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[PMID]: 29373935 [Au] Autor: Falcone M; Viale P; Tiseo G; Pai M [Ad] Endereço: a Department of Public Health and Infectious Diseases , "Sapienza" University of Rome , Rome , Italy. [Ti] Título: Pharmacokinetic drug evaluation of avibactam + ceftazidime for the treatment of hospital-acquired pneumonia. [So] Source: Expert Opin Drug Metab Toxicol;14(3):331-340, 2018 Mar. [Is] ISSN: 1744-7607 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a combination of a third-generation cephalosporin and a non-ß-lactam, ß-lactamase inhibitor, recently approved for urinary tract infections and complicated abdominal infections. Moreover, it represents a treatment option for patients with hospital acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR) bacteria. Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ-AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics (PD) in this field. Expert opinion: In vitro and in vivo data about PK/PD of CAZ-AVI confirm that penetration of CAZ-AVI in the epithelial lining fluid (ELF) represents approximately 30% of the plasma concentrations. Clinical studies documented that CAZ-AVI 2000 mg/500 mg every 8 h is the optimal dose regimen to achieve the PK/PD target attainment in patients with HAP. Thus, CAZ-AVI could represent an option both to treat HAP caused by Gram-negative bacilli (GNB) displaying resistance to most of the antibiotics and to reduce the use of carbapenems, limiting the onset of resistance profiles among GNB. Additional information about specific patients populations, such as critically-ill subjects or pediatric patients, are needed for a more individualized use of CAZ-AVI. [Mh] Termos MeSH primário: Antibacterianos/administração & dosagem Compostos Azabicíclicos/administração & dosagem Ceftazidima/administração & dosagem Pneumonia Bacteriana/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Antibacterianos/farmacocinética Compostos Azabicíclicos/farmacocinética Ceftazidima/farmacocinética Infecção Hospitalar/tratamento farmacológico Infecção Hospitalar/microbiologia Relação Dose-Resposta a Droga Farmacorresistência Bacteriana Múltipla Seres Humanos Pneumonia Bacteriana/microbiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Anti-Bacterial Agents); 0 (Azabicyclo Compounds); 0 (avibactam, ceftazidime drug combination); 9M416Z9QNR (Ceftazidime) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180309 [Lr] Data última revisão: 180309 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180128 [St] Status: MEDLINE [do] DOI: 10.1080/17425255.2018.1434142

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[PMID]: 28868930 [Au] Autor: Laskar S; Sánchez-Sánchez L; López-Ortiz M; López-Muñoz H; Escobar-Sánchez ML; Sánchez AT; Regla I [Ad] Endereço: a Lab. de Síntesis de Fármacos, Laboratorio 9 UMIEZ, Facultad de Estudios Superiores Zaragoza , Universidad Nacional Autónoma de México , Ciudad de México , Mexico. [Ti] Título: Multicomponent synthesis of some new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro anti-proliferative activity against CaSki, MDA-MB-231 and SK-Lu-1 tumour cells as apoptosis inducing agents without necrosis. [So] Source: J Enzyme Inhib Med Chem;32(1):1129-1135, 2017 Dec. [Is] ISSN: 1475-6374 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Identification of a new class of antitumor agent capable to induce apoptosis without triggering necrotic cell death event is challenging. The present communication describes the multicomponent synthesis of seven new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro antiproliferative activity on cervical cancer cell line (CaSki), breast cancer cell line (MDA-MB231), lung cancer cell line (SK-Lu-1) and human lymphocytes. Among the synthesized dithiocarbamates, compound 9e displayed significant antiproliferative activity without inducing any necrotic cell death (both on tumour cells and lymphocytes) and induced apoptosis in tumor cells by the caspase dependent apoptotic pathway. The compound 9e also exhibited greater tumor selectivity than human lymphocytes. In silico ADME predictions revealed that compound 9e has the potential to be developed as a drug candidate. Rapid chemical modifications of this lead are thus highly necessary for further investigation as a drug like safer antitumor candidate and also to achieve compounds with better activity profile. [Mh] Termos MeSH primário: Antineoplásicos/farmacologia Apoptose/efeitos dos fármacos Compostos Azabicíclicos/farmacologia Tiocarbamatos/farmacologia [Mh] Termos MeSH secundário: Antineoplásicos/síntese química Antineoplásicos/química Compostos Azabicíclicos/síntese química Compostos Azabicíclicos/química Linhagem Celular Tumoral Proliferação Celular/efeitos dos fármacos Relação Dose-Resposta a Droga Ensaios de Seleção de Medicamentos Antitumorais Seres Humanos Estrutura Molecular Relação Estrutura-Atividade Tiocarbamatos/síntese química Tiocarbamatos/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Azabicyclo Compounds); 0 (Thiocarbamates) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171009 [Lr] Data última revisão: 171009 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170905 [St] Status: MEDLINE [do] DOI: 10.1080/14756366.2017.1363197

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[PMID]: 28767588 [Au] Autor: Gugliandolo A; Caio C; Mezzatesta ML; Rifici C; Bramanti P; Stefani S; Mazzon E [Ad] Endereço: aIRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Messina bSection of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. [Ti] Título: Successful ceftazidime-avibactam treatment of MDR-KPC-positive Klebsiella pneumoniae infection in a patient with traumatic brain injury: A case report. [So] Source: Medicine (Baltimore);96(31):e7664, 2017 Aug. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RATIONALE: Carbapenem-resistant Enterobacteriaceae infections are a serious health care problem, because of the high mortality. Carbapenem resistance is mainly caused by carbapenemases production, including Klebsiella pneumoniae carbapenemase (KPC). Ceftazidime-avibactam is a new cephalosporin/ß-lactamase inhibitor combination for the treatment of complicated urinary, intra-abdominal infections, and nosocomial pneumonia caused by gram negative, or other serious gram-negative infections. PATIENT CONCERNS: We showed the case of a 27-year-old patient, hospitalized for traumatic brain injury and chest trauma, with KPC-producing Klebsiella pneumoniae infection. DIAGNOSES: Blood and bronchial aspirate culture analysis detected an infection caused by MDR Klebsiella pneumoniae, resistant to meropenem, ertapenem, piperacillin/tazobactam, amoxicillin/clavulanic acid, aztreonam, ceftazidime, cefotaxime, cefepime, amikacin, ciprofloxacin, trimethoprim/sulfamethoxazole, colistin while it showed an intermediate sensitivity to gentamicin and was sensitive to ceftazidime-avibactam. Molecular analyses revealed that the isolate belonged to the epidemic clone sequence type 258 (ST258) carrying blaKPC-3, blaTEM-1, and blaSHV-11genes. INTERVENTIONS: After various combined antibiotic therapies without improvements, he was treated with ceftazidime-avibactam, on a compassionate-use basis. OUTCOMES: With ceftazidime-avibactam monotherapy clinical and microbiological clearance was obtained. A week after the end of the therapy microbiological analysis was repeated and a positive rectal swab for KPC-Klebsiella pneumoniae was found, becoming negative after 1 month. Moreover, the patient did not show any relapses for up to 18 weeks. LESSONS: This case indicates that ceftazidime-avibactam monotherapy could be efficacious against KPC positive Klebsiella pneumoniae infections. [Mh] Termos MeSH primário: Compostos Azabicíclicos/uso terapêutico Lesões Encefálicas Traumáticas/complicações Ceftazidima/uso terapêutico Infecções por Klebsiella/tratamento farmacológico Klebsiella pneumoniae Inibidores de beta-Lactamases/uso terapêutico [Mh] Termos MeSH secundário: Adulto Lesões Encefálicas Traumáticas/microbiologia Ensaios de Uso Compassivo Estado Terminal Farmacorresistência Bacteriana Múltipla Seres Humanos Infecções por Klebsiella/complicações Klebsiella pneumoniae/efeitos dos fármacos Klebsiella pneumoniae/genética Masculino [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Azabicyclo Compounds); 0 (avibactam, ceftazidime drug combination); 0 (beta-Lactamase Inhibitors); 9M416Z9QNR (Ceftazidime) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 171013 [Lr] Data última revisão: 171013 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170803 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000007664

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[PMID]: 28649864 [Au] Autor: Rousselet M; Feuillet F; Gerardin M; Jolliet P; Hardouin JB; Victorri-Vigneau C [Ad] Endereço: a Centre for Evaluation and Information on Pharmacodependence - Addictovigilance , Clinical Pharmacology Department, University Hospital , Nantes , France. [Ti] Título: The French addictovigilance network clinical assessment: Z-drugs, true false twins. [So] Source: Expert Opin Drug Saf;16(9):1063-1069, 2017 Sep. [Is] ISSN: 1744-764X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: INTRODUCTION: In France, an addictovigilance network is responsible for evaluating drug dependence, by drawing on pharmacoepidemiological studies, clinical studies and by assessing healthcare professionals' reports on problematic consumption. METHODS: The aim of this study was to determine whether zolpidem and zopiclone have different dependence profiles, based on healthcare professionals' reports, and to identify various consumer dependence profiles among zolpidem users and among zopiclone users. Dependence in reports was assessed using the EGAP scale; a scale developed using the DSM diagnostic dependence criteria. RESULTS: The comparison of dependence profiles for zolpidem and zopiclone showed differences both in total EGAP score and EGAP item positivity. The descriptive analysis showed that EGAP scores were higher for zolpidem than for zopiclone, suggesting more severe problematic consumption with zolpidem. For zolpidem 2 subpopulations of consumers were identified, with one subpopulation's consumption being more severe than the other, with a significantly higher total EGAP score and more harmful consequences. No subpopulation was highlighted for zopiclone. CONCLUSION: These results were in favour of a higher prevalence of physical and compulsive signs of dependence and of harmful consequences of dependence, with zolpidem than with zopiclone. [Mh] Termos MeSH primário: Compostos Azabicíclicos/efeitos adversos Hipnóticos e Sedativos/efeitos adversos Piperazinas/efeitos adversos Piridinas/efeitos adversos Transtornos Relacionados ao Uso de Substâncias/epidemiologia [Mh] Termos MeSH secundário: Adulto Idoso Compostos Azabicíclicos/administração & dosagem Feminino França/epidemiologia Seres Humanos Hipnóticos e Sedativos/administração & dosagem Masculino Meia-Idade Farmacoepidemiologia Farmacovigilância Piperazinas/administração & dosagem Piridinas/administração & dosagem [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Azabicyclo Compounds); 0 (Hypnotics and Sedatives); 0 (Piperazines); 0 (Pyridines); 03A5ORL08Q (zopiclone); 7K383OQI23 (zolpidem) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170904 [Lr] Data última revisão: 170904 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170627 [St] Status: MEDLINE [do] DOI: 10.1080/14740338.2017.1346084

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[PMID]: 28648376 [Au] Autor: Benoit YD; Mitchell RR; Risueño RM; Orlando L; Tanasijevic B; Boyd AL; Aslostovar L; Salci KR; Shapovalova Z; Russell J; Eguchi M; Golubeva D; Graham M; Xenocostas A; Trus MR; Foley R; Leber B; Collins TJ; Bhatia M [Ad] Endereço: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4L8, Canada. [Ti] Título: Sam68 Allows Selective Targeting of Human Cancer Stem Cells. [So] Source: Cell Chem Biol;24(7):833-844.e9, 2017 Jul 20. [Is] ISSN: 2451-9456 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/ß-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/ß-catenin signaling within CSCs. Disruption of CBP-ß-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction. Our study identifies Sam68 as a regulator of human CSC vulnerability. [Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo Proteínas de Ligação a DNA/metabolismo Células-Tronco Neoplásicas/metabolismo Fragmentos de Peptídeos/metabolismo Proteínas de Ligação a RNA/metabolismo Sialoglicoproteínas/metabolismo [Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores Proteínas Adaptadoras de Transdução de Sinal/genética Adulto Idoso Animais Apoptose/efeitos dos fármacos Compostos Azabicíclicos/farmacologia Neoplasias da Mama/metabolismo Neoplasias da Mama/patologia Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia Diferenciação Celular/efeitos dos fármacos Células Cultivadas Neoplasias do Colo/metabolismo Neoplasias do Colo/patologia Proteínas de Ligação a DNA/antagonistas & inibidores Proteínas de Ligação a DNA/genética Feminino Seres Humanos Leucemia Mieloide Aguda/metabolismo Leucemia Mieloide Aguda/patologia Masculino Camundongos Camundongos Endogâmicos NOD Meia-Idade Células-Tronco Neoplásicas/citologia Células-Tronco Neoplásicas/transplante Organofosfatos/farmacologia Fragmentos de Peptídeos/antagonistas & inibidores Fragmentos de Peptídeos/genética Proteínas Proto-Oncogênicas c-myc/metabolismo Pirimidinonas/farmacologia Interferência de RNA Proteínas de Ligação a RNA/antagonistas & inibidores Proteínas de Ligação a RNA/genética Sialoglicoproteínas/antagonistas & inibidores Sialoglicoproteínas/genética Sumoilação/efeitos dos fármacos Transcriptoma/efeitos dos fármacos Via de Sinalização Wnt/efeitos dos fármacos beta Catenina/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Adaptor Proteins, Signal Transducing); 0 (Azabicyclo Compounds); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (CWP232228); 0 (DNA-Binding Proteins); 0 (ICG 001); 0 (KHDRBS1 protein, human); 0 (Organophosphates); 0 (Peptide Fragments); 0 (Proto-Oncogene Proteins c-myc); 0 (Pyrimidinones); 0 (RNA-Binding Proteins); 0 (Sialoglycoproteins); 0 (beta Catenin); 0 (bone sialoprotein (35-62), human) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171026 [Lr] Data última revisão: 171026 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170627 [St] Status: MEDLINE

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[PMID]: 28606623 [Au] Autor: Donvito G; Bagdas D; Toma W; Rahimpour E; Jackson A; Meade JA; AlSharari S; Kulkarni AR; Ivy Carroll F; Lichtman AH; Papke RL; Thakur GA; Imad Damaj M [Ad] Endereço: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: giulia.donvito@vcuhealth.org. [Ti] Título: The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice. [So] Source: Exp Neurol;295:194-201, 2017 Sep. [Is] ISSN: 1090-2430 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca -dependent manner. Here, we investigated potential crosstalk between α7 nAChR and PPAR-α, using the formalin test, a mouse model of tonic pain. Using pharmacological and genetic approaches, we found that PNU282987, a full α7 agonist, attenuated formalin-induced nociceptive behavior in α7-dependent manner. Interestingly, the selective PPAR-α antagonist GW6471 blocked the antinociceptive effects of PNU282987, but did not alter the antinociceptive responses evoked by the α7 nAChR PAM PNU120596, ago-PAM GAT107, and silent agonist NS6740. Moreover, GW6471 administered systemically or spinally, but not via the intraplantar surface of the formalin-injected paw blocked PNU282987-induced antinociception. Conversely, exogenous administration of the naturally occurring PPAR-α agonist PEA potentiated the antinociceptive effects of PNU282987. In contrast, the cannabinoid CB antagonist rimonabant and the CB antagonist SR144528 failed to reverse the antinociceptive effects of PNU282987. These findings suggest that PPAR-α plays a key role in a putative antinociceptive α7 nicotinic signaling pathway. [Mh] Termos MeSH primário: Nociceptividade/efeitos dos fármacos PPAR alfa/efeitos dos fármacos Transdução de Sinais/efeitos dos fármacos Receptor Nicotínico de Acetilcolina alfa7/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Compostos Azabicíclicos/farmacologia Benzamidas/farmacologia Compostos Bicíclicos com Pontes/farmacologia Antagonistas de Receptores de Canabinoides/farmacologia Etanolaminas/farmacologia Furanos/farmacologia Masculino Camundongos Camundongos Endogâmicos ICR Antagonistas Nicotínicos/farmacologia Oxazóis/farmacologia PPAR alfa/antagonistas & inibidores Medição da Dor/efeitos dos fármacos Ácidos Palmíticos/farmacologia Receptor Cross-Talk Tirosina/análogos & derivados Tirosina/farmacologia Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (1,4-diazabicyclo(3.2.2)nonan-4-yl(5-(3-(trifluoromethyl)phenyl)furan-2-yl)methanone); 0 (Azabicyclo Compounds); 0 (Benzamides); 0 (Bridged Bicyclo Compounds); 0 (Cannabinoid Receptor Antagonists); 0 (Ethanolamines); 0 (Furans); 0 (GW 6471); 0 (Nicotinic Antagonists); 0 (Oxazoles); 0 (PNU-282987); 0 (PPAR alpha); 0 (Palmitic Acids); 0 (alpha7 Nicotinic Acetylcholine Receptor); 42HK56048U (Tyrosine); 6R8T1UDM3V (palmidrol) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170614 [St] Status: MEDLINE

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[PMID]: 28573241 [Au] Autor: Li Z; Li S; Hu L; Li F; Cheung AC; Shao W; Que Y; Leung GP; Yang C [Ad] Endereço: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, P.R. China. [Ti] Título: MECHANISMS UNDERLYING ACTION OF INJECTION, A TRADITIONAL CHINESE MEDICINE IN CARDIAC FUNCTION IMPROVEMENT. [So] Source: Afr J Tradit Complement Altern Med;14(2):241-252, 2017. [Is] ISSN: 2505-0044 [Cp] País de publicação: Nigeria [La] Idioma: eng [Ab] Resumo: BACKGROUND: As a bioactive composite extracted from American cockroach, injection (XML) is used for the treatment of congestive heart failure (CHF) in China. Clinical data has provided evidence that XML has positive inotropic properties. The objective of this study was to assess the mechanisms involved in the therapeutical effect of XML on CHF. MATERIALS AND METHODS: The effects of XML on the cardiac function in isolated rat heart were measured. A Ca imaging technology was used in rat cardiomyocytes (H9c2 cells) to reveal the role of XML on Ca channels. Meanwhile, the effects of XML on the activities of Na+/K+ ATPase and sodium/calcium exchanger were measured. In addition, the level of reactive oxygen species and the protein expressions for the superoxide dismutase and hemeoxygenase were determined in the cardiomyocytes. RESULTS: The results showed that XML increased the electrical impulse-induced [Ca ] in H9c2 cells, which was dependant on extracellular Ca and was abolished by ML218-HCl (a T-type Ca channels antagonist) but not nimodipine (a L-type Ca channels antagonist). Ouabain, a Na+/K+-ATPase inhibitor, increased the electrical impulse-induced [Ca ] , which was significantly inhibited by XML. Moreover, XML markedly inhibited the Na+/K+ ATPase activity in H9c2 cells. In addition, XML notably reduced the production of reactive oxygen species and enhanced the protein expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and hemeoxygenase 1 in H9c2 cell. CONCLUSION: Our findings pave the ways to the better understandings of the therapeutic effects of XML on cardiovascular system. [Mh] Termos MeSH primário: Canais de Cálcio/metabolismo Cálcio/metabolismo Medicamentos de Ervas Chinesas/farmacologia Coração/efeitos dos fármacos Miócitos Cardíacos/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Compostos Azabicíclicos/farmacologia Benzamidas/farmacologia Bloqueadores dos Canais de Cálcio/farmacologia Cardiotônicos/farmacologia Linhagem Celular Baratas/química Coração/fisiologia Heme Oxigenase-1/metabolismo Medicina Tradicional Chinesa Miócitos Cardíacos/metabolismo Nimodipino/farmacologia Ouabaína/farmacologia Ratos Espécies Reativas de Oxigênio/metabolismo Trocador de Sódio e Cálcio/metabolismo ATPase Trocadora de Sódio-Potássio/metabolismo Superóxido Dismutase/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Azabicyclo Compounds); 0 (Benzamides); 0 (Calcium Channel Blockers); 0 (Calcium Channels); 0 (Cardiotonic Agents); 0 (Drugs, Chinese Herbal); 0 (ML218 compound); 0 (Reactive Oxygen Species); 0 (Sodium-Calcium Exchanger); 0 (xinmailong); 57WA9QZ5WH (Nimodipine); 5ACL011P69 (Ouabain); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.15.1.1 (Superoxide Dismutase); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); SY7Q814VUP (Calcium) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170816 [Lr] Data última revisão: 170816 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170603 [St] Status: MEDLINE [do] DOI: 10.21010/ajtcam.v14i2.26

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[PMID]: 28438958 [Au] Autor: Cimolai N [Ad] Endereço: Professor, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC. [Ti] Título: Zopiclone overdose and flumazenil rescue. [So] Source: CMAJ;189(16):E613, 2017 04 24. [Is] ISSN: 1488-2329 [Cp] País de publicação: Canada [La] Idioma: eng [Mh] Termos MeSH primário: Compostos Azabicíclicos Flumazenil [Mh] Termos MeSH secundário: Benzodiazepinas Overdose de Drogas Seres Humanos Piperazinas [Pt] Tipo de publicação: LETTER; COMMENT [Nm] Nome de substância: 0 (Azabicyclo Compounds); 0 (Piperazines); 03A5ORL08Q (zopiclone); 12794-10-4 (Benzodiazepines); 40P7XK9392 (Flumazenil) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171012 [Lr] Data última revisão: 171012 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170426 [St] Status: MEDLINE [do] DOI: 10.1503/cmaj.732933

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[PMID]: 28434765 [Au] Autor: Manzoni L; Samela A; Barbini S; Cairati S; Penconi M; Arosio D; Lecis D; Seneci P [Ad] Endereço: Istituto di Scienze e Tecnologie Molecolari (ISTM), Consiglio Nazionale delle Ricerche (CNR), Via Golgi 19, I-20133 Milan, Italy. [Ti] Título: 4-Connected azabicyclo[5.3.0]decane Smac mimetics-Zn chelators as dual action antitumoral agents. [So] Source: Bioorg Med Chem Lett;27(11):2336-2344, 2017 06 01. [Is] ISSN: 1464-3405 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Putative dual action compounds (DACs 3a-d) based on azabicyclo[5.3.0]decane (ABD) Smac mimetic scaffolds linked to Zn -chelating 2,2'-dipicolylamine (DPA) through their 4 position are reported and characterized. Their synthesis, their target affinity (cIAP1 BIR3, Zn ) in cell-free assays, their pro-apoptotic effects, and their cytotoxicity in tumor cells with varying sensitivity to Smac mimetics are described. A limited influence of Zn chelation on in vitro activity of DPA-substituted DACs 3a-d was sometimes perceivable, but did not lead to strong cellular synergistic effects. In particular, the linker connecting DPA with the ABD scaffold seems to influence cellular Zn -chelation, with longer lipophilic linkers/DAC 3c being the optimal choice. [Mh] Termos MeSH primário: Compostos Azabicíclicos/química Compostos Azabicíclicos/farmacologia Quelantes/farmacologia Peptídeos e Proteínas de Sinalização Intracelular/metabolismo Proteínas Mitocondriais/metabolismo Mimetismo Molecular Zinco/química [Mh] Termos MeSH secundário: Linhagem Celular Tumoral Quelantes/química Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Azabicyclo Compounds); 0 (Chelating Agents); 0 (DIABLO protein, human); 0 (Intracellular Signaling Peptides and Proteins); 0 (Mitochondrial Proteins); J41CSQ7QDS (Zinc) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171124 [Lr] Data última revisão: 171124 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170425 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28392315 [Au] Autor: Castón JJ; Lacort-Peralta I; Martín-Dávila P; Loeches B; Tabares S; Temkin L; Torre-Cisneros J; Paño-Pardo JR [Ad] Endereço: Infectious Diseases Unit Hospital Universitario Reina Sofía-IMIBIC, Córdoba, Spain. [Ti] Título: Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients. [So] Source: Int J Infect Dis;59:118-123, 2017 Jun. [Is] ISSN: 1878-3511 [Cp] País de publicação: Canada [La] Idioma: eng [Ab] Resumo: OBJECTIVES: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. METHODS: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia. A bivariate analysis was performed to compare the clinical variables between the study group and the control group. RESULTS: 31 patients were included. Bacteremia was considered primary in 14 (45%) patients. Overall crude mortality at 30days was 45.2% (n=14). Mortality was more frequent when septic shock (78.6% vs 11.8%; p>0.001) and higher Pitt score (6+14 vs 1.5+4; p<0.01) were present. 8 patients (25.8%) received treatment with ceftazidime/avibactam. No significant differences in crude mortality were found between study and comparator groups (p=0.19). In contrast, patients in study group had higher clinical cure rates than the comparator group within 14days of initiating treatment (85.7% vs. 34.8%, respectively, p=0.031). CONCLUSIONS: CPE bacteremia is associated with high mortality in patients with hematologic malignancies. Ceftazidime/avibactam may be an effective alternative for treating these patients. [Mh] Termos MeSH primário: Antibacterianos/uso terapêutico Compostos Azabicíclicos/uso terapêutico Bacteriemia/tratamento farmacológico Ceftazidima/uso terapêutico Infecções por Enterobacteriaceae/tratamento farmacológico Neoplasias Hematológicas/complicações [Mh] Termos MeSH secundário: Bacteriemia/complicações Bacteriemia/microbiologia Proteínas de Bactérias/biossíntese Estudos de Coortes Quimioterapia Combinada Enterobacteriaceae/enzimologia Feminino Seres Humanos Masculino Testes de Sensibilidade Microbiana Meia-Idade Estudos Retrospectivos Resultado do Tratamento beta-Lactamases/biossíntese [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY [Nm] Nome de substância: 0 (Anti-Bacterial Agents); 0 (Azabicyclo Compounds); 0 (Bacterial Proteins); 7352665165 (avibactam); 9M416Z9QNR (Ceftazidime); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (carbapenemase) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171025 [Lr] Data última revisão: 171025 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170411 [St] Status: MEDLINE

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