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[PMID]:28216685
[Au] Autor:Banse H; Cribb AE; UCVM Class of 2016
[Ad] Endereço:Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Drive, Calgary, Alberta T2N 4Z6.
[Ti] Título:Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse.
[So] Source:Can Vet J;58(2):157-167, 2017 Feb.
[Is] ISSN:0008-5286
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:The efficacy of oral phenylbutazone [PBZ; 4.4 mg/kg body weight (BW), q12h], a non-selective non-steroidal anti-inflammatory drug (NSAID), and oral meloxicam (MXM; 0.6 mg/kg BW, q24h), a COX-2 selective NSAID, were evaluated in 2 experimental pain models in horses: the adjustable heart bar shoe (HBS) model, primarily representative of mechanical pain, and the lipopolysaccharide-induced synovitis (SYN) model, primarily representative of inflammatory pain. In the HBS model, PBZ reduced multiple indicators of pain compared with the placebo and MXM. Meloxicam did not reduce indicators of pain relative to the placebo. In the SYN model, MXM and PBZ reduced increases in carpal skin temperature compared to the placebo. Meloxicam reduced lameness scores and lameness-induced changes in head movement compared to the placebo and PBZ. Phenylbutazone reduced lameness-induced change in head movement compared to the placebo. Overall, PBZ was more effective than MXM at reducing pain in the HBS model, while MXM was more effective at reducing pain in the SYN model at the oral doses used.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/administração & dosagem
Coxeadura Animal/tratamento farmacológico
Dor/veterinária
Fenilbutazona/administração & dosagem
Sinovite/tratamento farmacológico
Tiazinas/administração & dosagem
Tiazóis/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Feminino
Cavalos
Lipopolissacarídeos/administração & dosagem
Masculino
Dor/tratamento farmacológico
Temperatura Cutânea/efeitos dos fármacos
Sinovite/veterinária
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Lipopolysaccharides); 0 (Thiazines); 0 (Thiazoles); GN5P7K3T8S (Phenylbutazone); VG2QF83CGL (meloxicam)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


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[PMID]:28140763
[Au] Autor:Barnes P; Fodey TL; Smyth WG; Crooks SR
[Ad] Endereço:a Veterinary Sciences Division , Agri-Food and Biosciences Institute , Belfast , UK.
[Ti] Título:Investigation of the role of environmental contamination in the occurrence of residues of the veterinary drug phenylbutazone in cattle.
[So] Source:Food Addit Contam Part A Chem Anal Control Expo Risk Assess;34(4):520-524, 2017 Apr.
[Is] ISSN:1944-0057
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phenylbutazone is a non-steroidal anti-inflammatory drug licensed for use in horses to treat musculoskeletal disorders. It is not permitted in the European Union for use in animals destined for the food chain. Official statistics provided by the European Food Safety Authority (EFSA) show that 0.18% of bovines tested in the European Union between 2008 and 2014 for non-steroidal anti-inflammatory drugs were non-compliant, with phenylbutazone representing over 28% of these. Anecdotal evidence suggests animals that have not been treated with the drug may have produced non-compliant samples, possibly through some form of contamination. In this study, ultra-high-performance liquid chromatography coupled with mass-spectrometric detection was applied to bovine plasma samples to determine if detectable residues (CCα = 0.28 ng ml ) may occur in untreated animals as a result of environmental contamination through normal farming practice. The study demonstrates that waste from animals treated with phenylbutazone, and spread on an area of pasture, can contaminate untreated bovines grazing the pasture many weeks later. It was determined that this contamination, which can persist over a significant period, may be due to the ingestion of as little as 30 µg phenylbutazone by a 500 kg bullock.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/sangue
Resíduos de Drogas/análise
Poluição Ambiental/análise
Fenilbutazona/sangue
Drogas Veterinárias/sangue
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/administração & dosagem
Bovinos
Cromatografia Líquida de Alta Pressão
Controle de Medicamentos e Entorpecentes/legislação & jurisprudência
Contaminação de Alimentos/análise
Herbivoria/fisiologia
Cavalos
Masculino
Fenilbutazona/administração & dosagem
Recomendações Nutricionais/legislação & jurisprudência
Espectrometria de Massas em Tandem
Reino Unido
Drogas Veterinárias/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Veterinary Drugs); GN5P7K3T8S (Phenylbutazone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170308
[Lr] Data última revisão:
170308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1080/19440049.2016.1271143


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[PMID]:28045944
[Au] Autor:Baron MG; Mintram KS; Owen SF; Hetheridge MJ; Moody AJ; Purcell WM; Jackson SK; Jha AN
[Ad] Endereço:School of Biological Science, Plymouth University, Devon, United Kingdom.
[Ti] Título:Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance.
[So] Source:PLoS One;12(1):e0168837, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:At high internal doses, pharmaceuticals have the potential for inducing biological/pharmacological effects in fish. One particular concern for the environment is their potential to bioaccumulate and reach pharmacological levels; the study of these implications for environmental risk assessment has therefore gained increasing attention. To avoid unnecessary testing on animals, in vitro methods for assessment of xenobiotic metabolism could aid in the ecotoxicological evaluation. Here we report the use of a 3-D in vitro liver organoid culture system (spheroids) derived from rainbow trout to measure the metabolism of seven pharmaceuticals using a substrate depletion assay. Of the pharmaceuticals tested, propranolol, diclofenac and phenylbutazone were metabolised by trout liver spheroids; atenolol, metoprolol, diazepam and carbamazepine were not. Substrate depletion kinetics data was used to estimate intrinsic hepatic clearance by this spheroid model, which was similar for diclofenac and approximately 5 fold higher for propranolol when compared to trout liver microsomal fraction (S9) data. These results suggest that liver spheroids could be used as a relevant and metabolically competent in vitro model with which to measure the biotransformation of pharmaceuticals in fish; and propranolol acts as a reproducible positive control.
[Mh] Termos MeSH primário: Avaliação Pré-Clínica de Medicamentos
Fígado/efeitos dos fármacos
Oncorhynchus mykiss/metabolismo
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Animais
Atenolol/farmacologia
Biotransformação
Carbamazepina/farmacologia
Diazepam/farmacologia
Diclofenaco/farmacologia
Feminino
Cinética
Fígado/metabolismo
Metoprolol/farmacologia
Modelos Animais
Fenilbutazona/farmacologia
Propranolol/farmacologia
Espectrometria de Massas em Tandem
Xenobióticos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Water Pollutants, Chemical); 0 (Xenobiotics); 144O8QL0L1 (Diclofenac); 33CM23913M (Carbamazepine); 50VV3VW0TI (Atenolol); 9Y8NXQ24VQ (Propranolol); GEB06NHM23 (Metoprolol); GN5P7K3T8S (Phenylbutazone); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170104
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0168837


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[PMID]:27731498
[Au] Autor:Burkett BN; Thomason JM; Hurdle HM; Wills RW; Fontenot RL
[Ad] Endereço:Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
[Ti] Título:Effects of Firocoxib, Flunixin Meglumine, and Phenylbutazone on Platelet Function and Thromboxane Synthesis in Healthy Horses.
[So] Source:Vet Surg;45(8):1087-1094, 2016 Nov.
[Is] ISSN:1532-950X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Determine the effects of nonsteroidal anti-inflammatory drugs (NSAID) on platelet function and thromboxane synthesis immediately after drug administration and following 5 days of NSAID administration in healthy horses. STUDY DESIGN: Randomized cross-over study. ANIMALS: Healthy adult horses (n=9; 6 geldings and 3 mares). METHODS: Horses received either flunixin meglumine (1.1 mg/kg IV every 12 hours), phenylbutazone (2.2 mg/kg IV every 12 hours), or firocoxib (loading dose of 0.27 mg/kg IV on day 1, then 0.09 mg/kg IV every 24 hours for 4 days) for a total of 5 days. Blood samples were collected prior to drug administration (day 0), 1 hour after initial NSAID administration (day 1), and then 1 hour post-NSAID administration on day 5. Platelet function was assessed using turbidimetric aggregometry and a platelet function analyzer. Serum thromboxane B concentrations were determined by commercial ELISA kit. A minimum 14 day washout period occurred between trials. RESULTS: At 1 hour and 5 days postadministration of firocoxib, flunixin meglumine, or phenylbutazone, there was no significant effect on platelet aggregation or function using turbidimetric aggregometry or a platelet function analyzer. There was, however, a significant decrease in thromboxane synthesis at 1 hour and 5 days postadministration of flunixin meglumine and phenylbutazone that was not seen with firocoxib. CONCLUSION: Preoperative administration of flunixin meglumine, phenylbutazone, or firocoxib should not inhibit platelet function based on our model. The clinical implications of decreased thromboxane B synthesis following flunixin meglumine and phenylbutazone administration are undetermined.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Anti-Inflamatórios não Esteroides/administração & dosagem
Plaquetas/efeitos dos fármacos
Clonixino/análogos & derivados
Cavalos/metabolismo
Fenilbutazona/administração & dosagem
Sulfonas/administração & dosagem
Tromboxanos/metabolismo
[Mh] Termos MeSH secundário: 4-Butirolactona/administração & dosagem
4-Butirolactona/metabolismo
Animais
Anti-Inflamatórios não Esteroides/metabolismo
Clonixino/administração & dosagem
Clonixino/metabolismo
Estudos Cross-Over
Feminino
Masculino
Fenilbutazona/metabolismo
Sulfonas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Sulfones); 0 (Thromboxanes); 8Y3JK0JW3U (flunixin meglumine); GN5P7K3T8S (Phenylbutazone); OL659KIY4X (4-Butyrolactone); V7DXN0M42R (Clonixin); Y6V2W4S4WT (firocoxib)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161013
[St] Status:MEDLINE
[do] DOI:10.1111/vsu.12567


  5 / 4159 MEDLINE  
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[PMID]:27468043
[Au] Autor:Greunz EM; Simon M; Lemberger K; Galateanu G; Hermes R; Leclerc A
[Ti] Título:CLINICAL MANAGEMENT OF BILATERAL CUTANEOUS SQUAMOUS CELL CARCINOMA OF THE HIND FEET PADS IN A SOUTHERN WHITE RHINOCEROS (CERATOTHERIUM SIMUM SIMUM).
[So] Source:J Zoo Wildl Med;47(2):645-9, 2016 Jun.
[Is] ISSN:1042-7260
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The current report describes the temporary regression, due to intensive symptomatic treatment, of ulcerative skin lesions caused by squamous cell carcinoma in a white rhinoceros. A captive, 40-yr-old southern white rhinoceros (Ceratotherium simum simum) developed profound, ulcerative skin lesions on the pads of both hind feet. At the peak of the disease, at least one quarter of the pads was affected. A diagnosis of squamous cell carcinoma was made via biopsy. Treatment included anti-inflammatory drugs, antibiotics, and local care. The lesions regressed on both feet until they seemed clinically healed. It was presumed that long-term, anti-inflammatory treatment and local bandaging had induced the temporary regression of the lesions. Two years later, however, a small ulcerative lesion reappeared on one pad and post mortem examination confirmed that the carcinoma was also histologically present in the clinically intact tissue. No metastasis was found and computed tomography showed normal digital bones.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/veterinária
Doenças do Pé/veterinária
Perissodáctilos
Neoplasias Cutâneas/veterinária
[Mh] Termos MeSH secundário: Animais
Antibacterianos/uso terapêutico
Anti-Inflamatórios não Esteroides/uso terapêutico
Bandagens
Ácido Benzoico/administração & dosagem
Ácido Benzoico/uso terapêutico
Carcinoma de Células Escamosas/diagnóstico
Carcinoma de Células Escamosas/terapia
Clorexidina/administração & dosagem
Clorexidina/uso terapêutico
Feminino
Doenças do Pé/diagnóstico
Doenças do Pé/terapia
Malatos/administração & dosagem
Malatos/uso terapêutico
Fenilbutazona/uso terapêutico
Ácido Salicílico/administração & dosagem
Ácido Salicílico/uso terapêutico
Neoplasias Cutâneas/diagnóstico
Neoplasias Cutâneas/terapia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Malates); 817L1N4CKP (malic acid); 8SKN0B0MIM (Benzoic Acid); GN5P7K3T8S (Phenylbutazone); O414PZ4LPZ (Salicylic Acid); R4KO0DY52L (Chlorhexidine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160729
[St] Status:MEDLINE
[do] DOI:10.1638/2016-0001.1


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[PMID]:27443208
[Au] Autor:Boison JO; Dowling T; Johnson R; Kinar J
[Ad] Endereço:CFIA Saskatoon Laboratory, 116 Veterinary Road, Saskatoon, SK., Canada S7N 2R3.
[Ti] Título:Analysis of phenylbutazone residues in horse tissues with and without enzyme-hydrolysis by LC-MS/MS.
[So] Source:Drug Test Anal;8(5-6):535-8, 2016 May.
[Is] ISSN:1942-7611
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phenylbutazone (PBZ) is permitted to be used for the treatment of musculoskeletal pain and inflammation in race horses but it is not approved for use in horses destined for human consumption. In a recent study initiated in our laboratory to study the disposition of PBZ and its oxyphenbutazone (OXPBZ) metabolite in equine tissues, we compared the effect of an additional enzymatic hydrolysis step with ß-glucuronidase on the results of the analysis for PBZ without enzymatic hydrolysis. Incurred tissue samples obtained from a female horse dosed with PBZ at 8.8 mg/kg for 3 days and sacrificed 6 days following the last administration were used for this study. Liver, kidney, and muscle tissues were collected, extracted, cleaned up on a silica-based solid-phase extraction (SPE) preceded by a weak-anion exchange SPE and analyzed with our in-house validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for PBZ and OXPBZ. Addition of the hydrolysis step resulted in a significant increase in recovery of both PBZ and OXPBZ residues. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis © 2016 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/análise
Resíduos de Drogas/análise
Cavalos/metabolismo
Oxifenilbutazona/análise
Fenilbutazona/análise
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/metabolismo
Anti-Inflamatórios não Esteroides/farmacocinética
Cromatografia Líquida/métodos
Resíduos de Drogas/metabolismo
Resíduos de Drogas/farmacocinética
Feminino
Contaminação de Alimentos/análise
Análise de Perigos e Pontos Críticos de Controle/métodos
Seres Humanos
Hidrólise
Rim/química
Rim/metabolismo
Fígado/química
Fígado/metabolismo
Músculos/química
Músculos/metabolismo
Oxifenilbutazona/metabolismo
Oxifenilbutazona/farmacocinética
Fenilbutazona/metabolismo
Fenilbutazona/farmacocinética
Extração em Fase Sólida/métodos
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); GN5P7K3T8S (Phenylbutazone); H806S4B3NS (Oxyphenbutazone)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170222
[Lr] Data última revisão:
170222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[St] Status:MEDLINE
[do] DOI:10.1002/dta.2020


  7 / 4159 MEDLINE  
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[PMID]:26924025
[Au] Autor:Knych HK; Stanley SD; Seminoff KN; McKemie DS; Kass PH
[Ad] Endereço:K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
[Ti] Título:Pharmacokinetics of methocarbamol and phenylbutazone in exercised Thoroughbred horses.
[So] Source:J Vet Pharmacol Ther;39(5):469-77, 2016 Oct.
[Is] ISSN:1365-2885
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Methocarbamol (MCBL) is commonly used in performance horses for the treatment of skeletal muscle disorders. Current regulatory recommendations for show horses and racehorses are based on a single oral dose of 5 g, although doses in excess of this are often administered. The goal of the current study was to characterize the disposition of MCBL following higher dose administration and administration in combination with another commonly used drug in performance horses, phenylbutazone (PBZ). Exercised Thoroughbred horses were administered various doses of MCBL as a sole agent and MCBL in combination with PBZ. Blood samples were collected at various times, concentrations of MCBL and PBZ measured using LC-MS/MS and pharmacokinetic parameters calculated using compartmental analysis. Following administration of 15 g of MCBL, either as part of a single- or multiple-dose regimen, a number of horses exceeded the Association of Racing Commissioners International and the United States Equestrian Federation's recommended regulatory threshold at the recommended withdrawal time. There was not a significant difference between horses that received only MCBL and those that received MCBL and PBZ. Results of the current study support an extended withdrawal guideline when doses in excess of 5 g are administered.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacocinética
Metocarbamol/farmacocinética
Relaxantes Musculares Centrais/farmacocinética
Fenilbutazona/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Anti-Inflamatórios não Esteroides/administração & dosagem
Anti-Inflamatórios não Esteroides/sangue
Relação Dose-Resposta a Droga
Interações Medicamentosas
Quimioterapia Combinada
Feminino
Cavalos/sangue
Cavalos/metabolismo
Injeções Intravenosas
Masculino
Metocarbamol/administração & dosagem
Metocarbamol/sangue
Relaxantes Musculares Centrais/administração & dosagem
Relaxantes Musculares Centrais/sangue
Pomadas/administração & dosagem
Fenilbutazona/administração & dosagem
Fenilbutazona/sangue
Condicionamento Físico Animal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Muscle Relaxants, Central); 0 (Ointments); 125OD7737X (Methocarbamol); GN5P7K3T8S (Phenylbutazone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160301
[St] Status:MEDLINE
[do] DOI:10.1111/jvp.12298


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[PMID]:26808199
[Au] Autor:Zhou J; Li X; Zhu X; Sun J; Qiu Q; Huang W; Qian H
[Ad] Endereço:Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
[Ti] Título:Phenylbutazone, a New Long-Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier.
[So] Source:Chem Biol Drug Des;87(6):936-45, 2016 06.
[Is] ISSN:1747-0285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:As a NPY-2 receptor agonist, PYY24-36- Leu31 is reported to suppress appetite and has a potential in obesity treatment, but its short half-life limits the clinical application. The use of chemical modification to improve interactions with human serum albumin (HSA) is an effective strategy for prolonging the half-lives of peptide analogues. So based on the characteristics that phenylbutazone has a good combination with HSA, we selected a proper linker to link with PYY24-36 -Leu31 to create long-acting and highly biologically active PYY24-36 -Leu31 conjugates, and successfully find a novel, long-acting PYY24-36 -Leu31 conjugate 8 that, when dosed every other day in diet induce obese (DIO) mice for 2 weeks, results in a significant reduction in food intake and body weight and improvement in blood parameter and hepatic steatosis.
[Mh] Termos MeSH primário: Portadores de Fármacos
Fígado Gorduroso/tratamento farmacológico
Fenilbutazona
Receptores de Neuropeptídeo Y/agonistas
Albumina Sérica
[Mh] Termos MeSH secundário: Animais
Portadores de Fármacos/química
Portadores de Fármacos/farmacocinética
Portadores de Fármacos/farmacologia
Fígado Gorduroso/sangue
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos ICR
Camundongos Obesos
Fenilbutazona/química
Fenilbutazona/farmacocinética
Fenilbutazona/farmacologia
Receptores de Neuropeptídeo Y/metabolismo
Albumina Sérica/química
Albumina Sérica/farmacocinética
Albumina Sérica/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Receptors, Neuropeptide Y); 0 (Serum Albumin); 0 (neuropeptide Y2 receptor); GN5P7K3T8S (Phenylbutazone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170302
[Lr] Data última revisão:
170302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160126
[St] Status:MEDLINE
[do] DOI:10.1111/cbdd.12726


  9 / 4159 MEDLINE  
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[PMID]:25735846
[Au] Autor:Szkudlarek A; Sulkowska A; Maciazek-Jurczyk M; Chudzik M; Równicka-Zubik J
[Ad] Endereço:Medical University of Silesia, Faculty of Pharmacy, Department of Physical Pharmacy, Katowice, Poniatowskiego 15, Poland.
[Ti] Título:Effects of non-enzymatic glycation in human serum albumin. Spectroscopic analysis.
[So] Source:Spectrochim Acta A Mol Biomol Spectrosc;152:645-53, 2016 Jan 05.
[Is] ISSN:1873-3557
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human serum albumin (HSA), transporting protein, is exposed during its life to numerous factors that cause its functions become impaired. One of the basic factors --glycation of HSA--occurs in diabetes and may affect HSA-drug binding. Accumulation of advanced glycation end-products (AGEs) leads to diseases e.g. diabetic and non-diabetic cardiovascular diseases, Alzheimer disease, renal disfunction and in normal aging. The aim of the present work was to estimate how non-enzymatic glycation of human serum albumin altered its tertiary structure using fluorescence technique. We compared glycated human serum albumin by glucose (gHSA(GLC)) with HSA glycated by fructose (gHSA(FRC)). We focused on presenting the differences between gHSA(FRC) and nonglycated (HSA) albumin used acrylamide (Ac), potassium iodide (KI) and 2-(p-toluidino)naphthalene-6-sulfonic acid (TNS). Changes of the microenvironment around the tryptophan residue (Trp-214) of non-glycated and glycated proteins was investigated by the red-edge excitation shift method. Effect of glycation on ligand binding was examined by the binding of phenylbutazone (PHB) and ketoprofen (KP), which a primary high affinity binding site in serum albumin is subdomain IIA and IIIA, respectively. At an excitation and an emission wavelength of λex 335nm and λem 420nm, respectively the increase of fluorescence intensity and the blue-shift of maximum fluorescence was observed. It indicates that the glycation products decreases the polarity microenvironment around the fluorophores. Analysis of red-edge excitation shift method showed that the red-shift for gHSA(FRC) is higher than for HSA. Non-enzymatic glycation also caused, that the Trp residue of gHSA(FRC) becomes less accessible for the negatively charged quencher (I(-)), KSV value is smaller for gHSA(FRC) than for HSA. TNS fluorescent measurement demonstrated the decrease of hydrophobicity in the glycated albumin. KSV constants for gHSA-PHB systems are higher than for the unmodified serum albumin, while KSV values for gHSA-KP systems are only slightly lower than that obtained for HSA-KP. The affinity of PHB to the glycated HSA is stronger than to the non-glycated in the first class binding sites within subdomain IIA, in the vicinity of Trp-214. Ketoprofen bound to unmodified human serum albumin stronger than for glycated albumin and one class of binding sites is observed (Scatchard linear plots).
[Mh] Termos MeSH primário: Albumina Sérica/química
Albumina Sérica/metabolismo
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/metabolismo
Corantes Fluorescentes/química
Produtos Finais de Glicação Avançada/análise
Produtos Finais de Glicação Avançada/metabolismo
Glicosilação
Seres Humanos
Cetoprofeno/metabolismo
Modelos Moleculares
Naftalenossulfonatos/química
Fenilbutazona/metabolismo
Estrutura Terciária de Proteína
Espectrometria de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Fluorescent Dyes); 0 (Glycation End Products, Advanced); 0 (Naphthalenesulfonates); 0 (Serum Albumin); 0 (glycosylated serum albumin); 7724-15-4 (2-(4-toluidino)-6-naphthalenesulfonic acid); 90Y4QC304K (Ketoprofen); GN5P7K3T8S (Phenylbutazone)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150305
[St] Status:MEDLINE


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[PMID]:26512724
[Au] Autor:Fourie T; Cromarty D; Duncan N; Wolter K; Naidoo V
[Ad] Endereço:Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.
[Ti] Título:The Safety and Pharmacokinetics of Carprofen, Flunixin and Phenylbutazone in the Cape Vulture (Gyps coprotheres) following Oral Exposure.
[So] Source:PLoS One;10(10):e0141419, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The following study evaluates the overt toxic potential of carprofen (CRP), flunixin (FXN) and phenylbutazone (PBZ) in Old world vultures in relation to historic toxicity data for diclofenac and ketoprofen, with the Cape vulture (Gyps coprotheres) being the indicator species. The toxic potential of a single oral dose of CRP (11.5 mg/kg), FXN (1 mg/kg),PBZ (1.7 mg/kg) or water was evaluated by means of a four-way parallel study (n = 2), as means of ascertaining if these drugs were as toxic as diclofenac in the vulture. No unscheduled deaths or pathological lesions were noted following exposure. Clinical signs of lethargy and depression were, however, noted in one CRP, two FXN and one PBZ treated birds. Mild reversible inhibition of UA excretion was evident in all three groups, although UA remained within the population reference interval in contrast to the effects previously described for diclofenac and ketoprofen. All treatment groups had a drug concentration responsive increase in alanine transferase activity. CRP, FXN and PBZ were characterised by a maximum plasma concentration (Cmax) of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/ml at 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours (Tmax) respectively and a half-life of elimination of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. While we could not demonstrate a lethal effect of the tested substances, the presence of toxic clinical signs, clinical pathological changes and/or long half-lives of elimination suggests that all three drugs have a potential for toxicity in a larger population or on repeat administration. In conclusion while the studied substances were not as overtly toxic as diclofenac, they are of safety concern.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Carbazóis/farmacologia
Clonixino/análogos & derivados
Falconiformes
Fenilbutazona/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Anti-Inflamatórios não Esteroides/administração & dosagem
Anti-Inflamatórios não Esteroides/efeitos adversos
Anti-Inflamatórios não Esteroides/farmacocinética
Biomarcadores
Carbazóis/administração & dosagem
Carbazóis/efeitos adversos
Carbazóis/farmacocinética
Clonixino/administração & dosagem
Clonixino/efeitos adversos
Clonixino/farmacocinética
Clonixino/farmacologia
Testes de Função Hepática
Fenilbutazona/administração & dosagem
Fenilbutazona/efeitos adversos
Fenilbutazona/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Biomarkers); 0 (Carbazoles); 356IB1O400 (flunixin); FFL0D546HO (carprofen); GN5P7K3T8S (Phenylbutazone); V7DXN0M42R (Clonixin)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151030
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0141419



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