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  1 / 19005 MEDLINE  
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[PMID]:29458544
[Au] Autor:Aguilar-Ayala DA; Cnockaert M; Vandamme P; Palomino JC; Martin A; Gonzalez-Y-Merchand J
[Ad] Endereço:2​Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent 9000, Belgium.
[Ti] Título:Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions.
[So] Source:J Med Microbiol;67(3):282-285, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Lipídeos/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/fisiologia
[Mh] Termos MeSH secundário: Amicacina/farmacologia
Antituberculosos/farmacologia
Tolerância a Medicamentos
Fluoroquinolonas/farmacologia
Aptidão Genética
Genótipo
Seres Humanos
Metabolismo dos Lipídeos
Testes de Sensibilidade Microbiana
Modelos Biológicos
Infecções por Micobactéria não Tuberculosa/microbiologia
Mycobacterium tuberculosis/genética
Mycobacterium tuberculosis/crescimento & desenvolvimento
Nitroimidazóis/farmacologia
Rifampina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine); 0 (Anti-Bacterial Agents); 0 (Antitubercular Agents); 0 (Fluoroquinolones); 0 (Lipids); 0 (Nitroimidazoles); 84319SGC3C (Amikacin); U188XYD42P (moxifloxacin); VJT6J7R4TR (Rifampin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000681


  2 / 19005 MEDLINE  
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[PMID]:29458540
[Au] Autor:Li Y; Zhang L; Zhou Y; Zhang Z; Zhang X
[Ad] Endereço:1​Department of Immunology, College of Preclinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, PR China.
[Ti] Título:Survival of bactericidal antibiotic treatment by tolerant persister cells of Klebsiella pneumoniae.
[So] Source:J Med Microbiol;67(3):273-281, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Persister cells, a subpopulation of tolerant cells within the bacterial culture, are commonly thought to be responsible for antibiotic therapy failure and infection recurrence. Klebsiella pneumoniae is a notorious human pathogen for its increasing resistance to antibiotics and wide involvement in severe infections. In this study, we aimed to investigate the persister subpopulation of K. pneumoniae. METHODOLOGY: The presence of persisters in K. pneumoniae was determined by treatment with high concentrations of antibiotics, used alone or in combination. The effect of low level of antibiotics on persister formation was investigated by pre-exposure of cells to antibiotics with low concentrations followed by higher doses. The dependence of persister levels on growth phase was determined by measuring the survival ability of cells along the growth stages upon exposure to a high concentration of antibiotic. Analysis on persister type was carried out by persister elimination assays.Results/Key findings. We show that K. pneumoniae produces high levels of tolerant persister cells to survive treatment by a variety of high concentrations of bactericidal antibiotics and persister formation is prevalent among K. pneumoniae clinical strains. Besides, we find that persister cells can be induced by low concentrations of antibiotics. Finally, we provide evidence that persister formation is growth phase-dependent and Type II persisters dominate the persister subpopulation during the entire exponential phase of K. pneumoniae. CONCLUSION: Our study describes the formation of tolerant persister cells that allow survival of treatment by high concentrations of antibiotics in K. pneumoniae.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/fisiologia
Viabilidade Microbiana/efeitos dos fármacos
[Mh] Termos MeSH secundário: Contagem de Colônia Microbiana
Farmacorresistência Bacteriana Múltipla
Tolerância a Medicamentos
Seres Humanos
Infecções por Klebsiella/microbiologia
Klebsiella pneumoniae/crescimento & desenvolvimento
Testes de Sensibilidade Microbiana
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000680


  3 / 19005 MEDLINE  
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[PMID]:28987404
[Au] Autor:Xu H; Yu C; Xia X; Li M; Li H; Wang Y; Wang S; Wang C; Ma Y; Zhou G
[Ad] Endereço:Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Engineering Research Center of Biomass Resources and Environment, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China.
[Ti] Título:Comparative transcriptome analysis of duckweed (Landoltia punctata) in response to cadmium provides insights into molecular mechanisms underlying hyperaccumulation.
[So] Source:Chemosphere;190:154-165, 2018 Jan.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cadmium (Cd) is a detrimental environmental pollutant. Duckweeds have been considered promising candidates for Cd phytoremediation. Although many physiological studies have been conducted, the molecular mechanisms underlying Cd hyperaccumulation in duckweeds are largely unknown. In this study, clone 6001 of Landoltia punctata, which showed high Cd tolerance, was obtained by large-scale screening of over 200 duckweed clones. Subsequently, its growth, Cd flux, Cd accumulation, and Cd distribution characteristics were investigated. To further explore the global molecular mechanism, a comprehensive transcriptome analysis was performed. For RNA-Seq, samples were treated with 20 µM CdCl for 0, 1, 3, and 6 days. In total, 9,461, 9,847, and 9615 differentially expressed unigenes (DEGs) were discovered between Cd-treated and control (0 day) samples. DEG clustering and enrichment analysis identified several biological processes for coping with Cd stress. Genes involved in DNA repair acted as an early response to Cd, while RNA and protein metabolism would be likely to respond as well. Furthermore, the carbohydrate metabolic flux tended to be modulated in response to Cd stress, and upregulated genes involved in sulfur and ROS metabolism might cause high Cd tolerance. Vacuolar sequestration most likely played an important role in Cd detoxification in L. punctata 6001. These novel findings provided important clues for molecular assisted screening and breeding of Cd hyperaccumulating cultivars for phytoremediation.
[Mh] Termos MeSH primário: Araceae/efeitos dos fármacos
Araceae/genética
Biodegradação Ambiental
Cádmio/farmacocinética
Perfilação da Expressão Gênica
[Mh] Termos MeSH secundário: Araceae/metabolismo
Cádmio/metabolismo
Tolerância a Medicamentos/genética
Perfilação da Expressão Gênica/métodos
Genes de Plantas/efeitos dos fármacos
Genes de Plantas/genética
Análise de Sequência de RNA
Estresse Fisiológico/genética
Transcriptoma/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
00BH33GNGH (Cadmium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


  4 / 19005 MEDLINE  
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[PMID]:29297622
[Au] Autor:Tutelyan AV; Pisarev VM; Minaeva NZ; Gaponov AM; Gracheva AN; Solopova GG
[Ti] Título:Generation of Antibiotic Tolerant Bacterial Persisters in Immunocompromized Patients with Hematologic and Malignant Diseases: A New Problem of Health-Care Associated Infections.
[So] Source:Vestn Ross Akad Med Nauk;71(3):183-9, 2016.
[Is] ISSN:0869-6047
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:Background: Antibiotic tolerance (AT) represents one of the causes of the phenomenon of antibiotic resistance that allows escape of non-replicating metabolically inert microorganisms (persisters) from any antibiotics attack because molecular targets of antibiotics are lacking thereby creating the potential for chronic infections. Aims: Determine the heterogeneity of the strains of opportunistic pathogens E. coli and P. aeruginosa isolates from children with hematologic malignancies containing bacterial persisters that cause the AT phenomenon. Methods: Children with hematological malignancies were divided into 2 groups according to the intensity of antibiotic treatment of infectious complications. Ciprofloxacin-induced persisters were quantitatively determined in the biological materials obtained from sick children. Results: Within the clinical isolates of E. coli and P. aeruginosa, about a third of the strains belong to high-persisting. The numbers of persistent forms of bacteria did not correlate with a minimal inhibitory concentration values ciprofloxacin (r=0.148, n=25, p>0.05). Interestingly, higher level of formation of persistent E. coli and P. aeruginosa, is associated with higher frequencies of infection attacks, massive antibiotic use and unfavorable course of the disease in children. Conclusions: Therefore, detecting the persistent forms of bacterial pathogens including those associated with the health-care associated infection, specifically, in immunocompromised patients, should be included into the contemporary algorithms of microbiological observation and monitoring of patients and intrahospital environment.
[Mh] Termos MeSH primário: Ciprofloxacino/uso terapêutico
Tolerância a Medicamentos
Escherichia coli
Neoplasias Hematológicas
Infecções Oportunistas
Pseudomonas aeruginosa
[Mh] Termos MeSH secundário: Adolescente
Antibacterianos/uso terapêutico
Criança
Infecção Hospitalar/prevenção & controle
Resistência Microbiana a Medicamentos/efeitos dos fármacos
Escherichia coli/efeitos dos fármacos
Escherichia coli/isolamento & purificação
Feminino
Neoplasias Hematológicas/complicações
Neoplasias Hematológicas/microbiologia
Seres Humanos
Hospedeiro Imunocomprometido/efeitos dos fármacos
Masculino
Testes de Sensibilidade Microbiana/métodos
Infecções Oportunistas/diagnóstico
Infecções Oportunistas/tratamento farmacológico
Infecções Oportunistas/etiologia
Pseudomonas aeruginosa/efeitos dos fármacos
Pseudomonas aeruginosa/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 5E8K9I0O4U (Ciprofloxacin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE


  5 / 19005 MEDLINE  
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[PMID]:29357714
[Au] Autor:Quagliato LA; Freire RC; Nardi AE
[Ad] Endereço:a Laboratory of Panic & Respiration, Institute of Psychiatry , Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
[Ti] Título:Risks and benefits of medications for panic disorder: a comparison of SSRIs and benzodiazepines.
[So] Source:Expert Opin Drug Saf;17(3):315-324, 2018 Mar.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Panic disorder (PD) is a prevalent and disabling anxiety disorder that can be treated effectively. Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are among the most frequently prescribed drugs for PD. In this article, the authors review the current evidence on efficacy, adverse events, and limitations of these two treatment options. Areas covered: MEDLINE/Pubmed and Web of Science databases were searched for open or placebo-controlled trials on SSRIs and/or benzodiazepines in PD treatment. Expert opinion: The literature search yielded 4,957 articles related to the theme. Of these, 24 articles were included in this review. Despite their usefulness in PD, SSRIs are associated with a delay of several weeks in onset of therapeutic effect and have the potential to exacerbate anxiety and panic early in the treatment course. Benzodiazepines present rapid onset of action, but can cause tolerance and dependence. Despite strong evidence of the effectiveness of SSRIs and benzodiazepines in the treatment of PD, few trials have performed head-to-head comparisons of these two drug classes. Future studies on the pharmacological treatment of PD should make direct comparisons of risks, benefits, and limitations of each group. This could help improve the evidence-based pharmacotherapy of PD.
[Mh] Termos MeSH primário: Benzodiazepinas/uso terapêutico
Transtorno de Pânico/tratamento farmacológico
Inibidores da Captação de Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Benzodiazepinas/administração & dosagem
Benzodiazepinas/efeitos adversos
Tolerância a Medicamentos
Seres Humanos
Transtorno de Pânico/fisiopatologia
Inibidores da Captação de Serotonina/administração & dosagem
Inibidores da Captação de Serotonina/efeitos adversos
Transtornos Relacionados ao Uso de Substâncias/epidemiologia
Fatores de Tempo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Serotonin Uptake Inhibitors); 12794-10-4 (Benzodiazepines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2018.1429403


  6 / 19005 MEDLINE  
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[PMID]:27775684
[Au] Autor:Pader V; Hakim S; Painter KL; Wigneshweraraj S; Clarke TB; Edwards AM
[Ad] Endereço:MRC Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
[Ti] Título:Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids.
[So] Source:Nat Microbiol;2:16194, 2016 Oct 24.
[Is] ISSN:2058-5276
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) . Although resistance is rare, treatment failure can occur in more than 20% of cases and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S. aureus was killed rapidly by daptomycin, but Agr-defective mutants survived antibiotic exposure by releasing membrane phospholipids, which bound and inactivated the antibiotic. Although wild-type bacteria also released phospholipid in response to daptomycin, Agr-triggered secretion of small cytolytic toxins, known as phenol soluble modulins, prevented antibiotic inactivation. Phospholipid shedding by S. aureus occurred via an active process and was inhibited by the ß-lactam antibiotic oxacillin, which slowed inactivation of daptomycin and enhanced bacterial killing. In conclusion, S. aureus possesses a transient defence mechanism that protects against daptomycin, which can be compromised by Agr-triggered toxin production or an existing therapeutic antibiotic.
[Mh] Termos MeSH primário: Antibacterianos/metabolismo
Membrana Celular/efeitos dos fármacos
Daptomicina/metabolismo
Tolerância a Medicamentos
Fosfolipídeos/metabolismo
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas de Bactérias
Viabilidade Microbiana/efeitos dos fármacos
Staphylococcus aureus/genética
Transativadores/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Agr protein, Staphylococcus aureus); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Phospholipids); 0 (Trans-Activators); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180126
[Lr] Data última revisão:
180126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/nmicrobiol.2016.194


  7 / 19005 MEDLINE  
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Registro de Ensaios Clínicos
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[PMID]:28454526
[Au] Autor:Lee W; Lee S; Bae H; Kim CY; Seong GJ
[Ad] Endereço:Department of Ophthalmology, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea.
[Ti] Título:Efficacy and tolerability of preservative-free 0.0015% tafluprost in glaucoma patients: a prospective crossover study.
[So] Source:BMC Ophthalmol;17(1):61, 2017 Apr 28.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this work is to evaluate efficacy and tolerability of preservative containing 0.0015% tafluprost and preservative-free 0.0015% tafluprost using a prospective crossover study. METHODS: Primary open angle glaucoma (POAG) and normotensive glaucoma (NTG) patients were randomized enrolled. Group 1 ("NPT to PT") patients used preservative-free 0.0015% tafluprost (NPT) for 6 months and then changed to preservative containing 0.0015% tafluprost(PT) for 6 months. Group 2 ("PT to NPT") patients used preservative containing 0.0015% tafluprost for 6 months and changed to preservative-free 0.0015% tafluprost for 6 months. At 1, 3, 6, 7, 9, and 12 months, we measured intraocular pressure for efficacy and graded corneal erosion, tear break-up time (TBUT), and subjective discomfort. RESULTS: A total of 20 patients and 20 eyes were enrolled. In Group 1 and 2, intraocular pressure was well controlled to approximately 14 mmHg (9.38-18.46% decrease). Generally, subjective satisfaction was improved after changing from PT to NPT (p = 0.03) and TBUT using PT was numerically inferior to that using NPT (p = 0.06) but not when changing from NPT to PT. CONCLUSION: Both preservative containing and preservative-free 0.0015% tafluprost reduced intraocular pressure significantly. In addition, changing medication from PT to NPT might improve subjective satisfaction and tear break up time. TRIAL REGISTRATION: The trial registration number is NCT 03104621 (Apr/1/2017). Retrospectively registered.
[Mh] Termos MeSH primário: Tolerância a Medicamentos
Glaucoma/tratamento farmacológico
Pressão Intraocular/efeitos dos fármacos
Prostaglandinas F/administração & dosagem
[Mh] Termos MeSH secundário: Estudos Cross-Over
Relação Dose-Resposta a Droga
Feminino
Glaucoma/fisiopatologia
Seres Humanos
Masculino
Meia-Idade
Soluções Oftálmicas/administração & dosagem
Estudos Prospectivos
Tonometria Ocular
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Ophthalmic Solutions); 0 (Prostaglandins F); 1O6WQ6T7G3 (tafluprost)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-017-0453-z


  8 / 19005 MEDLINE  
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[PMID]:29223430
[Au] Autor:da Rosa PR; Rohde LE; Doebber M; Ribeiro ALP; Prado DP; Bertoldi EG; Figueiredo Neto JA; Kohler I; Beck-da-Silva L; Danzmann LC; Moura LZ; Rover M; Simões MV; Sant'Anna RT; Biolo A
[Ad] Endereço:Hospital de Clínicas de Porto Alegre e Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, (RS), Brazil; Hospital Moinhos de Vento, Porto Alegre, (RS), Brazil.
[Ti] Título:Rational and design of a randomized, double-blind, multicenter trial to evaluate the safety and tolerability of furosemide withdrawal in stable chronic outpatients with heart failure: The ReBIC-1 trial.
[So] Source:Am Heart J;194:125-131, 2017 Dec.
[Is] ISSN:1097-6744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals. METHODS: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned. PERSPECTIVE: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients.
[Mh] Termos MeSH primário: Tolerância a Medicamentos
Furosemida/administração & dosagem
Insuficiência Cardíaca/tratamento farmacológico
Pacientes Ambulatoriais
[Mh] Termos MeSH secundário: Idoso
Biomarcadores/sangue
Deterioração Clínica
Diuréticos/administração & dosagem
Relação Dose-Resposta a Droga
Método Duplo-Cego
Feminino
Insuficiência Cardíaca/sangue
Insuficiência Cardíaca/diagnóstico
Seres Humanos
Masculino
Meia-Idade
Peptídeo Natriurético Encefálico/sangue
Fragmentos de Peptídeos/sangue
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Diuretics); 0 (Peptide Fragments); 0 (pro-brain natriuretic peptide (1-76)); 114471-18-0 (Natriuretic Peptide, Brain); 7LXU5N7ZO5 (Furosemide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171215
[Lr] Data última revisão:
171215
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


  9 / 19005 MEDLINE  
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[PMID]:28977586
[Au] Autor:Payrits M; Sághy É; Cseko K; Pohóczky K; Bölcskei K; Ernszt D; Barabás K; Szolcsányi J; Ábrahám IM; Helyes Z; Szoke É
[Ad] Endereço:Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary.
[Ti] Título:Estradiol Sensitizes the Transient Receptor Potential Vanilloid 1 Receptor in Pain Responses.
[So] Source:Endocrinology;158(10):3249-3258, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sex differences exist in chronic pain pathologies, and gonadal estradiol (E2) alters the pain sensation. The nocisensor transient receptor potential vanilloid 1 (TRPV1) receptor plays a critical role in triggering pain. Here we examined the impact of E2 on the function of TRPV1 receptor in mice sensory neurons in vitro and in vivo. Both mechano- and thermonociceptive thresholds of the plantar surface of the paw of female mice were significantly lower in proestrus compared with the estrus phase. These thresholds were higher in ovariectomized (OVX) mice and significantly lower in sham-operated mice in proestrus compared with the sham-operated mice in estrus phase. This difference was absent in TRPV1 receptor-deficient mice. Furthermore, E2 potentiated the TRPV1 receptor activation-induced mechanical hyperalgesia in OVX mice. Long pretreatment (14 hours) with E2 induced a significant increase in TRPV1 receptor messenger RNA expression and abolished the capsaicin-induced TRPV1 receptor desensitization in primary sensory neurons. The short E2 incubation (10 minutes) also prevented the desensitization, which reverted after coadministration of E2 and the tropomyosin-related kinase A (TrkA) receptor inhibitor. Our study provides in vivo and in vitro evidence for E2-induced TRPV1 receptor upregulation and sensitization mediated by TrkAR via E2-induced genomic and nongenomic mechanisms. The sensitization and upregulation of TRPV1 receptor by E2 in sensory neurons may explain the greater pain sensitivity in female mice.
[Mh] Termos MeSH primário: Estradiol/farmacologia
Dor/fisiopatologia
Canais de Cátion TRPV/efeitos dos fármacos
Canais de Cátion TRPV/fisiologia
[Mh] Termos MeSH secundário: Animais
Capsaicina/farmacologia
Células Cultivadas
Tolerância a Medicamentos
Estro/fisiologia
Feminino
Expressão Gênica/efeitos dos fármacos
Temperatura Alta
Masculino
Mecanorreceptores/efeitos dos fármacos
Mecanorreceptores/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Nociceptores/efeitos dos fármacos
Nociceptores/fisiologia
Ovariectomia
Proestro/fisiologia
RNA Mensageiro/análise
Células Receptoras Sensoriais/química
Células Receptoras Sensoriais/fisiologia
Caracteres Sexuais
Canais de Cátion TRPV/genética
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (TRPV Cation Channels); 0 (TRPV1 receptor); 4TI98Z838E (Estradiol); S07O44R1ZM (Capsaicin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00101


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[PMID]:28924009
[Au] Autor:Leduc-Pessah H; Weilinger NL; Fan CY; Burma NE; Thompson RJ; Trang T
[Ad] Endereço:Departments of Comparative Biology & Experimental Medicine, and Physiology & Pharmacology.
[Ti] Título:Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance.
[So] Source:J Neurosci;37(42):10154-10172, 2017 Oct 18.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca responses in resident spinal microglia acutely isolated from morphine tolerant rats. The increased P2X7R function was blocked in cultured microglia by PP2, a Src family protein tyrosine kinase inhibitor. We identified Src family kinase activation mediated by µ-receptors as a key mechanistic step required for morphine potentiation of P2X7R function. Furthermore, we show by site-directed mutagenesis that tyrosine (Y ) within the P2X7R C-terminus is differentially modulated by repeated morphine treatment and has no bearing on normal P2X7R function. Intrathecal administration of a palmitoylated peptide corresponding to the Y site suppressed morphine-induced microglial reactivity and preserved the antinociceptive effects of morphine in male rats. Thus, site-specific regulation of P2X7R function mediated by Y is a novel cellular determinant of the microglial response to morphine that critically underlies the development of morphine analgesic tolerance. Controlling pain is one of the most difficult challenges in medicine and its management is a requirement of a large diversity of illnesses. Although morphine and other opioids offer dramatic and impressive relief of pain, their impact is truncated by loss of efficacy (analgesic tolerance). Understanding why this occurs and how to prevent it are of critical importance in improving pain therapies. We uncovered a novel site (Y ) within the P2X7 receptor that can be targeted to blunt the development of morphine analgesic tolerance, without affecting normal P2X7 receptor function. Our findings provide a critical missing mechanistic piece, site-specific modulation by Y , that unifies P2X7R function to the activation of spinal microglia and the development of morphine tolerance.
[Mh] Termos MeSH primário: Analgésicos Opioides/administração & dosagem
Microglia/fisiologia
Morfina/administração & dosagem
Medição da Dor/efeitos dos fármacos
Receptores Purinérgicos P2X7/fisiologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Analgésicos Opioides/metabolismo
Animais
Animais Recém-Nascidos
Sítios de Ligação/efeitos dos fármacos
Sítios de Ligação/fisiologia
Células Cultivadas
Relação Dose-Resposta a Droga
Tolerância a Medicamentos/fisiologia
Injeções Intraperitoneais
Injeções Espinhais
Masculino
Camundongos
Microglia/efeitos dos fármacos
Morfina/metabolismo
Medição da Dor/métodos
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Receptors, Purinergic P2X7); 76I7G6D29C (Morphine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0852-17.2017



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