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Pesquisa : D02.241.223.100.050.500.625 [Categoria DeCS]
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[PMID]:23562328
[Au] Autor:Mohamed AN; Abdelhady AM; Spencer D; Sowinski KM; Tisdale JE; Overholser BR
[Ti] Título:Pharmacokinetic modeling and simulation of procainamide and N-acetylprocainamide in a patient receiving continuous renal replacement therapy: a novel approach to guide renal dose adjustments.
[So] Source:Am J Kidney Dis;61(6):1046-8, 2013 Jun.
[Is] ISSN:1523-6838
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Acecainida/farmacocinética
Antiarrítmicos/farmacocinética
Procainamida/farmacocinética
Insuficiência Renal Crônica/terapia
Terapia de Substituição Renal/métodos
Taquicardia Ventricular/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Seres Humanos
Masculino
Modelos Biológicos
Insuficiência Renal Crônica/complicações
Insuficiência Renal Crônica/metabolismo
Taquicardia Ventricular/complicações
[Pt] Tipo de publicação:CASE REPORTS; LETTER; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 910Q707V6F (Acecainide); L39WTC366D (Procainamide)
[Em] Mês de entrada:1307
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130409
[St] Status:MEDLINE


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[PMID]:22894712
[Au] Autor:Ghosh SC; Ngiam JS; Seayad AM; Tuan DT; Chai CL; Chen A
[Ad] Endereço:Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, Neuros 07-01, Singapore 138665.
[Ti] Título:Copper-catalyzed oxidative amidation of aldehydes with amine salts: synthesis of primary, secondary, and tertiary amides.
[So] Source:J Org Chem;77(18):8007-15, 2012 Sep 21.
[Is] ISSN:1520-6904
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A practical method for the amidation of aldehydes with economic ammonium chloride or amine hydrochloride salts has been developed for the synthesis of a wide variety of amides by using inexpensive copper sulfate or copper(I) oxide as a catalyst and aqueous tert-butyl hydroperoxide as an oxidant. This amidation reaction is operationally straightforward and provides primary, secondary, and tertiary amides in good to excellent yields for most cases utilizing inexpensive and readily available reagents under mild conditions. In situ formation of amine salts from free amines extends the substrate scope of the reaction. Chiral amides are also synthesized from their corresponding chiral amines without detectable racemization. The practicality of this amide formation reaction has been demonstrated in an efficient synthesis of the antiarrhythmic drug N-acetylprocainamide.
[Mh] Termos MeSH primário: Acecainida/síntese química
Aldeídos/química
Antiarrítmicos/síntese química
Cobre/química
Sais/química
terc-Butil Hidroperóxido/química
[Mh] Termos MeSH secundário: Acecainida/química
Amidas/síntese química
Aminas/síntese química
Antiarrítmicos/química
Catálise
Estrutura Molecular
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aldehydes); 0 (Amides); 0 (Amines); 0 (Anti-Arrhythmia Agents); 0 (Salts); 789U1901C5 (Copper); 910Q707V6F (Acecainide); 955VYL842B (tert-Butylhydroperoxide)
[Em] Mês de entrada:1304
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120817
[St] Status:MEDLINE


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[PMID]:18489081
[Au] Autor:Siraki AG; Deterding LJ; Bonini MG; Jiang J; Ehrenshaft M; Tomer KB; Mason RP
[Ad] Endereço:Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Dr., Research Triangle Park, NC 27709, USA. sirakia@niehs.nih.gov
[Ti] Título:Procainamide, but not N-acetylprocainamide, induces protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis.
[So] Source:Chem Res Toxicol;21(5):1143-53, 2008 May.
[Is] ISSN:1520-5010
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Procainamide (PA) is a drug that is used to treat tachycardia in postoperative patients or for long-term maintenance of cardiac arrythmias. Unfortunately, its use has also been associated with agranulocytosis. Here, we have investigated the metabolism of PA by myeloperoxidase (MPO) and the formation of an MPO protein free radical. We hypothesized that PA oxidation by MPO/H 2O 2 would produce a PA cation radical that, in the absence of a biochemical reductant, would lead to the free radical oxidation of MPO. We utilized a novel anti-DMPO antibody to detect DMPO (5,5-dimethyl-1-pyrroline N-oxide) covalently bound to protein, which forms by the reaction of DMPO with a protein free radical. We found that PA metabolism by MPO/H 2O 2 induced the formation of DMPO-MPO, which was inhibited by MPO inhibitors and ascorbate. N-acetyl-PA did not cause DMPO-MPO formation, indicating that the unsubstituted aromatic amine was more oxidizable. PA had a lower calculated ionization potential than N-acetyl-PA. The DMPO adducts of MPO metabolism, as analyzed by electron spin resonance spectroscopy, included a nitrogen-centered radical and a phenyl radical derived from PA, either of which may be involved in the free radical formation on MPO. Furthermore, we also found protein-DMPO adducts in MPO-containing, intact human promyelocytic leukemia cells (HL-60). MPO was affinity-purified from HL-60 cells treated with PA/H 2O 2 and was found to contain DMPO using the anti-DMPO antibody. Mass spectrometry analysis confirmed the identity of the protein as human MPO. These findings were also supported by the detection of protein free radicals with electron spin resonance in the cellular cytosolic lysate. The formation of an MPO protein free radical is believed to be mediated by free radical metabolites of PA, which we characterized by spin trapping. We propose that drug-induced free radical formation on MPO may play a role in the origin of agranulocytosis.
[Mh] Termos MeSH primário: Radicais Livres/metabolismo
Granulócitos/patologia
Peroxidase/metabolismo
Procainamida/farmacologia
[Mh] Termos MeSH secundário: Acecainida/química
Acecainida/farmacologia
Ácido Ascórbico/farmacologia
Linhagem Celular Tumoral
Espectroscopia de Ressonância de Spin Eletrônica
Inibidores Enzimáticos/farmacologia
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Íons/química
Espectrometria de Massas
Estrutura Molecular
Peroxidase/antagonistas & inibidores
Procainamida/química
Procainamida/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Free Radicals); 0 (Ions); 910Q707V6F (Acecainide); BBX060AN9V (Hydrogen Peroxide); EC 1.11.1.7 (Peroxidase); L39WTC366D (Procainamide); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:0807
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:080521
[St] Status:MEDLINE
[do] DOI:10.1021/tx700415b


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[PMID]:17616997
[Au] Autor:Dasgupta A; Hovanetz M; Olsen M; Wells A; Actor JK
[Ad] Endereço:Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.292, Houston, TX 77030, USA. Amitava.Dasgupta@uth.tmc.edu
[Ti] Título:Drug-herb interaction: effect of St John's wort on bioavailability and metabolism of procainamide in mice.
[So] Source:Arch Pathol Lab Med;131(7):1094-8, 2007 Jul.
[Is] ISSN:1543-2165
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CONTEXT: St John's wort induces the activity of the cytochrome P450 enzyme system causing treatment failure because of increased metabolism of many drugs. Procainamide is metabolized by a different pathway to N-acetyl procainamide. OBJECTIVE: To study St John's wort-procainamide interaction using a mouse (Swiss Webster) model. DESIGN: One group of mice (group A, 4 mice in each group) was fed St John's wort each day for 2 weeks (last dose 1 day before administration of procainamide); another group (group B) received the same dose of St John's wort for 1 week. The third group (group C) received only a single dose 1 hour before administration of procainamide, and the control group (group D) received no St John's wort. All groups later received a single oral dose of procainamide. Blood was drawn 1, 4, and 24 hours after administration of procainamide and concentrations in serum of procainamide as well as N-acetyl procainamide were measured using immunoassays. RESULTS: The procainamide concentrations 1 hour after administration was highest in group C (mean, 11.59 microg/mL) followed by group A (9.92 microg/mL), whereas group B (7.44 microg/mL) and control group D (7.36 microg/mL) showed comparable values. The concentration in group C was significantly greater than the control group D (P = .03, 2-tailed independent t test). N-Acetyl procainamide concentrations and estimated half-life of procainamide among groups were comparable. In a separate experiment when mice were fed purified hypericin, the active component of St John's wort, a significant increase in bioavailability (53%) of procainamide was observed compared with the control group. CONCLUSIONS: St John's wort has an acute effect to increase bioavailability of procainamide but has no effect on its metabolism.
[Mh] Termos MeSH primário: Interações Ervas-Drogas
Hypericum
Procainamida/farmacocinética
[Mh] Termos MeSH secundário: Acecainida/farmacocinética
Animais
Disponibilidade Biológica
Feminino
Camundongos
Perileno/análogos & derivados
Perileno/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5QD5427UN7 (Perylene); 7V2F1075HD (hypericin); 910Q707V6F (Acecainide); L39WTC366D (Procainamide)
[Em] Mês de entrada:0707
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:070710
[St] Status:MEDLINE


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[PMID]:17125432
[Au] Autor:Moffett BS; Cannon BC; Friedman RA; Kertesz NJ
[Ad] Endereço:Department of Pharmacy, Texas Children's Hospital, Houston, Texas 77030. bsmoffet@texaschildrenshospital.org
[Ti] Título:Therapeutic levels of intravenous procainamide in neonates: a retrospective assessment.
[So] Source:Pharmacotherapy;26(12):1687-93, 2006 Dec.
[Is] ISSN:0277-0008
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:STUDY OBJECTIVES: To evaluate dosing and pharmacokinetic parameters of intravenous continuous-infusion procainamide in neonates, and to identify dosage regimens and factors leading to therapeutic procainamide levels and minimal adverse events. DESIGN: Retrospective, observational study. SETTING: Pediatric hospital. PATIENTS: . Twenty-one patients (seven preterm, 14 full term) younger than 30 days who received continuous-infusion procainamide therapy for more than 15 hours or had two consecutive therapeutic procainamide levels obtained while receiving therapy between June 1, 2002, and December 31, 2005. MEASUREMENTS AND MAIN RESULTS: Data on demographics, dosing, drug levels, and adverse effects were collected. Doses that achieved therapeutic levels were documented, and procainamide clearance was calculated and evaluated with regard to renal function and gestational age in patients who were at steady state. Mean clearance and mean N-acetylprocainamide (NAPA):procainamide ratios were compared between preterm and term neonates. No patients experienced hemodynamic instability or other adverse effects due to procainamide. Procainamide was given as a mean +/- SD 9.6 +/- 1.5-mg/kg bolus in 20 of 21 patients before continuous infusion. The mean +/- SD dose at which two therapeutic levels were achieved was 37.56 +/- 13.52 microg/kg/minute. Procainamide clearance was 6.36 +/- 8.85 ml/kg/minute and correlated with creatinine clearance (r=0.78, p<0.00001) and age at day of sampling (r=0.49, p<0.00001). The NAPA:procainamide ratio at steady state was 0.84 +/- 0.53; two patients were determined to be fast acetylators (ratio > 1). Preterm infants had lower mean clearance rates (p<0.001) but higher NAPA:procainamide ratios (p<0.01) than those of term infants. Five patients experienced seven supratherapeutic levels while receiving therapy; four of these patients were preterm, and all had creatinine clearances less than 30 ml/minute/1.73 m(2). Three patients had four pairs of levels obtained after discontinuation of procainamide, and elimination rate constant and half-life were calculated. CONCLUSION: Procainamide can be safely used in neonates, with no short-term adverse effects. The dosage regimen for intravenous procainamide required to achieve therapeutic levels in neonates is similar to that of older infants and children. Doses may need to be reduced in premature infants and in those with renal dysfunction.
[Mh] Termos MeSH primário: Antiarrítmicos/administração & dosagem
Antiarrítmicos/farmacocinética
Procainamida/administração & dosagem
Procainamida/farmacocinética
[Mh] Termos MeSH secundário: Acecainida/sangue
Creatinina/metabolismo
Relação Dose-Resposta a Droga
Idade Gestacional
Seres Humanos
Recém-Nascido
Infusões Intravenosas
Taxa de Depuração Metabólica
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 910Q707V6F (Acecainide); AYI8EX34EU (Creatinine); L39WTC366D (Procainamide)
[Em] Mês de entrada:0701
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:061128
[St] Status:MEDLINE


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[PMID]:16221756
[Au] Autor:Brightman FA; Leahy DE; Searle GE; Thomas S
[Ad] Endereço:Cyprotex Discovery Ltd., Macclesfield, Cheshire, United Kingdom, SK10 2DR.
[Ti] Título:Application of a generic physiologically based pharmacokinetic model to the estimation of xenobiotic levels in human plasma.
[So] Source:Drug Metab Dispos;34(1):94-101, 2006 Jan.
[Is] ISSN:0090-9556
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Estimation of xenobiotic kinetics in humans frequently relies upon extrapolation from experimental data generated in animals. In an accompanying paper, we have presented a unique, generic, physiologically based pharmacokinetic model and described its application to the prediction of rat plasma pharmacokinetics from in vitro data alone. Here we demonstrate the application of the same model, parameterized for human physiology, to the estimation of plasma pharmacokinetics in humans and report a comparative evaluation against some recently published predictive methods that involve scaling from in vivo animal data. The model was parameterized through an optimization process, using a training set of in vivo data taken from the literature, and validated using a separate test set of published in vivo data. On average, the vertical divergence of the predicted plasma concentrations from the observed data, on a semilog concentration-time plot, was 0.47 log unit. For the training set, more than 80% of the predicted values of a standardized measure of the area under the concentration-time curve were within 3-fold of the observed values; over 70% of the test set predictions were within the same margin. Furthermore, in terms of predicting human clearance for the test set, the model was found to match or exceed the performance of three published interspecies scaling methods, all of which showed a distinct bias toward overprediction. We conclude that the generic physiologically based pharmacokinetic model, as a means of integrating readily determined in vitro and/or in silico data, is potentially a powerful, cost-effective tool for predicting human xenobiotic kinetics in drug discovery and risk assessment.
[Mh] Termos MeSH primário: Modelos Biológicos
Xenobióticos/sangue
Xenobióticos/farmacocinética
[Mh] Termos MeSH secundário: Acecainida/sangue
Acecainida/farmacocinética
Animais
Área Sob a Curva
Biperideno/sangue
Biperideno/farmacocinética
Dexametasona/sangue
Dexametasona/farmacocinética
Seres Humanos
Injeções Intravenosas
Taxa de Depuração Metabólica
Modelos Animais
Reprodutibilidade dos Testes
Especificidade da Espécie
Fatores de Tempo
Verapamil/sangue
Verapamil/farmacocinética
Xenobióticos/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Xenobiotics); 0FRP6G56LD (Biperiden); 7S5I7G3JQL (Dexamethasone); 910Q707V6F (Acecainide); CJ0O37KU29 (Verapamil)
[Em] Mês de entrada:0602
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:051014
[St] Status:MEDLINE


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[PMID]:15793163
[Au] Autor:Bauer LA; Black DJ; Lill JS; Garrison J; Raisys VA; Hooton TM
[Ad] Endereço:Department of Pharmacy, Box 357630, University of Washington, Seattle, WA 98195. labauer@u.washington.edu.
[Ti] Título:Levofloxacin and ciprofloxacin decrease procainamide and N-acetylprocainamide renal clearances.
[So] Source:Antimicrob Agents Chemother;49(4):1649-51, 2005 Apr.
[Is] ISSN:0066-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ten healthy adults participated in a randomized, crossover drug interaction study testing procainamide only, procainamide plus levofloxacin, and procainamide plus ciprofloxacin. During levofloxacin therapy, most procainamide and N-acetylprocainamide (NAPA) pharmacokinetic parameters, including decreased renal clearances and renal clearance/creatinine clearance ratios, changed (P < 0.05). During ciprofloxacin treatment, only procainamide and NAPA renal clearances decreased significantly.
[Mh] Termos MeSH primário: Acecainida/farmacocinética
Antiarrítmicos/farmacocinética
Antibacterianos/farmacocinética
Ciprofloxacino/farmacocinética
Rim/metabolismo
Levofloxacino
Ofloxacino/farmacocinética
Procainamida/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Estudos Cross-Over
Interações Medicamentosas
Feminino
Seres Humanos
Rim/efeitos dos fármacos
Masculino
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Anti-Bacterial Agents); 5E8K9I0O4U (Ciprofloxacin); 6GNT3Y5LMF (Levofloxacin); 910Q707V6F (Acecainide); A4P49JAZ9H (Ofloxacin); L39WTC366D (Procainamide)
[Em] Mês de entrada:0505
[Cu] Atualização por classe:140608
[Lr] Data última revisão:
140608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:050329
[St] Status:MEDLINE


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[PMID]:15732917
[Au] Autor:Flarakos J; Morand KL; Vouros P
[Ad] Endereço:Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA.
[Ti] Título:High-throughput solution-based medicinal library screening against human serum albumin.
[So] Source:Anal Chem;77(5):1345-53, 2005 Mar 01.
[Is] ISSN:0003-2700
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High-throughput screening of combinatorial libraries has evolved from studying large diverse libraries to analyzing small, structurally similar, focused libraries. This paradigm shift has generated a need for rapid screening technologies to screen both diverse and focused libraries in a simple, efficient, and inexpensive manner. We have proactively addressed these needs by developing a high-throughput, solution-based method combining size exclusion (SEC), two-dimensional liquid chromatography (2-D LC), and mass spectrometry (MS) for determining the relative binding of drug candidates in small, focused medicinal libraries against human serum albumin (HSA). Two types of libraries were used to evaluate the performance of the system. The first consisted of five diverse ligands with a wide range of hydrophobicities and whose association constants to HSA cover 3 orders of magnitude. A beta-lactam library composed of structurally similar compounds was used to further confirm the validity of the methodology. The ability to distinguish site-specific interactions of drugs competing for individual domains of the HSA receptor is also demonstrated. Comparison of chromatographic profiles of the library components before and after incubation with the receptor using multiple reaction monitoring allowed a ranking of the ligands according to their relative binding affinities. The observed rankings correlate closely with literature values of the association constants between the respective ligands and HSA. This simple, rugged methodology can screen a wide spectrum of chemical entities from combinatorial mixtures in less than 6 min.
[Mh] Termos MeSH primário: Técnicas de Química Combinatória
Preparações Farmacêuticas/química
Albumina Sérica/química
[Mh] Termos MeSH secundário: Acecainida/análise
Acecainida/química
Acecainida/metabolismo
Cromatografia em Gel/métodos
Cromatografia Líquida/métodos
Compostos de Dansil/análise
Compostos de Dansil/química
Compostos de Dansil/metabolismo
Seres Humanos
Imipramina/análise
Imipramina/química
Imipramina/metabolismo
Indometacina/análise
Indometacina/química
Indometacina/metabolismo
Preparações Farmacêuticas/análise
Preparações Farmacêuticas/metabolismo
Ligação Proteica
Quinidina/análise
Quinidina/química
Quinidina/metabolismo
Reprodutibilidade dos Testes
Sarcosina/análogos & derivados
Sarcosina/análise
Sarcosina/química
Sarcosina/metabolismo
Albumina Sérica/análise
Albumina Sérica/metabolismo
Espectrometria de Massas em Tandem/métodos
Triptofano/análise
Triptofano/química
Triptofano/metabolismo
Varfarina/análise
Varfarina/química
Varfarina/metabolismo
beta-Lactamas/análise
beta-Lactamas/química
beta-Lactamas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dansyl Compounds); 0 (Pharmaceutical Preparations); 0 (Serum Albumin); 0 (beta-Lactams); 1093-96-5 (dansylsarcosine); 5Q7ZVV76EI (Warfarin); 8DUH1N11BX (Tryptophan); 910Q707V6F (Acecainide); ITX08688JL (Quinidine); OGG85SX4E4 (Imipramine); XXE1CET956 (Indomethacin); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:0701
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:050301
[St] Status:MEDLINE


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[PMID]:11566320
[Au] Autor:Lindgren H; Pero RW; Ivars F; Leanderson T
[Ad] Endereço:Department of Cell and Molecular Biology, Section for Immunology, BMC I:13, Lund University, S-221 84, Lund, Sweden. hanna.lindgren@immuno.lu.se
[Ti] Título:N-substituted benzamides inhibit nuclear factor-kappaB and nuclear factor of activated T cells activity while inducing activator protein 1 activity in T lymphocytes.
[So] Source:Mol Immunol;38(4):267-77, 2001 Aug.
[Is] ISSN:0161-5890
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:N-substituted benzamides are compounds that have recently been reported to inhibit nuclear factor-kappaB (NF-kappaB) activity and induce apoptosis in a pre-B cell line. In this study, we focused on the effects of N-substituted benzamides on transcriptional regulation in Jurkat T cells. We used a model system where the cells can be stimulated either through TCR/CD28 or by treatment of the cells with PMA and ionomycin to induce transcription factors typical for T lymphocyte activation. Treatment of the Jurkat cells with procainamide did not influence the transcription factor profile of stimulated cells, while treatment with a derivative having an acetyl group in position 4 of the aromatic ring inhibited NF-kappaB and nuclear factor of activated T cells (NFAT) activity. Declopramide, which contains a chloride in position 3 of the aromatic ring, was inactive in this system, whereas also the acetylated derivative of this compound inhibited NF-kappaB and NFAT activity. In contrast, the transcriptional activity and nuclear expression of activator protein 1 induced by TCR/CD28 stimulation or PMA and ionomycin treatment was enhanced by the acetylated variants of the N-substituted benzamides. Finally, we investigated the effect of N-substituted benzamides on intact promoters for two genes central in immune regulation; the CD40 ligand (CD40L) and IL-2 promoters. The transcriptional activity of the CD40L promoter as well as surface expression of the CD40L induced by signaling through TCR/CD28 was inhibited by addition of acetylated N-substituted benzamides, while the transcriptional activity of the IL-2 promoter was enhanced. Taken together, these data indicate that derivatives of N-substituted benzamides are potential drug candidates for quantitative as well as qualitative modulation of immune functions.
[Mh] Termos MeSH primário: Benzamidas/farmacologia
Proteínas de Ligação a DNA/antagonistas & inibidores
NF-kappa B/antagonistas & inibidores
Proteínas Nucleares
Procainamida/análogos & derivados
Linfócitos T/imunologia
Fator de Transcrição AP-1/metabolismo
Fatores de Transcrição/antagonistas & inibidores
[Mh] Termos MeSH secundário: Acecainida/farmacologia
Ligante de CD40/metabolismo
Núcleo Celular/metabolismo
Ativação Enzimática
Seres Humanos
Interleucina-2/genética
Células Jurkat
NF-kappa B/análise
NF-kappa B/química
Subunidade p50 de NF-kappa B
Fatores de Transcrição NFATC
Procainamida/farmacologia
Regiões Promotoras Genéticas
Linfócitos T/efeitos dos fármacos
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzamides); 0 (DNA-Binding Proteins); 0 (Interleukin-2); 0 (N-acetyldeclopramide); 0 (NF-kappa B); 0 (NF-kappa B p50 Subunit); 0 (NFATC Transcription Factors); 0 (Nuclear Proteins); 0 (Transcription Factor AP-1); 0 (Transcription Factors); 147205-72-9 (CD40 Ligand); 910Q707V6F (Acecainide); 916GJF577D (declopramide); L39WTC366D (Procainamide)
[Em] Mês de entrada:0110
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:010922
[St] Status:MEDLINE


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Fotocópia
[PMID]:11384853
[Au] Autor:He YL; Kitada N; Yasuhara M; Hori R
[Ad] Endereço:Department of Anaesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Yhe@partners.org
[Ti] Título:Quantitative estimation of renal clearance of N-acetylprocainamide in rats with various experimental acute renal failure.
[So] Source:Eur J Pharm Sci;13(3):303-8, 2001 Jun.
[Is] ISSN:0928-0987
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The dosage regimen of a drug eliminated predominantly through the kidney need to be adjusted for the patients with renal disease. The objective of the present study was to establish a quantitative approach to precisely predicting the renal clearances of basic drugs using N-1-methylnicotinamide (NMN). A variety of experimental acute renal failure (ARF) in rats were prepared and N-acetylprocainamide (NAPA) was used as a model drug. The renal clearances of NAPA were significantly decreased in rats with ARF, resulting in significantly increased plasma concentrations. Remarkable reduction in clearance ratios (CL(ratio)) was observed, indicating that the impairment in tubular and glomerular function did not proceed in a parallel manner. The renal clearance of NAPA (CL(rNAPA)) was better predicted from the renal clearance of NMN (CL(rNMN)) than from GFR. A mathematical equation was also constructed to estimate the CL(rNMN) from the NMN plasma concentration. Therefore, the renal clearance of basic drugs excreted predominantly from the kidney can be easily and more accurately estimated based on the concentrations of endogenous NMN to provide a precise dosage regimen for patients with renal failure.
[Mh] Termos MeSH primário: Acecainida/farmacocinética
Acecainida/urina
Lesão Renal Aguda/urina
[Mh] Termos MeSH secundário: Animais
Proteínas Sanguíneas/metabolismo
Taxa de Filtração Glomerular
Glicosúria/urina
Testes de Função Renal
Masculino
Ligação Proteica
Proteinúria/urina
Ratos
Ratos Wistar
Circulação Renal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Proteins); 910Q707V6F (Acecainide)
[Em] Mês de entrada:0109
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:010601
[St] Status:MEDLINE



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