversos , Fitoestrógenos/administração & dosagem , Pueraria/química , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Malondialdeído/sangue , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoestrógenos/química , Fitoestrógenos/farmacologia
15.
Nutrients ; 13(6)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208400

RESUMO

BACKGROUND: Obesity is a state of excess energy storage resulting in body fat accumulation, and postmenopausal obesity is a rising issue. In this study using ovariectomized (OVX) rats, we mimicked low estrogen levels in a postmenopausal state in order to investigate the effects of different amounts and types of dietary fatty acids on body fat accumulation and body lipid metabolism. METHODS: At 9 weeks of age, rats (n = 40) were given an ovariectomy, eight of which were sham-operated to serve as a control group (S). We then divided OVX rats into four different intervention groups: diet with 5% soybean oil (C), and diet with 5% (L), 15% (M), and 20% (H) (w/w) experimental oil, containing 60% monounsaturated fatty acids (MUFAs) and with a polyunsaturated/saturated fatty acid (P/S) ratio of 5. RESULTS: After OVX, compared to the S group, the C group showed significantly higher body weight, and insulin and leptin levels. Compared to the C group, the H group had lower hepatic triglyceride level and FAS enzyme activity, and higher hepatic ACO and CPT-1 gene expressions and enzyme activities. CONCLUSIONS: An OVX leads to severe weight gain and lipid metabolism abnormalities, while according to previous studies, high fat diet may worsen the situation. However, during our experiment, we discovered that the experimental oil mixture with 60% MUFAs and P/S = 5 may ameliorate these imbalances.


Assuntos
Tecido Adiposo , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos/administração & dosagem , Metabolismo dos Lipídeos , Animais , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Ácidos Graxos Monoinsaturados/administração & dosagem , Feminino , Insulina/sangue , Leptina/sangue , Fígado/metabolismo , Ovariectomia , Ratos , Ratos Sprague-Dawley , Óleo de Soja/administração & dosagem , Triglicerídeos/metabolismo , Ganho de Peso
16.
Medicine (Baltimore) ; 100(27): e26472, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232179

RESUMO

RATIONALE: Teratomas are solid tumors that may occur in both gonadal and extragonadal locations, depending on the age of the child. Benign cystic teratomas are relatively common tumors among women of reproductive age, but they can occur at any age. The clinical presentation is not specific. They can be found incidentally when patients are investigated for other conditions or they can present as emergencies when the ovarian teratoma is torsioned or ruptured. PATIENT CONCERNS: We present the case of a 17-year-old adolescent girl that was seen in our emergency department on several occasions for recurrent episodes of abdominal pain ongoing for 6 months. DIAGNOSIS: An ultrasonography (US) was performed as an outpatient and a left ovarian mass was found along with right ureterohydronephrosis (UHN). Further assessment of the mass was done by abdominal and pelvic CT and tumoral markers. CT appearance was more suggestive of a teratoma. INTERVENTIONS: She underwent laparotomy with complete excision of the tumor. OUTCOME: The patient had an uneventful recovery. A renal US follow up showed reduction of the dilatation, demonstrating that the condition was secondary to tumor compression. LESSONS: In a teenager with nonspecific symptoms, a high suspicion index for tumors is mandatory. An early diagnosis and management avoid complications like UHN.


Assuntos
Hidronefrose/etiologia , Neoplasias Ovarianas/complicações , Ovariectomia/métodos , Teratoma/complicações , Adolescente , Feminino , Humanos , Hidronefrose/diagnóstico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Teratoma/diagnóstico , Teratoma/cirurgia , Ultrassonografia
17.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203300

RESUMO

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17ß-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.


Assuntos
Hiperalgesia/tratamento farmacológico , Neurônios Aferentes/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Gânglio Trigeminal/metabolismo , Acrilamidas/farmacologia , Animais , Western Blotting , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Estradiol/genética , Estradiol/metabolismo , Feminino , Imunofluorescência , Hiperalgesia/metabolismo , Ovariectomia , Ratos , Ratos Sprague-Dawley , Gânglio Trigeminal/efeitos dos fármacos
18.
Biomed Pharmacother ; 139: 111697, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243614

RESUMO

Excessive osteoclast activity, along with relatively weak osteoblast function, is strongly associated with bone disease. Therefore, studies to identify novel anti-osteoporosis candidates with dual actions of inhibiting osteoclastogenesis and increasing osteoblastogenesis may provide an ideal approach for treating osteoporosis. Pitavastatin, an inhibitor of 3-hydroxy-3 methyl-glutaryl coenzyme A reductase, has demonstrated various pharmacological activities, including anti-inflammation, bone anabolic effects, vasodilation, and inhibition of revascularization; however, the precise effects and mechanisms of pitavastatin on the regulation of osteoblast and osteoclast activity need to be comprehensively elucidated. Herein, we demonstrated that pitavastatin is a potential candidate for treating osteoporosis by enhancing osteoblast differentiation and bone growth and inhibiting osteoclast differentiation and bone resorption. Pitavastatin exerted dose-dependent inhibitory effects on receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation, bone resorption, and osteoclast-specific marker gene expression. These inhibitory effects were achieved by inhibiting the Akt, NF-κB, and mitogen-activated protein kinase (p38, ERK, and JNK) signaling pathways, resulting in the downregulation of major transcription factors c-Fos and NFATc1. Furthermore, pitavastatin potentially stimulated osteoblast differentiation by activating alkaline phosphatase (ALP), enhancing mineralization by Alizarin Red S, and increasing the expression of osteoblastogenic marker genes such as runt-related transcription factor 2, ALP, osteocalcin, and collagen type 1 alpha. Furthermore, we evaluated the therapeutic potential of pitavastatin in ovariectomy-induced systematic bone loss based on micro-computed tomography and histological analysis of femurs. Our findings demonstrated a new function and mechanism for pitavastatin in bone remodeling, indicating its potential as a therapeutic candidate in treating osteoporosis by inhibiting osteoclastic resorption and promoting osteoblastic formation.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ovariectomia/efeitos adversos , Quinolinas/farmacologia , Animais , Biomarcadores/metabolismo , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Bone ; 152: 116072, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34171514

RESUMO

Microstructural adaptation of bone in response to mechanical stimuli is diminished with estrogen deprivation. Here we tested in vivo whether ovariectomy (OVX) alters the acute response of osteocytes, the principal mechanosensory cells of bone, to mechanical loading in mice. We also used super resolution microscopy (Structured Illumination microscopy or SIM) in conjunction with immunohistochemistry to assess changes in the number and organization of "osteocyte mechanosomes" - complexes of Panx1 channels, P2X7 receptors and CaV3 voltage-gated Ca2+ channels clustered around αvß3 integrin foci on osteocyte processes. Third metatarsals bones of mice expressing an osteocyte-targeted genetically encoded Ca2+ indicator (DMP1-GCaMP3) were cyclically loaded in vivo to strains from 250 to 3000 µÎµ and osteocyte intracellular Ca2+ signaling responses were assessed in mid-diaphyses using multiphoton microscopy. The number of Ca2+ signaling osteocytes in control mice increase monotonically with applied strain magnitude for the physiological range of strains. The relationship between the number of Ca2+ signaling osteocytes and loading was unchanged at 2 days post-OVX. However, it was altered markedly at 28 days post-OVX. At loads up to 1000 µÎµ, there was a dramatic reduction in number of responding (i.e. Ca2+ signaling) osteocytes; however, at higher strains the numbers of Ca2+ signaling osteocytes were similar to control mice. OVX significantly altered the abundance, make-up and organization of osteocyte mechanosome complexes on dendritic processes. Numbers of αvß3 foci also staining with either Panx 1, P2X7R or CaV3 declined by nearly half after OVX, pointing to a loss of osteocyte mechanosomes on the dendritic processes with estrogen depletion. At the same time, the areas of the remaining foci that stained for αvß3 and channel proteins increased significantly, a redistribution of mechanosome components suggesting a potential compensatory response. These results demonstrate that the deleterious effects of estrogen depletion on skeletal mechanical adaptation appear at the level of mechanosensation; osteocytes lose the ability to sense small (physiological) mechanical stimuli. This decline may result at least partly from changes in the structure and organization of osteocyte mechanosomes, which contribute to the distinctive sensitivity of osteocytes (particularly their dendritic processes) to mechanical stimulation.


Assuntos
Sinalização do Cálcio , Osteócitos , Animais , Osso e Ossos , Conexinas , Estrogênios , Feminino , Camundongos , Proteínas do Tecido Nervoso , Ovariectomia , Estresse Mecânico
20.
eNeuro ; 8(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135001

RESUMO

Gonadotropin-releasing hormone (GnRH) drives pituitary secretion of luteinizing hormone and follicle-stimulating hormone, which in turn regulate gonadal functions including steroidogenesis. The pattern of GnRH release and thus fertility depend on gonadal steroid feedback. Under homeostatic (negative) feedback conditions, removal of the gonads from either females or males increases the amplitude and frequency of GnRH release and alters the long-term firing pattern of these neurons in brain slices. The neurobiological mechanisms intrinsic to GnRH neurons that are altered by homeostatic feedback are not well studied and have not been compared between sexes. During estradiol-positive feedback, which is unique to females, there are correlated changes in voltage-gated potassium currents and neuronal excitability. We thus hypothesized that these same mechanisms would be engaged in homeostatic negative feedback. Voltage-gated potassium channels play a direct role in setting excitability and action potential properties. Whole-cell patch-clamp recordings of GFP-identified GnRH neurons in brain slices from sham-operated and castrated adult female and male mice were made to assess fast and slow inactivating potassium currents as well as action potential properties. Surprisingly, no changes were observed among groups in most potassium current properties, input resistance, or capacitance, and this was reflected in a lack of differences in excitability and specific action potential properties. These results support the concept that, in contrast to positive feedback, steroid-negative feedback regulation of GnRH neurons in both sexes is likely conveyed to GnRH neurons via mechanisms that do not induce major changes in the biophysical properties of these cells.


Assuntos
Retroalimentação Fisiológica , Hormônio Liberador de Gonadotropina , Potássio , Animais , Estradiol , Feminino , Masculino , Camundongos , Neurônios , Ovariectomia
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