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[PMID]:29409851
[Au] Autor:Tan M; Li G; Qi S; Liu X; Chen X; Ma J; Zhang D; Han M
[Ad] Endereço:College of Horticulture, Northwest A & F University, Yangling, Shaanxi 712100, China.
[Ti] Título:Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).
[So] Source:Gene;651:106-117, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth.
[Mh] Termos MeSH primário: Alquil e Aril Transferases/genética
Genes de Plantas
Malus/genética
Oxirredutases/genética
[Mh] Termos MeSH secundário: Arabidopsis/genética
Compostos de Benzil/farmacologia
Mapeamento Cromossômico
Cromossomos de Plantas
Evolução Molecular
Flores/genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Genoma de Planta
Lovastatina/farmacologia
Malus/enzimologia
Malus/crescimento & desenvolvimento
Família Multigênica
Filogenia
Reguladores de Crescimento de Planta
Purinas/farmacologia
Sintenia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Plant Growth Regulators); 0 (Purines); 9LHU78OQFD (Lovastatin); EC 1.- (Oxidoreductases); EC 1.5.99.12 (cytokinin oxidase); EC 2.5.- (Alkyl and Aryl Transferases); EC 2.5.1.27 (adenylate isopentenyltransferase); KXG6A989PS (benzylaminopurine)
[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:180208
[St] Status:MEDLINE


  2 / 16617 MEDLINE  
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[PMID]:28463380
[Au] Autor:Su L; Shi L; Liu J; Huang L; Huang Y; Nie X
[Ad] Endereço:School of Pharmacy, Second Military Medical University, Shanghai, China.
[Ti] Título:Metabolic profiling of asthma in mice and the interventional effects of SPA using liquid chromatography and Q-TOF mass spectrometry.
[So] Source:Mol Biosyst;13(6):1172-1181, 2017 May 30.
[Is] ISSN:1742-2051
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Asthma is a chronic inflammatory lung disease that leads to 250 000 deaths annually. There is a need to better understand asthma by identifying new pathogenic molecules. We conducted a liquid-chromatography time-of-flight mass spectrometry (LC-Q-TOF-MS)-based metabolomics study to test for asthma and investigate the interventional mechanisms of surfactant protein A (SPA) in OVA-induced asthma mice. The results revealed that asthma disturbed 32 metabolites in 9 metabolic pathways. After SPA treatment, the metabolomics profile found in asthma was significantly reversed, shifting much closer to that of the control group, indicating that SPA has therapeutic effects against asthma. Metabolomic pathway analysis by the ingenuity pathway analysis demonstrated that several pathways including fatty acid metabolism, lipid metabolism, and purine metabolism were significantly altered in asthma. This study offers new methodologies for the understanding of asthma and the mechanisms of SPA in treating asthma.
[Mh] Termos MeSH primário: Asma/metabolismo
Cromatografia Líquida/métodos
Espectrometria de Massas/métodos
Proteína A Associada a Surfactante Pulmonar/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Metabolismo dos Lipídeos/fisiologia
Camundongos
Purinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pulmonary Surfactant-Associated Protein A); 0 (Purines); W60KTZ3IZY (purine)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.1039/c7mb00025a


  3 / 16617 MEDLINE  
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[PMID]:29231001
[Au] Autor:Wu JY; Wang D; Kong J; Wang XX; Yu XJ
[Ad] Endereço:Department of Forensic Pathology, Medical College, Shantou University, Shantou 515041, China.
[Ti] Título:[Metabolic Characteristics of Lethal Bradycardia Induced by Myocardial Ischemia].
[So] Source:Fa Yi Xue Za Zhi;33(1):11-16, 2017 Feb.
[Is] ISSN:1004-5619
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVES: To explore the metabolic characteristics of lethal bradycardia induced by myocardial ischemia in rat's serum. METHODS: A rat myocardial ischemia-bradycardia-sudden cardiac death (MI-B-SCD) model was established, which was compared with the sham-operation group. The metabolic profile of postmortem serum was analyzed by gas chromatography-mass spectrometry (GC-MS), coupled with the analysis of serum metabolic characteristics using metabolomics strategies. RESULTS: The serum metabolic profiles were significantly different between the MI-B-SCD rats and the control rats. Compared to the control rats, the MI-B-SCD rats had significantly higher levels of lysine, ornithine, purine, serine, alanine, urea and lactic acid; and significantly lower levels of succinate, hexadecanoic acid, 2-ketoadipic acid, glyceraldehyde, hexendioic acid and octanedioic acid in the serum. There were some correlations among different metabolites. CONCLUSIONS: There is obvious metabolic alterations in the serum of MI-B-SCD rat. Both lysine and purine have a high value in diagnosing MI-B-SCD. The results are expected to provide references for forensic and clinical applications of prevention and control of sudden cardiac death.
[Mh] Termos MeSH primário: Bradicardia/metabolismo
Morte Súbita Cardíaca
Cromatografia Gasosa-Espectrometria de Massas/métodos
Metabolômica/métodos
Isquemia Miocárdica/metabolismo
[Mh] Termos MeSH secundário: Animais
Bradicardia/patologia
Doença da Artéria Coronariana
Modelos Animais de Doenças
Lisina/sangue
Lisina/metabolismo
Isquemia Miocárdica/diagnóstico
Purinas/sangue
Purinas/metabolismo
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purines); K3Z4F929H6 (Lysine); W60KTZ3IZY (purine)
[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:171213
[St] Status:MEDLINE
[do] DOI:10.3969/j.issn.1004-5619.2017.01.003


  4 / 16617 MEDLINE  
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[PMID]:28453705
[Au] Autor:Mato AR; Hill BT; Lamanna N; Barr PM; Ujjani CS; Brander DM; Howlett C; Skarbnik AP; Cheson BD; Zent CS; Pu JJ; Kiselev P; Foon K; Lenhart J; Henick Bachow S; Winter AM; Cruz AL; Claxton DF; Goy A; Daniel C; Isaac K; Kennard KH; Timlin C; Fanning M; Gashonia L; Yacur M; Svoboda J; Schuster SJ; Nabhan C
[Ad] Endereço:Center for CLL, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.
[Ti] Título:Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients.
[So] Source:Ann Oncol;28(5):1050-1056, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results: A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions: In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem
Intervalo Livre de Doença
Esquema de Medicação
Seres Humanos
Estimativa de Kaplan-Meier
Leucemia Linfocítica Crônica de Células B/mortalidade
Meia-Idade
Modelos de Riscos Proporcionais
Purinas/administração & dosagem
Pirazóis/administração & dosagem
Pirimidinas/administração & dosagem
Quinazolinonas/administração & dosagem
Estudos Retrospectivos
Sulfonamidas/administração & dosagem
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (PCI 32765); 0 (Purines); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Quinazolinones); 0 (Sulfonamides); N54AIC43PW (venetoclax); YG57I8T5M0 (idelalisib)
[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:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx031


  5 / 16617 MEDLINE  
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[PMID]:29177261
[Au] Autor:Koutsikos J; Angelidis G; Zafeirakis A; Mamarelis I; Vogiatzis M; Ilia E; Lazaridis K; Demakopoulos N
[Ad] Endereço:Department of Nuclear Medicine Army Share Fund Hospital (417 NIMTS) Athens, Greece. jtkoutsik@yahoo.gr.
[Ti] Título:Performance and safety profile of regadenoson myocardial perfusion imaging: first experience in Greece.
[So] Source:Hell J Nucl Med;20(3):232-236, 2017 Sep-Dec.
[Is] ISSN:1790-5427
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: MPI can provide valuable information in the investigation of patients with known or suspected coronary artery disease. The stress component of the studies can be conducted with regadenoson, which was approved for clinical use in Greece in 2016. We investigated the performance and safety profile of regadenoson MPI based on our 7 months institutional experience. PATIENTS AND METHODS: We studied 96 consecutive patients (59 males, 37 females, mean age 70.35y.o, range: 46-87y.o.) referred to our department for a clinically indicated MPI study with pharmacological stress. Eleven patients suffered from chronic obstructive pulmonary disease. Patients underwent regadenoson stress test, combined with both stress and rest imaging. Data on the symptoms and electrocardiographic changes due to regadenoson administration were recorded. Symptoms were graded as 1-mild: a symptom that did not distress the patient, 2-moderate: a symptom that distressed the patient but it was self-limiting, or 3-severe: a symptom that distressed the patient requiring medical intervention. RESULTS: Regadenoson-related symptoms were reported in 56 patients and were: dyspnea, discomfort, dizziness, chest pain, epigastric pain, neck pain, headache, flushing, nausea, heartburn, weakness, and upper limbs numbness. The severity of symptoms was recorded as grade 1 in 30 patients, grade 2 in 25 patients, and grade 3 in 1 patient. Two or more different symptoms were reported in 28 patients. Ischemic electrocardiographic changes and arrhythmias were observed in 8 patients. CONCLUSION: Our findings support previously published data indicating the optimal safety profile of regadenoson MPI, even in the group of patients suffering from chronic obstructive pulmonary disease.
[Mh] Termos MeSH primário: Doença da Artéria Coronariana/diagnóstico por imagem
Doença da Artéria Coronariana/epidemiologia
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
Teste de Esforço/estatística & dados numéricos
Imagem de Perfusão do Miocárdio/métodos
Purinas
Pirazóis
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Causalidade
Comorbidade
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico
Feminino
Grécia/epidemiologia
Seres Humanos
Masculino
Meia-Idade
Imagem de Perfusão do Miocárdio/estatística & dados numéricos
Projetos Piloto
Tomografia por Emissão de Pósitrons/métodos
Tomografia por Emissão de Pósitrons/estatística & dados numéricos
Prevalência
Reprodutibilidade dos Testes
Fatores de Risco
Sensibilidade e Especificidade
Resultado do Tratamento
Vasodilatadores
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purines); 0 (Pyrazoles); 0 (Vasodilator Agents); 2XLN4Y044H (regadenoson)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1967/s002449910607


  6 / 16617 MEDLINE  
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[PMID]:29195143
[Au] Autor:Rashid MM; Lee H; Jung BH
[Ad] Endereço:Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea.
[Ti] Título:Metabolite identification and pharmacokinetic profiling of PP242, an ATP-competitive inhibitor of mTOR using ultra high-performance liquid chromatography and mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1072:244-251, 2018 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:PP242 is a second generation novel selective ATP-competitive inhibitor of mTOR that displayed promising anti-cancer activity over several cancer types by inhibiting both the complexes of mTOR (mTORC1 and mTORC2). The purpose of this study is to identify the possible metabolites and to evaluate the pharmacokinetic profile of PP242 after a single oral administration to Sprague-Dawley (SD) rats. Two metabolites, including one phase I and one phase II, were identified by in vitro and in vivo studies using rat liver microsomes (RLMs) as well as rat plasma, urine and feces, respectively, through ultra high-performance liquid chromatography-linear ion trap quadrupole-orbitrap-mass spectrometry (UHPLC-LTQ-Orbitrap-MS). The major biotransformation pathways of PP242 were hydroxylation and glucuronide conjugation. Additionally, a simple and rapid quantification method was developed and validated. The method recovery was within 79.7-84.6%, whereas the matrix effect was 78.1-96.0% in all three quality control (QC) concentrations (low, medium and high) including the LLOQ. Other parameters showed acceptable results according to the US food and drug administration (FDA) guidelines for bioanalytical method validation. Afterwards, pharmacokinetic parameters were evaluated in rat plasma by successfully applying the validated method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). After a single oral administration at a dose of 5mg/kg, the maximum plasma concentration (C ) of PP242 was 0.17±0.08µg/mL, while the elimination was moderately fast (T : 172.18±45.54min). All of the obtained information on the metabolite identification and pharmacokinetic parameter elucidation could facilitate the further development of PP242.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Indóis/metabolismo
Indóis/farmacocinética
Espectrometria de Massas/métodos
Purinas/metabolismo
Purinas/farmacocinética
[Mh] Termos MeSH secundário: Animais
Calibragem
Estabilidade de Medicamentos
Indóis/análise
Indóis/química
Modelos Lineares
Masculino
Microssomos Hepáticos/metabolismo
Purinas/análise
Purinas/química
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Indoles); 0 (PP242); 0 (Purines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE


  7 / 16617 MEDLINE  
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[PMID]:29311512
[Au] Autor:Murakami N; Yoshida M; Yoshino T; Matsunaga S
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Hokkaido University.
[Ti] Título:Synthesis of Fluorine-Containing 6-Arylpurine Derivatives via Cp*Co(III)-Catalyzed C-H Bond Activation.
[So] Source:Chem Pharm Bull (Tokyo);66(1):51-54, 2018.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Cp*Co(III)-catalyzed (Cp*=pentamethylcyclopentadienyl) C-H bond functionalization of 6-arylpurines using gem-difluoroalkenes and allyl fluorides is described. The reaction with gem-difluoroalkenes afforded monofluoroalkenes with high (Z)-selectivity, while the reaction with allyl fluorides led to C-H allylation in moderate (Z)-selectivity. Both reactions proceeded using a user-friendly single-component catalyst [Cp*Co(CH CN) ](SbF ) in fluorinated alcohol solvents without any additives. Robustness was also demonstrated by a preparative-scale reaction under air.
[Mh] Termos MeSH primário: Cobalto/química
Ciclopentanos/química
Flúor/química
Compostos Organometálicos/química
Purinas/síntese química
[Mh] Termos MeSH secundário: Catálise
Estrutura Molecular
Purinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclopentanes); 0 (Organometallic Compounds); 0 (Purines); 284SYP0193 (Fluorine); 3G0H8C9362 (Cobalt); W60KTZ3IZY (purine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00797


  8 / 16617 MEDLINE  
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[PMID]:29324786
[Au] Autor:Reipa V; Atha DH; Coskun SH; Sims CM; Nelson BC
[Ad] Endereço:Materials Measurement Laboratory, Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, Maryland, United States of America.
[Ti] Título:Controlled potential electro-oxidation of genomic DNA.
[So] Source:PLoS One;13(1):e0190907, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Exposure of mammalian cells to oxidative stress can result in DNA damage that adversely affects many cell processes. Lack of dependable DNA damage reference materials and standardized measurement methods, despite many case-control studies hampers the wider recognition of the link between oxidatively degraded DNA and disease risk. We used bulk electrolysis in an electrochemical system and gas chromatographic mass spectrometric analysis (GC/MS/MS) to control and measure, respectively, the effect of electrochemically produced reactive oxygen species on calf thymus DNA (ct-DNA). DNA was electro-oxidized for 1 h at four fixed oxidizing potentials (E = 0.5 V, 1.0 V, 1.5 V and 2 V (vs Ag/AgCl)) using a high surface area boron-doped diamond (BDD) working electrode (WE) and the resulting DNA damage in the form of oxidatively-modified DNA lesions was measured using GC/MS/MS. We have shown that there are two distinct base lesion formation modes in the explored electrode potential range, corresponding to 0.5 V < E < 1.5 V and E > 1.5 V. Amounts of all four purine lesions were close to a negative control levels up to E = 1.5 V with evidence suggesting higher levels at the lowest potential of this range (E = 0.5 V). A rapid increase in all base lesion yields was measured when ct-DNA was exposed at E = 2 V, the potential at which hydroxyl radicals were efficiently produced by the BDD electrode. The present results demonstrate that controlled potential preparative electrooxidation of double-stranded DNA can be used to purposely increase the levels of oxidatively modified DNA lesions in discrete samples. It is envisioned that these DNA samples may potentially serve as analytical control or quality assurance reference materials for the determination of oxidatively induced DNA damage.
[Mh] Termos MeSH primário: DNA/química
[Mh] Termos MeSH secundário: Animais
Boro
Bovinos
Diamante
Eletrodos
Eletrólise
Cromatografia Gasosa-Espectrometria de Massas
Radical Hidroxila/química
Oxirredução
Purinas/química
Pirimidinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Purines); 0 (Pyrimidines); 3352-57-6 (Hydroxyl Radical); 7782-40-3 (Diamond); 9007-49-2 (DNA); 91080-16-9 (calf thymus DNA); N9E3X5056Q (Boron)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190907


  9 / 16617 MEDLINE  
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[PMID]:29244467
[Au] Autor:Dyakova ME
[Ti] Título:Features purine metabolism in patients with pulmonary tuberculosis.
[So] Source:Patol Fiziol Eksp Ter;60(3):36-41, 2016 Jul-Sep.
[Is] ISSN:0031-2991
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:The purpose - comprehensive study of the purine metabolic enzymes in serum and immune cells in patients with pulmonary tuberculosis for the understanding of the pathogenesis of a specific lung disease. Methods: The enzymes of purine metabolism (adenosine deaminase (ADA) and its isoenzymes (ADA-1 and ADA-2), dipeptidylpeptidase IV (DPPIV - CD26), ecto-5'-nucleotidase (5'-NC) in the blood and immune cells was studied in 29 and 76 patients with fibro-cavernous (FCPT) and infiltrative (IPT) pulmonary tuberculosis correspondingly. Results: In patients found changes in purine metabolism, the severity and pathophysiological significance of which depend of clinical forms of tuberculosis, that is, from the gravity specific of the process. Reduced activity of ADA mononuclear cells was accompanied by a decrease in the expression of CD26 in patients with FCPT and the growth of the IPT ectopeptidase patients, that is, the concentration of CD26 mononuclear cells and neutrophils are associated with form of pulmonary tuberculosis. The increased levels of another enzyme purine metabolism - 5'-NC registered in both forms of pulmonary tuberculosis. Conclusion: In the context of the ADA and CD26 association with the IPT can assume increased participation of each of them in the activation of cell proliferation and cytokine production. Low levels of CD26 immune cells in the absence of their connection with the activity of ADA is typical for patients with FCPT and reflects their inherent failure of cellular immunity. We can assume that the formation of complexes with the ADA ectopeptidases (CD26 and 5'-NC) for newly diagnosed IPT provides a balance CD26_ADA extracellular / intracellular adenosine and 5'-NC / adenosine and thereby adequate metabolism of immunocompetent cells.
[Mh] Termos MeSH primário: Dipeptidil Peptidase 4/sangue
Purinas/sangue
Tuberculose Pulmonar/sangue
[Mh] Termos MeSH secundário: Adulto
Dipeptidil Peptidase 4/imunologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Purinas/imunologia
Tuberculose Pulmonar/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purines); EC 3.4.14.5 (DPP4 protein, human); EC 3.4.14.5 (Dipeptidyl Peptidase 4)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


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[PMID]:29174506
[Au] Autor:Qiu X; Huang Y; Wu D; Mao F; Zhu J; Yan W; Luo HB; Li J
[Ad] Endereço:Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
[Ti] Título:Discovery of novel purine nucleoside derivatives as phosphodiesterase 2 (PDE2) inhibitors: Structure-based virtual screening, optimization and biological evaluation.
[So] Source:Bioorg Med Chem;26(1):119-133, 2018 01 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phosphodiesterase 2 (PDE2) has received much attention for the potential treatment of the central nervous system (CNS) disorders and pulmonary hypertension. Herein, we identified that clofarabine (4), an FDA-approved drug, displayed potential PDE2 inhibitory activity (IC = 3.12 ±â€¯0.67 µM) by structure-based virtual screening and bioassay. Considering the potential therapeutic benefit of PDE2, a series of purine nucleoside derivatives based on the structure and binding mode of 4 were designed, synthesized and evaluated, which led to the discovery of the best compound 14e with a significant improvement of inhibitory potency (IC = 0.32 ±â€¯0.04 µM). Further molecular docking and molecular dynamic (MD) simulations studies revealed that 5'-benzyl group of 14e could interact with the unique hydrophobic pocket of PDE2 by forming extra van der Waals interactions with hydrophobic residues such as Leu770, Thr768, Thr805 and Leu809, which might contribute to its enhancement of PDE2 inhibition. These potential compounds reported in this article and the valuable structure-activity relationships (SARs) might bring significant instruction for further development of potent PDE2 inhibitors.
[Mh] Termos MeSH primário: Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores
Descoberta de Drogas
Nucleosídeos/farmacologia
Inibidores de Fosfodiesterase/farmacologia
Purinas/farmacologia
[Mh] Termos MeSH secundário: Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo
Relação Dose-Resposta a Droga
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Nucleosídeos/síntese química
Nucleosídeos/química
Inibidores de Fosfodiesterase/síntese química
Inibidores de Fosfodiesterase/química
Purinas/síntese química
Purinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nucleosides); 0 (Phosphodiesterase Inhibitors); 0 (Purines); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 2); EC 3.1.4.17 (PDE2A protein, human); W60KTZ3IZY (purine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180106
[Lr] Data última revisão:
180106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE



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