RESUMO
Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.
Assuntos
Qualidade do Sono , Humanos , Feminino , Gravidez , Estudos Transversais , Adulto , China , Poluentes Ambientais/urina , Poluentes Ambientais/toxicidade , Selênio/urina , Arsênio/urina , Arsênio/toxicidade , Metais/urina , Metais/toxicidade , Metais Pesados/urina , Metais Pesados/toxicidade , Mercúrio/urina , Mercúrio/toxicidade , Adulto Jovem , Chumbo/urina , Chumbo/toxicidade , Exposição Materna , Cádmio/urina , Cádmio/toxicidade , Primeiro Trimestre da GravidezRESUMO
Survivors of ischemic stroke are still at a significant risk for recurrence. Antiplatelet agents are the treatment of first choice for long-term secondary prevention of vascular events. This study aims to assess a health promotion program on medication adherence to antiplatelet therapy among ischemic stroke patients in Hainan province, China. In five hospitals from the intervention group, four highly experienced physicians trained 62 neurologists, who in turn trained 613 stroke patients to improve their awareness and adherence to antiplatelet therapy. Physicians and patients of the control group received usual stroke management programs. After one-year follow-up, the proportion of patients who took the antiplatelet therapy increased significantly in the intervention group, reaching 73.2%, with a pre-post difference between two arms of 22.9% ( P < 0.01). There was also a significant net increase in the proportion of patients with awareness of antiplatelet therapy (24.4%, P < 0.01). Multivariate analysis illustrated health promotion program, higher education, annual household income, insurance, and medical status affected antiplatelet drug use in stroke patients. In conclusion, the health promotion program, based on a train-the-trainer approach, showed positive eï¬ects on awareness of and adherence to antiplatelet therapy, which has the potential to be scaled up to other resource-limited areas.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Promoção da Saúde/métodos , Adesão à Medicação , Educação de Pacientes como Assunto , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Conscientização , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/psicologia , China , Educação Médica Continuada , Escolaridade , Estudos de Viabilidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Nível de Saúde , Humanos , Renda , Capacitação em Serviço , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neurologistas/educação , Avaliação de Programas e Projetos de Saúde , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Endothelial injury and dysfunction precede accelerated arterial disease in allograft vasculopathy and systemic autoimmune diseases and involve pathogenic Abs and complement. Recent reports suggest that switching to rapamycin from calcineurin antagonists reduces posttransplant vasculopathy and prolongs survival following cardiac transplantion. The majority of these patients also receive statin therapy. We examined potential mechanisms underlying this protective response in human endothelial cells and identified synergy between rapamycin and atorvastatin. Mechanistically, atorvastatin and rapamycin activated a protein kinase Cα, AMP-activated kinase, and CREB-dependent vasculoprotective pathway, which induced decay-accelerating factor (DAF) promoter activity via binding to the cAMP response element, mutation of which attenuated promoter activity. This response significantly increased endothelial cell surface DAF and enhanced protection against complement-mediated injury. Synergy with rapamycin was reproduced by simvastatin, whereas combining atorvastatin with cyclosporine or mycophenolate in place of rapamycin was ineffective. Importantly, synergy was reproduced in vivo, in which only atorvastatin and rapamycin therapy in combination was sufficient to induce DAF on murine aortic endothelium. We believe this pathway represents an important therapeutically inducible vasculoprotective mechanism for diseases mediated by pathogenic Abs and complement, including posttransplant vasculopathy and systemic lupus erythematosus. Although our study focuses on the vascular endothelium, the findings are likely to be broadly applicable, given the diverse cellular expression of DAF.
Assuntos
Citoproteção/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Ácidos Heptanoicos/administração & dosagem , Pirróis/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Sirolimo/administração & dosagem , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Atorvastatina , Antígenos CD55/metabolismo , Ativação do Complemento/efeitos dos fármacos , Ativação do Complemento/fisiologia , Proteínas do Sistema Complemento/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Citoproteção/fisiologia , Sinergismo Farmacológico , Endotélio Vascular/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Imunossupressores/administração & dosagem , Camundongos , Proteína Quinase C/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Catabolism of free heme by heme oxygenase-1 (HO-1) generates carbon monoxide, biliverdin, and free iron (Fe). These end-products are responsible for much of the biologic activity of HO-1, including anti-inflammatory, antiapo-ptotic, antiproliferative, and antioxidant effects. We have identified an additional cytoprotective action, the regulation of complement activation, mediated via induction of decay-accelerating factor (DAF). Pharmacologic inhibition or short-interfering RNA (siRNA) depletion of HO-1 prevented induction of DAF expression in human endothelial cells. In contrast, HO-1 agonists hemin and cobalt protoporphyrin IX significantly increased DAF protein expression, reflecting an increase in transcription and steady-state mRNA. Adenoviral-mediated overexpression of HO-1 increased DAF expression, enhancing protection against C3 deposition and complement-mediated lysis, and this was reversed by DAF inhibitory monoclonal antibody (mAb) 1H4. Likewise, bilirubin, Fe chelation, and overexpression of heavy-chain ferritin all induced DAF expression in endothelial cells (EC). Analysis of cardiac endothelial cells isolated from Hmox1(-/-) mice revealed a 60% reduction in DAF expression compared with Hmox1(+/+) EC, and Hmox1(-/-) cells showed enhanced sensitivity to complement. We propose that modulation of complement activation through induction of DAF represents an important component of the cytoprotective effects of HO-1 against vascular injury, such as that associated with posttransplant vasculopathy, allograft rejection, and ischemia reperfusion.
Assuntos
Bilirrubina/metabolismo , Antígenos CD55/metabolismo , Proteínas do Sistema Complemento/imunologia , Células Endoteliais/imunologia , Ferritinas/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Animais , Antígenos CD55/genética , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/fisiologia , Heme Oxigenase-1/genética , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Protoporfirinas/farmacologia , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo , Veias Umbilicais/citologia , Doenças Vasculares/imunologia , Doenças Vasculares/metabolismoRESUMO
OBJECTIVE: The aim of this study is to analyse the efficacy and toxicity of CEOP regimen in the treatment of non-Hodgkin's lymphoma (NHL). METHODS: From January 1995 to December 2000, 121 patients with NHL were treated by CEOP regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analysed retrospectively. RESULTS: Of these 121 patients, 83 (68.6%) had B-cell NHL and 38(31.4%) peripheral T or NK-cell NHL; 55. 4% (67/121) had early disease (stage I or II), and 89.3% (108/121) had IPI score 0-2. The median age was 53 years (range: 7-79 yr). All patients were treated by CEOP regimen (totally, 471 cycles) with or without radiotherapy. The overall response (OR) rate in this series was 90.9% (110/121) with a complete remission (CR) rate of 71.9% (87/121); whereas the response rate of chemotherapy alone was 88.4% (107/121) with a CR rate of 67.8% (82/121). Major toxicity consisted of grade III-IV myelosuppression (11.9%), neutropenia (1.9%) and thrombocytopenia and anemia (1.1%). Alopecia was observed in 46.3%. However, cardiotoxicity was mild and reversible. Median follow-up duration in this series was 63 months (range: 2-116 months). The overall 1-, 3- and 5-year survival rate was 84.8%, 62.7% and 55.9%, respectively, with a median survival time of 85 months (2-118 months). CONCLUSION: Our data show that CEOP regimen combined with or without radiotherapy for the involved field is effective and well tolerated by the patients with non-Hodgkin's lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Alopecia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Epirubicina/efeitos adversos , Epirubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/radioterapia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/radioterapia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Linfoma de Células T/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Vincristina/efeitos adversos , Vincristina/uso terapêuticoAssuntos
Isquemia Encefálica , Atenção à Saúde , Acidente Vascular Cerebral , Isquemia Encefálica/economia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , China , Análise Custo-Benefício , Atenção à Saúde/economia , Atenção à Saúde/métodos , Atenção à Saúde/normas , Humanos , Tempo de Internação/estatística & dados numéricos , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
Although nonsteroidal anti-inflammatory drugs (NSAIDs) provide important control of pain and inflammation, they have been overshadowed by concerns regarding atherothrombotic complications. However, celecoxib seems to have a relatively good cardiovascular profile and may improve endothelial function in coronary heart disease. This led us to the hypothesis that celecoxib induces the vasculoprotective enzyme heme oxygenase-1 (HO-1). In human umbilical vein and aortic endothelial cells, 24-48 h treatment with celecoxib induced HO-1 mRNA and protein expression and increased HO-1 enzyme activity. This effect was not seen with rofecoxib or indomethacin. Supplementation of culture medium with iloprost or prostaglandin E(2) failed to reverse celecoxib-mediated HO-1 induction, indicating a cyclooxygenase-independent mechanism. Rather, this action of celecoxib involved generation of mitochondria-derived reactive oxygen species, Akt phosphorylation, and nuclear translocation of the transcription factor Nrf2, with N-acetylcysteine, PI-3K antagonist LY290042, and dominant-negative Akt abrogating the effects. Furthermore, celecoxib-induced HO-1 was inhibited by dominant-negative Nrf2. The functional significance of HO-1 induction was revealed by celecoxib-mediated inhibition of VCAM-1 expression, a response reversed by the HO-1 antagonist zinc protoporphyrin. HO-1 induction provides a molecular mechanism for clinical observations indicating relative freedom from atherothrombotic complications in patients taking celecoxib compared to other NSAIDs with comparable anti-inflammatory activity.
Assuntos
Heme Oxigenase-1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Acetilcisteína/farmacologia , Celecoxib , Cromonas/farmacologia , Células Endoteliais/efeitos dos fármacos , Indução Enzimática , Humanos , Lactonas/farmacologia , Morfolinas/farmacologia , Fator 2 Relacionado a NF-E2/farmacologia , Oxirredução , Transporte Proteico/efeitos dos fármacos , Protoporfirinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Molécula 1 de Adesão de Célula Vascular/biossínteseRESUMO
BACKGROUND & OBJECTIVE: The incidence of mucositis caused by autologous hematopoietic stem cell transplantation (AHSCT) is relatively high. The severe painful mucositis can reduce the quality of life of patients obviously. Transdermal fentanyl is efficient in treating chronic pain of cancer, and also can relieve the severe pain of mucositis resulted from chemotherapy. This study was to investigate the efficacy and safety of transdermal fentanyl for the severe painful mucositis caused by AHSCT. METHODS: A total of 22 malignant tumor patients suffered from severe mucositis caused by high dose chemotherapy combined AHSCT. The analgesic degree before and after treatment was evaluated by the scores of Visual Analogue Scale (VAS) (range 0-10). The median VAS scores of all patients were above 4 (moderate to severe pain) before the administration of transdermal fentanyl. The quality of life before and after treatment was evaluated by the Standard of Quality of Life drew up in China in 1990. The adverse events after treatment were evaluated by Common Toxicity Criteria formulated by National Cancer Institute of the USA. RESULTS: The median VAS score has been decreased from baseline at 6 (4-9) to 3.5 (0-9) on Day 3, 2 (0-6) on Day 5, 0.5 (0-8) on Day 7, 0 (0-6) on Day 10, and 0 (0-5) on Day 15 after treatment (P<0.001). The overall response rate was 100%, while the complete response rate was 45.5%. The quality of life of the patients was improved significantly (P<0.01). The adverse events after treatment of transdermal fentanyl included dizziness, somnolence, dysuria, mild and transient nausea, vomiting, discomfort of stomach, and so on. All the adverse events disappeared within several days after proper managements. Neither severe adverse event nor drug addiction was found. CONCLUSIONS: Transdermal fentanyl has good analgesic effect on painful severe mucositis induced by AHSCT. It is convenient and well tolerated, and could improve quality of life significantly.
Assuntos
Analgésicos Opioides/uso terapêutico , Fentanila/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucosite/tratamento farmacológico , Dor/tratamento farmacológico , Administração Cutânea , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/efeitos adversos , Carmustina/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Feminino , Fentanila/administração & dosagem , Humanos , Linfoma não Hodgkin/terapia , Masculino , Melfalan/efeitos adversos , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mucosite/etiologia , Dor/etiologia , Medição da Dor , Podofilotoxina/efeitos adversos , Podofilotoxina/uso terapêutico , Qualidade de Vida , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: The prognosis of relapsed or refractory T-cell non-Hodgkin's lymphoma (T-NHL) is poor. There is no definite prognostic factors and standard regimens for these patients. This study was to explore the prognostic factors and effective regimens for relapsed or refractory T-NHL. METHODS: Clinical records of 45 patients with relapsed or refractory T-NHL, treated in Cancer Center of Sun Yat-sen University from Jan. 1997 to Mar. 2003, were analyzed in terms of response, long-term survival and prognostic factors. RESULTS: By the end of Jul. 2006, 5 patients still alive; the median follow-up time was 30 (2-70) months. The median survival time after relapse was 22 (2-62) months. Of the 45 patients, 42 (93.3%) received salvage regimen, the response rate was 61.9% (26/42); for those received second-line chemotherapy, the response rate was 52.4% (22/42). The 1-, 3-, and 5-year overall survival rates were 75.6%, 17.8%, and 4.4% for the whole group, 82.1%, 25.0%, and 5.8% for low risk group and 64.7%, 6.5%, and 6.5% for high risk group, respectively (P=0.026). Multivariate analysis showed that serum lactate dehydrogenase (LDH) level (P=0.010), second-line Ann Arbor stage (P=0.009), second-line IPI score (P=0.015), autologous stem cell transplantation (P=0.026), performance status (P=0.002), and IMVP-16 regimen (P=0.026) were independent prognostic factors of relapsed or refractory T-NHL. CONCLUSIONS: Second-line IPI score, autologous stem cell transplantation, and so on, may be independent prognostic factors for relapsed or refractory T-NHL. The prognosis of this disease is poor and the addition of intensive treatments, such as stem cell transplantation, should be considered when alleviated after chemotherapy.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação , Adolescente , Adulto , Idoso , Criança , Terapia Combinada , Feminino , Seguimentos , Humanos , L-Lactato Desidrogenase/sangue , Linfoma de Células T/sangue , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: Peripheral T-cell lymphoma (PTCL) is a group of heterogeneous malignancy with poor prognosis. The role of international prognostic index (IPI) in PTCL remains to be determined. It is necessary to find new molecular markers for PTCL. This study was to evaluate the clinical significance of nm23-H1 and MUC-1 in predicting the prognosis of PTCL. METHODS: The expression of nm23-H1 and MUC-1 proteins in 96 specimens of PTCL was detected by SP immunohistochemistry. The correlations of nm23-H1 and MUC-1 expression to clinical features, objective response, and overall survival of PTCL patients were analyzed. RESULTS: Of the 96 patients, 78 (81.2%) were nm23-H1-positive, 56 (58.3%) were MUC-1-positive. Neither of the expression of nm23-H1 and MUC-1 was correlated to the pathologic subtype of PTCL (P>0.05). The high expression of nm23-H1 was associated with some poor prognostic factors such as stage III-IV, performance status (PS)> or =2, extranodal involvement, and more than one site of extranodal involvement (P<0.05). The high expression of MUC-1 was only associated with stage III-IV and more than one site of extranodal involvement (P<0.05). Of the 89 patients with evaluable disease, the overall response rate was 87.8% with a complete remission (CR) rate of 56.7%. The CR rate was significantly higher in nm23-H1-negative patients than in nm23-H1-positive patients (66.7% vs. 55.4%, P<0.05), and significantly higher in the patients with low nm23-H1 expression than in those with high nm23-H1 expression (79.9% vs. 44.0%, P<0.05); the CR rate was higher in MUC-1-negative patients than in MUC-1-positive patients, and higher in the patients with low MUC-1 expression than in those with high MUC-1 expression, but the differences were not significant. The median follow-up of the whole group was 30 months (range, 2-98 months), and the median survival time was 32 months [95% confidence interval (CI)= 26-34 months]. The overall 5-year survival rate of the whole group was 35.1%. The overall 5-year survival rate was significantly higher in nm23-H1-negative patients than in nm23-H1-positive patients (86.7% vs. 24.9%, P=0.001), and significantly higher in the patients with low nm23-H1 expression than in those with high nm23-H1 expression (52.3% vs. 21.7%, P<0.001). The overall 5-year survival rate was slightly higher in MUC-1-negative patients than in MUC-1-positive patients (47.9% vs. 28.5%, P>0.05), and slightly higher in the patients with low MUC-1 expression than in those with high MUC-1 expression (46.2% vs. 22.2%, P>0.05). Multivariant analysis showed that IPI score and nm23-H1 expression were independent prognostic factors of PTCL. CONCLUSIONS: Overexpression of nm23-H1 is related to poor prognosis of PTCL; it may be a potential prognostic index of PTCL. Overexpression of MUC-1 is not related to.