Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(10): 1012-1017, 2019 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-31607047

RESUMO

Objective: Using three models too estimate excess mortality associated with influenza of Shanxi Province during 2013-2017. Methods: Mortality data and influenza surveillance data of 11 cities of Shanxi Province from the 2013-2014 through 2016-2017 were used to estimate influenza-associated all cause deaths, circulatory and respiratory deaths and respiratory deaths. Three models were used: (i) Serfling regression, (ii)Poisson regression, (iii)General line model. Results: The total reported death cases of all cause were 157 733, annual death cases of all cause were 39 433, among these cases, male cases 93 831 (59.50%), cases above 65 years old 123 931 (78.57%). Annual influenza-associated excess mortality, for all causes, circulatory and respiratory deaths, respiratory deaths were 8.62 deaths per 100 000, 6.33 deaths per 100 000 and 0.68 deaths per 100 000 estimated by Serfling model, respectively; and 21.30 deaths per 100 000, 16.89 deaths per 100 000 and 2.14 deaths per 100 000 estimated by General line model, respectively; and 21.76 deaths per 100 000, 17.03 deaths per 100 000 and 2.05 deaths per 100 000, estimated by Poisson model, respectively. Influenza-related excess mortality was higher in people over 75 years old; influenza-associated excess mortalityfor all causes, circulatory and respiratory deaths, respiratory deaths were 259.67 deaths per 100 000, 229.90 deaths per 100 000 and 32.63 deaths per 100 000, estimated by GLM model, respectively; and 269.49 deaths per 100 000, 233.69 deaths per 100 000 and 31.27 deaths per 100 000, estimated by Poisson model,respectively. Conclusion: Excess mortality associated with influenza mainly caused by A (H3N2), Influenza caused the most associated death amongold people.


Assuntos
Influenza Humana/epidemiologia , China/epidemiologia , Cidades , Humanos , Vírus da Influenza A Subtipo H3N2 , Mortalidade/tendências
2.
Zhonghua Yi Xue Za Zhi ; 99(10): 778-782, 2019 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-30884635

RESUMO

Objective: To evaluate the effectiveness and safety of transurethral bipolar plasmakinetic prostatectomy in the treatment of benign prostatic hyperplasia in high-risk and senior patients in China. Methods: The PubMed, Cochrane Library, CBM, CNKI and WanFang databases were searched with computer for collecting relevant interventional case series from establishment dates to September 14, 2018. After quality evaluation and data extraction independently conducted by two authors, the Meta-analysis was performed using the Comprehensive Meta-analysis V2 software. Results: Eighteen studies involving 1 899 patients are included. Maximum flow rate increased to 12.28 ml/s (95%CI: 8.42-16.14), 12.88 ml/s (95%CI: 9.85-15.92) ,14.32 ml/s (95%CI: 10.47-18.18), 14.93 ml/s (95%CI: 10.19-19.67) and 20.00 ml/s (95%CI: 19.08-20.92) in 1, 3, 6, 12 and 24 months after surgery, respectively. International prostate symptom score decreased to -18.60 (95%CI: -23.20--14.00), -17.62 (95%CI: -20.21--15.03), -19.14 (95%CI: -20.70--17.59), -19.06 (95%CI: -21.53--16.60) and -22.90 (95%CI: -24.26--21.54), respectively. Quality of life decreased to -2.38 (95%CI: -4.26--0.50), -3.39 (95%CI: -4.57--2.21),-3.75 (95%CI: -4.14--3.36), -3.36(95%CI: -4.56--2.16), and -4.58(95%CI: -4.75--4.41). Post void residual decreased to -231.16 ml (95%CI: -288.30--174.01), -76.10 ml (95%CI: -116.71--35.50), -159.90 ml(95%CI: -207.21--112.59) and -87.70 ml (95%CI: -91.91--83.48). The event rate of postoperative adverse reactions all were not high. Conclusion: Transurethral bipolar plasmakinetic prostatectomy has better clinical efficacy and no obvious side effects in the treatment of benign prostatic hyperplasia in high-risk and senior patients in China.


Assuntos
Transtorno Bipolar , Hiperplasia Prostática , Ressecção Transuretral da Próstata , China , Humanos , Masculino , Prostatectomia , Qualidade de Vida , Resultado do Tratamento
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 52(11): 1101-1114, 2018 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-30419692

RESUMO

Seasonal influenza vaccination is the most effective way to prevent influenza virus infection and complications from infection. Currently, China has licensed trivalent inactivated influenza vaccine (IIV3) and quadrivalent inactivated influenza vaccine (IIV4), including split-virus influenza vaccine and subunit vaccine. Except for a few major cities, influenza vaccine is a category Ⅱ vaccine, which means influenza vaccination is voluntary, and recipients must pay for it. To strengthen the technical guidance for prevention and control of influenza and operational research on influenza vaccination in China, the National Immunization Advisory Committee (NIAC) Influenza Vaccine Technical Working Group (TWG), updated the 2014 technical guidelines and compiled the "Technical guidelines for seasonal influenza vaccination in China (2018-2019)" . The main updates in this version include: epidemiology, disease burden, types of influenza vaccines, northern hemisphere influenza vaccination composition for the 2018-2019 season, IIV3 and IIV4 immune response, durability of immunity, immunogenicity, vaccine efficacy, effectiveness, safety, cost-effectiveness and cost-benefit. The influenza vaccine TWG provided the recommendations for influenza vaccination for the 2018-2019 influenza season based on existing scientific evidence. The recommendations described in this report include the following: Points of Vaccination clinics (PoVs) should provide influenza vaccination to all persons aged 6 months and above who are willing to be vaccinated and do not have contraindications. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended, and appropriate product is available. To decrease the risk of severe infections and complications due to influenza virus infection among high risk groups, the recommendations prioritize seasonal influenza vaccination for children aged 6-59 months, adults ≥60 years of age, persons with specific chronic diseases, healthcare workers, the family members and caregivers of infants <6 months of age, and pregnant women or women who plan to become pregnant during the influenza season. Children aged 6 months through 8 years require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection. If they were vaccinated in 2017-2018 influenza season or a prior season, 1 dose is recommended. People more than 8 years old require 1 dose of influenza vaccine. It is recommended that people receive their influenza vaccination by the end of October. Influenza vaccination should be offered as soon as the vaccination is available. For the people unable to be vaccinated before the end of October, influenza vaccination will continue to be offered for the whole season. Influenza vaccine is also recommended for use in pregnant women during any trimester. These guidelines are intended for use by staff members of the Centers for Disease Control and Prevention at all levels who work on influenza control and prevention, PoVs staff members, healthcare workers from the departments of pediatrics, internal medicine, and infectious diseases, and staff members of maternity and child care institutions at all levels.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Gravidez , Estações do Ano
4.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(11): 1413-1425, 2018 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-30462947

RESUMO

Seasonal influenza vaccination is the most effective way to prevent influenza virus infection and its complications. Currently, China has licensed trivalent (IIV3) and quadrivalent inactivated influenza vaccine (IIV4), including split-virus influenza vaccine and subunit vaccine. In most parts of China, influenza vaccine is a category Ⅱ vaccine, which means influenza vaccination is voluntary, and recipients need to pay for it. To strengthen the technical guidance for prevention and control of influenza and the operational research on influenza vaccination in China, the National Immunization Advisory Committee (NIAC), Influenza Vaccine Technical Working Group (TWG), updated the 2014 technical guidelines and compiled the "Technical guidelines for seasonal influenza vaccination in China (2018-2019)" , based on most recent existing scientific evidences. The main updates include: epidemiology and disease burden of influenza, types of influenza vaccines, northern hemisphere influenza vaccination composition for the 2018-2019 season, and, IIV3 and IIV4 vaccines'major immune responses, durability of immunity, immunogenicity, vaccine efficacy, effectiveness, safety, cost-effectiveness and cost-benefit. The recommendations include: Points of Vaccination clinics (PoVs) should provide influenza vaccination to all persons aged 6 months and above who are willing to be vaccinated and do not have contraindications. No preferential recommendation is made for any influenza vaccine product for persons who can accept ≥1 licensed, recommended, and appropriate products. To decrease the risk of severe infections and complications due to influenza virus infection among high risk groups, the recommendations prioritize seasonal influenza vaccination for children aged 6-60 months, adults ≥60 years of age, persons with specific chronic diseases, healthcare workers, the family members and caregivers of infants <6 months of age, and pregnant women or women who plan to pregnant during the influenza season. Children aged 6 months to 8 years old require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection. If they were vaccinated in previous influenza season, 1 dose is recommended. People ≥ 9 years old require 1 dose of influenza vaccine. It is recommended that people receive their influenza vaccination by the end of October. Influenza vaccination should be offered as soon as the vaccination is available. Influenza vaccination should continue to be available for those unable to be vaccinated before the end of October during the whole season. Influenza vaccine is also recommended for use in pregnant women during any trimester. These guidelines are intended for CDC members who are working on influenza control and prevention, PoVs members, healthcare workers from the departments of pediatrics, internal medicine, and infectious diseases, and members of maternity and child care institutions at all levels.


Assuntos
Guias como Assunto , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Estações do Ano , Adulto , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Gravidez , Vacinação
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(8): 1028-1031, 2018 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-30180422

RESUMO

Five influenza pandemics had occurred during the past century (1918 "Spanish flu" , 1957 "Asian flu" , 1968 "Hong Kong flu" , 1977 "Russian flu" and 2009 H1N1 Pandemic), accounting for hundreds of millions of people infected and tens of millions dead. China was influenced by all the five pandemics, and three of them (1957 "Asian flu" , 1968 "Hong Kong flu" and 1977 "Russian flu" ) were originated from China. The pandemics triggered the establishment of public health agencies and influenza surveillance capacities. In addition, more resources were allocated to influenza-related research, prevention and control. As a leader in the field of influenza, China should further strengthen its pandemic preparedness and response to contribute to global health.


Assuntos
Surtos de Doenças/história , Influenza Humana/epidemiologia , Pandemias/história , Saúde Pública , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , História do Século XX , História do Século XXI , Hong Kong , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/história
6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(8): 1045-1050, 2018 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-30180426

RESUMO

Influenza can be prevented through annual appropriate vaccination against the virus concerned. In China, influenza vaccine is categorized as "Class Ⅱ" infectious diseases which the cost is paid out of the user's pockets. The annual coverage of influenza vaccination had been 2%-3%. The main reasons for the low coverage would include the following factors: lacking awareness on both the disease and vaccine, poor accessibility of vaccination service, and the cost of vaccination. To reduce the health and economic burden associated with influenza, comprehensive policies should be improved, targeting the coverage of seasonal influenza vaccination. These items would include: ① Different financing reimbursement schemes and mechanisms to improve the aspiration on vaccination and on the vaccine coverage in high-risk groups, as young children, elderly, people with underlying medical conditions; ② to ameliorate equality of vaccination services; ③ to improve knowledge of the health care workers (HCWs) and the public on influenza and related vaccines; ④ to improve clinical and preventive medical practice and vaccination among HCWs through revising clinical guidelines, pathway and consensus of experts; ⑤ to provide more convenient, accessible and normative vaccination service system; ⑥ to strengthen research and development as well as marketing on novel influenza vaccines; ⑦ to revise items regarding the contraindication for influenza vaccine on pregnancy women, stated in the Chinese Pharmacopoeia.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Promoção da Saúde/métodos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinação , Idoso , Conscientização , Criança , China , Custos e Análise de Custo , Feminino , Humanos , Vacinas contra Influenza/economia , Masculino , Gravidez
7.
Braz J Med Biol Res ; 51(7): e7218, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29742266

RESUMO

The aim of this study was to investigate the efficacy, acceptability, and tolerability of antidepressants in treating post-stroke depression (PSD) by performing a network meta-analysis of randomized controlled trials of the current literature. Eligible studies were retrieved from online databases, and relevant data were extracted. The primary outcome was efficacy as measured by the mean change in overall depressive symptoms. Secondary outcomes included discontinued treatment for any reason and specifically due to adverse events. Fourteen trials were eligible, which included 949 participants and 9 antidepressant treatments. Few significant differences were found for all outcomes. For the primary outcome, doxepin, paroxetine, and nortriptyline were significantly more effective than a placebo [standardized mean differences: -1.93 (95%CI=-3.56 to -0.29), -1.39 (95%CI=-2.59 to -0.21), and -1.25 (95%CI=-2.46 to -0.04), respectively]. Insufficient evidence exists to select a preferred antidepressant for treating patients with post-stroke depression, and our study provides little evidence that paroxetine may be the potential choice when starting treatment for PSD. Future studies with paroxetine and larger sample sizes, multiple medical centers, and sufficient intervention durations is needed for improving the current evidence.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/etiologia , Acidente Vascular Cerebral/complicações , Feminino , Humanos , Masculino , Meta-Análise em Rede , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Resultado do Tratamento
8.
Andrology ; 6(1): 37-46, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28950433

RESUMO

Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta-analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta-analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of -6.44 (95% CI: -11.82 to -1.06; I2  = 28%; p = 0.02) and -27.94 (95% CI: -52.33 to -3.54; I2  = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2  = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2  = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL-C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2  = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: -4.55 to 6.60; I2  = 91%; p = 0.72). However, LDL-C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.


Assuntos
Androgênios/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Eunuquismo/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Testosterona/uso terapêutico , Idoso , Eunuquismo/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Cell Mol Biol (Noisy-le-grand) ; 63(5): 68-74, 2017 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-28719348

RESUMO

Renal cell carcinoma (RCC) is the most common renal neoplasms and metastatic is common. Previous data have shown that the tripartite motif (TRIM) family proteinswere implicated in human tumoriogenesis. In this study, we aimed to investigate the role of TRIM59 in the cell growth and migration in RCC. The expression of TRIM59 in human RCC tissues was initially examined by qRT-PCR. Alentivirus-based shRNA against TRIM59 (Lv-shTRIM59) was constructed. The effects of TRIM59 knockdown on cell proliferation were examined by in vitro MTT assay, colony formation assay and in vivo a mouse xenograft model of RCC. Cell migration and invasion after knockdown of TRIM59 were also examined by transwell assay. Our data showed that the mRNA level of TRIM59 in cancerous tissues was 2-fold increased as compared with non-cancerous tissues. Knockdown of TRIM59 in a RCC cell line 786-O significantly slowed down cell proliferative rate and decreased both the colony number and sizes. In the mouse model, knockdown of TRIM59 consistently inhibited tumor growth in vivo. Moreover, it was shown that cell migration and invasion were suppressed by 68% and 50%, respectively in TRIM59-depleted 786-O cells. Our data suggest that TRIM59 may serve as a pro-oncogenic protein in promoting the progression of RCC. Knockdown of TRIM59 may be a promising strategy concerning the early detection and treatment of RCC.


Assuntos
Carcinoma de Células Renais/patologia , Movimento Celular , Neoplasias Renais/patologia , Proteínas de Membrana/metabolismo , Metaloproteínas/metabolismo , Animais , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/genética , Lentivirus/metabolismo , Proteínas de Membrana/genética , Metaloproteínas/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 38(3): 374-377, 2017 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-28329943

RESUMO

Objective: To estimate the influence of the ambient PM(l0) and PM(2.5) pollution on the hospital outpatient department visit due to respiratory diseases in local residents in Jinan quantitatively. Methods: Time serial analysis using generalized addictive model (GAM) was conducted. After controlling the confounding factors, such as long term trend, weekly pattern and meteorological factors, considering lag effect and the influence of other air pollutants, the excess relative risks of daily hospital visits associated with increased ambient PM(10) and PM(2.5) levels were estimated by fitting a Poisson regression model. Results: A 10 µg/m(3) increase of PM(10) and PM(2.5) levels was associated with an increase of 0.36%(95%CI: 0.30%-0.43%) and 0.50%(95%CI: 0.30%-0.70%) respectively for hospital visits due to respiratory diseases. Lag effect of 6 days was strongest, the excess relative risks were 0.65% (95% CI: 0.58% -0.71% ) and 0.54% (95% CI: 0.42%-0.67%) respectively. When NO(2) concentration was introduced, the daily hospital visits due to respiratory disease increased by 0.83% as a 10 µg/m(3) increase of PM(10) concentration (95% CI: 0.76%-0.91%). Conclusion: The ambient PM(l0) and PM(2.5) pollution was positively associated with daily hospital visits due to respiratory disease in Jinan, and ambient NO(2) concentration would have the synergistic effect.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Ambulatório Hospitalar/estatística & dados numéricos , Material Particulado/efeitos adversos , Doenças Respiratórias/etiologia , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Assistência Ambulatorial , Exposição Ambiental/análise , Humanos , Conceitos Meteorológicos , Modelos Teóricos , Pacientes Ambulatoriais , Material Particulado/análise , Doenças Respiratórias/epidemiologia
11.
12.
13.
Sci Rep ; 5: 15001, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26462875

RESUMO

In order to enhance the mechanical strength of Low-E glass, Fluorine-doped tin oxide (FTO) films have to be tempered at high temperatures together with glass substrates. The effects of tempering temperature (600 °C ~ 720 °C) and time (150 s ~ 300 s) on the structural and electrical properties of FTO films were investigated. The results show all the films consist of non-stoichiometric, polycrystalline SnO2 without detectable amounts of fluoride. 700 °C and 260 s may be the critical tempering temperature and time, respectively. FTO films tempered at 700 °C for 260 s possesses the resistivity of 7.54 × 10(-4) Ω â€¢ cm, the average transmittance in 400 ~ 800 nm of ~80%, and the calculated emissivity of 0.38. Hall mobility of FTO films tempered in this proper condition is mainly limited by the ionized impurity scattering. The value of [O]/[Sn] at the film surface is much higher than the stoichiometric value of 2.0 of pure crystalline SnO2.

14.
Genetika ; 42(3): 391-6, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16649666

RESUMO

Genetic map containing 103 microsatellite loci obtained on 200 F2 plants derived from the cross R15 x 478 was used for quantitative trait loci (QTL) mapping in maize. QTL were characterized in a population of 200 F2:4 lines, derived from selfing the F2 plants, and were evaluated with two replications in two environments. QTL determinations were made from the mean of these two environments. Plant height (PH) and ear height (EH) were measured. Using composite interval mapping (CIM) method, a total of 14 distinct QTLs were identified: nine for PH and five for EH. Additive, partial dominance, dominance, and overdominance actions existed among all detected QTL affecting plant height and ear height. The QTL explained 78.27% of the phenotypic variance of PH and 41.50% of EH. The 14 QTLs displayed mostly dominance or partial dominance gene action and mapped to chromosomes 2, 3, 4, 8 and 9.


Assuntos
Cromossomos de Plantas/genética , Repetições de Microssatélites/genética , Locos de Características Quantitativas , Zea mays/anatomia & histologia , Zea mays/genética , Mapeamento Cromossômico , Genes Dominantes , Genes de Plantas , Fenótipo
15.
Int J Hyperthermia ; 20(8): 835-49, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15764345

RESUMO

The 70 kD heat shock protein (HSP70) plays essential cellular roles in mediating intracellular protein folding and protecting cells from proteotoxic stress. This study has examined the role of HSP70 in the expression of apoptosis in prostate carcinoma cells. Apoptosis was negatively correlated with HSP70 expression in PC-3 cells heat shocked in vivo. Further experiments carried out on an in vitro reconstituted system with isolated nuclei and cytoplasm from PC-3 cells showed that purified HSP70 directly inhibits apoptosis in a dose-dependant manner. Therefore, the potential role of depletion of intracellular HSP70 was examined as a means of inducing apoptosis in PC-3 cancer cells. Depletion of HSP70 by two independent strategies, either with anti-sense oligonucleotides directed against HSP70 mRNA or with the bioflavinoid drug quercetin, led to apoptosis in the absence of stress. In addition, quercetin pre-treatment synergistically enhanced apoptosis in combination with heat shock. Thus, HSP70 plays a physiological role in tumour cells as an inhibitor of apoptosis occurring both spontaneously and after stress and is a potential target for apoptosis-based cancer therapy.


Assuntos
Apoptose/fisiologia , Proteínas de Choque Térmico HSP70/fisiologia , Neoplasias da Próstata/fisiopatologia , Esfingosina/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Inibidores de Caspase , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Sistema Livre de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , DNA Antissenso/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/farmacologia , Proteínas de Choque Térmico HSP72 , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico/efeitos dos fármacos , Temperatura Alta , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Neoplasias da Próstata/patologia , Quercetina/farmacologia , Serpinas/farmacologia , Esfingosina/farmacologia , Proteínas Virais/farmacologia
16.
J Immunol ; 163(10): 5608-16, 1999 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-10553090

RESUMO

Sodium salicylate (NaSal) and other nonsteroidal anti-inflammatory drugs (NSAIDs) coordinately inhibit the activity of NF-kappa B, activate heat shock transcription factor 1 and suppress cytokine gene expression in activated monocytes and macrophages. Because our preliminary studies indicated that these effects could be mimicked by inhibitors of signal transduction, we have studied the effects of NSAIDs on signaling molecules potentially downstream of LPS receptors in activated macrophages. Our findings indicate that ribosomal S6 kinase 2 (RSK2), a 90-kDa ribosomal S6 kinase with a critical role as an effector of the RAS-mitogen-activated protein kinase pathway and a regulator of immediate early gene transcription is a target for inhibition by the NSAIDs. NSAIDs inhibited the activity of purified RSK2 kinase in vitro and of RSK2 in mammalian cells and suppressed the phosphorylation of RSK2 substrates cAMP response element binding protein (CREB) and I-kappa B alpha in vivo. Additionally, NaSal inhibited the phosphorylation by RSK2 of CREB and I-kappa B alpha on residues crucial for their transcriptional activity in vivo and thus repressed CREB and NF-kappa B-dependent transcription. These experiments suggest that RSK2 is a target for NSAIDs in the inhibition of monocyte-specific gene expression and indicate the importance of RSK2 and related kinases in cell regulation, indicating a new area for anti-inflammatory drug discovery.


Assuntos
Aspirina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Inibidores Enzimáticos/farmacologia , NF-kappa B/genética , Proteínas Quinases S6 Ribossômicas/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas/fisiologia , Ácido Salicílico/farmacologia , Transcrição Genética/efeitos dos fármacos , Células 3T3 , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Ativação Enzimática , Células HeLa , Humanos , Interfase/efeitos dos fármacos , Interfase/imunologia , Lipopolissacarídeos/imunologia , Camundongos , Mitógenos/imunologia , Monócitos/efeitos dos fármacos , Monócitos/enzimologia , NF-kappa B/antagonistas & inibidores , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas/isolamento & purificação , Proteínas Quinases S6 Ribossômicas/metabolismo , Especificidade por Substrato/efeitos dos fármacos
17.
Yao Xue Xue Bao ; 32(6): 447-50, 1997 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-11596326

RESUMO

Three compounds have been isolated from the dichloromethane soluble fraction of the fruiting body of Ganoderma lucidum (Fr.) Karst. On basis of spectral analyses (UV, IR, MS, 1HNMR, 13CNMR and 2D-NMR), they were identified as 3, 7-dioxo-lanosta-8, 24(E)-dien-26-oic acid (I), 7 beta-15 alpha-dihydroxy-3, 11, 23-trioxo-5 alpha-lanost-8-en-26-oic acid (II) and 3 beta, 7 beta, 15 alpha-trihydroxy-11, 23-dioxo-5 alpha-lanosta-8-en-26-oic acid (III). Compound I is a new compound named ganoderic acid DM.


Assuntos
Medicamentos de Ervas Chinesas/química , Lanosterol/isolamento & purificação , Polyporaceae/química , Reishi/química , Triterpenos/isolamento & purificação , Lanosterol/análogos & derivados , Lanosterol/química , Estrutura Molecular , Triterpenos/química
18.
Free Radic Res ; 23(3): 229-43, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7581818

RESUMO

The competition method in which the Fenton reaction is employed as an .OH radical generator and deoxyribose as a detecting molecule, has been used to determine the rate constants for reactions of the .OH radical with its scavengers. Nonlinear competition plots were obtained for those scavengers which reacted with the Fenton reagents (Fe2+ or H2O2). Ascorbic acid is believed to overcome this problem. We have investigated the kinetics of deoxyribose degradation by .OH radicals generated by the Fenton reaction in the presence of ascorbic acid, and observed that the inclusion of ascorbic acid in the Fenton system greatly increased the rate of .OH radical generation. As a result, the interaction between some scavengers and the Fenton reagents became negligeable and linear competition plots of A degree/A vs scavenger concentrations were obtained. The effects of experimental conditions such as, the concentrations of ascorbic acid, deoxyribose, H2O2 and Fe(2+)-EDTA, the EDTA/Fe2+ ratio as well as the incubation time, on the deoxyribose degradation and the determination of the rate constant for mercaptoethanol chosen as a reference compound were studied. The small standard error, (6.76 +/- 0.21) x 10(9) M-1s-1, observed for the rate constant values for mercaptoethanol determined under 13 different experimental conditions, indicates the latter did not influence the rate constant determination. This is in fact assured by introducing a term, kx, into the kinetic equation. This term represents the rate of .OH reactions with other reagents such as ascorbic acid, Fe(2+)-EDTA, H2O2 etc. The agreement of the rate constants obtained in this work with that determined by pulse radiolysis techniques for cysteine, thiourea and many other scavengers, suggests that this simple competition method is applicable to a wide range of compounds, including those which react with the Fenton reagents and those whose solubility in water is low.


Assuntos
Ácido Ascórbico/metabolismo , Desoxirribose/metabolismo , Radical Hidroxila/metabolismo , Peróxido de Hidrogênio , Ferro , Cinética
19.
J Chromatogr B Biomed Appl ; 656(2): 441-6, 1994 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-7987500

RESUMO

A relatively rapid, inexpensive, sensitive and stereospecific gas chromatographic-mass spectrometric method was developed for the quantification of S(+) and R(-)-ibuprofen in human plasma. This method uses a commercially available internal standard and has no interference from endogenous substances nor metabolites. The method involves derivatization of ibuprofen enantiomers with optically active R(-)-2,2,2-trifluoro-1-(9-anthryl)ethanol using oxalyl chloride as the coupling reagent. The subsequently formed diastereoisomers are separated by gas chromatography and analysed by mass spectrometry using selected-ion monitoring. The assay is successfully applied to a pharmacokinetic study. The simplicity, sensitivity and precision of the method make it convenient for the quantification of ibuprofen enantiomers in biological samples.


Assuntos
Ibuprofeno/sangue , Antracenos , Artrite Reumatoide/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Ibuprofeno/farmacocinética , Indicadores e Reagentes , Estereoisomerismo , Trifluoretanol/análogos & derivados
20.
J Biol Chem ; 267(28): 20181-7, 1992 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-1356975

RESUMO

The adenovirus E1a protein (E1A) regulates transcription through interaction with transcription factors bound to DNA, like cAMP response element BP1/ATF2, or through dissociating E2F transcription factor complex. However, it was also reported that E1A can bind to DNA (Chatterjee, P. K., Bruner, M., Flint, S. J., and Harter, M. L. (1988) EMBO J. 7, 835-841), and it is not clear whether DNA binding of E1A is involved in a part of the process of transcriptional regulation by E1A. In this paper, the small region of E1A that is responsible for DNA binding was identified and a point mutant lacking DNA binding activity was constructed. Analysis of deletion mutants of E1A proteins expressed in bacteria showed that a basic region between amino acids 201 and 216 of E1A is essential for DNA binding. Point mutation of arginines at amino acid numbers 205 and 206 to aspartic acids completely abolished the DNA binding activity of E1A. Using this mutant, the requirement of the E1A DNA binding for E1A-dependent transcriptional regulation was examined. trans-Activation of the adenovirus E4 promoter and trans-repression of the human c-erbB-2 promoter by this point mutant were examined by cotransfection experiments. Mutations of the E1A DNA-binding domain affected neither the E1A-induced trans-activation nor trans-repression at all. These results give complete proof that the DNA binding activity of E1A is not required for transcriptional regulation by E1A.


Assuntos
Proteínas E1A de Adenovirus/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Viral da Expressão Gênica , Mutação , Transcrição Genética , Sequência de Bases , Dados de Sequência Molecular , Plasmídeos , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Receptor ErbB-2 , Ativação Transcricional
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA