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[PMID]:29446275
[Au] Autor:Volkova VN; Mukhina LP; Chistova ZA; Fedorova SG
[Ti] Título:[Determination of polioksin B in the air environment and in washouts from skin of operators by HPLC].
[So] Source:Gig Sanit;95(11):1105-7, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Polyoxin B being an effective inhibitor of synthesis of chitin of the cell wall of many phytopathogenic fungi, is recommended as a fungicide for control of phytopathogenic organisms that cause damage to crop. For the determination of the exposure of employees working with pesticides there was developed the method of the measurement of concentrations of polyoxin B in air of working area, atmospheric air of populated areas and washouts from the operators ' integuments, based on high performance liquid chromatography with ultraviolet detector (detection wavelength of270 nm), including sampling air environment in the sorption tube ORBO-44, filled with sorbent XAD-2, extraction of the sorbent with polyoxin by a mixture of carbinol-water (in a ratio of 95:5,on volume), washout from the surface of the skin with ethyl alcohol by way of washing, concentrating, quantitative chromatographic analysis. Lower limits of the quantification ofpolyoxin B in the air ofworking area - 0.2 mg/m at the aspiration of 2 dm of air, atmospheric air - 0.016 mg/m at the aspiration of 25 dm of air, in washouts from the operators' integuments - 0.4 pg/wash, the linear range of the defined concentrations accounted for of 0.2 - 2.4 pg/cm, the total error of measurement of the concentrations of polyoxin B in air is 17%; in washouts from the operators' integuments - 16%. The developed method was approbated for the determination of polyoxin in samples of air of working zone, atmospheric air within the sanitary gap, washouts from the operators ' integuments and air drift samples taken under processing of roses in the hothouse and in the monitoring of the phytosanitary condition of the plants every other day after treatment.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Exposição Ocupacional
[Mh] Termos MeSH secundário: Antifúngicos/análise
Monitoramento Ambiental/métodos
Seres Humanos
Exposição Ocupacional/análise
Exposição Ocupacional/prevenção & controle
Nucleosídeos de Pirimidina/análise
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Pyrimidine Nucleosides); 11113-80-7 (polyoxin)
[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:180216
[St] Status:MEDLINE


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[PMID]:28454912
[Au] Autor:Pertusati F; Serafini S; Albadry N; Snoeck R; Andrei G
[Ad] Endereço:School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, CF10 3NB, Cardiff, Wales, United Kingdom. Electronic address: pertusatif1@cardiff.ac.uk.
[Ti] Título:Phosphonoamidate prodrugs of C5-substituted pyrimidine acyclic nucleosides for antiviral therapy.
[So] Source:Antiviral Res;143:262-268, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Acyclic nucleoside phosphonates (ANPs) are nowadays one of the key drugs in the treatment of DNA virus and retrovirus infections. In this work, we report the synthesis and antiviral evaluation of phosphonoamidate and diamidates prodrugs of C5-pyrimidine acyclic nucleosides derivatives functionalized with but-2-enyl- chain. In the phosphonoamidate series, the most active compound 15, showed sub-micromolar activity against varicella zoster virus (VZV) (EC = 0.09-0.5 µM) and µM activity against human cytomegalovirus (HCMV) and herpes simplex virus (HSV). Separation of single diastereoisomers for compound 14, showed that 14b had better anti-herpesvirus activity and no cytotoxicity compared to the diastereoisomeric mixture 14. Very interestingly, phosphonodiamidate 21 showed anti-herpesvirus activity with excellent activity against wild type and thymidine kinase-deficient (TK ) VZV strains (EC = 0.47 and 0.2 µM, respectively) and HCMV (EC = 3.5-7.2 µM) without any cytotoxicity (CC > 100).
[Mh] Termos MeSH primário: Pró-Fármacos/síntese química
Pró-Fármacos/farmacologia
Nucleosídeos de Pirimidina/síntese química
Nucleosídeos de Pirimidina/farmacologia
[Mh] Termos MeSH secundário: Antivirais/síntese química
Antivirais/farmacologia
Linhagem Celular
Citomegalovirus/efeitos dos fármacos
Herpesvirus Humano 3/efeitos dos fármacos
Seres Humanos
Simplexvirus/efeitos dos fármacos
Timidina Quinase
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Prodrugs); 0 (Pyrimidine Nucleosides); EC 2.7.1.21 (Thymidine Kinase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:29087802
[Au] Autor:Halay E; Ay E; Salva E; Ay K; Karayildirim T
[Ad] Endereço:a Scientific Analysis Technological Application and Research Center , Usak University , Usak , Turkey.
[Ti] Título:Syntheses of 1,2,3-triazole-bridged pyranose sugars with purine and pyrimidine nucleobases and evaluation of their anticancer potential.
[So] Source:Nucleosides Nucleotides Nucleic Acids;36(9):598-619, 2017 Sep 02.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:With the aim to create a library of compounds with potential bioactivities by combining special characteristics of two important groups such as nucleobases and carbohydrates, twenty 1,4-disubstituted-triazole nucleosides were synthesized in good yields (80-94%) using the copper catalyzed 'Click' reaction between azido-modified pento- or hexopyranoses and alkyne-bearing pyrimidine or purine nucleobases. Structural elucidation was made with the assistance of spectroscopic techniques such as FTIR, 1D-, 2D-NMR, and ESI-TOFMS. All the synthesized triazole nucleosides were evaluated for their cytotoxic activity against three human cancer cell lines (MDA-MB-231, Hep3B, PC-3) by using the MTT assay. Particularly, compounds 3a and 1b were identified as potential hits against Hep3B cell.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Nucleosídeos de Purina/química
Piranos/química
Nucleosídeos de Pirimidina/química
Triazóis/síntese química
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/química
Linhagem Celular Tumoral
Técnicas de Química Sintética
Seres Humanos
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Purine Nucleosides); 0 (Pyrans); 0 (Pyrimidine Nucleosides); 0 (Triazoles)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171101
[St] Status:MEDLINE
[do] DOI:10.1080/15257770.2017.1346258


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[PMID]:28757102
[Au] Autor:Krecmerová M; Dracínský M; Snoeck R; Balzarini J; Pomeisl K; Andrei G
[Ad] Endereço:Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, CZ-166 10, Prague 6, Czech Republic. Electronic address: marcela@uochb.cas.cz.
[Ti] Título:New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.
[So] Source:Bioorg Med Chem;25(17):4637-4648, 2017 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:New 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME-5-azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC 's of 0.15-1.12µM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis(hexadecylamido-l-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug.
[Mh] Termos MeSH primário: Antivirais/síntese química
Organofosfonatos/química
Pró-Fármacos/síntese química
Nucleosídeos de Pirimidina/química
[Mh] Termos MeSH secundário: Antivirais/química
Antivirais/farmacologia
Linhagem Celular
Citomegalovirus/efeitos dos fármacos
Herpesvirus Humano 3/efeitos dos fármacos
Seres Humanos
Organofosfonatos/síntese química
Organofosfonatos/farmacologia
Pró-Fármacos/química
Pró-Fármacos/farmacologia
Simplexvirus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Organophosphonates); 0 (Prodrugs); 0 (Pyrimidine Nucleosides)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


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[PMID]:28571825
[Au] Autor:Alzahrani KJ; Matyugina ES; Khandazhinskaya AL; Kochetkov SN; Seley-Radtke KL; Koning HP
[Ad] Endereço:Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK; Department of Clinical Laboratory, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
[Ti] Título:Evaluation of the antiprotozoan properties of 5'-norcarbocyclic pyrimidine nucleosides.
[So] Source:Bioorg Med Chem Lett;27(14):3081-3086, 2017 07 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Carbocyclic nucleoside analogues have a distinguished history as anti-infectious agents, including key antiviral agents. Toxicity was initially a concern but this was reduced by the introduction of 5'-nor variants. Here, we report the result of our preliminary screening of a series of 5'-norcarbocyclic uridine analogues against protozoan parasites, specifically the major pathogens Leishmania mexicana and Trypanosoma brucei. The series displayed antiparasite activity in the low to mid-micromolar range and establishes a preliminary structure-activity relationship, with the 4',N -di-(3,5-dimethylbenzoyl)-substituted analogues showing the most prominent activity. Utilizing an array of specially adapted cell lines, it was established that this series of analogues likely act through a common target. Moreover, the strong correlation between the trypanocidal and anti-leishmanial activities indicates that this mechanism is likely shared between the two species. EC values were unaffected by the disabling of pyrimidine biosynthesis in T. brucei, showing that these uridine analogues do not act directly on the enzymes of pyrimidine nucleotide metabolism. The lack of cross-resistance with 5-fluorouracil, also establishes that the carbocyclic analogues are not imported through the known uracil transporters, thus offering forth new insights for this class of nucleosides. The lack of cross-resistance with current trypanocides makes this compound class interesting for further exploration.
[Mh] Termos MeSH primário: Antiprotozoários/química
Nucleosídeos de Pirimidina/química
[Mh] Termos MeSH secundário: Antiprotozoários/farmacologia
Resistência a Medicamentos/efeitos dos fármacos
Fluoruracila/farmacologia
Leishmania mexicana/efeitos dos fármacos
Nucleosídeos de Pirimidina/farmacologia
Relação Estrutura-Atividade
Trypanosoma brucei brucei/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Pyrimidine Nucleosides); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE


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[PMID]:28431244
[Au] Autor:García-González AP; Ritter AD; Shrestha S; Andersen EC; Yilmaz LS; Walhout AJM
[Ad] Endereço:Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
[Ti] Título:Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics.
[So] Source:Cell;169(3):431-441.e8, 2017 Apr 20.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT). We find numerous bacterial nucleotide metabolism genes that affect drug efficacy in C. elegans. Surprisingly, we find that 5-FU and FUDR act through bacterial ribonucleotide metabolism to elicit their cytotoxic effects in C. elegans rather than by thymineless death or DNA damage. Our study provides a blueprint for characterizing the role of bacteria in the host response to chemotherapeutics.
[Mh] Termos MeSH primário: Antineoplásicos/metabolismo
Caenorhabditis elegans/microbiologia
Comamonas/metabolismo
Escherichia coli/metabolismo
Microbioma Gastrointestinal
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Camptotecina/metabolismo
Camptotecina/farmacologia
Neoplasias Colorretais/tratamento farmacológico
Comamonas/genética
Desoxiuridina/análogos & derivados
Desoxiuridina/metabolismo
Desoxiuridina/farmacologia
Dieta
Escherichia coli/genética
Fluoruracila/metabolismo
Fluoruracila/farmacologia
Seres Humanos
Modelos Animais
Nucleosídeos de Pirimidina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-fluoro-2'-deoxyuridine); 0 (Antineoplastic Agents); 0 (Pyrimidine Nucleosides); U3P01618RT (Fluorouracil); W78I7AY22C (Deoxyuridine); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE


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[PMID]:28252180
[Au] Autor:Maity J; Srivastava S; Sanghvi YS; Prasad AK; Stromberg R
[Ad] Endereço:Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Sweden.
[Ti] Título:Facile Access to Bromonucleosides Using Sodium Monobromoisocyanurate (SMBI).
[So] Source:Curr Protoc Nucleic Acid Chem;68:1.39.1-1.39.9, 2017 Mar 02.
[Is] ISSN:1934-9289
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bromonucleosides constitute a significant class of molecules and are well known for their biological activity. 5-Bromouridine, 5-bromo-2'-deoxyuridine, 5-bromouridine-5'-triphosphate, and nucleotides containing 5-bromouridine have been tested and used for numerous biological studies. 8-Bromopurine nucleosides have been used as essential precursors for the synthesis of nucleosides with fluorescent properties. This unit describes protocols for the synthesis of bromonucleosides using sodium monobromoisocyanurate (SMBI) in a straightforward way. Reactions are carried out at room temperature, and aqueous solvent mixtures are used to dissolve the nucleosides. Sodium azide is used as catalyst for the bromination of pyrimidine nucleosides, and no catalyst is necessary for the bromination of purine nucleosides. Unprotected 2'-deoxy pyrimidine and 2'-deoxy purine nucleosides are treated with SMBI to afford C-5 bromo pyrimidine and C-8 bromo purine nucleosides, respectively. This methodology has been found to be efficient for the synthesis of bromonucleosides on gram scale with consistently high yields. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Nucleosídeos de Purina/síntese química
Nucleosídeos de Pirimidina/síntese química
[Mh] Termos MeSH secundário: Bromodesoxicitidina/síntese química
Bromodesoxicitidina/química
Bromodesoxiuridina/síntese química
Técnicas de Química Sintética
Desoxiadenosinas/síntese química
Desoxiadenosinas/química
Desoxiguanosina/análogos & derivados
Desoxiguanosina/síntese química
Desoxiguanosina/química
Nucleosídeos de Purina/química
Nucleosídeos de Pirimidina/química
Uridina/análogos & derivados
Uridina/síntese química
Uridina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-bromo-2'-deoxyguanosine); 0 (Deoxyadenosines); 0 (Purine Nucleosides); 0 (Pyrimidine Nucleosides); 1022-79-3 (Bromodeoxycytidine); 14985-44-5 (8-bromo-2'-deoxyadenosine); G34N38R2N1 (Bromodeoxyuridine); G9481N71RO (Deoxyguanosine); KEY8PG1BRC (5-bromouridine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170303
[St] Status:MEDLINE
[do] DOI:10.1002/cpnc.24


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[PMID]:28096517
[Au] Autor:Friesen WJ; Trotta CR; Tomizawa Y; Zhuo J; Johnson B; Sierra J; Roy B; Weetall M; Hedrick J; Sheedy J; Takasugi J; Moon YC; Babu S; Baiazitov R; Leszyk JD; Davis TW; Colacino JM; Peltz SW; Welch EM
[Ad] Endereço:PTC Therapeutics, Inc., South Plainfield, New Jersey 07080, USA wfriesen@ptcbio.com.
[Ti] Título:The nucleoside analog clitocine is a potent and efficacious readthrough agent.
[So] Source:RNA;23(4):567-577, 2017 Apr.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonsense mutations resulting in a premature stop codon in an open reading frame occur in critical tumor suppressor genes in a large number of the most common forms of cancers and are known to cause or contribute to the progression of disease. Low molecular weight compounds that induce readthrough of nonsense mutations offer a new means of treating patients with genetic disorders or cancers resulting from nonsense mutations. We have identified the nucleoside analog clitocine as a potent and efficacious suppressor of nonsense mutations. We determined that incorporation of clitocine into RNA during transcription is a prerequisite for its readthrough activity; the presence of clitocine in the third position of a premature stop codon directly induces readthrough. We demonstrate that clitocine can induce the production of p53 protein in cells harboring p53 nonsense-mutated alleles. In these cells, clitocine restored production of full-length and functional p53 as evidenced by induced transcriptional activation of downstream p53 target genes, progression of cells into apoptosis, and impeded growth of nonsense-containing human ovarian cancer tumors in xenograft tumor models. Thus, clitocine induces readthrough of nonsense mutations by a previously undescribed mechanism and represents a novel therapeutic modality to treat cancers and genetic diseases caused by nonsense mutations.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/farmacologia
Materiais Biomiméticos/farmacologia
Códon sem Sentido/efeitos dos fármacos
Furanos/farmacologia
Nucleosídeos/farmacologia
Neoplasias Ovarianas/tratamento farmacológico
Nucleosídeos de Pirimidina/farmacologia
Proteína Supressora de Tumor p53/agonistas
[Mh] Termos MeSH secundário: Animais
Antimetabólitos Antineoplásicos/síntese química
Antimetabólitos Antineoplásicos/metabolismo
Apoptose/efeitos dos fármacos
Materiais Biomiméticos/síntese química
Materiais Biomiméticos/metabolismo
Linhagem Celular Tumoral
Feminino
Furanos/síntese química
Furanos/metabolismo
Genes Reporter
Seres Humanos
Luciferases/genética
Luciferases/metabolismo
Camundongos
Camundongos Nus
Nucleosídeos/síntese química
Nucleosídeos/metabolismo
Neoplasias Ovarianas/genética
Neoplasias Ovarianas/metabolismo
Neoplasias Ovarianas/patologia
Biossíntese de Proteínas
Nucleosídeos de Pirimidina/síntese química
Nucleosídeos de Pirimidina/metabolismo
Transdução de Sinais
Ativação Transcricional
Carga Tumoral/efeitos dos fármacos
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Codon, Nonsense); 0 (Furans); 0 (Nucleosides); 0 (Pyrimidine Nucleosides); 0 (Tumor Suppressor Protein p53); 105798-74-1 (clitocine); EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE
[do] DOI:10.1261/rna.060236.116


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[PMID]:27979259
[Au] Autor:Rahman MM; Abd El-Aty AM; Kim SW; Na TW; Shin HC; Hong SM; Shim JH
[Ad] Endereço:Biotechnology Research Institute, College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
[Ti] Título:A simple extraction method for the detection and quantification of polyoxin D, a nucleoside antibiotic, in butterbur using UPLC-MS/MS.
[So] Source:Food Chem;221:683-688, 2017 Apr 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An effective analytical method was developed for the detection and quantification of polyoxin D in butterbur using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were extracted using acidified deionised water and purified via solid-phase extraction (SPE) using an HLB cartridge. An external matrix-matched standard calibration curve was prepared, which provided an excellent linearity with a coefficient of determination (R ) ⩾0.999. Limits of detection (LOD) and quantification (LOQ) were 0.015 and 0.0.05µg/g, respectively. The developed method was validated in terms of recovery performance using two fortification levels in triplicate. The storage stabilities of the various field samples were also determined. Our method provided consistent recovery (86.26-87.37%) with a relative standard deviation (RSD) of <5%, and was successfully applied to field-treated butterbur grown under greenhouse conditions and collected at various times following commercial fungicide application. As expected, a gradual degradation of polyoxin D was observed, with a half-life (t ) of 2.11d being recorded. Finally, we propose that the developed method can be extrapolated to other crops for routine analysis and can be used to determine the pre-harvest intervals (PHIs), thus preventing the development of antibiotic resistance genes in humans and in the environment.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Petasites/química
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Nucleosídeos de Pirimidina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pyrimidine Nucleosides); A2468O1N7D (polyoxorim)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE


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[PMID]:27923747
[Au] Autor:Park SS; Jwa E; Shin SH; Ju EJ; Park I; Pak JH; Hwang JJ; Cho DH; Kim BM; Kim SB; Lee JS; Song SY; Jeong SY; Choi EK
[Ad] Endereço:Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea; Institute for Innovative Cancer Research, University of Ulsan College of Medicine, Seoul, Republic of Korea.
[Ti] Título:Ibulocydine sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis via calpain-mediated Bax cleavage.
[So] Source:Int J Biochem Cell Biol;83:47-55, 2017 Feb.
[Is] ISSN:1878-5875
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells without affecting the majority of normal human cells. However, hepatocellular carcinoma (HCC) cells often display resistance to TRAIL-induced apoptosis. Ibulocydine (IB) is an isobutyrate ester pro-drug of a novel synthetic Cdk inhibitor that targets Cdk7 and Cdk9. In this study, we show that treatment with subtoxic doses of IB in combination with TRAIL displays potent cytotoxicity in TRAIL-resistant human HCC cells. Combination of IB and TRAIL was found to synergistically induce apoptosis through activation of caspases, which was blocked by a pan-caspase inhibitor (zVAD). Although the expression of Mcl-1 and survivin were reduced by IB plus TRAIL, overexpression of Mcl-1 and survivin did not block the cell death induced by co-treatment. Moreover, overexpression of Bcl-xL did not significantly interfere with the cell death induced by co-treatment of IB and TRAIL. Interestingly, the combination treatment induced cleavage of Bax, which was translocated to mitochondria upon induction of apoptosis. Furthermore, down-regulation of Bax by small interfering RNA effectively reduced the cell death and loss of mitochondrial membrane potential (MMP) caused by co-treatment with IB and TRAIL. Finally, pre-treatment of HCC cells with a calpain inhibitor effectively blocked IB plus TRAIL-induced cleavage of Bax and apoptosis. Collectively, our results demonstrate that IB increases the sensitivity of human HCC cells to TRAIL via mitochondria signaling pathway mediated by calpain-induced cleavage of Bax, suggesting that combined treatment with IB and TRAIL may offer an effective therapeutic strategy for human HCC.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Calpaína/metabolismo
Carcinoma Hepatocelular/tratamento farmacológico
Neoplasias Hepáticas/tratamento farmacológico
Pró-Fármacos/farmacologia
Nucleosídeos de Pirimidina/farmacologia
Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
Proteína X Associada a bcl-2/metabolismo
[Mh] Termos MeSH secundário: Apoptose/fisiologia
Carcinoma Hepatocelular/metabolismo
Carcinoma Hepatocelular/patologia
Caspases/metabolismo
Linhagem Celular Tumoral
Sinergismo Farmacológico
Seres Humanos
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Pró-Fármacos/administração & dosagem
Nucleosídeos de Pirimidina/administração & dosagem
RNA Interferente Pequeno/genética
Transdução de Sinais/efeitos dos fármacos
Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem
Regulação para Cima
Proteína X Associada a bcl-2/antagonistas & inibidores
Proteína X Associada a bcl-2/genética
Proteína bcl-X/genética
Proteína bcl-X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((5-(4-amino-6-bromo-5-carbamoyl-1H-pyrrolo(2,3-d)pyrimidin-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl isobutyrate); 0 (BAX protein, human); 0 (BCL2L1 protein, human); 0 (Prodrugs); 0 (Pyrimidine Nucleosides); 0 (RNA, Small Interfering); 0 (TNF-Related Apoptosis-Inducing Ligand); 0 (TNFSF10 protein, human); 0 (bcl-2-Associated X Protein); 0 (bcl-X Protein); EC 3.4.22.- (Calpain); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE



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