RESUMO
BACKGROUND/AIM: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored. MATERIALS AND METHODS: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death. RESULTS: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1ß. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins. CONCLUSION: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD.
Assuntos
Apoptose , Colite , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Mesilato de Imatinib , Animais , Mesilato de Imatinib/farmacologia , Sulfato de Dextrana/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Mediadores da Inflamação/metabolismo , BiomarcadoresRESUMO
BACKGROUND/AIM: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. MATERIALS AND METHODS: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. RESULTS: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. CONCLUSION: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.
Assuntos
Modelos Animais de Doenças , Prurido , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Ratos , Prurido/tratamento farmacológico , Masculino , Pele/efeitos dos fármacos , Pele/patologia , Pele/lesões , Pomadas , Creme para a Pele , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêuticoRESUMO
BACKGROUND: Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short-term adherence. Psoriasis is a chronic disease, and long-term adherence is an even bigger problem. OBJECTIVES: To determine how well medication is used in the long-term topical treatment of psoriasis and to assess the potential of an internet-based reporting intervention to improve treatment adherence and outcomes. METHODS: An investigator-blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild-to-moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard-of-care or internet-based reporting group. Adherence was objectively monitored with Medication Event Monitoring System® caps. RESULTS: Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard-of-care group (50% vs. 35%, P = 0·08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1·61 vs. -0·12, P = 0·003), month 3 (2·50 vs. 0·79, P = 0·025) and month 12 (3·32 vs. 0·34, P = 0·038) than in the standard-of-care group. CONCLUSIONS: This study likely underestimates the challenge of long-term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients' treatment outcomes.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Fluocinonida/administração & dosagem , Adesão à Medicação , Psoríase/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Análise de Variância , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Adulto JovemAssuntos
Fármacos Dermatológicos/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Psoríase/tratamento farmacológico , Administração Cutânea , Corticosteroides/uso terapêutico , Feminino , Humanos , Gravidez , Resultado da Gravidez , Trimestres da Gravidez , Medicamentos sob Prescrição/uso terapêutico , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Radiofrequency electrical currents have a tendency to move toward the center of the bulk of biologic tissues. OBJECTIVES: To evaluate the effect of the frequency of currents on their entrance and propagation pattern in biologic tissues. MATERIALS AND METHODS: Three electrosurgical generators with 0.4, 1.5, and 3 MHz frequency outputs were studied. Current was applied using a metallic needle introduced into a piece of cow liver, with different amounts of energy delivered at multiple points. Cross-sections of the liver were then studied for tissue effect. The diameters of the coagulated areas at the deepest and most superficial parts were measured. The tendency of the currents for penetration in the deeper layers of tissue rather than in the superficial layers was assessed using the superficial diameter/deep diameter ratio. RESULTS: Diameter of coagulated area was larger around deeper parts than around superficial parts of the electrode. No correlation between frequency of current and the superficial/deep diameter ratio of the coagulation zone was found. CONCLUSION: Radiofrequency currents have a tendency to move toward the center of the tissue. Frequency of current over the range of 0.4-3 MHz did not show any effect on this tendency.
Assuntos
Ablação por Cateter/métodos , Hepatectomia/métodos , Fígado/patologia , Fígado/cirurgia , Absorção de Radiação , Animais , Bovinos , Condutividade Elétrica , Técnicas In Vitro , Fígado/fisiopatologia , Doses de Radiação , Ondas de RádioRESUMO
The onset of the menopause is often a time when women's concerns can act as a powerful trigger to encourage healthy modifications in lifestyle which will maintain, or improve, their general health. This document aims to help women to understand their potential risks, to encourage them to find proactive preventive strategies by modifying some of their attitudes, and to use health resources (when available) to be screened. Cancer is an important cause of death but not the primary cause of mortality. Cardio/circulatory diseases represent 35-40% of causes of death in most developed countries and 20-25% of women will die from cancers in Western Europe, Australasia, high-income North America, high-income Asia Pacific, East Asia and Southern Latin America. Breast cancer, lung cancer and colorectal cancer are prevalent in most regions of the world. Cervical cancer remains a hallmark of low access to health care. Preventive strategies (decreasing smoking and alcohol consumption, losing weight, eating a healthy diet and undertaking physical activity) and implementation of screening could help to significantly decrease the incidence of and mortality from cancer. The mortality/incidence ratio is higher in developing countries compared to high-income regions as well as in subgroups of populations in developed countries with lower socioeconomic levels. Implementation of better diagnostic methods and management of cancer according to the local resources will help to decrease the mortality rate in developing countries, and effort has to be made to decrease social inequities and improve access to health care for low-income groups. In conclusion, cancer incidence is increasing as a consequence of longer life expectancy all over the world. National health programs are mandatory to implement screening and to improve individual management. Finally, educating women so that they are aware of ways to improve their general health, to minimize their own risk factors and to identify signs of change in their own health which may be markers of impending cancer will help to reduce the burden of disease and improve the prognosis for tumors detected at an earlier stage.
Assuntos
Menopausa , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Dieta , Neoplasias do Endométrio/epidemiologia , Etnicidade , Feminino , Promoção da Saúde , Humanos , Renda , Expectativa de Vida , Estilo de Vida , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/mortalidade , Neoplasias/prevenção & controle , Obesidade/complicações , Neoplasias Ovarianas , Neoplasias do Colo do Útero/epidemiologiaRESUMO
Commitment of differentiating embryonic stem cells (ESCs) toward the various lineages is influenced by many factors, including androgens. However, the mechanisms underlying proteotoxic stress conferred by androgen receptor (AR) actions on embryonic cell fate remains unclear. Here we show that mouse ESCs display stress-related cellular phenotypes in response to androgens during early phase of differentiation. Androgen induced a significant increase in the percentage of ESCs and embryoid bodies with the intranuclear and juxtanuclear AR inclusions, which were colocalized with the E3 ubiquitin ligase, C terminus of Hsc70-interacting protein. Caspase-3 activity corresponded with AR expression, was enhanced in cells engaged more differentiation phenotypes. Androgen-mediated accumulation of AR aggregates exacerbated endoplasmic reticulum (ER) stress and rendered ESCs susceptible to apoptosis. Increasing expression levels of the ER chaperones, GRP78/BiP and GRP94, as well as ER stress markers, such as ATF6, phosphorylated PERK, GADD153/CHOP and spliced XBP-1 mRNA, were dramatically elevated in ESCs overexpressing AR. We found that androgen induced GRP78/BiP to dissociate from ATF6, and act as an AR-interacting protein, which was recruited into AR inclusions in ESCs. GRP78/BiP was also colocalized with AR inclusions in the cells of spinal bulbar muscular atrophy transgenic mouse model. Overexpression of GRP78/BiP suppressed ubiquitination of AR aggregates and ameliorated the misfolded AR-mediated cytopathology in ESCs, whereas knockdown of GRP78/BiP increased the accumulation of AR aggregates and significantly higher levels of caspase-3 activity and cell apoptosis. These results generate novel insight into how ESCs respond to stress induced by misfolded AR proteins and identify GRP78/BiP as a novel regulator of the AR protein quality control.
Assuntos
Androgênios/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Receptores Androgênicos/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diferenciação Celular , Linhagem Celular , Modelos Animais de Doenças , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/antagonistas & inibidores , Proteínas de Choque Térmico/genética , Camundongos , Camundongos Transgênicos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , UbiquitinaçãoRESUMO
SUMMARY: Bisphosphonates have been used for the treatment of postmenopausal osteoporosis since the early 1990s and studies show that compliant patients experience a lower fracture rate. This cohort study showed that the compliance of Taiwanese patients was poor and the refracture risk was related to compliance with bisphosphonate therapy. INTRODUCTION: Bisphosphonates are potent inhibitors of osteoclast activity, and reduce bone turnover by inhibiting bone resorption. According to Taiwanese reimbursement guidelines, patients with osteoporosis-related fractures are eligible for bisphosphonate treatment. This study aimed to elucidate the relationship of refracture risk with compliance/persistence with bisphosphonate therapy in Taiwan. METHODS: This was a retrospective, administrative, database analysis measuring the adherence status and impact of poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the National Health Insurance Research Database (NHIRD) were used to assemble a cohort of all osteoporosis patients who initiated bisphosphonate treatment between January 1, 2004, and December 31, 2005. Patients were followed until death, end of registration in NHIRD, or end of study period (December 31, 2006), whichever occurred first. Compliance was calculated as medication possession ratio (MPR; sum of days of supply of osteoporosis medications divided by follow-up duration). RESULTS: The refracture rates for osteoporosis patients were 5.15 %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and were significantly lower for patients with >80 % compliance than with <80 % compliance (p < 0.05). Nearly 50 % patients were noncompliant (MPR < 80 %) at 3 months, and only around 30 % patients were adherent at 1 year. Refracture risk increased with MPR < 80 %, age, and co-morbidities like diabetes mellitus or dementia. Patients with concomitant statin medication had significantly lower refracture risk. CONCLUSIONS: The compliance of Taiwanese patients with osteoporosis medication is poor, and refracture risk is related to compliance with bisphosphonate therapy.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Fraturas por Osteoporose/prevenção & controle , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Prevenção Secundária , Taiwan/epidemiologiaRESUMO
Following the announcement of the first results of the Women's Health Initiative (WHI) to the media in 2002, prior to their scientific publication, the resulting panic headlines had an immediate and lasting negative effect on use of menopausal hormone replacement therapy (HRT) around the world. Rates of use dropped by 40-80%. Symptomatic women then sought multiple alternative therapies but the majority of these have no greater effect than the effect seen from placebo in well-conducted trials of HRT. Some of these therapies have risks. Although anecdotally most menopause practitioners after 2002 can attest to having to counsel large numbers of women with debilitating menopausal symptoms who were too frightened to consider HRT, it is difficult to document loss of health-related quality of life in large population studies as they were not conducted. Similarly, the positive or negative effects of the marked decline in HRT on long-term morbidities and mortality have yet to be fully assessed. Recent studies have shown an increase in postmenopausal fractures and in some, but not all, populations a small temporary decline in breast cancer. Cardiovascular outcomes may not be apparent for another decade. Short-term, randomized, placebo-controlled trials confirm that HRT is the only therapy that effectively improves health-related quality of life in symptomatic women through a reduction in vasomotor and urogenital symptoms, joint pains and insomnia, while improving sexuality. The results of the re-analyses of the WHI data and new data from other studies do not justify the continuing negative attitude to HRT in symptomatic women who start HRT near menopause.
Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Medicina Baseada em Evidências , Menopausa , Saúde da Mulher , Idoso , Terapias Complementares , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
OBJECTIVE: The aim of this study was to assess the efficacy and safety of Diascorea alata for treatment of menopausal symptoms. MATERIALS AND METHODS: Two-center, randomized, double-blind, placebo-controlled clinical investigation on 50 menopausal women randomly assigned to two groups, treated for 12 months with either placebo or two sachets daily of Diascorea extracts containing 12 mg/sachet. Primary outcome measures were changes in the Greene Climacteric Scale caused by Diascorea compared with placebo; secondary outcomes were changes in plasma hormone profiles. One-way ANCOVA test was performed to investigate the significance. RESULTS: At 6 months and at the end of treatment, those women who received Diascorea showed general improvement in almost all the clinical symptoms investigated. A significant reduction was noted in the total Greene scores in the Diascorea group assessed at the end of 12 months' treatment (pâ<â0.01). This phenomenon was more significant for the psychological parameters of anxiety than for other parameters. Apparent improvements were noted in the parameters 'feeling tense or nervous' (pâ=â0.007), 'insomnia' (pâ=â0.004), 'excitable' (pâ=â0.047) and 'musculoskeletal pain' (pâ=â0.019) among those receiving Diascorea. Diascorea consumption also resulted in positive effects on blood hormone profiles. CONCLUSIONS: Compared with placebo, Diascorea alata improves symptoms, particularly the psychological parameters in menopausal women. Safety monitoring indicated that standardized extracts of Diascorea alata were safe during daily administration over a period of 12 months.
Assuntos
Climatério/efeitos dos fármacos , Climatério/psicologia , Dioscorea , Medicamentos de Ervas Chinesas , Fitoterapia , Ansiedade/tratamento farmacológico , Índice de Massa Corporal , Sulfato de Desidroepiandrosterona/sangue , Método Duplo-Cego , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , TaiwanRESUMO
Tibolone, which is indicated for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women, has a tissue-specific mode of action different to that of conventional hormone replacement therapy (HRT). A large proportion of Asian postmenopausal women experience symptoms that most frequently include musculoskeletal pain, insomnia, forgetfulness, hot flushes and sexual dysfunction, and there is a need to address their specific requirements. Recent studies show that, in comparison to HRT, tibolone is as effective in alleviating menopausal symptoms and preventing bone loss, has a greater positive effect on sexual dysfunction and is associated with less vaginal bleeding, but it is rarely mentioned in guidelines for menopausal treatment. Levels of awareness amongst women about treatments for menopausal symptoms vary between Asian countries but, even in countries where awareness is high, HRT usage is much lower than in the West. To provide a practical approach to the use of tibolone in Asian postmenopausal women, a panel of experts in the management of menopause from 11 Asia Pacific countries has developed recommendations for its use, based on the evidence from clinical studies published since 2005. However, as much of the clinical data reviewed are from international studies, the recommendations and the treatment algorithm presented here are widely applicable.
Assuntos
Norpregnenos/uso terapêutico , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa , Artralgia , Neoplasias da Mama , Doenças Cardiovasculares , Contraindicações , Moduladores de Receptor Estrogênico , Terapia de Reposição de Estrogênios , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Fogachos/epidemiologia , Humanos , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/prevenção & controle , Norpregnenos/efeitos adversos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , População Rural , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/epidemiologia , População UrbanaRESUMO
These Guidelines summarize the position of an Expert Panel on Menopause in Asian Women regarding the use of hormone replacement therapy (HRT) during the menopausal transition and thereafter. They are intended to aid gynecologists, family physicians and other health-care professionals in providing optimal care to menopausal Asian women who desire HRT.
Assuntos
Terapia de Reposição de Estrogênios/normas , Ginecologia/normas , Menopausa , Padrões de Prática Médica/normas , Ásia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The study sought to compare the vascular resistance and serum lipids of postmenopausal women assigned to tibolone therapy or continuous combined hormone replacement therapy. DESIGN: This was a 6-month, prospective, single-blind, single-center, randomized study. A total of 50 healthy postmenopausal women were enrolled. At study end, 40 women had completed a 6-month follow-up. The first group (23 subjects) received conjugated equine estrogens (CEE) 0.625 mg/day and medroxyprogesterone acetate (MPA) 5 mg/day. The second group (17 subjects) received tibolone 2.5 mg/day. The pulsatility and resistance indexes of the carotid and middle cerebral arteries, and serum lipid profiles were monitored. RESULTS: Comparisons demonstrated that there were no significant differences between the groups in terms of changes in the pulsatility index (PI) and the resistance index (RI) of the common carotid artery (CCA), internal carotid artery (ICA), and middle cerebral artery (MCA) within the study period. Both treatments effectively reduced the total cholesterol level and with no significant differences found between the two regimens. However, in comparing the two groups, we found that high-density lipoprotein (HDL) cholesterol levels were significantly lower in the tibolone group at either 3 months or 6 months after treatment, whereas a significantly higher triglycerides level was observed in the CEE + MPA group after 3 months of treatment. Low-density lipoprotein (LDL) cholesterol levels indicated no significant differences between the two groups after treatment. CONCLUSIONS: The study demonstrated that major neck and cerebral vascular impedance was not influenced significantly by either regimen. Nonetheless, lipid profiles were affected differently by tibolone and by continuous combined CEE + MPA. However, whether or not these findings might modify cardiovascular risk is still unknown.
Assuntos
Artéria Carótida Primitiva/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Norpregnenos/farmacologia , Resistência Vascular/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo , Encéfalo/irrigação sanguínea , Artéria Carótida Primitiva/fisiologia , Artéria Carótida Interna/efeitos dos fármacos , Artéria Carótida Interna/fisiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Circulação Coronária/efeitos dos fármacos , Esquema de Medicação , Moduladores de Receptor Estrogênico/farmacologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Fluxo Pulsátil/efeitos dos fármacos , Método Simples-Cego , Resultado do Tratamento , Triglicerídeos/sangue , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: The beneficial effect of hormone replacement therapy (HRT) on cardiovascular disease has been documented in postmenopausal women, but has a significant time trend. Thus, it is worthwhile to further study whether there are different effects on cardiovascular factors between short- and long-term use of HRT. METHOD: Prospective study of the changes on lipoprotein profile, hemostatic factors, and platelet aggregation was evaluated in 21 postmenopausal women receiving oral E2 valerate (2 mg/d) combined with medroxyprogesterone acetate (10 mg/d) during the last 10 days of each 21-day cycle. The treatment period was 24 months. RESULTS: During the 24 months of treatment, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and atherogenic indices- total cholesterol-to-high-density lipoprotein cholesterol (HDL-C) and LDL-C-to-HDL-C, were significantly reduced. The concentrations of tissue plasminogen activator and plasminogen activator inhibitor-1 were significantly reduced after 12 months of HRT. In addition, the concentrations of antithrombin III were significantly increased, but protein S was statistically decreased during the 18 months of HRT. The maximum aggregation and slope of platelet aggregation were significantly reduced only during the first 12 months of HRT. CONCLUSION: This study demonstrates that there were some differences in cardiovascular risk factors between short- and long-term HRT, especially in changes in platelet aggregation and hemostatic factors. However, the long-term favorable effect on lipoprotein metabolism and fibrinolytic activity among hormone users may explain, in part, the inverse association between HRT and cardiovascular disease.
Assuntos
Terapia de Reposição de Estrogênios , Hemostasia , Lipídeos/sangue , Agregação Plaquetária , Pós-Menopausa/sangue , Feminino , Humanos , Lipoproteínas/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: To determine the effects of oral and transdermal hormone replacement therapy on lipid profile and hemostatic factors in postmenopausal women. DESIGN: Twenty subjects were treated with oral E2 valerate (2 mg) combined with cyproterone acetate (1 mg) (group I) and 21 with transdermal E2 (1.5 mg) plus oral medroxyprogesterone acetate (5 mg) (group II). The effects on lipid profile and hemostatic parameters were evaluated at baseline and after 3, 6, and 12 months of treatment. RESULTS: Group I showed a stronger increase of high-density lipoprotein (HDL) cholesterol levels (2-8%) and stronger reduction of atherogenic indices (total cholesterol/HDL cholesterol and low-density lipoprotein/HDL cholesterol) than group II. Group II showed a more pronounced reduction of triglyceride (21-31%) and factor VII (6-10%) levels than group I. Both groups showed reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, and protein S, whereas protein C was increased after 12 months of treatment. CONCLUSIONS: The cardioprotective effects of hormone replacement therapy are demonstrated by favorable effects on lipid profile and fibrinolytic activity. Oral hormone replacement therapy showed a more prominent effect on lipoprotein metabolism than did transdermal administration, but transdermal medication had a stronger effect on triglyceride and coagulation factors. However, it needs to be considered that there is an increased risk of venous thrombotic events in the first year of treatment.
Assuntos
Doenças Cardiovasculares/epidemiologia , Estradiol/análogos & derivados , Terapia de Reposição de Estrogênios , Hemostasia/efeitos dos fármacos , Administração Cutânea , Administração Oral , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Acetato de Ciproterona/administração & dosagem , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Fibrinólise/efeitos dos fármacos , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Congêneres da Progesterona/administração & dosagem , Fatores de RiscoRESUMO
Although transforming growth factor-beta (TGF-beta) has been identified to mainly inhibit cell growth, the correlation of elevated TGF-beta with increasing serum prostate-specific antigen (PSA) levels in metastatic stages of prostate cancer has also been well documented. The molecular mechanism for these two contrasting effects of TGF-beta, however, remains unclear. Here we report that Smad3, a downstream mediator of the TGF-beta signaling pathway, functions as a coregulator to enhance androgen receptor (AR)-mediated transactivation. Compared with the wild-type AR, Smad3 acts as a strong coregulator in the presence of 1 nM 5alpha-dihydrotestosterone, 10 nM 17beta-estradiol, or 1 microM hydroxyflutamide for the LNCaP mutant AR (mtAR T877A), found in many prostate tumor patients. We further showed that endogenous PSA expression in LNCaP cells can be induced by 5alpha-dihydrotestosterone, and the addition of the Smad3 further induces PSA expression. Together, our findings establish Smad3 as an important coregulator for the androgen-signaling pathway and provide a possible explanation for the positive role of TGF-beta in androgen-promoted prostate cancer growth.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Receptores Androgênicos/metabolismo , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Ativação Transcricional , Fator de Crescimento Transformador beta/metabolismo , Androgênios/metabolismo , Linhagem Celular , Proteínas de Ligação a DNA/fisiologia , Expressão Gênica , Humanos , Masculino , Antígeno Prostático Específico/genética , Neoplasias da Próstata , Receptores Androgênicos/genética , Receptores de Calcitriol/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Elementos de Resposta , Proteína Smad3 , Transativadores/fisiologiaRESUMO
We treated 116 healthy postmenopausal women (age 47-66 years, mean 57 years) in Taiwan with either raloxifene (RLX) 60 mg (n = 92) or 0.625 mg conjugated equine estrogen plus 5 mg medroxyprogesterone acetate (CCEP, n = 24) daily for 12 months in a randomized, double-masked, active-controlled fashion. The results showed that both regimens increased bone mineral density (BMD) at hip sites (means: RLX 2.5-4.9%, CCEP 4.6-7.9%, all p<0.005 compared with baseline), and the difference between the two regimens was not significant. The spinal BMD increased significantly in both groups (1.4% with RLX and 6.0% with CCEP, both p<0.01), and more with CCEP (p<0.003). Osteocalcin levels and urinary type I collagen C-telopeptide/creatinine ratios decreased significantly in both regimens, but the decreases were significantly larger with CCEP. Compared with baseline, both RLX and CCEP decreased the total cholesterol (median 4.9% and 8.6% respectively, p<0.001) and LDL-cholesterol (median 11% and 19% respectively, p<0.001), and increased HDL-cholesterol (median 8.6% and 10.7% respectively, p<0.01). Both regimens increased triglyceride levels (median 3.2% and 18.9% respectively, both p<0.05), although to a lesser extent with RLX than with CCEP (p<0.05). Only 3 subjects (3.3%) reported vaginal bleeding in the RLX group, as compared with 31% (7/22) with CCEP (p<0.05). We conclude that in healthy, postmenopausal Taiwanese women, RLX 60 mg given daily has favorable results in BMD, bone turnover and serum lipids, although the dosage we used showed a potency less than that of conventional CCEP.
Assuntos
Densidade Óssea/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Pós-Menopausa/fisiologia , Cloridrato de Raloxifeno/farmacologia , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Endométrio/anatomia & histologia , Endométrio/efeitos dos fármacos , Estrogênios Conjugados (USP)/farmacologia , Feminino , Articulação do Quadril/fisiologia , Humanos , Lipídeos/sangue , Vértebras Lombares/fisiologia , Acetato de Medroxiprogesterona/farmacologia , Pessoa de Meia-Idade , Congêneres da Progesterona/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Útero/anatomia & histologia , Útero/efeitos dos fármacosRESUMO
OBJECTIVE: The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women. METHODS: Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale. RESULTS: Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse. CONCLUSIONS: The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT.
Assuntos
Moduladores de Receptor Estrogênico/uso terapêutico , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/uso terapêutico , Acetato de Medroxiprogesterona/uso terapêutico , Norpregnenos/uso terapêutico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Adulto , Colesterol/sangue , Estradiol/sangue , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Testes de Função Hepática , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Qualidade de Vida , Disfunções Sexuais Psicogênicas/psicologia , Método Simples-Cego , Inquéritos e Questionários , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
PURPOSE: This study investigated the sperm retrieval success rates, fertilization rates, pregnancy rates, and complications of percutaneous epididymal sperm aspiration (PESA) and microsurgical epididymal sperm aspiration (MESA) in cases of irreparable obstructive azoospermia. METHODS: During a period of 36 months, 100 men with irreparable obstructive azoospermia underwent 109 cycles of sperm retrieval procedures and intracytoplasmic sperm injection (ICSI). We routinely performed PESA first in each retrieval cycle; MESA and/or testicular sperm extraction (TESE) were performed if PESA failed. The sperm retrieval success rates, mean fertilization rates, and pregnancy rates of PESA and MESA were evaluated. RESULTS: PESA was performed in all 109 retrieval cycles with a successful sperm retrieval rate of 61%. When PESA failed to retrieve a sufficient number of viable sperm, MESA was subsequently performed with a sperm retrieval rate of 93%. Three cases, which had failed retrieval with both the PESA and MESA procedures, received TESE successfully. The rates of fertilization and pregnancy were 56% and 39% in the 66 PESA-ICSI cycles, respectively, and 47% and 45% in the 40 MESA-ICSI cycles. No significant differences were found in fertilization rates or pregnancy rates among the various sperm retrieval methods and obstruction etiologies. The overall mean fertilization rate and pregnancy rate were 51% and 41%, respectively. CONCLUSION: Both PESA and MESA can be used successfully to obtain sufficient sperm for ICSI. PESA cannot replace MESA in some cases as some epididymal pathologies prevent its success. The results of this study indicate that PESA should be the treatment of choice for patients with ductal obstruction distal to the epididymis, owing to its higher initial success rate. In contrast, patients with irreparable epididymal obstruction might achieve better success rates with MESA.