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[PMID]:28458354
[Au] Autor:Koide H; Hira D; Tsujimoto M; Katsube Y; Minegaki T; Uzu T; Ikeda Y; Morita SY; Nishiguchi K; Terada T
[Ad] Endereço:Department of Clinical Pharmacy, Faculty of Pharmaceutical Science, Kyoto Pharmaceutical University.
[Ti] Título:Previous Dosage of Allopurinol Is a Strong Determinant of Febuxostat Efficacy.
[So] Source:Biol Pharm Bull;40(5):681-686, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Febuxostat has currently played pivotal role in the treatment of hyperuricemia, but there is little comprehensive information for the determinants of individual difference in efficacy of febuxostat. Therefore, the present study, a retrospective investigation, was carried out to analyze the effects of patient characteristics on the efficacy of febuxostat. A total of 225 patients who were continuously prescribed the same dose of febuxostat for 8-12 weeks from the initial therapy were enrolled in the present study. The data, including patient information and laboratory data, were collected from electronic medical records. Serum urate lowering effects of febuxostat were evaluated by calculating the change in serum urate level at baseline and at 8-12 weeks after starting febuxostat. The multiple regression analysis showed the change in serum urate level was significantly lower in male patients and in those with a lower baseline serum urate level, higher previous dose of allopurinol, lower dose of febuxostat and lower body surface area-unadjusted estimated glomerular filtration rate. Concomitantly administered drugs did not show a significantly influence on the efficacy of febuxostat. In conclusion, it should be noted that the serum urate lowering efficacy of febuxostat may decrease in patients with a higher previous dose of allopurinol, renal impairment or male patients. The basic findings of the present study are believed to contribute to the proper use of febuxostat.
[Mh] Termos MeSH primário: Alopurinol/administração & dosagem
Febuxostat/uso terapêutico
Supressores da Gota/administração & dosagem
Hiperuricemia/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Alopurinol/uso terapêutico
Taxa de Filtração Glomerular
Gota/tratamento farmacológico
Supressores da Gota/uso terapêutico
Seres Humanos
Hiperuricemia/fisiopatologia
Masculino
Meia-Idade
Estudos Retrospectivos
Resultado do Tratamento
Ácido Úrico/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gout Suppressants); 101V0R1N2E (Febuxostat); 268B43MJ25 (Uric Acid); 63CZ7GJN5I (Allopurinol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00972


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[PMID]:29324838
[Au] Autor:Travi BL; Cordeiro-da-Silva A; Dantas-Torres F; Miró G
[Ad] Endereço:Department of Internal Medicine-Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
[Ti] Título:Canine visceral leishmaniasis: Diagnosis and management of the reservoir living among us.
[So] Source:PLoS Negl Trop Dis;12(1):e0006082, 2018 01.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article reviews essential topics of canine visceral leishmaniasis (CVL) due to Leishmania infantum infection. It focuses on the current serological and molecular diagnostic methods used in epidemiological research and veterinary clinics to diagnose CVL and includes new point-of-care (POC) tests under development. The efficacy of different treatment regimens on the clinical improvement and infectiousness of dogs is also addressed. In the last section, the review provides a critical appraisal of the effectiveness of different control measures that have been implemented to curb disease transmission.
[Mh] Termos MeSH primário: Antiprotozoários/uso terapêutico
Doenças do Cão/diagnóstico
Doenças do Cão/tratamento farmacológico
Leishmaniose Visceral/diagnóstico
Leishmaniose Visceral/veterinária
Técnicas de Diagnóstico Molecular
[Mh] Termos MeSH secundário: Alopurinol/uso terapêutico
Animais
Reservatórios de Doenças/parasitologia
Reservatórios de Doenças/veterinária
Doenças do Cão/parasitologia
Cães
Leishmania infantum/efeitos dos fármacos
Leishmaniose Visceral/parasitologia
Meglumina/uso terapêutico
Compostos Organometálicos/uso terapêutico
Fosforilcolina/análogos & derivados
Fosforilcolina/uso terapêutico
Sistemas Automatizados de Assistência Junto ao Leito
Testes Sorológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Organometallic Compounds); 107-73-3 (Phosphorylcholine); 53EY29W7EC (miltefosine); 63CZ7GJN5I (Allopurinol); 6HG8UB2MUY (Meglumine); 75G4TW236W (meglumine antimoniate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006082


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[PMID]:29216590
[Au] Autor:Kong Y; Li X; Zhang N; Miao Y; Feng H; Wu T; Cheng Z
[Ad] Endereço:Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, The Shanghai Key Laboratory for Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
[Ti] Título:Improved bioautographic assay on TLC layers for qualitative and quantitative estimation of xanthine oxidase inhibitors and superoxide scavengers.
[So] Source:J Pharm Biomed Anal;150:87-94, 2018 Feb 20.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A new agar-free bioautographic assay for xanthine oxidase (XO) inhibitors and superoxide scavengers on TLC layers was developed and validated. Compared to the first version of TLC bioautographic agar overlay method, our bioautographic assay greatly improved the sensitivity and quantification ability. The limit of detection (LOD) of this assay was 0.017ng for allopurinol. Quantitative estimation of XO inhibitors and superoxide scavengers was achieved by densitometry scanning, expressed as allopurinol equivalents in millimoles on a per sample weight basis. This assay has acceptable accuracy (95.37-99.23%), intra-day and inter-day precisions (RSD, 2.56-6.69%), as well as intra-plate and inter-plate precisions (RSD, 2.93-9.62%). Six pure compounds and three herbal extracts were evaluated for their potential XO inhibitory and superoxide scavenging activity by this bioautographic assay on TLC layers. Four active components were separated, located and identified in Astragalus membranaceus var. mongholicus extract by the bioautographic assay after TLC separation. The developed method is rapid, simple, sensitive and stable for screening and estimation of the potential XO inhibitors and superoxide scavengers.
[Mh] Termos MeSH primário: Cromatografia em Camada Delgada/métodos
Inibidores Enzimáticos/análise
Depuradores de Radicais Livres/análise
Extratos Vegetais/análise
[Mh] Termos MeSH secundário: Alopurinol/análise
Alopurinol/farmacologia
Astragalus membranaceus/química
Inibidores Enzimáticos/farmacologia
Depuradores de Radicais Livres/farmacologia
Limite de Detecção
Extratos Vegetais/farmacologia
Reprodutibilidade dos Testes
Xantina Oxidase/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Free Radical Scavengers); 0 (Plant Extracts); 63CZ7GJN5I (Allopurinol); EC 1.17.3.2 (Xanthine Oxidase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


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[PMID]:29318274
[Ti] Título:Lesinurad/Allopurinol (Duzallo) for Gout-Associated Hyperuricemia.
[So] Source:JAMA;319(2):188-189, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Alopurinol/administração & dosagem
Supressores da Gota/uso terapêutico
Gota/tratamento farmacológico
Hiperuricemia/tratamento farmacológico
Tioglicolatos/administração & dosagem
Tioglicolatos/uso terapêutico
Triazóis/administração & dosagem
[Mh] Termos MeSH secundário: Alopurinol/efeitos adversos
Alopurinol/uso terapêutico
Combinação de Medicamentos
Interações Medicamentosas
Gota/complicações
Supressores da Gota/efeitos adversos
Seres Humanos
Hiperuricemia/complicações
Transportadores de Ânions Orgânicos/antagonistas & inibidores
Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores
Tioglicolatos/efeitos adversos
Triazóis/efeitos adversos
Xantina Oxidase/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Duzallo); 0 (Gout Suppressants); 0 (Organic Anion Transporters); 0 (Organic Cation Transport Proteins); 0 (SLC22A12 protein, human); 0 (Thioglycolates); 0 (Triazoles); 09ERP08I3W (lesinurad); 63CZ7GJN5I (Allopurinol); EC 1.17.3.2 (Xanthine Oxidase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20189


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[PMID]:29023512
[Au] Autor:Bochimoto H; Matsuno N; Ishihara Y; Shonaka T; Koga D; Hira Y; Nishikawa Y; Furukawa H; Watanabe T
[Ad] Endereço:Health Care Administration Center, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
[Ti] Título:The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation.
[So] Source:PLoS One;12(10):e0186352, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The effects of warm machine perfusion preservation of liver grafts donated after cardiac death on the intracellular three-dimensional ultrastructure of the organelles in hepatocytes remain unclear. Here we analyzed comparatively the ultrastructure of the endomembrane systems in porcine hepatocytes under warm ischemia and successive hypothermic and midthermic machine perfusion preservation, a type of the warm machine perfusion. Porcine liver grafts which had a warm ischemia time of 60 minutes were perfused for 4 hours with modified University of Wisconsin gluconate solution. Group A grafts were preserved with hypothermic machine perfusion preservation at 8°C constantly for 4 hours. Group B grafts were preserved with rewarming up to 22°C by warm machine perfusion preservation for 4 hours. An analysis of hepatocytes after 60 minutes of warm ischemia by scanning electron microscope revealed the appearance of abnormal vacuoles and invagination of mitochondria. In the hepatocytes preserved by subsequent hypothermic machine perfusion preservation, strongly swollen mitochondria were observed. In contrast, the warm machine perfusion preservation could preserve the functional appearance of mitochondria in hepatocytes. Furthermore, abundant vacuoles and membranous structures sequestrating cellular organelles like autophagic vacuoles were frequently observed in hepatocytes after warm machine perfusion preservation. In conclusion, the ultrastructure of the endomembrane systems in the hepatocytes of liver grafts changed in accordance with the temperature conditions of machine perfusion preservation. In addition, temperature condition of the machine perfusion preservation may also affect the condition of the hepatic graft attributed to autophagy systems, and consequently alleviate the damage of the hepatocytes.
[Mh] Termos MeSH primário: Hepatócitos/ultraestrutura
Fígado/ultraestrutura
Preservação de Órgãos/normas
[Mh] Termos MeSH secundário: Adenosina/farmacologia
Alopurinol/farmacologia
Animais
Membrana Celular/ultraestrutura
Citocromos c/metabolismo
Morte
Feminino
Glutationa/farmacologia
Insulina/farmacologia
Fígado/efeitos dos fármacos
Fígado/metabolismo
Microscopia Eletrônica de Varredura
Microscopia Eletrônica de Transmissão
Microscopia de Fluorescência
Proteínas Associadas aos Microtúbulos/metabolismo
Mitocôndrias/ultraestrutura
Soluções para Preservação de Órgãos/farmacologia
Rafinose/farmacologia
Suínos
Isquemia Quente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (Microtubule-Associated Proteins); 0 (Organ Preservation Solutions); 0 (University of Wisconsin-lactobionate solution); 63CZ7GJN5I (Allopurinol); 9007-43-6 (Cytochromes c); GAN16C9B8O (Glutathione); K72T3FS567 (Adenosine); N5O3QU595M (Raffinose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186352


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[PMID]:28982910
[Au] Autor:Kishimoto K; Kobayashi R; Hori D; Sano H; Suzuki D; Kobayashi K
[Ad] Endereço:Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan ken@yacht.ocn.ne.jp.
[Ti] Título:Febuxostat as a Prophylaxis for Tumor Lysis Syndrome in Children with Hematological Malignancies.
[So] Source:Anticancer Res;37(10):5845-5849, 2017 10.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:AIM: The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies. PATIENTS AND METHODS: A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxostat (10 mg daily, n=20) or allopurinol (300 mg/m daily, n=25) as a prophylaxis for TLS. RESULTS: A significant decrease of serum uric acid (UA) level was observed in patients with febuxostat over the first 2 days (6.6±3.8 mg/dl vs. 4.5±2.8 mg/dl, p<0.001). The febuxostat group also showed significant reduction of urinary UA/creatinine ratios during the first two days of treatment (0.98±0.85 vs. 0.51±0.26, p=0.010). No significant differences were observed between febuxostat-treated and allopurinol-treated patients regarding the percent change in serum UA level. CONCLUSION: Febuxostat had a notable effect in reducing serum UA level in children with hematological malignancies.
[Mh] Termos MeSH primário: Alopurinol/administração & dosagem
Antineoplásicos/efeitos adversos
Inibidores Enzimáticos/administração & dosagem
Febuxostat/administração & dosagem
Neoplasias Hematológicas/tratamento farmacológico
Quimioterapia de Indução/efeitos adversos
Síndrome de Lise Tumoral/prevenção & controle
[Mh] Termos MeSH secundário: Adolescente
Fatores Etários
Alopurinol/efeitos adversos
Biomarcadores/sangue
Criança
Pré-Escolar
Creatinina/sangue
Regulação para Baixo
Inibidores Enzimáticos/efeitos adversos
Febuxostat/efeitos adversos
Feminino
Seres Humanos
Japão
Masculino
Estudos Retrospectivos
Fatores de Risco
Resultado do Tratamento
Síndrome de Lise Tumoral/sangue
Síndrome de Lise Tumoral/diagnóstico
Síndrome de Lise Tumoral/etiologia
Ácido Úrico/sangue
Xantina Oxidase/antagonistas & inibidores
Xantina Oxidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers); 0 (Enzyme Inhibitors); 101V0R1N2E (Febuxostat); 268B43MJ25 (Uric Acid); 63CZ7GJN5I (Allopurinol); AYI8EX34EU (Creatinine); EC 1.17.3.2 (Xanthine Oxidase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


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[PMID]:28957559
[Au] Autor:Plumpton CO; Alfirevic A; Pirmohamed M; Hughes DA
[Ad] Endereço:Centre for Health Economics and Medicines Evaluation, Bangor University, Wales.
[Ti] Título:Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout.
[So] Source:Rheumatology (Oxford);56(10):1729-1739, 2017 Oct 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objective: To determine whether prospective testing for HLA-B*58:01, as a strategy to prevent serious adverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the National Health Service in the UK. Methods: A systematic review and meta-analysis for the association of HLA-B*58:01 with cutaneous and hypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetime costs and outcomes associated with testing vs standard care (with febuxostat prescribed for patients who test positive). Scenario analyses assessed alternative treatment assumptions and patient populations. Results: The number of patients needed to test to prevent one case of adverse drug reaction was 11 286 (95% central range (CR): 2573, 53 594). Cost and quality-adjusted life-year (QALY) gains were small, £103 (95% CR: £98, £106) and 0.0023 (95% CR: -0.0006, 0.0055), respectively, resulting in an incremental cost-effectiveness ratio (ICER) of £44 954 per QALY gained. The probability of testing being cost-effective at a threshold of £30 000 per QALY was 0.25. Reduced costs of testing or febuxostat resulted in an ICER below £30 000 per QALY gained. The ICER for patients with chronic renal insufficiency was £38 478 per QALY gained. Conclusion: Routine testing for HLA-B*58:01 in order to reduce the incidence of adverse drug reactions in patients being prescribed allopurinol for gout is unlikely to be cost-effective in the UK; however testing is expected to become cost-effective with reductions in the cost of genotyping, and with the future availability of cheaper, generic febuxostat.
[Mh] Termos MeSH primário: Análise Custo-Benefício
Técnicas de Genotipagem/economia
Gota/genética
Antígenos HLA-B/análise
Testes Farmacogenômicos/economia
[Mh] Termos MeSH secundário: Adulto
Alopurinol/efeitos adversos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/economia
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle
Feminino
Técnicas de Genotipagem/métodos
Gota/tratamento farmacológico
Supressores da Gota/efeitos adversos
Seres Humanos
Masculino
Meia-Idade
Testes Farmacogenômicos/métodos
Anos de Vida Ajustados por Qualidade de Vida
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Gout Suppressants); 0 (HLA-B Antigens); 0 (HLA-B*58:01 antigen); 63CZ7GJN5I (Allopurinol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex253


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[PMID]:28931035
[Au] Autor:Rodríguez-Fanjul J; Durán Fernández-Feijóo C; Lopez-Abad M; Lopez Ramos MG; Balada Caballé R; Alcántara-Horillo S; Camprubí Camprubí M
[Ad] Endereço:Department of Neonatology, BCNatal, Sant Joan de Déu-Hospital Clínic, Barcelona, Spain.
[Ti] Título:Neuroprotection with hypothermia and allopurinol in an animal model of hypoxic-ischemic injury: Is it a gender question?
[So] Source:PLoS One;12(9):e0184643, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the most important causes of neonatal brain injury. Therapeutic hypothermia (TH) is the standard treatment for term newborns after perinatal hypoxic ischemic injury (HI). Despite this, TH does not provide complete neuroprotection. Allopurinol seems to be a good neuroprotector in several animal studies, but it has never been tested in combination with hypothermia. Clinical findings show that male infants with (HI) fare more poorly than matched females in cognitive outcomes. However, there are few studies about neuroprotection taking gender into account in the results. The aim of the present study was to evaluate the potential additive neuroprotective effect of allopurinol when administrated in association with TH in a rodent model of moderate HI. Gender differences in neuroprotection were also evaluated. METHODS: P10 male and female rat pups were subjected to HI (Vannucci model) and randomized into five groups: sham intervention (Control), no treatment (HI), hypothermia (HIH), allopurinol (HIA), and dual therapy (hypothermia and allopurinol) (HIHA). To evaluate a treatment's neuroprotective efficiency, 24 hours after the HI event caspase3 activation was measured. Damaged area and hippocampal volume were also measured 72 hours after the HI event. Negative geotaxis test was performed to evaluate early neurobehavioral reflexes. Learning and spatial memory were assessed via Morris Water Maze (MWM) test at 25 days of life. RESULTS: Damaged area and hippocampal volume were different among treatment groups (p = 0.001). The largest tissue lesion was observed in the HI group, followed by HIA. There were no differences between control, HIH, and HIHA. When learning process was analyzed, no differences were found. Females from the HIA group had similar results to the HIH and HIHA groups. Cleaved caspase 3 expression was increased in both HI and HIA. Despite this, in females cleaved caspase-3 was only differently increased in the HI group. All treated animals present an improvement in short-term (Negative geotaxis) and long-term (WMT) functional tests. Despite this, treated females present better long-term outcome. In short-term outcome no sex differences were observed. CONCLUSIONS: Our results suggest that dual therapy confers great neuroprotection after an HI event. There were functional, histological, and molecular improvements in all treated groups. These differences were more important in females than in males. No statistically significant differences were found between HIHA and HIH; both of them present a great improvement. Our results support the idea of different regulation mechanisms and pathways of cell death, depending on gender.
[Mh] Termos MeSH primário: Alopurinol/uso terapêutico
Modelos Animais de Doenças
Hipotermia Induzida
Hipóxia-Isquemia Encefálica/terapia
Fármacos Neuroprotetores/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Antimetabólitos/uso terapêutico
Terapia Combinada
Feminino
Masculino
Neuroproteção
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites); 0 (Neuroprotective Agents); 63CZ7GJN5I (Allopurinol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184643


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[PMID]:28892476
[Au] Autor:Yasur-Landau D; Jaffe CL; Doron-Faigenboim A; David L; Baneth G
[Ad] Endereço:Koret School of Veterinary Medicine, The Hebrew University, Rehovot, Israel.
[Ti] Título:Induction of allopurinol resistance in Leishmania infantum isolated from dogs.
[So] Source:PLoS Negl Trop Dis;11(9):e0005910, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Resistance to allopurinol in zoonotic canine leishmaniasis has been recently shown to be associated with disease relapse in naturally-infected dogs. However, information regarding the formation of resistance and its dynamics is lacking. This study describes the successful in-vitro induction of allopurinol resistance in Leishmania infantum cultured under increasing drug pressure. Allopurinol susceptibility and growth rate of induced parasites were monitored over 23 weeks and parasite clones were tested at selected time points and compared to their parental lines, both as promastigotes and as amastigotes. Allopurinol resistance was formed in strains from two parasite stocks producing a 20-fold rise in IC50 along three distinct growth phases. In addition, characteristic differential clustering of single nucleotide polymorphisms (SNP) was found in drug sensitive and resistant parasite clones. Results confirm that genetic polymorphism, as well as clonal heterogeneity, contribute to in-vitro resistance to allopurinol, which is likely to occur in natural infection.
[Mh] Termos MeSH primário: Alopurinol/farmacologia
Antiprotozoários/farmacologia
Doenças do Cão/parasitologia
Leishmania infantum/efeitos dos fármacos
Leishmaniose Visceral/veterinária
[Mh] Termos MeSH secundário: Alopurinol/administração & dosagem
Animais
Doenças do Cão/tratamento farmacológico
Cães
Resistência a Medicamentos
Concentração Inibidora 50
Leishmania infantum/genética
Leishmania infantum/crescimento & desenvolvimento
Leishmania infantum/isolamento & purificação
Leishmaniose Visceral/tratamento farmacológico
Leishmaniose Visceral/parasitologia
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 63CZ7GJN5I (Allopurinol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005910


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[PMID]:28764846
[Au] Autor:Aroor AR; Jia G; Habibi J; Sun Z; Ramirez-Perez FI; Brady B; Chen D; Martinez-Lemus LA; Manrique C; Nistala R; Whaley-Connell AT; Demarco VG; Meininger GA; Sowers JR
[Ad] Endereço:Diabetes and Cardiovascular Research Center, Department of Medicine, University of Missouri Columbia, School of Medicine, Columbia, MO 65212, USA; Research Service Harry S Truman Memorial Veterans Hospital, University of Missouri School of Medicine, Columbia, MO 65212, USA. Electronic address: aroor
[Ti] Título:Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice.
[So] Source:Metabolism;74:32-40, 2017 Sep.
[Is] ISSN:1532-8600
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Aortic vascular stiffness has been implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese individuals. However, the mechanism promoting these adverse effects are unclear. In this context, promotion of obesity through consumption of a western diet (WD) high in fat and fructose leads to excess circulating uric acid. There is accumulating data implicating elevated uric acid in the promotion of CVD and CKD. Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with allopurinol would prevent a rise in vascular stiffness and proteinuria in a translationally relevant model of WD-induced obesity. MATERIALS/METHODS: Four-week-old C57BL6/J male mice were fed a WD with excess fat (46%) and fructose (17.5%) with or without allopurinol (125mg/L in drinking water) for 16weeks. Aortic endothelial and extracellular matrix/vascular smooth muscle stiffness was evaluated by atomic force microscopy. Aortic XO activity, 3-nitrotyrosine (3-NT) and aortic endothelial sodium channel (EnNaC) expression were evaluated along with aortic expression of inflammatory markers. In the kidney, expression of toll like receptor 4 (TLR4) and fibronectin were assessed along with evaluation of proteinuria. RESULTS: XO inhibition significantly attenuated WD-induced increases in plasma uric acid, vascular XO activity and oxidative stress, in concert with reductions in proteinuria. Further, XO inhibition prevented WD-induced increases in aortic EnNaC expression and associated endothelial and subendothelial stiffness. XO inhibition also reduced vascular pro-inflammatory and maladaptive immune responses induced by consumption of a WD. XO inhibition also decreased WD-induced increases in renal TLR4 and fibronectin that associated proteinuria. CONCLUSIONS: Consumption of a WD leads to elevations in plasma uric acid, increased vascular XO activity, oxidative stress, vascular stiffness, and proteinuria all of which are attenuated with allopurinol administration.
[Mh] Termos MeSH primário: Dieta Ocidental
Inflamação/induzido quimicamente
Proteinúria/induzido quimicamente
Ácido Úrico/sangue
Rigidez Vascular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Alopurinol/administração & dosagem
Alopurinol/farmacologia
Animais
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Ácido Úrico/farmacologia
Xantina Oxidase/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
268B43MJ25 (Uric Acid); 63CZ7GJN5I (Allopurinol); EC 1.17.3.2 (Xanthine Oxidase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE



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