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1.
Gynecol Endocrinol ; 36(2): 152-155, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31317814

RESUMO

The aim of this retrospective study was to evaluate the effects of a long-term treatment with α-lipoic acid (ALA) combined with myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Fifty-seven women with PCOS and a history of oligoamenorrhea were treated with MI and ALA (800 mg + 2000 mg per day). Forty-four of them had complete clinical charts and were considered eligible for the study. Information about cycle length and body mass index (BMI) was checked after 6, 12, and 24 months. After 12 months ovarian volume, total testosterone plasma levels and changes in hirsutism were also evaluated. The metabolic parameters were evaluated in 16 women after 6 and 18 months of the treatment. Cycle length was significantly reduced at 6 (p < .001), 12, and 24 months of treatment (p < .01). BMI showed a reduction only at 6 months (p < .05), thereafter returning similar to the basal values. No changes of testosterone and ovarian volume were observed. HOMA-IR and fasting insulin were unchanged, but the insulin response to a 3 h OGTT was improved after 6 (p < .01) and 18 months (p < .05) of treatment. No individual suffered from any adverse event. In conclusion, the combination of ALA and MI showed to be useful as long-term therapy in PCOS women, providing a normalization of the menstrual cycle and an amelioration of insulin levels with a high tolerability.

2.
Fertil Steril ; 109(4): 594-600.e1, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605405

RESUMO

OBJECTIVE: To evaluate the association between estrogen (E) exposure and deficiency and cardiovascular disease (CVD) risk among women with primary ovarian insufficiency (POI). DESIGN: Cross-sectional study conducted between 1996 and 2016. SETTING: Tertiary referral centers. PATIENT(S): A total of 385 women with POI, defined by amenorrhea and FSH levels ≥40 IU/L before 40 years of age, were recruited. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women underwent a standardized intake questionnaire including data on menstrual cyclicity. Lifetime E exposure and E-free period were assessed. Serum was analyzed for endocrine and CVD profiles. The Framingham 30-year risk of CVD was calculated. RESULT(S): Lifetime E exposure (mean ± SD) was 19.3 ± 7.0 years, E-free period was 3.1 ± 4.1 years, and age at screening was 34.8 ± 7.4 years. In multivariate models E-free interval associated positively with estimated risk of hard and general CVD events (ß 0.18 [95% confidence interval 0.08, 0.29]; 0.20 [0.05, 0.35], respectively), and lifetime E exposure associated negatively with estimated risk of hard and general CVD events (-0.15 [-0.24, -0.05]; -0.16 [-0.29, -0.03], respectively), as well as low density lipoprotein cholesterol (-0.03 [-0.06, 0.00]) and non-high density lipoprotein cholesterol (-0.04 [-0.07, 0.00]). CONCLUSION(S): Prolonged E deprivation is associated with an increased estimated risk of CVD, whereas prolonged E exposure is associated with a reduced estimated risk. These results support the policy of early and continued use of E replacement therapy in women with POI. CLINICAL TRIAL REGISTRATION NUMBER: NCT0230904.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Estradiol/deficiência , Terapia de Reposição de Estrogênios , Insuficiência Ovariana Primária/tratamento farmacológico , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Estradiol/sangue , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Países Baixos/epidemiologia , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/epidemiologia , Prognóstico , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo
3.
Maturitas ; 99: 1-9, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28364860

RESUMO

BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17ß-estradiol (E2). STUDY DESIGN: Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. RESULTS: E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. CONCLUSIONS: These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration.


Assuntos
Movimento Celular/efeitos dos fármacos , Estetrol/farmacologia , Fibrinólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Ativador de Plasminogênio Tecidual/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/efeitos dos fármacos , Western Blotting , Células Cultivadas , Células Endoteliais , Endotélio Vascular/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
4.
Surg Endosc ; 31(8): 3405-3410, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27815747

RESUMO

BACKGROUND: To present the first case series of total robotic hysterectomy (TRH), using integrated table motion (ITM), which is a new feature comprising a unique operating table by Trumpf Medical that communicates wirelessly with the da Vinci Xi surgical system. ITM has been specifically developed to improve multiquadrant robotic surgery such as that conducted in colorectal surgery. METHODS: Between May and October 2015, a prospective post-market study was conducted on ITM in the EU in 40 cases from different specialties. The gynecological study group comprised 12 patients. Primary endpoints were ITM feasibility, safety and efficacy. RESULTS: Ten patients underwent TRH. Mean number of ITM moves was three during TRH; there were 31 instances of table moves in the ten procedures. Twenty-eight of 31 ITM moves were made to gain internal exposure. The endoscope remained inserted during 29 of the 31 table movements (94%), while the instruments remained inserted during 27 of the 31 moves (87%). No external instrument collisions or other problems related to the operating table were noted. There were no ITM safety-related observations and no adverse events. CONCLUSIONS: This preliminary study demonstrated the feasibility, safety and efficacy of ITM for the da Vinci Xi surgical system in TRH. ITM was safe, with no adverse events related to its use. Further studies will be useful to define the real role and potential benefit of ITM in gynecological surgery.


Assuntos
Histerectomia/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Equipamentos Cirúrgicos , Resultado do Tratamento
5.
Int J Gynaecol Obstet ; 135(3): 338-342, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27622684

RESUMO

OBJECTIVE: To determine the effect of a simulation training program for residents in obstetrics and gynecology in terms of technical and nontechnical skills for the management of shoulder dystocia. METHODS: A prospective study was performed at a center in Italy in April-May 2015. Thirty-two obstetrics and gynecology residents were divided into two groups. Residents in the control group were immediately exposed to an emergency shoulder dystocia scenario, whereas those in the simulation group completed a 2-hour training session with the simulator before being exposed to the scenario. After 8weeks, the residents were again exposed to the shoulder dystocia scenario and reassessed. Participants were scored on their demonstration of technical and nontechnical skills. RESULTS: In the first set of scenarios, the mean score was higher in the simulation group than the control group in terms of both technical skills (P=0.008) and nontechnical skills (P<0.001). This difference was retained after 8weeks. CONCLUSION: High-fidelity simulation programs could be used for the training of residents in obstetrics and gynecology to diagnose and manage obstetric emergencies such as shoulder dystocia.


Assuntos
Competência Clínica/normas , Parto Obstétrico/educação , Distocia/terapia , Treinamento com Simulação de Alta Fidelidade/métodos , Internato e Residência/normas , Gerenciamento Clínico , Feminino , Ginecologia/educação , Humanos , Itália , Obstetrícia/educação , Gravidez , Estudos Prospectivos , Autoavaliação , Ombro/fisiopatologia
6.
Maturitas ; 79(1): 86-90, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25015014

RESUMO

OBJECTIVE: To measure serum levels of adipsin, leptin, resistin, adiponectin, visfatin, ghrelin and insulin in postmenopausal women screened for the metabolic syndrome (METS). METHODS: Serum of 100 postmenopausal women was analyzed using multiplex technology for the mentioned analytes. In addition, values for the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Comparisons were performed in accordance to the presence or not of the METS and each of its components. Criteria of the American Heart Association were used to define the METS. RESULTS: Age and time since menopause onset were similar in women with the METS (n=57) as compared to those without the syndrome (n=43). METS women displayed significantly higher levels of adipsin, leptin, resistin, insulin and HOMA-IR values and lower adiponectin levels. These differences were mainly observed among women with abdominal obesity, independent of fulfilling METS criteria or not. In this same sense, lower adiponectin levels significantly related to low HDL-C and high triglyceride levels; and higher insulin and HOMA-IR values related to high triglyceride and glucose levels, respectively. CONCLUSION: In this sample, postmenopausal women with the METS displayed higher insulin and adipokine levels. These were mainly related to abdominal obesity and metabolic and lipid abnormalities. More research is warranted in this regard.


Assuntos
Adipocinas/sangue , Citocinas/sangue , Grelina/sangue , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pós-Menopausa/sangue , Adiponectina , Adulto , Idoso , Glicemia/análise , HDL-Colesterol/sangue , Estudos de Coortes , Fator D do Complemento/análise , Feminino , Humanos , Hipertensão/sangue , Insulina/sangue , Leptina/sangue , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Resistina , Triglicerídeos/classificação
7.
Artigo em Inglês | MEDLINE | ID: mdl-24904530

RESUMO

Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17ß-estradiol (E2) on T47-D ER+ breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, re-distribution of actin fibers toward the cell membrane was observed. However, when E4 was added to E2, an inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr(558), which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of estrogen receptor-α. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring ER modulator in the breast.

8.
Maturitas ; 77(4): 370-4, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24598235

RESUMO

BACKGROUND: Prevalence of the metabolic syndrome (METS) increases after the menopause; nevertheless, concomitant vascular, inflammatory and endothelial changes have not been completely elucidated. OBJECTIVE: To measure serum markers of angiogenesis, inflammation and endothelial function in postmenopausal women screened for the METS. METHODS: Serum of 100 postmenopausal women was analyzed for angiopoietin-2, interleukin-8 (IL-8), soluble FAS ligand (sFASL), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), soluble CD40 ligand (sCD40L), plasminogen activator inhibitor-1 (PAI-1), and urokinase-type plasminogen activator (uPA). Comparisons were made in accordance to the presence or not of the METS and each of its components. Modified Adult Treatment Panel III criteria were used to define the METS. RESULTS: Women with the METS (n=57) had similar age and time since menopause as compared to those without the syndrome (n=43). In general, women with the METS displayed a trend for higher levels of the analyzed markers. Nevertheless, only IL-6 levels were found to be significantly higher and uPA levels significantly lower among METS women as compared to those without the syndrome. When analyte levels were compared as to presenting or not each of the diagnostic features of the METS, it was found that IL-6 levels were higher among women with abdominal obesity, low HDL-C and high triglyceride levels. Women with low HDL-C and high triglyceride levels presented significantly lower uPA levels and those with high glucose and low HDL-C displayed significantly higher sCD40L levels. CONCLUSION: Postmenopausal women with the METS in this sample displayed higher IL-6 (inflammation) and lower uPA levels (endothelial dysfunction). These were mainly related to metabolic and lipid abnormalities. More research is warranted in this regard.


Assuntos
Inflamação/fisiopatologia , Síndrome Metabólica/fisiopatologia , Adulto , Angiopoietina-2/sangue , Ligante de CD40/sangue , Endotélio/patologia , Proteína Ligante Fas/sangue , Feminino , Humanos , Inflamação/patologia , Interleucina-6/sangue , Interleucina-8/sangue , Modelos Lineares , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Neovascularização Patológica/fisiopatologia , Inibidor 1 de Ativador de Plasminogênio/sangue , Pós-Menopausa , Fator de Necrose Tumoral alfa/sangue , Ativador de Plasminogênio Tipo Uroquinase/sangue
9.
Maturitas ; 76(3): 230-4, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24055286

RESUMO

Female pelvic floor is a complex functional unit involved in multiple functions that extend beyond the sole support of pelvic organs. Pelvic floor dysfunction globally affects micturition, defecation and sexual activity. Evolutionary modifications such ad adaptation to upright standing, walking and the need to deliver fetuses with larger head diameters made the fascial and muscle support of the pelvic floor vulnerable, therefore predisposing women to pelvic organ prolapse and incontinence. Different than in males, the female pelvic floor undergoes a number of adaptive changes related to life and endocrine events. Most of the clinical manifestations of these changes become apparent after menopause and throughout aging in women. This review article summarizes the key aspects of the pathophysiology and the clinics of the modifications of the pelvic floor in women through midlife and beyond. A particular focus is given to the relationship between urinary and bowel dysfunction.


Assuntos
Envelhecimento/fisiologia , Constipação Intestinal/etiologia , Diafragma da Pelve/fisiopatologia , Incontinência Urinária/fisiopatologia , Prolapso Uterino/fisiopatologia , Feminino , Humanos , Menopausa
10.
Mol Hum Reprod ; 18(8): 410-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22389473

RESUMO

Endothelial plasminogen activator inhibitor (PAI-1) controls vascular remodeling, angiogenesis and fibrinolysis. PAI-1 blood levels in women are related to estrogen. The aim of this study was to characterize the signaling pathways through which estrogen regulates PAI-1 in endothelial cells. Furthermore, we aimed to investigate whether PAI-1 is implicated in the control of endothelial migration by estrogen. Cultured human umbilical vein endothelial cells (HUVECs) and ovariectomized rats were used to test the effects of 17ß-estradiol (E(2)) on PAI-1 expression and its role on endothelial migration. At physiological concentrations, E(2) increases the expression of PAI-1 in HUVEC within 6-12 h through activation of a signaling cascade initiated by estrogen receptor α and involving G proteins, phosphatidylinositol-3-OH kinase and Rho-associated kinase II. ROCK-II activation turns into an over-expression of c-Jun and c-Fos that is required for E(2)-induced expression of PAI-1. Estrogen-induced PAI-1 expression is implicated in HUVEC horizontal migration. PAI-1 regulation is found also in vivo, in female rats, where ovariectomy is associated with reduced PAI-1 expression, while estrogen replacement counteracts this change. In conclusion, E(2) increases PAI-1 synthesis in human endothelial cells and in rodent aorta through a G protein-initiated signaling that targets early-immediate gene expression. This regulatory pathway is implicated in endothelial cell migration. These findings describe new mechanisms of action of estrogens in the vessels, which may be important for vascular remodeling and hemostasis.


Assuntos
Aorta/metabolismo , Movimento Celular , Estradiol/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Animais , Células Cultivadas , Estradiol/sangue , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Estrogênios/sangue , Estrogênios/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/biossíntese , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Ovariectomia , Fosfatidilinositol 3-Quinase/metabolismo , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-fos/genética , Interferência de RNA , RNA Interferente Pequeno , Ratos , Ratos Wistar , Transdução de Sinais , Quinases Associadas a rho/metabolismo
11.
Mol Hum Reprod ; 18(1): 44-51, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21971309

RESUMO

Clinical observations and basic studies show that progesterone and progestins have a variable influence on endothelial function. Dydrogesterone (DG) is a widely used progestin, but its endothelial actions have not been thoroughly assessed. In this study, we investigated the effects of DG and its metabolite 20-α-dihydro-dydrogesterone (DHD), natural progesterone as well as medroxyprogesterone acetate, on the expression of leukocyte adhesion molecules in human endothelial cells using an in vitro experimental endothelial inflammation system. Our findings show that all progestins significantly suppress endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule-1 (ICAM-1) induced by bacterial lypopolysaccharide (LPS). These inhibitory effects of DG and DHD require activation of progesterone receptor. DG and DHD decrease adhesion molecule expression associated with LPS administration by preventing nuclear translocation of the pro-inflammatory transcription factor nuclear factor-κB. In addition, DG and DHD do not alter the anti-inflammatory effects of 17ß-estradiol. In conclusion, DG and DHD decrease endothelial inflammatory responses induced by LPS, via reduced expression of the pro-atherogenic adhesion molecules VCAM-1 and ICAM-1. These actions may be relevant for the vascular effects of DG.


Assuntos
Anti-Inflamatórios/farmacologia , Moléculas de Adesão Celular/metabolismo , Didrogesterona/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Progestinas/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Didrogesterona/análogos & derivados , Células Endoteliais/citologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo
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