RESUMO
Objective: To explore correlative factors and construct predictive model of intestinal flora imbalance in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods: The patients in acute exacerbation stage of COPD (AECOPD) hospitalized in Yixing People's Hospital from January 1 to December 31, 2019 were included. According to the clinical symptoms and results of fecal examination, the subjects were divided into case group (n=45) and control group (n=83). Multivariate logistic regression was used to analyze the correlative factors of intestinal flora imbalance in AECOPD patients. The prediction model of intestinal flora imbalance in patients with AECOPD was constructed according to the results of factor logistic regression analysis, and the effectiveness of the prediction model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The ages of subjects in case group and control group were (76±9) and (74±8) years old, respectively, among which males accounted for 80.0% (36/45) and 69.9% (58/83), respectively. The multivariate logistic regression model analysis showed that serum albumin concentration, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus were correlative factors of intestinal flora imbalance in patients with AECOPD. The OR (95%CI) were 0.98 (0.80-0.97), 3.70 (1.79-11.72), 2.62 (1.46-10.80) and 3.85 (1.17-8.58), respectively. The prediction model of intestinal flora imbalance was logit P=3.858-0.13×serum albumin consentration+1.52×acute exacerbation ≥2 times/year+1.379×chronic cor pulmonale+1.155×diabetes mellitus. The area under the ROC curve of this model was 0.847 and the sensitivity and specificity of the prediction model were 88.9% and 71.1%, respectively. Conclusions: Serum albumin, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus are correlative factors of intestinal flora imbalance in patients with AECOPD. The predictive model shows high clinical value in predicting intestinal flora imbalance in patients with AECOPD.
Assuntos
Microbioma Gastrointestinal , Doença Pulmonar Obstrutiva Crônica , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Análise Fatorial , Humanos , Modelos Logísticos , Masculino , Curva ROCRESUMO
In this study, a Bayesian risk-induced interval stochastic modeling framework (BRISF) is proposed for planning effluent trading program among point and nonpoint sources as well as identifying interactions of important trading factors under system risk. BRISF incorporates nutrient fate modeling with soil and water assessment tool (SWAT), Bayesian inference with random walk Metropolis algorithm (RWM), and constraint-violation risk-based two-stage stochastic programming (CRTSP) within a general framework. Bayesian inference is employed for uncertainty analysis of SWAT model parameters and uncertain prediction of nutrient loadings; this process provides the random inputs for optimization process. CRTSP is capable of dealing with multiple uncertainties in modeling effluent trading program as well as system risk of environmental allowance violation. BRISF is applied to a real case of Xiangxihe watershed in China for water quality management. Solutions for optimal trading scheme corresponding to different risk levels are generated. Thousands of scenarios are examined to analyze the individual and interactive effects of trading ratios and treatment rates on trading system. Comparison between cross-industry and intra-industry effluent trading scheme is also conducted. It is proved that cross-industry trading would bring about higher benefit with reduced pollution loading; cross-industry effluent trading scheme would be recommended to achieve optimal water quality management and system benefit.
Assuntos
Monitoramento Ambiental , Poluição da Água/prevenção & controle , Qualidade da Água , Teorema de Bayes , China , Modelos Teóricos , Solo , Incerteza , Poluição da Água/economia , Poluição da Água/estatística & dados numéricosRESUMO
AIM: To investigate nurses' knowledge, attitudes and practices related to physical restraint in tertiary hospitals and identify the factors that influence physical restraint use. BACKGROUND: Physical restraint is used to maintain patient safety. Nurses play an important role in the restraint process. It is important to identify their understanding, feelings and approach regarding the use of physical restraint. INTRODUCTION: Physical restraint is widely practiced in hospitals in China. However, it results in a range of serious negative consequences. This article provides a clear description of nurses' knowledge, attitudes and practices related to physical restraint. METHODS: A cross-sectional survey was conducted. The participants were asked to complete a questionnaire examining their knowledge, attitudes and practices related to physical restraint use. A total of 200 questionnaires were distributed in four tertiary hospitals in Hubei Province, China between August and October 2014. RESULTS: The nurses' responses indicated a good level of knowledge regarding physical restraint use. However, they held some misconceptions. The nurses' attitudes towards physical restraint tended to be neutral. The nurses were well experienced in the use of physical restraint. Nurses who had received on-the-job training performed better than those who had received no training related to knowledge and practices regarding physical restraint use. CONCLUSIONS AND IMPLICATION FOR NURSING/HEALTH POLICY: In-service training is highly recommended for nursing managers to improve nurses' physical restraint related knowledge and practices. Regulations regarding the use of restraints should be established as soon as possible by healthcare administration system. IMPLICATIONS FOR NURSING: Nurses should be open to evaluate and improve their views and attitudes regarding effective physical restraint use via multidimensional interventions.
Assuntos
Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Recursos Humanos de Enfermagem Hospitalar/psicologia , Restrição Física/psicologia , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Atenção Terciária , Adulto JovemRESUMO
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 TratamentoRESUMO
In recent years, increscent emissions in the city of Beijing due to expanded population, accelerated industrialization and inter-regional pollutant transportation have led to hazardous atmospheric pollution issues. Although a number of anthropogenic control measures have been put into use, frequent/severe haze events have still challenged regional governments. In this study, a hybrid population-production-pollution nexus model (PPP) is proposed for air pollution management and air quality planning (AMP) with the aim to coordinate human activities and environmental protection. A fuzzy-stochastic mixed quadratic programming method (FSQ) is developed and introduced into a PPP for tackling atmospheric pollution issues with uncertainties. Based on the contribution of an index of population-production-pollution, a hybrid PPP-based AMP model that considers employment structure, industrial layout pattern, production mode, pollutant purification efficiency and a pollution mitigation scheme have been applied in Beijing. Results of the adjustment of employment structure, pollution mitigation scheme, and green gross domestic product under various environmental regulation scenarios are obtained and analyzed. This study can facilitate the identification of optimized policies for alleviating population-production-emission conflict in the study region, as well as ameliorating the hazardous air pollution crisis at an urban level.
Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Poluição do Ar , Pequim , China , Cidades , Humanos , Material ParticuladoRESUMO
Objective: To systematically evaluate the quality of clinical practice guidelines for the diagnosis and treatment of benign prostatic hyperplasia (BPH), and to compare the context of recommendations in order to provide references for clinical application. Methods: We searched databases such as the National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, and Medlive from their establishment until August 13, 2016, to collect evidence-based guidelines and/or consensus on BPH. Method: Methodological quality of included guidelines was assessed according to the AGREE â ¡ instrument, and differences and similarities among recommendations were compared. Results: A total of 15 guidelines were included. According to the AGREE â ¡ instrument, the score of scope and purpose, stakeholder involvement, rigour of formulate, clarity of presentation, applicability, and editorial independence was 72%, 38%, 30%, 58%, 16%, and 40%, respectively. The recommendations of different guidelines were basically similar, only with conflicts in some areas. Conclusions: The quality of included guidelines remains to be unified, the context of them can provide valuable implications for development or improvement.
Assuntos
Hiperplasia Prostática/diagnóstico , Consenso , Medicina Baseada em Evidências , Humanos , Masculino , Guias de Prática Clínica como AssuntoRESUMO
AIM: To determine and compare the diagnostic value of computed tomography (CT)-guided percutaneous core needle biopsy (PCNB) and percutaneous fine-needle aspiration biopsy (PNAB) in pulmonary lesions. MATERIALS AND METHODS: PubMed, EMBASE, and the Web of Science were systematically searched for relevant studies that investigated the diagnostic accuracy of CT-guided PCNB and/or PNAB for pulmonary lesions up to December 2014. After study selection, data extraction, and quality assessment, the sensitivity (SEN), specificity (SPE), diagnostic odds rate (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and summary receiver operating characteristic (SROC) curves were calculated using the Meta-Disc 1.4 software. RESULTS: Nineteen publications, including 21 independent studies, met the inclusion criteria. Of them, 15 studies were included in the PCNB group and six studies in the PNAB group. The pooled SEN, SPE, DOR, PLR, NLR, and SROC were 0.95, 0.99, 54.72, 0.06, 821.90, and 0.98 in the PCNB group and 0.90, 0.99, 24.71, 0.14, 210.72, and 0.98 in the PNAB group, respectively. CONCLUSION: Based on current evidence, both PCNB and PNAB can be used as diagnostic methods to distinguish benign and malignant pulmonary lesions; the difference between PCNB and PNAB regarding diagnostic accuracy of benign or malignant pulmonary lesions is not obvious.
Assuntos
Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Biópsia Guiada por Imagem , Pneumopatias/patologia , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Humanos , Pneumopatias/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
The tumor necrosis factor-alpha (TNF-α) G-308A polymorphism has been suggested to be a susceptibility factor for myocardial infarction (MI). However, differing results from various studies have led to controversial conclusions. Hence, we performed a meta-analysis to evaluate the association between TNF-α G-308A polymorphism and MI. Reported studies published before March 30, 2015 were included and analyzed from the PubMed and Embase databases. Study selection and data extraction were carried out independently by two authors. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association between the selected variables using the Comprehensive Meta-Analysis v2.2 software. In total, 12 publications with 13 case-control studies consisting of 6037 cases and 7262 controls were included in our meta-analysis. The overall results showed that there was no significant association between TNF-α G-308A polymorphism and MI risk [A vs G: OR = 1.18, 95%CI = 0.94-1.48; AA vs GG: OR = 1.23, 95%CI = 0.74-2.05; GA vs GG: OR = 1.22, 95%CI = 0.98-1.51; (GA+AA) vs G: OR = 1.21, 95%CI = 0.96-1.54; AA vs (GG+GA): OR = 1.16, 95%CI = 0.72-1.88]. However, when subgroup analysis was performed according to the stages of MI, results indicated that there was a significant association between TNF-α G-308A polymorphism and the risk of acute MI. Other subgroup analyses revealed no significant associations. Current evidence suggests that TNF-α G-308A polymorphism may be associated with increased risk for acute MI.
Assuntos
Predisposição Genética para Doença , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Estudos de Casos e Controles , Expressão Gênica , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/patologia , Razão de Chances , Fatores de RiscoRESUMO
This review aimed to evaluate the clinical outcome of different lasers management on orthodontic pain. Cochrane Library (Issue 7, 2014) and MEDLINE (1966-2014.7) were searched to collect randomized controlled trials on lasers for orthodontic pain. Studies meeting the inclusion criteria were systematically evaluated. The Cochrane Collaboration tools RevMan5.1.7 and GRADEpro 3.6 were used in this systematic review and meta-analysis. As a result, 11 randomized controlled trials (RCTs) studying on low-level laser therapy (LLLT) for orthodontic pain control were included. Meta-analysis and risk of bias assessment were implemented using RevMan5.1.7, and level of evidence assessments was measured by GRADEpro 3.6. In the outcome of the score of the most painful day, the comparison of laser versus placebo (pain associated with tooth movement) demonstrated that LLLT reduced the pain score significantly compared with placebo groups (MD = -4.39, 95% CI range -5.9--2.88, P < 0.00001). In the same way, the most painful day was significantly brought forward in laser versus control group (MD = -0.42, 95% CI range -0.74--0.10, P = 0.009). Furthermore, the outcome of the end of pain day showed a trend of pain termination earlier in laser versus control and placebo groups, but without statistical significance (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18 and MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, for the reason of downgrade factors, all the GRADE level of evidences of eight comparisons for three outcomes showed a very low quality. Therefore, for the methodological shortcomings and risk of bias of RCTs included, insufficient evidence was submitted to judge whether LLLT was effective in relieving orthodontic pain. Further and more perfect researches should be done in order to recommend LLLT as a routine method for orthodontic pain.
Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Dor/radioterapia , Adolescente , Adulto , Criança , Feminino , Humanos , Lasers , Masculino , Manejo da Dor , Placebos , Adulto JovemRESUMO
A simple steam-assisted solid phase synthesis method was developed for synthesis of boehmite nanowires in the presence of TEAOH surfactant. The boehmite nanowires had uniform diameters (12-16 nm) and length up to 1-2 microm. The morphology of the nanostructured wires was well preserved after being converted to pure gamma-Al2O3 by thermal treatment at 600 degrees C for 5 h. The nanowires of Al2O3 exhibited excellent thermal stability by retarding the phase transformation and maintaining the wires-like nanostructure after being aged up to 1300 degrees C by preventing sintering between particles at high temperatures. The surface areas of Al2O3 nanowires could be maintained as high as 68 m2/g at 1300 degrees C while the surface areas of Al2O3 micropowder shrank to 0.89 m2/g after same thermal treatment. Both in-situ XRD and 27Al NMR results indicated that the crystal structure of gamma-Al2O3 nanowires was not transformed to alpha-Al2O3 at 1300 degrees C whereas micropowder Al2O3 was fully converted to alpha-Al2O3 at 1100 degrees C.
Assuntos
Óxido de Alumínio/química , Nanopartículas/química , Nanofios/química , Hidróxido de Alumínio/química , Cristalização , Temperatura Alta , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Nanotecnologia/métodos , Pós , Análise Espectral Raman , Temperatura , Fatores de Tempo , Difração de Raios XRESUMO
Objective: To understand the current situation and trend on the relations between erectile dysfunction (ED) and cardiovascular disease (CVD) through analyzing the epidemiologic research data. Methods: We conducted a literature search on the Scopus for potentially relevant epidemiologic studies on ED and CVD published from 1957 to October, 28, 2016. Age of the article, types, regions, citation, and co-authorship of the documents were recorded. Results: A total number of 412 pieces of literature were published in the past six decades, with original articles the most common types of ED and CVD. ED and CVD associated epidemiologic topics had an annual increase in number, and remained stable in the past decade, with occident countries as the United States and Italy taking the lead in this area. Clinical and epidemiological studies were the hottest areas, with most authors sharing a co-authorship. Conclusion: Our results suggested that inter-disciplinary cooperation with emphasize on clinical application were the effective starting points for ED and CVD associated epidemiologic studies.
Assuntos
Doenças Cardiovasculares/fisiopatologia , Artérias/fisiopatologia , Bibliometria , Disfunção Erétil/fisiopatologia , Humanos , MasculinoRESUMO
Meta-analysis used for genetic association studies became popular among researchers, with the amount of published papers increased rapidly. In this paper, we will focus on the introduction on the selection of genetic models. Traditionally, methods used for Meta-analysis on genetic association studies was to calculate the statistics based on available genetic models which not only increasing the probability of false-positives but also making the interpretation of results more difficult. Hence, a critical step in the Meta-analysis of genetic association studies was to choose the appropriate inheritance model. The aim of this paper was to introduce the theory of Bayesian analysis regarding the genetic model-free approach, in performing the Meta-analysis for studies related to genetic associations.
Assuntos
Teorema de Bayes , Estudos de Associação Genética , Modelos Genéticos , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , ProbabilidadeRESUMO
In this study, an interval-stochastic-based risk analysis (RSRA) method is developed for supporting river water quality management in a rural system under uncertainty (i.e., uncertainties exist in a number of system components as well as their interrelationships). The RSRA method is effective in risk management and policy analysis, particularly when the inputs (such as allowable pollutant discharge and pollutant discharge rate) are expressed as probability distributions and interval values. Moreover, decision-makers' attitudes towards system risk can be reflected using a restricted resource measure by controlling the variability of the recourse cost. The RSRA method is then applied to a real case of water quality management in the Heshui River Basin (a rural area of China), where chemical oxygen demand (COD), total nitrogen (TN), total phosphorus (TP), and soil loss are selected as major indicators to identify the water pollution control strategies. Results reveal that uncertainties and risk attitudes have significant effects on both pollutant discharge and system benefit. A high risk measure level can lead to a reduced system benefit; however, this reduction also corresponds to raised system reliability. Results also disclose that (a) agriculture is the dominant contributor to soil loss, TN, and TP loads, and abatement actions should be mainly carried out for paddy and dry farms; (b) livestock husbandry is the main COD discharger, and abatement measures should be mainly conducted for poultry farm; (c) fishery accounts for a high percentage of TN, TP, and COD discharges but a has low percentage of overall net benefit, and it may be beneficial to cease fishery activities in the basin. The findings can facilitate the local authority in identifying desired pollution control strategies with the tradeoff between socioeconomic development and environmental sustainability.
Assuntos
Monitoramento Ambiental/métodos , Rios/química , Poluentes Químicos da Água/análise , Poluição da Água/prevenção & controle , Análise da Demanda Biológica de Oxigênio , China , Cidades , Nitrogênio/análise , Fósforo/análise , Reprodutibilidade dos Testes , Poluição da Água/análise , Qualidade da ÁguaRESUMO
This study developed a fuzzy-stochastic programming with Green Z-score criterion (FSGZ) method for water resources allocation and water quality management with a trading-mechanism (WAQT) under uncertainties. FSGZ can handle uncertainties expressed as probability distributions, and it can also quantify objective/subjective fuzziness in the decision-making process. Risk-averse attitudes and robustness coefficient are joined to express the relationship between the expected target and outcome under various risk preferences of decision makers and systemic robustness. The developed method is applied to a real-world case of WAQT in the Kaidu-Kongque River Basin in northwest China, where an effective mechanism (e.g., market trading) to simultaneously confront severely diminished water availability and degraded water quality is required. Results of water transaction amounts, water allocation patterns, pollution mitigation schemes, and system benefits under various scenarios are analyzed, which indicate that a trading-mechanism is a more sustainable method to manage water-environment crisis in the study region. Additionally, consideration of anthropogenic (e.g., a risk-averse attitude) and systemic factors (e.g., the robustness coefficient) can support the generation of a robust plan associated with risk control for WAQT when uncertainty is present. These findings assist local policy and decision makers to gain insights into water-environment capacity planning to balance the basin's social and economic growth with protecting the region's ecosystems.
Assuntos
Modelos Teóricos , Poluição da Água , Qualidade da Água , Recursos Hídricos , Abastecimento de Água , China , Tomada de Decisões , Lógica Fuzzy , Probabilidade , Risco , IncertezaRESUMO
Stx1 and Stx2 produced by Shiga toxin-producing Escherichia coli are cytotoxic due to their N-glycosidase activity on 28S rRNA. In this study, we have shown that proinflammatory cytokine mRNAs, especially IL-8, were induced by Stx1 and Stx2 in Caco-2 cells. A non-toxic mutant of Stxl which lacks N-glycosidase activity did not induce cytokine mRNAs. IL-8 production at the protein level was enhanced by Stx1 and Stx2, but not by the mutant Stx1. These results demonstrate that Shiga toxins induce expression and synthesis of cytokines in Caco-2 cells and their N-glycosidase activity is essential for the induction.
Assuntos
Toxinas Bacterianas/farmacologia , Citocinas/genética , Glicosídeo Hidrolases/metabolismo , Mutação , Shigella/enzimologia , Substituição de Aminoácidos , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Sítios de Ligação , Células CACO-2 , Quimiocina CCL2/genética , Quimiocina CCL4 , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/farmacologia , Humanos , Interleucina-8/biossíntese , Interleucina-8/genética , Proteínas Inflamatórias de Macrófagos/genética , Biossíntese de Proteínas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Toxinas Shiga , Triexosilceramidas/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
1. In rat left ventricular papillary muscle, phenylephrine, an alpha 1-adrenoceptor agonist, had a staurosporine-sensitive positive inotropic effect and increased the particulate-associated protein kinase C (PKC) activity without significant changes in total PKC activity or in cytosolic Ca2+/phospholipid-independent kinase (PKI) activity. 2. A PKC stimulant, phorbol 12,13-dibutyrate (PDBu), decreased contractility and slightly increased PKC activity in the particulate fractions, with a marked decrease and increase in total PKC and PKI activities, respectively. 3. The PDBu-induced negative inotropic response was attenuated by two protease inhibitors, leupeptine and a microbial peptide isolated from Aspergillus japonicus (E-64), which are known to inhibit the conversion of particulate-associated PKC to PKI. 4. Such differences in the patterns of PKC redistribution, i.e. marked increases in particulate PKC and cytosolic PKI activities caused by phenylephrine and PDBu, respectively, may account for the opposite inotropic effects of PKC stimulation by an alpha 1-agonist and a phorbol ester.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Contração Miocárdica/efeitos dos fármacos , Músculos Papilares/enzimologia , Dibutirato de 12,13-Forbol/farmacologia , Proteína Quinase C/metabolismo , Receptores Adrenérgicos alfa/fisiologia , Animais , Leucina/análogos & derivados , Leucina/farmacologia , Leupeptinas/farmacologia , Masculino , Músculos Papilares/efeitos dos fármacos , Fenilefrina/farmacologia , Inibidores de Proteases/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Rat brain Cl(-)-ATPase was solubilized and reconstituted in asolectin liposomes. Phosphatidylinositol-4-monophosphate increased Cl(-)-ATPase and ATP-dependent Cl- uptake activities in proteoliposomes. The ATP-dependent Cl- uptake was inhibited by a Cl(-)-ATPase inhibitor, ethacrynic acid, and increased at an inside-positive membrane potential or in the presence of a protonophore. These findings suggest that Cl(-)-ATPase is an electrogenic Cl- transporter, or a primary Cl- pump, probably regulated by phosphoinositide turnover in vivo.
Assuntos
Adenosina Trifosfatases/metabolismo , Encéfalo/efeitos dos fármacos , Fosfatos de Fosfatidilinositol/farmacologia , Adenosina Trifosfatases/antagonistas & inibidores , Animais , Proteínas de Transporte de Ânions , Transporte Biológico/efeitos dos fármacos , Encéfalo/metabolismo , Ácido Etacrínico/farmacologia , Lipossomos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Fosfatidilcolinas , Fosfolipídeos , Ratos , Ratos Wistar , SolubilidadeRESUMO
We examined the mechanisms of the inhibitory effects of calcitonin gene-related peptide (CGRP) on substance-P-induced superoxide anion (O2-) production in human neutrophils. Substance P (30 microM) caused O2- production associated with an inositol-1,4,5-trisphosphate (IP3)-induced transient increase in intracellular Ca2+ concentrations ([Ca2+]i). CGRP (10 microM) significantly inhibited substance-P-induced O2- production and transient increase in [Ca2+]i, but it only slightly suppressed IP3 formation. In addition, CGRP inhibited IP3-induced O2- production and transient increase in [Ca2+]i, caused by exogenous addition of IP3 in saponin-permeabilized neutrophils. These findings suggest that CGRP inhibits the response of neutrophils to substance P through the inhibition of IP3-induced Ca2+ release from intracellular Ca2+ stores. The inhibitory effects of CGRP on substance P- or IP3-induced O2- production and increases in [Ca2+]i were abolished by pretreating the neutrophils with a CGRP receptor antagonist, CGRP-(8 - 37), or cyclic AMP (cAMP)-dependent protein kinase inhibitors, N-[2-(methylamino) ethyl]-5-isoquinoline-sulfonamide dihydrochloride (H-8) and 9-n-hexyl ester derivative of K-572a (8R, 9S, 11 S)-(--)-9-hydroxy-9-methoxycarbonyl-8-methyl-8-methyl-2,3,9,10- tetrahydro-8,11-epoxy-1H,8H, 11 H-2,7b,11a-triazadibenzo (a,g)cycloocta(cde)trinden-1-one (KT5720). We concluded that CGRP receptor stimulation reduces substance-P-induced O2- production by the inhibition of IP3-induced transient increase in [Ca2+]i, probably via the phosphorylation of IP3 receptor by cAMP-dependent protein kinase.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Superóxidos/metabolismo , Cálcio/metabolismo , Humanos , Inositol 1,4,5-Trifosfato/biossíntese , Substância P/antagonistas & inibidores , Substância P/farmacologiaRESUMO
The intracerebroventricular injection of ethacrynic acid (a 50% convulsive dose; 50 micrograms/mouse) accelerated brain noradrenaline turnover and decreased noradrenaline contents. The decrease in noradrenaline contents was antagonized by 2-amino-5-phosphonovalerate but not by diazepam. Both 2-amino-5-phosphonovalerate and diazepam suppressed the incidence of ethacrynic acid-induced convulsions while reserpine, alpha-methyl-para-tyrosine or FLA-63 augmented it. The results suggest that stimulation by ethacrynic acid of excitatory amino acid neurons enhances-noradrenergic neuronal anticonvulsive activity.
Assuntos
Química Encefálica , Ácido Etacrínico/farmacologia , Norepinefrina/análise , Convulsões/induzido quimicamente , Animais , Cromatografia Líquida de Alta Pressão , Dopamina beta-Hidroxilase/farmacologia , Ácido Etacrínico/administração & dosagem , Injeções Intraventriculares , Masculino , Metiltirosinas/farmacologia , Camundongos , Norepinefrina/metabolismo , Fatores de TempoRESUMO
We purified Cl- pump in the rat brain and obtained 520 or 580 kDa protein complexes which consisted of 62, 60, 55 and 51 kDa proteins. An antiserum against 520 kDa protein complex recognized 51 kDa protein in both 520 and 580 kDa complexes, and reduced both Cl(-)-ATPase and Cl(-) pump activities. Such an immunoreactive 51 kDa protein was found in the brain, spinal cord and kidney. When incubated with [gamma-(32)P]ATP, the protein complex yielded phosphorylated 51 kDa protein, the label being hydroxylamine-sensitive and increased in the presence of Cl- and/or an inhibitor of Cl- pump, ethacrynic acid. Thus, the antibody appears to recognize a possible catalytic subunit of Cl- pump, 51 kDa protein, in the rat.