Base de dados : MEDLINE
Pesquisa : D02.886.675.867.537 [Categoria DeCS]
Referências encontradas : 253 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 26 ir para página                         

  1 / 253 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27526715
[Au] Autor:Henry EK; Sy CB; Inclan-Rico JM; Espinosa V; Ghanny SS; Dwyer DF; Soteropoulos P; Rivera A; Siracusa MC
[Ad] Endereço:Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103 Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103.
[Ti] Título:Carbonic anhydrase enzymes regulate mast cell-mediated inflammation.
[So] Source:J Exp Med;213(9):1663-73, 2016 Aug 22.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine-mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2-associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy-like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell-mediated inflammation.
[Mh] Termos MeSH primário: Anidrases Carbônicas/fisiologia
Inflamação/etiologia
Mastócitos/fisiologia
[Mh] Termos MeSH secundário: Animais
Inibidores da Anidrase Carbônica/farmacologia
Imunoglobulina E/sangue
Mastocitose/prevenção & controle
Metazolamida/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 37341-29-0 (Immunoglobulin E); EC 4.2.1.1 (Carbonic Anhydrases); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160817
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20151739


  2 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26920803
[Au] Autor:Eminoglu A; Vullo D; Asik A; Çolak DN; Çanakçi S; Beldüz AO; Supuran CT
[Ad] Endereço:Recep Tayyip Erdogan University, Faculty of Art and Science, Department of Biology, Molecular Biology Research Laboratories, Rize, Turkey.
[Ti] Título:Sulfonamide inhibition studies of the ß-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.
[So] Source:Bioorg Med Chem Lett;26(7):1821-6, 2016 Apr 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a ß-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7-96.5nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103-138nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384-938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the ß-class CAs in bacterial pathogenicity/virulence.
[Mh] Termos MeSH primário: Anidrase Carbônica I/antagonistas & inibidores
Inibidores da Anidrase Carbônica/química
Inibidores da Anidrase Carbônica/farmacologia
Enterobacter/enzimologia
Infecções por Enterobacteriaceae/tratamento farmacológico
Sulfonamidas/química
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Acetazolamida/química
Acetazolamida/farmacologia
Anidrase Carbônica I/metabolismo
Enterobacter/efeitos dos fármacos
Infecções por Enterobacteriaceae/microbiologia
Seres Humanos
Metazolamida/análogos & derivados
Metazolamida/farmacologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); 98-10-2 (benzenesulfonamide); EC 4.2.1.- (Carbonic Anhydrase I); O3FX965V0I (Acetazolamide); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160228
[St] Status:MEDLINE


  3 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26878088
[Au] Autor:Supuran CT
[Ad] Endereço:a Polo Scientifico, NEUROFARBA Department, Section of Pharmaceutical and Nutriceutical Sciences , Università degli Studi di Firenze , 50019 Sesto Fiorentino , Florence , Italy.
[Ti] Título:Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors.
[So] Source:Expert Opin Drug Metab Toxicol;12(4):423-31, 2016.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Carbonic anhydrase inhibitors (CAIs) of the sulfonamide and sulfamate type are clinically used drugs as diuretics, antiglaucoma, antiepileptic, antiobesity and anti-high altitude disease agents. Anticancer agents based on CAIs are also in clinical development for the management of hypoxic, metastatic tumors. Acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide are mainly used as antiglaucoma drugs, sulthiame, topiramate and zonisamide as antiepileptic/antiobesity agents, celecoxib and polmacoxib are dual carbonic anhydrase/cycloxygenase inhibitors. Girentuximab, a monoclonal antibody and SLC-0111, a sulfonamide inhibitor, are in clinical trials as anticancer agents. AREAS COVERED: The drug interactions with many classes of pharmacological agents are reviewed. Some of these drugs, such as acetazolamide, topiramate and celecoxib show a large number of interactions with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, antiepileptics, immunosupressants, anticholinesterase drugs, ß-blockers, anesthetics, oral contraceptives, anticancer agents, antifungals, anti-mycobacterials, lithium, metformin and clopidogrel. EXPERT OPINION: The multiple drug interactions in which CAIs are involved should be carefully considered when such drugs are used in combination with the drug classes mentioned above, as the risks of developing toxicity and serious side effects if the dosages are not adjusted are high. There are also synergistic effects between CAIs and some NSAIDs, anticancer agents and benzodiazepines for the management of cystoid macular edema, some tumor types and neuropathic pain, respectively.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/uso terapêutico
[Mh] Termos MeSH secundário: Acetazolamida/uso terapêutico
Anti-Inflamatórios não Esteroides/uso terapêutico
Fármacos Antiobesidade/uso terapêutico
Anticorpos Monoclonais/uso terapêutico
Anticonvulsivantes/uso terapêutico
Antineoplásicos/uso terapêutico
Benzodiazepinas/uso terapêutico
Celecoxib/uso terapêutico
Ensaios Clínicos como Assunto
Contraindicações
Interações Medicamentosas
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle
Frutose/análogos & derivados
Frutose/uso terapêutico
Seres Humanos
Isoxazóis/uso terapêutico
Metazolamida/uso terapêutico
Fenobarbital/análogos & derivados
Fenobarbital/uso terapêutico
Sulfanilamidas/uso terapêutico
Sulfonamidas/uso terapêutico
Ácidos Sulfônicos/uso terapêutico
Tiazinas/uso terapêutico
Tiofenos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Anti-Obesity Agents); 0 (Antibodies, Monoclonal); 0 (Anticonvulsants); 0 (Antineoplastic Agents); 0 (Carbonic Anhydrase Inhibitors); 0 (G250 monoclonal antibody); 0 (Isoxazoles); 0 (Sulfanilamides); 0 (Sulfonamides); 0 (Sulfonic Acids); 0 (Thiazines); 0 (Thiophenes); 0H73WJJ391 (topiramate); 12794-10-4 (Benzodiazepines); 21240MF57M (sulfanilamide); 23256-01-1 (dichlorophenobarbital); 30237-26-4 (Fructose); 459384H98V (zonisamide); 9451Z89515 (brinzolamide); 9JDX055TW1 (dorzolamide); 9NFU33906Q (sulfamic acid); I00Q766CZ2 (sulthiame); JCX84Q7J1L (Celecoxib); O3FX965V0I (Acetazolamide); W733B0S9SD (Methazolamide); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160216
[St] Status:MEDLINE
[do] DOI:10.1517/17425255.2016.1154534


  4 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26581638
[Au] Autor:Fossati S; Giannoni P; Solesio ME; Cocklin SL; Cabrera E; Ghiso J; Rostagno A
[Ad] Endereço:Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States. Electronic address: silvia.fossati@nyumc.org.
[Ti] Título:The carbonic anhydrase inhibitor methazolamide prevents amyloid beta-induced mitochondrial dysfunction and caspase activation protecting neuronal and glial cells in vitro and in the mouse brain.
[So] Source:Neurobiol Dis;86:29-40, 2016 Feb.
[Is] ISSN:1095-953X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial dysfunction has been recognized as an early event in Alzheimer's disease (AD) pathology, preceding and inducing neurodegeneration and memory loss. The presence of cytochrome c (CytC) released from the mitochondria into the cytoplasm is often detected after acute or chronic neurodegenerative insults, including AD. The carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) was identified among a library of drugs as an inhibitor of CytC release and proved to be neuroprotective in Huntington's disease and stroke models. Here, using neuronal and glial cell cultures, in addition to an acute model of amyloid beta (Aß) toxicity, which replicates by intra-hippocampal injection the consequences of interstitial and cellular accumulation of Aß, we analyzed the effects of MTZ on neuronal and glial degeneration induced by the Alzheimer's amyloid. MTZ prevented DNA fragmentation, CytC release and activation of caspase 9 and caspase 3 induced by Aß in neuronal and glial cells in culture through the inhibition of mitochondrial hydrogen peroxide production. Moreover, intraperitoneal administration of MTZ prevented neurodegeneration induced by intra-hippocampal Aß injection in the mouse brain and was effective at reducing caspase 3 activation in neurons and microglia in the area surrounding the injection site. Our results, delineating the molecular mechanism of action of MTZ against Aß-mediated mitochondrial dysfunction and caspase activation, and demonstrating its efficiency in a model of acute amyloid-mediated toxicity, provide the first combined in vitro and in vivo evidence supporting the potential of a new therapy employing FDA-approved CAIs in AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/enzimologia
Peptídeos beta-Amiloides/metabolismo
Encéfalo/enzimologia
Inibidores da Anidrase Carbônica/administração & dosagem
Caspases/metabolismo
Metazolamida/administração & dosagem
Neuroglia/enzimologia
Neurônios/enzimologia
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/administração & dosagem
Animais
Apoptose/efeitos dos fármacos
Encéfalo/efeitos dos fármacos
Caspase 3/metabolismo
Caspase 9/metabolismo
Células Cultivadas
Citocromos c/metabolismo
Fragmentação do DNA/efeitos dos fármacos
Seres Humanos
Peróxido de Hidrogênio/metabolismo
Técnicas In Vitro
Camundongos
Camundongos Endogâmicos C57BL
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/enzimologia
Neuroglia/efeitos dos fármacos
Neurônios/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Carbonic Anhydrase Inhibitors); 9007-43-6 (Cytochromes c); BBX060AN9V (Hydrogen Peroxide); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 9); EC 3.4.22.- (Caspases); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170201
[Lr] Data última revisão:
170201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151120
[St] Status:MEDLINE


  5 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25918017
[Au] Autor:Yang F; Xuan J; Chen J; Zhong H; Luo H; Zhou P; Sun X; He L; Chen S; Cao Z; Luo X; Xing Q
[Ad] Endereço:Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
[Ti] Título:HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese.
[So] Source:Pharmacogenomics J;16(1):83-7, 2016 Feb.
[Is] ISSN:1473-1150
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Methazolamide is an intraocular pressure-lowering drug that is used in the treatment of glaucoma and other ophthalmologic abnormalities. The use of methazolamide has been shown to cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients of Asian ancestry. Methazolamide-induced SJS/TEN is associated with the presence of HLA-B59 serotype/HLA-B*59:01 in Korean and Japanese populations. To better understand the genetic risk factors for these adverse reactions in the Han Chinese population, we characterized the HLA class I genotypes of eight Chinese patients with methazolamide-induced SJS/TEN from 2008 to 2014. The frequency of HLA-B*59:01 was 87.5% (7/8) in the case patients, which was significantly different from 0% (0/30) in the methazolamide-tolerant patients (odds ratio (OR)=305.0; P=6.3 × 10(-7)) and 0.35% (1/283) in healthy subjects from the human major histocompatibility complex database (OR=1974.0; P=2.0 × 10(-12)). HLA-C*01:02, which is closely linked to HLA-B*59:01, had a weaker but notable association with methazolamide-induced SJS/TEN compared with the tolerant controls (OR=12.1; P=0.016) and general population (OR=15.5; P=2.0 × 10(-3)). The distribution of the HLA-B*59:01-C*01:02 haplotype was also significantly different in cases and controls. This study demonstrated a strong association between HLA-B*59:01 and methazolamide-induced SJS/TEN in the Han Chinese population for the first time. Pretherapy screening for HLA-B*59:01 would be useful to reduce the risk of methazolamide-induced SJS/TEN.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/efeitos adversos
Antígenos HLA-B/genética
Metazolamida/efeitos adversos
Síndrome de Stevens-Johnson/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Grupo com Ancestrais do Continente Asiático
Estudos de Casos e Controles
Feminino
Estudos de Associação Genética
Marcadores Genéticos
Genótipo
Seres Humanos
Masculino
Meia-Idade
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Síndrome de Stevens-Johnson/etnologia
Síndrome de Stevens-Johnson/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Genetic Markers); 0 (HLA-B Antigens); 0 (HLA-B59 antigen); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150429
[St] Status:MEDLINE
[do] DOI:10.1038/tpj.2015.25


  6 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Registro de Ensaios Clínicos
Texto completo
[PMID]:26680684
[Au] Autor:Scalzo RL; Binns SE; Klochak AL; Giordano GR; Paris HL; Sevits KJ; Beals JW; Biela LM; Larson DG; Luckasen GJ; Irwin D; Schroeder T; Hamilton KL; Bell C
[Ad] Endereço:1 Department of Health and Exercise Science, Colorado State University , Fort Collins, Colorado.
[Ti] Título:Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment.
[So] Source:High Alt Med Biol;16(4):331-42, 2015 Dec.
[Is] ISSN:1557-8682
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m(2); mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.
[Mh] Termos MeSH primário: Aminofilina/administração & dosagem
Exercício/fisiologia
Hipóxia/tratamento farmacológico
Metazolamida/administração & dosagem
Resistência Física/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Altitude
Quimioterapia Combinada
Teste de Esforço/efeitos dos fármacos
Voluntários Saudáveis
Seres Humanos
Hipóxia/fisiopatologia
Masculino
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
27Y3KJK423 (Aminophylline); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:151219
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1089/ham.2015.0066


  7 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26458485
[Au] Autor:Xu Y; Wu M; Sheng F; Sun Q
[Ti] Título:Methazolamide-induced toxic epidermal necrolysis in a Chinese woman with HLA-B5901.
[So] Source:Indian J Ophthalmol;63(7):623-4, 2015 Jul.
[Is] ISSN:1998-3689
[Cp] País de publicação:India
[La] Idioma:eng
[Mh] Termos MeSH primário: Antígenos HLA-B/imunologia
Metazolamida/efeitos adversos
Síndrome de Stevens-Johnson/diagnóstico
[Mh] Termos MeSH secundário: Inibidores da Anidrase Carbônica/efeitos adversos
Inibidores da Anidrase Carbônica/uso terapêutico
China
Feminino
Glaucoma/tratamento farmacológico
Glucocorticoides/administração & dosagem
Seres Humanos
Injeções Intravenosas
Metazolamida/uso terapêutico
Metilprednisolona/administração & dosagem
Meia-Idade
Síndrome de Stevens-Johnson/tratamento farmacológico
Síndrome de Stevens-Johnson/imunologia
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Glucocorticoids); 0 (HLA-B Antigens); 0 (HLA-B59 antigen); W733B0S9SD (Methazolamide); X4W7ZR7023 (Methylprednisolone)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151014
[St] Status:MEDLINE
[do] DOI:10.4103/0301-4738.167105


  8 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26365738
[Au] Autor:Domigan LJ; Andersson M; Alberti KA; Chesler M; Xu Q; Johansson J; Rising A; Kaplan DL
[Ad] Endereço:Department of Biomedical Engineering, Tufts University, Medford, MA, USA; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
[Ti] Título:Carbonic anhydrase generates a pH gradient in Bombyx mori silk glands.
[So] Source:Insect Biochem Mol Biol;65:100-6, 2015 Oct.
[Is] ISSN:1879-0240
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Silk is a protein of interest to both biological and industrial sciences. The silkworm, Bombyx mori, forms this protein into strong threads starting from soluble silk proteins using a number of biochemical and physical cues to allow the transition from liquid to fibrous silk. A pH gradient has been measured along the gland, but the methodology employed was not able to precisely determine the pH at specific regions of interest in the silk gland. Furthermore, the physiological mechanisms responsible for the generation of this pH gradient are unknown. In this study, concentric ion selective microelectrodes were used to determine the luminal pH of B. mori silk glands. A gradient from pH 8.2 to 7.2 was measured in the posterior silk gland, with a pH 7 throughout the middle silk gland, and a gradient from pH 6.8 to 6.2 in the beginning of the anterior silk gland where silk processing into fibers occurs. The small diameter of the most anterior region of the anterior silk gland prevented microelectrode access in this region. Using a histochemical method, the presence of active carbonic anhydrase was identified in the funnel and anterior silk gland of fifth instar larvae. The observed pH gradient collapsed upon addition of the carbonic anhydrase inhibitor methazolamide, confirming an essential role for this enzyme in pH regulation in the B. mori silk gland. Plastic embedding of whole silk glands allowed clear visualization of the morphology, including the identification of four distinct epithelial cell types in the gland and allowed correlations between silk gland morphology and silk stages of assembly related to the pH gradient. B. mori silk glands have four different epithelial cell types, one of which produces carbonic anhydrase. Carbonic anhydrase is necessary for the mechanism that generates an intraluminal pH gradient, which likely regulates the assembly of silk proteins and then the formation of fibers from soluble silk proteins. These new insights into native silk formation may lead to a more efficient production of artificial or regenerated silkworm silk fibers.
[Mh] Termos MeSH primário: Bombyx/enzimologia
Anidrases Carbônicas/metabolismo
Glândulas Exócrinas/enzimologia
[Mh] Termos MeSH secundário: Animais
Inibidores da Anidrase Carbônica/farmacologia
Glândulas Exócrinas/citologia
Concentração de Íons de Hidrogênio
Larva/enzimologia
Metazolamida/farmacologia
Força Próton-Motriz
Seda/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Silk); EC 4.2.1.1 (Carbonic Anhydrases); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150915
[St] Status:MEDLINE


  9 / 253 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26067314
[Au] Autor:Yang F; Yang Y; Zhu Q; Chen SA; Fu X; Yan S; Meng C; Ma L; Sun X; Xu J; Luo X; Xing Q
[Ad] Endereço:Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
[Ti] Título:Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.
[So] Source:J Investig Dermatol Symp Proc;17(1):29-31, 2015 Jul.
[Is] ISSN:1529-1774
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Erupção por Droga/genética
Erupção por Droga/imunologia
Antígenos HLA-B/genética
Antígenos HLA-B/imunologia
[Mh] Termos MeSH secundário: Alopurinol/efeitos adversos
Alopurinol/imunologia
Amoxicilina/efeitos adversos
Antibacterianos/efeitos adversos
Anti-Inflamatórios não Esteroides/efeitos adversos
Anti-Inflamatórios não Esteroides/imunologia
Anticonvulsivantes/efeitos adversos
Anticonvulsivantes/imunologia
Biomarcadores
Carbamazepina/efeitos adversos
Carbamazepina/imunologia
Inibidores da Anidrase Carbônica/efeitos adversos
Inibidores da Anidrase Carbônica/imunologia
Estudos de Casos e Controles
Cefalosporinas/efeitos adversos
China/etnologia
Citocinas/imunologia
Predisposição Genética para Doença/genética
Estudo de Associação Genômica Ampla
Técnicas de Genotipagem
Supressores da Gota/efeitos adversos
Supressores da Gota/imunologia
Seres Humanos
Metazolamida/efeitos adversos
Metazolamida/imunologia
Polimorfismo de Nucleotídeo Único
Sulfassalazina/efeitos adversos
Sulfassalazina/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Anticonvulsants); 0 (Biomarkers); 0 (Carbonic Anhydrase Inhibitors); 0 (Cephalosporins); 0 (Cytokines); 0 (Gout Suppressants); 0 (HLA-B Antigens); 33CM23913M (Carbamazepine); 3XC8GUZ6CB (Sulfasalazine); 63CZ7GJN5I (Allopurinol); 804826J2HU (Amoxicillin); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:161021
[Lr] Data última revisão:
161021
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150613
[St] Status:MEDLINE
[do] DOI:10.1038/jidsymp.2015.6


  10 / 253 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26010545
[Au] Autor:Modak JK; Modakh JK; Liu YC; Machuca MA; Supuran CT; Roujeinikova A
[Ti] Título:Structural Basis for the Inhibition of Helicobacter pylori α-Carbonic Anhydrase by Sulfonamides.
[So] Source:PLoS One;10(5):e0127149, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Periplasmic α-carbonic anhydrase of Helicobacter pylori (HpαCA), an oncogenic bacterium in the human stomach, is essential for its acclimation to low pH. It catalyses the conversion of carbon dioxide to bicarbonate using Zn(II) as the cofactor. In H. pylori, Neisseria spp., Brucella suis and Streptococcus pneumoniae this enzyme is the target for sulfonamide antibacterial agents. We present structural analysis correlated with inhibition data, on the complexes of HpαCA with two pharmacological inhibitors of human carbonic anhydrases, acetazolamide and methazolamide. This analysis reveals that two sulfonamide oxygen atoms of the inhibitors are positioned proximal to the putative location of the oxygens of the CO2 substrate in the Michaelis complex, whilst the zinc-coordinating sulfonamide nitrogen occupies the position of the catalytic water molecule. The structures are consistent with acetazolamide acting as site-directed, nanomolar inhibitors of the enzyme by mimicking its reaction transition state. Additionally, inhibitor binding provides insights into the channel for substrate entry and product exit. This analysis has implications for the structure-based design of inhibitors of bacterial carbonic anhydrases.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/farmacologia
Anidrases Carbônicas/metabolismo
Helicobacter pylori/efeitos dos fármacos
Helicobacter pylori/metabolismo
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Acetazolamida/farmacologia
Sequência de Aminoácidos
Antibacterianos/farmacologia
Infecções por Helicobacter/tratamento farmacológico
Infecções por Helicobacter/microbiologia
Seres Humanos
Metazolamida/farmacologia
Dados de Sequência Molecular
Periplasma/efeitos dos fármacos
Periplasma/metabolismo
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); EC 4.2.1.1 (Carbonic Anhydrases); O3FX965V0I (Acetazolamide); W733B0S9SD (Methazolamide)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150527
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0127149



página 1 de 26 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde