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Pesquisa : D12.644.861.060.750 [Categoria DeCS]
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[PMID]:28087279
[Au] Autor:Li J; Liu X; Xiang Y; Ding X; Wang T; Liu Y; Yin M; Tan C; Deng F; Chen L
[Ad] Endereço:Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
[Ti] Título:Alpha-2-macroglobulin and heparin cofactor II and the vulnerability of carotid atherosclerotic plaques: An iTRAQ-based analysis.
[So] Source:Biochem Biophys Res Commun;483(3):964-971, 2017 Feb 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rupture of carotid atherosclerotic plaque may cause stroke, while few biomarker in clinic can evaluate carotid plaque vulnerability. In this study, we divided the recruited participants into no plaque, stable plaque, and vulnerable plaque group according to carotid ultrasonography, and screened the differentially expressed proteins in plasma of these participants using isobaric tags for relative and absolute quantitation labeling coupled with liquid chromatography-tandem mass spectrometry. 28 proteins were identified differentially expressed, among which alpha-2-macroglobulin (α2M) and heparin cofactor II (HCII) were found to be at hub position in the interactions of these proteins by STRING analysis and were selected for enzyme-linked immunosorbent assay measurement to assess their relevance with carotid plaques vulnerability and diagnostic efficiency. The plasma level of α2M was found positively correlated, while HCII level was negatively correlated with higher vulnerability of carotid plaques. Both proteins were efficient in differentiating stable and vulnerable carotid plaques. These findings provide potential new targets for the research of carotid plaque vulnerability. Plasma α2M and HCII may be potential biomarkers for evaluation of the vulnerability of carotid plaques if further studied.
[Mh] Termos MeSH primário: Estenose das Carótidas/sangue
Cofator II da Heparina/metabolismo
Placa Aterosclerótica/sangue
alfa-Macroglobulinas/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Biomarcadores/sangue
Análise Química do Sangue/métodos
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A2M protein, human); 0 (Biomarkers); 0 (SERPIND1 protein, human); 0 (alpha-Macroglobulins); 81604-65-1 (Heparin Cofactor II)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE


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[PMID]:28042854
[Au] Autor:Suleria HA; Hines BM; Addepalli R; Chen W; Masci P; Gobe G; Osborne SA
[Ad] Endereço:School of Medicine, The University of Queensland, Translational Research Institute, Kent Street, Woolloongabba 4102, Australia. hafiz.suleria@uqconnect.edu.au.
[Ti] Título:In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste.
[So] Source:Mar Drugs;15(1), 2016 Dec 31.
[Is] ISSN:1660-3397
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone ( ) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 µg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin.
[Mh] Termos MeSH primário: Organismos Aquáticos/química
Fibrinolíticos/química
Fibrinolíticos/farmacologia
Gastrópodes/química
[Mh] Termos MeSH secundário: Animais
Anticoagulantes/química
Anticoagulantes/farmacologia
Testes de Coagulação Sanguínea/métodos
Cofator II da Heparina/farmacologia
Tempo de Tromboplastina Parcial/métodos
Polissacarídeos/química
Polissacarídeos/farmacologia
Tempo de Protrombina/métodos
Trombina/metabolismo
Trombose/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Fibrinolytic Agents); 0 (Polysaccharides); 81604-65-1 (Heparin Cofactor II); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170512
[Lr] Data última revisão:
170512
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170103
[St] Status:MEDLINE


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[PMID]:27664921
[Au] Autor:Pawlaczyk-Graja I; Balicki S; Ziewiecki R; Matulová M; Capek P; Gancarz R
[Ad] Endereço:Departament of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 29, 50-370, Wroclaw, Poland. Electronic address: izabela.pawlaczyk@pwr.wroc.pl.
[Ti] Título:Polyphenolic-polysaccharide conjugates of Sanguisorba officinalis L. with anticoagulant activity mediated mainly by heparin cofactor II.
[So] Source:Int J Biol Macromol;93(Pt A):1019-1029, 2016 Dec.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A macromolecular complex has been isolated from the dried flowering parts of medicinal plant Sanguisorba officinalis L. (So) by multi-step extraction procedure, including that with extraction by organic solvents to degrease the plant material, then with hot alkali, followed by neutralization, partitioning with organic solvents and dialysis. The complex was purified by size-exclusion chromatography into five fractions labeled as So1-So5. Individual fractions differed in the chemical composition and molecular weight distribution patterns. In vitro anticoagulant activity tests showed in all fractions more or less important inhibition of plasma clots, however, So3 and So4 were the most active. The anticoagulant activity of So3 was even more significant than that of the unfractionated complex So. These S. officinalis conjugates were able to inhibit mainly the activity of thrombin when they were mediated by heparin cofactor II, but what was unexpected they were the non-direct inhibitors of factor Xa, mediated by antitrombin, where such mechanism of action is typical for a highly sulphated glycosaminoglycans.
[Mh] Termos MeSH primário: Anticoagulantes/farmacologia
Cofator II da Heparina/fisiologia
Extratos Vegetais/farmacologia
Polifenóis/farmacologia
Polissacarídeos/farmacologia
[Mh] Termos MeSH secundário: Anticoagulantes/isolamento & purificação
Avaliação Pré-Clínica de Medicamentos
Flores/química
Seres Humanos
Tempo de Tromboplastina Parcial
Extratos Vegetais/isolamento & purificação
Polifenóis/isolamento & purificação
Polissacarídeos/isolamento & purificação
Tempo de Protrombina
Sanguisorba/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Plant Extracts); 0 (Polyphenols); 0 (Polysaccharides); 81604-65-1 (Heparin Cofactor II)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160925
[St] Status:MEDLINE


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[PMID]:27430660
[Au] Autor:Zhu L; Guo Q; Jin S; Feng H; Zhuang H; Liu C; Tan M; Liu J; Li X; Lin B
[Ad] Endereço:Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
[Ti] Título:Analysis of the gene expression profile in response to human epididymis protein 4 in epithelial ovarian cancer cells.
[So] Source:Oncol Rep;36(3):1592-604, 2016 Sep.
[Is] ISSN:1791-2431
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Currently, there are emerging multiple studies on human epididymis protein 4 (HE4) in ovarian cancer. HE4 possesses higher sensitivity and specificity than CA125 in the confirmative early diagnosis for ovarian cancer. Although much attention has been given to explore its clinical application, research of the basic mechanisms of HE4 in ovarian cancer are still unclear. In the present study, we provide fundamental data to identify full-scale differentially expressed genes (DEGs) in response to HE4 by use of human whole-genome microarrays in human epithelial ovarian cancer cell line ES-2 following overexpression and silencing of HE4. We found that a total of 717 genes were upregulated and 898 genes were downregulated in the HE4-overexpressing cells vs. the HE4-Mock cells, and 166 genes were upregulated and 285 were downregulated in the HE4-silenced cells vs. the HE4-Mock cells. An overlap of 16 genes consistently upregulated and 8 genes downregulated in response to HE4 were noted. These DEGs were involved in MAPK, steroid biosynthesis, cell cycle, the p53 hypoxia pathway, and focal adhesion pathways. Interaction network analysis predicted that the genes participated in the regulatory connection. Highly differential expression of the FOXA2, SERPIND1, BDKRD1 and IL1A genes was verified by quantitative real-time PCR in 4 cell line samples. Finally, SERPIND1 (HCII) was validated at the protein level by immunohistochemistry in 107 paraffin-embedded ovarian tissues. We found that SERPIND1 may act as a potential oncogene in the development of ovarian cancer. The present study displayed the most fundamental and full-scale data to show DEGs in response to HE4. These identified genes may provide a theoretical basis for investigations of the underlying molecular mechanism of HE4 in ovarian cancer.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica/genética
Cofator II da Heparina/genética
Neoplasias Epiteliais e Glandulares/genética
Neoplasias Ovarianas/genética
Proteínas/metabolismo
[Mh] Termos MeSH secundário: Western Blotting
Linhagem Celular Tumoral
Feminino
Técnicas de Silenciamento de Genes
Cofator II da Heparina/metabolismo
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Neoplasias Epiteliais e Glandulares/mortalidade
Análise de Sequência com Séries de Oligonucleotídeos
Oncogenes/genética
Neoplasias Ovarianas/mortalidade
Proteínas/genética
Reação em Cadeia da Polimerase em Tempo Real
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 0 (SERPIND1 protein, human); 0 (WFDC2 protein, human); 81604-65-1 (Heparin Cofactor II)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170317
[Lr] Data última revisão:
170317
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160720
[St] Status:MEDLINE
[do] DOI:10.3892/or.2016.4926


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[PMID]:27136540
[Au] Autor:Fu Q; Huang Y; Wang Z; Chen F; Huang D; Lu Y; Liang X; Zhang M
[Ad] Endereço:State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresource, Guangxi University, Nanning 530004, China. gxfuq@163.com.
[Ti] Título:Proteome Profile and Quantitative Proteomic Analysis of Buffalo (Bubalusbubalis) Follicular Fluid during Follicle Development.
[So] Source:Int J Mol Sci;17(5), 2016 Apr 29.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Follicular fluid (FF) accumulates in the antrum of the ovarian follicle and provides the microenvironment for oocyte development. FF plays an important role in follicle growth and oocyte maturation. The FF provides a unique window to investigate the processes occurring during buffalo follicular development. The observed low quality of buffalo oocytes may arise from the poor follicular microenvironment. Investigating proteins found in buffalo FF (BFF) should provide insight into follicular development processes and provide further understanding of intra-follicular maturation and oocytes quality. Here, a proteomic-based approach was used to analyze the proteome of BFF. SDS-PAGE separation combined with mass spectrometry was used to generate the proteomic dataset. In total, 363 proteins were identified and classified by Gene Ontology terms. The proteins were assigned to 153 pathways, including signaling pathways. To evaluate difference in proteins expressed between BFF with different follicle size (small, <4 mm; and large, >8 mm), a quantitative proteomic analysis based on multi-dimensional liquid chromatography pre-fractionation tandem Orbitrap mass spectrometry identification was performed. Eleven differentially expressed proteins (six downregulated and five upregulated in large BFF) were identified and assigned to a variety of functional processes, including serine protease inhibition, oxidation protection and the complement cascade system. Three differentially expressed proteins, Vimentin, Peroxiredoxin-1 and SERPIND1, were verified by Western blotting, consistent with the quantitative proteomics results. Our datasets offers new information about proteins present in BFF and should facilitate the development of new biomarkers. These differentially expressed proteins illuminate the size-dependent protein changes in follicle microenvironment.
[Mh] Termos MeSH primário: Búfalos/metabolismo
Folículo Ovariano/metabolismo
Proteoma/análise
Proteômica
[Mh] Termos MeSH secundário: Animais
Western Blotting
Cromatografia Líquida de Alta Pressão
Estradiol/análise
Feminino
Líquido Folicular/metabolismo
Cofator II da Heparina/metabolismo
Folículo Ovariano/crescimento & desenvolvimento
Peptídeos/análise
Peroxirredoxinas/metabolismo
Progesterona/análise
Espectrometria de Massas em Tandem
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 0 (Proteome); 0 (Vimentin); 4G7DS2Q64Y (Progesterone); 4TI98Z838E (Estradiol); 81604-65-1 (Heparin Cofactor II); EC 1.11.1.15 (Peroxiredoxins)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160503
[St] Status:MEDLINE


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[PMID]:27034473
[Au] Autor:Grandoch M; Kohlmorgen C; Melchior-Becker A; Feldmann K; Homann S; Müller J; Kiene LS; Zeng-Brouwers J; Schmitz F; Nagy N; Polzin A; Gowert NS; Elvers M; Skroblin P; Yin X; Mayr M; Schaefer L; Tannock LR; Fischer JW
[Ad] Endereço:From the Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany (M.G., C.K., A.M.-B., K.F., S.H., J.M., L.-S.K., F.S., N.N., J.W.F.); Cardiovascular Research Institute Düsseldorf (CARID), Universitätsklinikum der He
[Ti] Título:Loss of Biglycan Enhances Thrombin Generation in Apolipoprotein E-Deficient Mice: Implications for Inflammation and Atherosclerosis.
[So] Source:Arterioscler Thromb Vasc Biol;36(5):e41-50, 2016 May.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Thrombin signaling promotes atherosclerosis by initiating inflammatory events indirectly through platelet activation and directly via protease-activated receptors. Therefore, endogenous thrombin inhibitors may be relevant modulators of atheroprogression and cardiovascular risk. In addition, endogenous thrombin inhibitors may affect the response to non-vitamin K-dependent oral anticoagulants. Here, the question was addressed whether the small leucine-rich proteoglycan biglycan acts as an endogenous thrombin inhibitor in atherosclerosis through activation of heparin cofactor II. APPROACH AND RESULTS: Biglycan concentrations were elevated in the plasma of patients with acute coronary syndrome and in male Apolipoprotein E-deficient (ApoE(-/-)) mice. Biglycan was detected in the glycocalyx of capillaries and the subendothelial matrix of arterioles of ApoE(-/-) mice and in atherosclerotic plaques. Thereby a vascular compartment is provided that may mediate the endothelial and subendothelial activation of heparin cofactor II through biglycan. ApoE and Bgn double-deficient (ApoE(-/-)/Bgn(-/0)) mice showed higher activity of circulating thrombin, increased platelet activation and platelet adhesion in vivo, supporting a role of biglycan in balancing thrombin activity. Furthermore, concentrations of circulating cytokines and aortic macrophage content were elevated in ApoE(-/-)/Bgn(-/0) mice, suggesting a proinflammatory phenotype. Elevated platelet activation and macrophage accumulation were reversed by treating ApoE(-/-)/Bgn(-/0) mice with the thrombin inhibitor argatroban. Ultimately, ApoE(-/-)/Bgn(-/0) mice developed aggravated atherosclerosis. CONCLUSIONS: The present results indicate that biglycan plays a previously unappreciated protective role during the progression of atherosclerosis by inhibiting thrombin activity, platelet activation, and finally macrophage-mediated plaque inflammation.
[Mh] Termos MeSH primário: Aorta/metabolismo
Doenças da Aorta/metabolismo
Apolipoproteínas E/deficiência
Aterosclerose/metabolismo
Biglicano/deficiência
Inflamação/metabolismo
Trombina/metabolismo
[Mh] Termos MeSH secundário: Síndrome Coronariana Aguda/sangue
Animais
Antitrombinas/farmacologia
Aorta/efeitos dos fármacos
Aorta/patologia
Doenças da Aorta/sangue
Doenças da Aorta/genética
Doenças da Aorta/prevenção & controle
Apolipoproteínas E/genética
Aterosclerose/sangue
Aterosclerose/genética
Aterosclerose/prevenção & controle
Biglicano/sangue
Biglicano/genética
Citocinas/sangue
Modelos Animais de Doenças
Genótipo
Cofator II da Heparina/metabolismo
Seres Humanos
Inflamação/sangue
Inflamação/genética
Inflamação/prevenção & controle
Macrófagos/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fenótipo
Placa Aterosclerótica
Ativação Plaquetária
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antithrombins); 0 (Apolipoproteins E); 0 (BGN protein, human); 0 (Bgn protein, mouse); 0 (Biglycan); 0 (Cytokines); 0 (Serpind1 protein, mouse); 81604-65-1 (Heparin Cofactor II); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160402
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.115.306973


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[PMID]:25871288
[Au] Autor:Wu M; Xu L; Zhao L; Xiao C; Gao N; Luo L; Yang L; Li Z; Chen L; Zhao J
[Ad] Endereço:State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. wumingyi@mail.kib.ac.cn.
[Ti] Título:Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber.
[So] Source:Mar Drugs;13(4):2063-84, 2015 Apr 13.
[Is] ISSN:1660-3397
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC-MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants.
[Mh] Termos MeSH primário: Anticoagulantes/isolamento & purificação
Descoberta de Drogas
Polissacarídeos/isolamento & purificação
Pepinos-do-Mar/química
[Mh] Termos MeSH secundário: Animais
Anticoagulantes/química
Anticoagulantes/farmacologia
Coagulação Sanguínea/efeitos dos fármacos
Brasil
Sequência de Carboidratos
Fenômenos Químicos
China
Cofator II da Heparina/antagonistas & inibidores
Cofator II da Heparina/metabolismo
Holothuria/química
Seres Humanos
Cinética
Peso Molecular
Polissacarídeos/química
Polissacarídeos/farmacologia
Pepinos-do-Mar/crescimento & desenvolvimento
Especificidade da Espécie
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Polysaccharides); 0 (SERPIND1 protein, human); 81604-65-1 (Heparin Cofactor II); 9072-19-9 (fucoidan)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150415
[St] Status:MEDLINE
[do] DOI:10.3390/md13042063


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[PMID]:25769326
[Au] Autor:Lu H; Guo P
[Ad] Endereço:Department of Vascular Surgery, First Affi liated Hospital of Fujian Medical University, Fuzhou 350001, China.
[Ti] Título:[Plasma heparin cofactor II activity correlates with the incidence of in-stent restenosis after the intervention of arteriosclerosis obliterans in lower extremity].
[So] Source:Zhong Nan Da Xue Xue Bao Yi Xue Ban;40(2):177-81, 2015 Feb.
[Is] ISSN:1672-7347
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To explore the relationship between activity of plasma heparin cofactor II (HC II) and the incidence of in-stent restenosis aft er the intervention of arteriosclerosis obliterans in lower extremity. METHODS: A total of 62 patients with arteriosclerosis obliterans in lower extremity underwent femoropopliteal stent implantation. They were divided into 2 groups: A high HC II activity group (≥100%, n=40) and a low HC II activity group (<100%, n=22). All patients filled in follow up tables and conducted body examination. Possible risk factors resulting in restenosis were collected. Patients were followed up for 6 months after femoropopliteal stent implantation. RESULTS: Baseline clinical characteristics were not significantly different between the 2 groups. The degree and incidence of angiographic restenosis at the end of the 6th month after the implantation in the high HC II activity group were all significantly lower than those in the low HC II activity group (P<0.05). Multivariate analysis demonstrated that high plasma HC II activity was an independent factor in reducing the incidence of angiographic restenosis (OR=0.982, P=0.048, 95%CI, 0.966, 0.998). CONCLUSION: High plasma HC II activity is an independent factor in reducing the degree of in-stent restenosis. The lower the plasma HC II activity, the severer the degree of in-stent restenosis.
[Mh] Termos MeSH primário: Arteriosclerose Obliterante/cirurgia
Cofator II da Heparina/metabolismo
Stents
[Mh] Termos MeSH secundário: Constrição Patológica
Seres Humanos
Incidência
Extremidade Inferior
Fatores de Risco
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (SERPIND1 protein, human); 81604-65-1 (Heparin Cofactor II)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:150315
[Lr] Data última revisão:
150315
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150315
[St] Status:MEDLINE
[do] DOI:10.11817/j.issn.1672-7347.2015.02.010


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[PMID]:25742429
[Au] Autor:Boothello RS; Sarkar A; Tran VM; Nguyen TK; Sankaranarayanan NV; Mehta AY; Alabbas A; Brown S; Rossi A; Joice AC; Mencio CP; Quintero MV; Kuberan B; Desai UR
[Ti] Título:Chemoenzymatically prepared heparan sulfate containing rare 2-O-sulfonated glucuronic acid residues.
[So] Source:ACS Chem Biol;10(6):1485-94, 2015 Jun 19.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The structural diversity of natural sulfated glycosaminoglycans (GAGs) presents major promise for discovery of chemical biology tools or therapeutic agents. Yet, few GAGs have been identified so far to exhibit this promise. We reasoned that a simple approach to identify such GAGs is to explore sequences containing rare residues, for example, 2-O-sulfonated glucuronic acid (GlcAp2S). Genetic algorithm-based computational docking and filtering suggested that GlcAp2S containing heparan sulfate (HS) may exhibit highly selective recognition of antithrombin, a key plasma clot regulator. HS containing only GlcAp2S and 2-N-sulfonated glucosamine residues, labeled as HS2S2S, was chemoenzymatically synthesized in just two steps and was found to preferentially bind antithrombin over heparin cofactor II, a closely related serpin. Likewise, HS2S2S directly inhibited thrombin but not factor Xa, a closely related protease. The results show that a HS containing rare GlcAp2S residues exhibits the unusual property of selective antithrombin activation and direct thrombin inhibition. More importantly, HS2S2S is also the first molecule to activate antithrombin nearly as well as the heparin pentasaccharide although being completely devoid of the critical 3-O-sulfonate group. Thus, this work shows that novel functions and mechanisms may be uncovered by studying rare GAG residues/sequences.
[Mh] Termos MeSH primário: Antitrombinas/química
Ácido Glucurônico/química
Glicosaminoglicanos/química
Bibliotecas de Moléculas Pequenas
[Mh] Termos MeSH secundário: Algoritmos
Sítios de Ligação
Fator Xa/química
Cofator II da Heparina/antagonistas & inibidores
Cofator II da Heparina/química
Heparitina Sulfato/química
Cinética
Simulação de Acoplamento Molecular
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antithrombins); 0 (Glycosaminoglycans); 0 (Small Molecule Libraries); 81604-65-1 (Heparin Cofactor II); 8A5D83Q4RW (Glucuronic Acid); 9050-30-0 (Heparitin Sulfate); EC 3.4.21.6 (Factor Xa)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:160417
[Lr] Data última revisão:
160417
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150306
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.5b00071


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[PMID]:25600805
[Au] Autor:Saito A
[Ad] Endereço:Division of Basic Medicine, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Electronic address: asaito@med.kindai.ac.jp.
[Ti] Título:Heparin cofactor II is degraded by heparan sulfate and dextran sulfate.
[So] Source:Biochem Biophys Res Commun;457(4):585-8, 2015 Feb 20.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heparan sulfate normally binds to heparin cofactor II and modulates the coagulation pathway by inhibiting thrombin. However, when human heparin cofactor II was incubated with heparan sulfate, heparin cofactor II became degraded. Other glycosaminoglycans were tested, including hyaluronic acid, chondroitin sulfates, dermatan sulfate, and heparin, but only dextran sulfate also degraded heparin cofactor II. Pretreatment of heparan sulfate with heparinase reduced its heparin cofactor II-degrading activity. Heparan sulfate and dextran sulfate diminished the thrombin inhibitory activity of heparin cofactor II. Other serpins, including antithrombin III and pigment epithelium-derived factor, were also degraded by heparan sulfate. This is the first evidence of acidic polysaccharides exhibiting protein-degrading activity without the aid of other proteins.
[Mh] Termos MeSH primário: Antitrombinas/metabolismo
Sulfato de Dextrana/metabolismo
Cofator II da Heparina/metabolismo
Heparitina Sulfato/metabolismo
Proteólise
[Mh] Termos MeSH secundário: Animais
Antitrombina III/metabolismo
Antitrombinas/farmacologia
Bovinos
Flavobacterium/enzimologia
Cofator II da Heparina/farmacologia
Heparina Liase/metabolismo
Seres Humanos
Indicadores e Reagentes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antithrombins); 0 (Indicators and Reagents); 81604-65-1 (Heparin Cofactor II); 9000-94-6 (Antithrombin III); 9042-14-2 (Dextran Sulfate); 9050-30-0 (Heparitin Sulfate); EC 4.2.2.7 (Heparin Lyase)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:150218
[Lr] Data última revisão:
150218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150121
[St] Status:MEDLINE



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