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Pesquisa : D08.811.913.555.500.500 [Categoria DeCS]
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[PMID]:28233178
[Au] Autor:Shan L; Bao AM; Swaab DF
[Ad] Endereço:Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
[Ti] Título:Changes in Histidine Decarboxylase, Histamine N-Methyltransferase and Histamine Receptors in Neuropsychiatric Disorders.
[So] Source:Handb Exp Pharmacol;241:259-276, 2017.
[Is] ISSN:0171-2004
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Compared to other monoamine neurotransmitters, information on the association between the histaminergic system and neuropsychiatric disorders is scarce, resulting in a lack of histamine-related treatment for these disorders. The current chapter tries to combine information obtained from genetic studies, neuroimaging, post-mortem human brain studies and cerebrospinal fluid measurements with data from recent clinical trials on histamine receptor agonists and antagonists, with a view to determining the possible role of the histaminergic system in neuropsychiatric disorders and to pave the way for novel histamine-related therapeutic strategies.
[Mh] Termos MeSH primário: Histamina N-Metiltransferase/metabolismo
Histidina Descarboxilase/metabolismo
Transtornos Mentais/metabolismo
Receptores Histamínicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Histamina/metabolismo
Seres Humanos
Neuropsiquiatria/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Receptors, Histamine); 820484N8I3 (Histamine); EC 2.1.1.8 (Histamine N-Methyltransferase); EC 4.1.1.22 (Histidine Decarboxylase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE
[do] DOI:10.1007/164_2016_125


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[PMID]:27632021
[Au] Autor:Schwelberger HG; Feurle J; Houen G
[Ad] Endereço:Molecular Biology Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Schöpfstraße 41, 6020, Innsbruck, Austria. hubert.schwelberger@i-med.ac.at.
[Ti] Título:Monoclonal antibodies for human and porcine histamine N-methyltransferase (HMT) facilitate protein expression and localization studies.
[So] Source:Inflamm Res;66(1):67-77, 2017 Jan.
[Is] ISSN:1420-908X
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The lack of suitable antibodies for the histamine inactivating enzyme histamine N-methyltransferase (HMT) has so far prevented the direct analysis of HMT proteins in man and other mammals. METHODS: A series of monoclonal antibodies was produced by immunizing mice with human and porcine HMT expressed in vitro. Antibodies were characterized by immunoblotting and immunohistochemical staining. RESULTS: Six different monoclonal antibodies specific for human HMT and four different monoclonal antibodies specific for porcine HMT were obtained that can detect HMT with up to tenfold greater sensitivity than the most sensitive enzymatic assays currently available. Using these antibodies allowed us to confirm the expression and cellular localization of HMT in various human and porcine tissues, where the presence of the enzyme had previously been deduced from activity measurement and HMT mRNA analysis. Immunohistochemical staining of human and porcine tissue sections clearly showed that HMT is a cytosolic protein, which is localized in specific cells of most mammalian tissues. CONCLUSIONS: The new monoclonal antibodies not only allow a comprehensive quantitative evaluation of the expression of HMT at the cellular level in man and other mammals but will also facilitate sensitive analyses of disease-associated alterations of this protein.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
Histamina N-Metiltransferase/imunologia
Histamina N-Metiltransferase/metabolismo
[Mh] Termos MeSH secundário: Adulto
Animais
Feminino
Glutationa Transferase/genética
Histamina N-Metiltransferase/genética
Seres Humanos
Rim/metabolismo
Masculino
Camundongos Endogâmicos BALB C
Meia-Idade
Proteínas Recombinantes de Fusão/imunologia
Suínos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Recombinant Fusion Proteins); EC 2.1.1.8 (Histamine N-Methyltransferase); EC 2.5.1.18 (Glutathione Transferase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171114
[Lr] Data última revisão:
171114
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160916
[St] Status:MEDLINE
[do] DOI:10.1007/s00011-016-0987-1


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[PMID]:27399132
[Au] Autor:Jiménez-Jiménez FJ; Alonso-Navarro H; García-Martín E; Agúndez JA
[Ad] Endereço:aSection of Neurology, Hospital Universitario del Sureste, Arganda del Rey bDepartment of Medicine-Neurology, Hospital "Príncipe de Asturias," Universidad de Alcalá, Alcalá de Henares, Madrid cDepartment of Pharmacology, University of Extremadura, Cáceres, Spain.
[Ti] Título:Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease: A PRISMA-compliant systematic review and meta-analysis.
[So] Source:Medicine (Baltimore);95(27):e4147, 2016 Jul.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Several neuropathological, biochemical, and pharmacological data suggested a possible role of histamine in the etiopathogenesis of Parkinson disease (PD). The single nucleotide polymorphism (SNP) rs11558538 in the histamine N-methyltransferase (HNMT) gene has been associated with the risk of developing PD by several studies but not by some others. We carried out a systematic review that included all the studies published on PD risk related to the rs11558538 SNP, and we conducted a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: We used several databases to perform the systematic review, the software Meta-DiSc 1.1.1 to perform the meta-analysis of the eligible studies, and the Q-statistic to test heterogeneity between studies. RESULTS: The meta-analysis included 4 eligible case-control association studies for the HNMT rs11558538 SNP and the risk for PD (2108 patients, 2158 controls). The frequency of the minor allele positivity showed a statistically significant association with a decreased risk for PD, both in the total series and in Caucasians. Although homozygosity for the minor allele did not reach statistical significance, the test for trend indicates the occurrence of a gene-dose effect. Global diagnostic odds ratios (95% confidence intervals) for rs11558538T were 0.61 (0.46-0.81) for the total group, and 0.63 (0.45-0.88) for Caucasian patients. CONCLUSION: The present meta-analysis confirms published evidence suggesting that the HNMT rs11558538 minor allele is related to a reduced risk of developing PD.
[Mh] Termos MeSH primário: Histamina N-Metiltransferase/genética
Doença de Parkinson/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Seres Humanos
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
EC 2.1.1.8 (Histamine N-Methyltransferase)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160712
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000004147


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[PMID]:27255477
[Au] Autor:Meza-Velázquez R; López-Márquez F; Espinosa-Padilla S; Rivera-Guillen M; Gutíerrez-Díaz N; Pérez-Armendáriz L; Rosales-González M
[Ad] Endereço:Facultad de Medicina, Universidad Juárez del Estado de Durango, Gómez Palacio, Durango, Mexico; Facultad de Medicina, Universidad Autonóma de Coahuila, Mexico.
[Ti] Título:Association between two polymorphisms of histamine-metabolising enzymes and the severity of allergic rhinitis in a group of Mexican children.
[So] Source:Allergol Immunopathol (Madr);44(5):433-8, 2016 Sep-Oct.
[Is] ISSN:1578-1267
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: It has been suggested that polymorphisms of histamine metabolising enzymes can be a risk factor for developing histamine-involving diseases. The aim of the present study is to research the possible association between two functional single nucleotide polymorphisms (SNPs): C314T in the Histamine-N-Methyl Transferase gene and C2029G in the Diamine Oxidase gene, with the severity of allergic rhinitis and the number of allergic diseases, in a group of allergic Mexican children. METHODS: We studied 154 unrelated allergic children. SNPs were analysed by RT-PCR. The total serum IgE was measured by chemiluminescence and the serum histamine by ELISA. We used logistic regression analysis to determine OR. RESULTS: Patients carrying the mutant allele for any SNP had more risk to develop higher rhinitis severity or a bigger number of allergic diseases. Haplotype analysis revealed that this effect is synergistic. In patients carrying one or two mutant alleles, serum histamine levels were higher than those of patients carrying only wild alleles. Serum IgE levels were not associated with the presence of mutant alleles. CONCLUSION: The presence of these SNPs in patients with allergic rhinitis can lead to higher serum histamine, therefore to a higher risk of developing more severe symptoms or more associated allergic diseases, even if the serum IgE remains low.
[Mh] Termos MeSH primário: Amina Oxidase (contendo Cobre)/genética
Histamina N-Metiltransferase/genética
Rinite Alérgica/genética
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Análise Mutacional de DNA
Progressão da Doença
Feminino
Frequência do Gene
Estudos de Associação Genética
Predisposição Genética para Doença
Genótipo
Histamina/sangue
Seres Humanos
Imunoglobulina E/sangue
Masculino
México
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
37341-29-0 (Immunoglobulin E); 820484N8I3 (Histamine); EC 1.4.3.21 (Amine Oxidase (Copper-Containing)); EC 2.1.1.8 (Histamine N-Methyltransferase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160604
[St] Status:MEDLINE


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[PMID]:26989676
[Au] Autor:He GH; Cai WK; Zhang JB; Ma CY; Yan F; Lu J; Xu GL
[Ad] Endereço:Department of Pharmacy, Kunming General Hospital of Chengdu Military Region, Kunming 650032, China.
[Ti] Título:Associations of Polymorphisms in HRH2, HRH3, DAO, and HNMT Genes with Risk of Chronic Heart Failure.
[So] Source:Biomed Res Int;2016:1208476, 2016.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pathophysiological functions of cardiac histamine level and related histamine receptors during the development of chronic heart failure (CHF) were intensively investigated previously. However, the relevance of polymorphisms in histamine-related genes, such as HRH2, HRH3, DAO, and HNMT, with CHF remains largely neglected. This study herein aims to analyze the clinical associations of polymorphisms in those genes with CHF risk. A total of 333 unrelated Chinese Han CHF patients and 354 ethnicity-matched healthy controls were recruited and 11 single nucleotide polymorphisms (SNPs) were genotyped. We found that the HRH3 rs3787429 polymorphism was associated with CHF risk (p < 0.001). The T allele of rs3787429 exhibited protective effect against CHF under the dominant (ORs = 0.455; 95% CIs = 0.322-0.642) and additive models (ORs = 0.662; 95% CIs = 0.523-0.838), while, for SNPs in HRH2, DAO, and HNMT, no significant associations were observed in the present study. These findings for the first time screen out one SNP (rs3787429) of HRH3 gene that was significantly associated with CHF in Chinese Han population, which may be a novel biomarker for personal prevention and treatment of CHF and provides novel highlights for investigating the contribution of this disease.
[Mh] Termos MeSH primário: D-Aminoácido Oxidase/genética
Insuficiência Cardíaca/genética
Histamina N-Metiltransferase/genética
Receptores Acoplados a Proteínas-G/genética
Receptores Histamínicos H3/genética
Receptores Histamínicos/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Doença Crônica
Feminino
Estudos de Associação Genética
Genótipo
Haplótipos
Insuficiência Cardíaca/patologia
Histamina/genética
Seres Humanos
Masculino
Meia-Idade
Receptores Histamínicos H4
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HRH4 protein, human); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Histamine); 0 (Receptors, Histamine H3); 0 (Receptors, Histamine H4); 820484N8I3 (Histamine); EC 1.4.3.- (DAO protein, human); EC 1.4.3.3 (D-Amino-Acid Oxidase); EC 2.1.1.8 (Histamine N-Methyltransferase)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160319
[St] Status:MEDLINE
[do] DOI:10.1155/2016/1208476


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[PMID]:26641046
[Au] Autor:Kröger S; Pieper R; Aschenbach JR; Martin L; Liu P; Rieger J; Schwelberger HG; Neumann K; Zentek J
[Ti] Título:Effects of high levels of dietary zinc oxide on ex vivo epithelial histamine response and investigations on histamine receptor action in the proximal colon of weaned piglets.
[So] Source:J Anim Sci;93(11):5265-72, 2015 Nov.
[Is] ISSN:1525-3163
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of the study was to identify the effect of high dietary zinc oxide (ZnO) levels on the histamine-induced secretory-type response and histamine metabolism in the porcine proximal colon. After weaning at d 26, 3 diets with low (LZn), normal (NZn), and high (HZn) concentrations of zinc (57, 164, or 2,425 mg/kg) were fed to a total of 120 piglets. Digesta and tissue samples were taken from the ascending colon after 7 ± 1, 14 ± 1, 21 ± 1, and 28 ± 1 d. Partially stripped tissue was mounted in Ussing chambers, and histamine was applied either to the serosal or mucosal compartments. Tissue was pretreated with or without aminoguanidine and amodiaquine to block the histamine-degrading enzymes diamine oxidase (DAO) and histamine -methyltransferase (HMT), respectively. Gene expression and catalytic activity of DAO and HMT in the tissue were analyzed. The numbers of mast cells were determined in tissue samples, and histamine concentration was measured in the colon digesta. Colon tissue from another 12 piglets was used for functional studies on histamine H and H receptors by using the neuronal conduction blocker tetrodotoxin (TTX) and the H and H receptor blocker chloropyramine and famotidine, respectively. After serosal histamine application to colonic tissue in Ussing chambers, the change of short-circuit current (Δ) was not affected by pretreatment and was not different between Zn feeding groups. The Δ after mucosal histamine application was numerically lower ( = 0.168) in HZn compared to LZn and NZn pigs. Mast cell numbers increased from 32 to 46 d of life ( < 0.05). Further studies elucidated that the serosal histamine response was partly inhibited by chloropyramine or famotidine ( < 0.01). The response to mucosal histamine tended to be decreased when chloropyramine but not famotidine was applied from either the serosal or the mucosal side ( = 0.055). Tetrodotoxin alone or in combination with chloropyramine resulted in a similar reduction in the mucosal histamine response ( < 0.01). In conclusion, the present study could not identify marked changes in colonic histamine metabolism on dietary ZnO oversupplementation. For the first time, however, H receptors were functionally identified in the pig colon that are localized either on neurons or on cells that activate secretion via neurons. Luminal histamine can elicit a secretory-type response via these receptors.
[Mh] Termos MeSH primário: Colo/metabolismo
Histamina/metabolismo
Receptores Histamínicos/metabolismo
Suínos/fisiologia
Óxido de Zinco/administração & dosagem
[Mh] Termos MeSH secundário: Amina Oxidase (contendo Cobre)/metabolismo
Animais
Transporte Biológico/efeitos dos fármacos
Dieta
Histamina N-Metiltransferase/metabolismo
Mucosa Intestinal/metabolismo
Mastócitos
Óxidos
Sus scrofa/metabolismo
Desmame
Zinco/administração & dosagem
Zinco/metabolismo
Óxido de Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oxides); 0 (Receptors, Histamine); 820484N8I3 (Histamine); EC 1.4.3.21 (Amine Oxidase (Copper-Containing)); EC 2.1.1.8 (Histamine N-Methyltransferase); J41CSQ7QDS (Zinc); SOI2LOH54Z (Zinc Oxide)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151208
[Lr] Data última revisão:
151208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151208
[St] Status:MEDLINE
[do] DOI:10.2527/jas.2015-9095


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[PMID]:26206890
[Au] Autor:Heidari A; Tongsook C; Najafipour R; Musante L; Vasli N; Garshasbi M; Hu H; Mittal K; McNaughton AJ; Sritharan K; Hudson M; Stehr H; Talebi S; Moradi M; Darvish H; Arshad Rafiq M; Mozhdehipanah H; Rashidinejad A; Samiei S; Ghadami M; Windpassinger C; Gillessen-Kaesbach G; Tzschach A; Ahmed I; Mikhailov A; Stavropoulos DJ; Carter MT; Keshavarz S; Ayub M; Najmabadi H; Liu X; Ropers HH; Macheroux P; Vincent JB
[Ad] Endereço:Molecular Neuropsychiatry and Development (MiND) Lab, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada M5T 1R8, Cellular and Molecular Research Center.
[Ti] Título:Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.
[So] Source:Hum Mol Genet;24(20):5697-710, 2015 Oct 15.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability.
[Mh] Termos MeSH primário: Genes Recessivos
Histamina N-Metiltransferase/genética
Deficiência Intelectual/genética
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Adolescente
Adulto
Sequência de Aminoácidos
Domínio Catalítico
Criança
Pré-Escolar
Simulação por Computador
Análise Mutacional de DNA
Grupo com Ancestrais do Continente Europeu/genética
Exoma
Feminino
Histamina N-Metiltransferase/metabolismo
Seres Humanos
Lactente
Deficiência Intelectual/enzimologia
Iraque
Masculino
Dados de Sequência Molecular
Linhagem
Alinhamento de Sequência
Turquia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.1.1.8 (Histamine N-Methyltransferase)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150725
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddv286


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[PMID]:25909280
[Au] Autor:Anvari S; Vyhlidal CA; Dai H; Jones BL
[Ad] Endereço:1 Division of Allergy/Asthma/Immunology.
[Ti] Título:Genetic Variation along the Histamine Pathway in Children with Allergic versus Nonallergic Asthma.
[So] Source:Am J Respir Cell Mol Biol;53(6):802-9, 2015 Dec.
[Is] ISSN:1535-4989
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine pathway between children with allergic versus nonallergic asthma. Children (7-18 yr of age; n = 202) with asthma were classified as allergic or nonallergic based on allergy skin testing. Genotyping was performed to detect known SNPs (n = 10) among genes (HDC, HNMT, ABP1, HRH1, and HRH4) within the histamine pathway. Chi square tests and Cochran-Armitage Trend were used to identify associations between genetic variants and allergic or nonallergic asthma. Significance was determined by P < 0.05 and false-positive report probability. After correction for race differences in genotype were observed, HRH1-17 TT (6% allergic versus 0% nonallergic; P = 0.04), HNMT-464 TT (41% allergic versus 29% nonallergic; P = 0.04), and HNMT-1639 TT (30% allergic versus 20% nonallergic; P = 0.04) were overrepresented among children with allergic asthma. Genotype differences specifically among the African-American children were also observed: HRH1-17 TT (13% allergic versus 0% nonallergic; P = 0.04) and HNMT-1639 TT (23% allergic versus 3% nonallergic; P = 0.03) genotypes were overrepresented among African-American children with allergic asthma. Our study suggests that genetic variation within the histamine pathway may be associated with an allergic versus nonallergic asthma phenotype. Further studies are needed to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease.
[Mh] Termos MeSH primário: Amina Oxidase (contendo Cobre)/genética
Asma/genética
Histamina N-Metiltransferase/genética
Histamina/fisiologia
Receptores Histamínicos/genética
[Mh] Termos MeSH secundário: Adolescente
Afroamericanos
Asma/etnologia
Asma/imunologia
Criança
Grupo com Ancestrais do Continente Europeu
Feminino
Frequência do Gene
Estudos de Associação Genética
Predisposição Genética para Doença
Haplótipos
Seres Humanos
Masculino
Polimorfismo de Nucleotídeo Único
Transdução de Sinais
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Receptors, Histamine); 820484N8I3 (Histamine); EC 1.4.3.21 (Amine Oxidase (Copper-Containing)); EC 1.4.3.22 (ABP1 protein, human); EC 2.1.1.8 (Histamine N-Methyltransferase)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150425
[St] Status:MEDLINE
[do] DOI:10.1165/rcmb.2014-0493OC


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[PMID]:25768024
[Au] Autor:Yang X; Liu C; Zhang J; Han H; Wang X; Liu Z; Xu Y
[Ad] Endereço:Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan Province, 610041, PR China.
[Ti] Título:Association of histamine N-methyltransferase Thr105Ile polymorphism with Parkinson's disease and schizophrenia in Han Chinese: a case-control study.
[So] Source:PLoS One;10(3):e0119692, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Parkinson's disease (PD) and schizophrenia (SCZ) are frequent central nervous disorders that have unclear etiologies but that show similarities in their pathogenesis. Since elevated histamine levels in the brain have been associated with PD and SCZ, we wanted to explore whether the Thr105Ile substitution in the histamine N-methyltransferase gene (HNMT-Thr105Ile), which impairs histamine degradation, is associated with either disease. We used the ligase detection reaction to genotype a case-control cohort of Han Chinese patients with PD or SCZ and healthy controls at the HNMT-Thr105Ile locus. The Ile allele was associated with reduced risk of PD (OR 0.516, 95% CI 0.318 to 0.838, p = 0.007) and of SCZ (OR 0.499, 95% CI 0.288 to 0.865, p = 0.011). Genotype frequencies and minor allele frequencies were similar between patients and controls when we compared males with females or early-onset patients with late-onset ones. Genotype and allele frequencies were not significantly different between PD patients with dyskinesia and PD patients without dyskinesia. Our results suggest that the heterozygous Thr/Ile genotype at the HNMT-Thr105Ile locus and the minor Ile105 allele protect against PD and SCZ in Han Chinese.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Predisposição Genética para Doença/genética
Histamina N-Metiltransferase/genética
Doença de Parkinson/genética
Polimorfismo Genético/genética
Esquizofrenia/genética
[Mh] Termos MeSH secundário: Adulto
Alelos
Estudos de Casos e Controles
China/etnologia
Feminino
Frequência do Gene/genética
Genótipo
Histamina/genética
Seres Humanos
Isoleucina/genética
Masculino
Treonina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
04Y7590D77 (Isoleucine); 2ZD004190S (Threonine); 820484N8I3 (Histamine); EC 2.1.1.8 (Histamine N-Methyltransferase)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150314
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0119692


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[PMID]:25425329
[Au] Autor:Nikolic K; Mavridis L; Bautista-Aguilera OM; Marco-Contelles J; Stark H; do Carmo Carreiras M; Rossi I; Massarelli P; Agbaba D; Ramsay RR; Mitchell JB
[Ad] Endereço:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Institute of Pharmaceutical Chemistry, University of Belgrade, Vojvode Stepe 450, 11000, Belgrade, Serbia, knikolic@pharmacy.bg.ac.rs.
[Ti] Título:Predicting targets of compounds against neurological diseases using cheminformatic methodology.
[So] Source:J Comput Aided Mol Des;29(2):183-98, 2015 Feb.
[Is] ISSN:1573-4951
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8).
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Doenças do Sistema Nervoso/tratamento farmacológico
Doença de Parkinson/tratamento farmacológico
[Mh] Termos MeSH secundário: Acetilcolinesterase/química
Acetilcolinesterase/metabolismo
Bases de Dados Factuais
Descoberta de Drogas
Histamina N-Metiltransferase/química
Histamina N-Metiltransferase/metabolismo
Seres Humanos
Ligantes
Monoaminoxidase/química
Monoaminoxidase/metabolismo
Relação Quantitativa Estrutura-Atividade
Receptor 5-HT2A de Serotonina/química
Receptor 5-HT2A de Serotonina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ligands); 0 (Receptor, Serotonin, 5-HT2A); EC 1.4.3.4 (Monoamine Oxidase); EC 2.1.1.8 (Histamine N-Methyltransferase); EC 3.1.1.7 (Acetylcholinesterase)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:171021
[Lr] Data última revisão:
171021
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141127
[St] Status:MEDLINE
[do] DOI:10.1007/s10822-014-9816-1



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