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[PMID]:28817602
[Au] Autor:Regad L; Chéron JB; Triki D; Senac C; Flatters D; Camproux AC
[Ad] Endereço:Molécules thérapeutiques in silico (MTi), INSERM UMR-S973, Paris, France.
[Ti] Título:Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.
[So] Source:PLoS One;12(8):e0182972, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.
[Mh] Termos MeSH primário: Análise de Sequência de Proteína/métodos
Software
[Mh] Termos MeSH secundário: Animais
Domínio Catalítico
Protease de HIV/química
Protease de HIV/metabolismo
Seres Humanos
Ativadores de Plasminogênio/química
Ativadores de Plasminogênio/metabolismo
Ligação Proteica
Conformação Proteica
Proteína Supressora de Tumor p53/química
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Suppressor Protein p53); EC 3.4.21.- (Plasminogen Activators); EC 3.4.23.- (HIV Protease)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182972


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[PMID]:28710283
[Au] Autor:Constantinescu P; Brown RA; Wyatt AR; Ranson M; Wilson MR
[Ti] Título:Amorphous protein aggregates stimulate plasminogen activation, leading to release of cytotoxic fragments that are clients for extracellular chaperones.
[So] Source:J Biol Chem;292(35):14425-14437, 2017 Sep 01.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The misfolding of proteins and their accumulation in extracellular tissue compartments as insoluble amyloid or amorphous protein aggregates are a hallmark feature of many debilitating protein deposition diseases such as Alzheimer's disease, prion diseases, and type II diabetes. The plasminogen activation system is best known as an extracellular fibrinolytic system but was previously reported to also be capable of degrading amyloid fibrils. Here we show that amorphous protein aggregates interact with tissue-type plasminogen activator and plasminogen, via an exposed lysine-dependent mechanism, to efficiently generate plasmin. The insoluble aggregate-bound plasmin is shielded from inhibition by α -antiplasmin and degrades amorphous protein aggregates to release smaller, soluble but relatively hydrophobic fragments of protein (plasmin-generated protein fragments (PGPFs)) that are cytotoxic. , both endothelial and microglial cells bound and internalized PGPFs before trafficking them to lysosomes. Clusterin and α -macroglobulin bound to PGPFs to significantly ameliorate their toxicity. On the basis of these findings, we hypothesize that, as part of the extracellular proteostasis system, the plasminogen activation system may work synergistically with extracellular chaperones to safely clear large and otherwise pathological protein aggregates from the body.
[Mh] Termos MeSH primário: Fibrinolisina/metabolismo
Microglia/efeitos dos fármacos
Fragmentos de Peptídeos/toxicidade
Ativadores de Plasminogênio/toxicidade
Agregados Proteicos
Ativador de Plasminogênio Tecidual/metabolismo
alfa 2-Antiplasmina/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Clusterina/química
Clusterina/metabolismo
Conalbumina/química
Conalbumina/metabolismo
Endotélio Vascular/efeitos dos fármacos
Endotélio Vascular/metabolismo
Endotélio Vascular/patologia
Endotélio Vascular/ultraestrutura
Fibrinolisina/antagonistas & inibidores
Fibrinolisina/química
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Camundongos
Microglia/metabolismo
Microglia/patologia
Microglia/ultraestrutura
Mutação
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Plasminogênio/química
Plasminogênio/metabolismo
Ativadores de Plasminogênio/química
Ativadores de Plasminogênio/genética
Ativadores de Plasminogênio/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Solubilidade
Superóxido Dismutase-1/química
Superóxido Dismutase-1/genética
Superóxido Dismutase-1/metabolismo
Ativador de Plasminogênio Tecidual/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CLU protein, human); 0 (Clusterin); 0 (Peptide Fragments); 0 (Protein Aggregates); 0 (Recombinant Proteins); 0 (SERPINF2 protein, human); 0 (SOD1 protein, human); 0 (alpha-2-Antiplasmin); 1391-06-6 (Conalbumin); 9001-91-6 (Plasminogen); EC 1.15.1.1 (Superoxide Dismutase-1); EC 3.4.21.- (Plasminogen Activators); EC 3.4.21.68 (PLAT protein, human); EC 3.4.21.68 (Tissue Plasminogen Activator); EC 3.4.21.7 (Fibrinolysin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170716
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.786657


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[PMID]:28472076
[Au] Autor:Csutak A; Steiber Z; Tozsér J; Jakab A; Berta A; Silver DM
[Ad] Endereço:Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
[Ti] Título:Plasminogen activator activity in tears of pregnant women.
[So] Source:PLoS One;12(5):e0177003, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Plasminogen activator activity (PAA) in tears of pregnant women was investigated at various gestation times to assess the availability of plasminogen activator for aiding potential corneal wound healing processes during pregnancy. METHODS: PAA was measured by a spectrophotometric method. The analysis used 91 tear samples from pregnant and non-pregnant women, supplemented with 10 additional tear PAA measurements from non-pregnant women obtained in a previous study. RESULTS: Tear levels of PAA in pregnant women formed a bimodal distribution. Either the tear PAA level was zero or non-zero during pregnancy. When non-zero, the tear PAA level was dissociated from gestation time and not different than non-pregnant and post-pregnant levels. The frequency of occurrence of zero level tear PAA increased with gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women in the first, second and third trimester, respectively. CONCLUSIONS: Overall, of the tear samples taken from women during pregnancy, a total of 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAA values throughout gestation equivalent to non-pregnant tear PAA values, suggesting local control of the source of PAA in tears. Given the importance of the plasminogen activator system in tears to wound healing in the cornea, and the high occurrence of zero tear PAA in our sample of pregnant women, elective corneal surgery would be contraindicated. If corneal surgery is nevertheless necessary, the tear PAA level would be worth checking and patients with low level should be closely observed during the postoperative period.
[Mh] Termos MeSH primário: Ativadores de Plasminogênio/metabolismo
Lágrimas/metabolismo
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Gravidez
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177003


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[PMID]:28471961
[Au] Autor:Li X; Ling L; Li C; Ma Q
[Ad] Endereço:aDepartment of Neurology, Shenzhen Hospital of Southern Medical University, Shenzhen bDepartment of Neurology, Xiaolan Hospital of Southern Medical University, Zhongshan, Guangdong cDepartment of Neurology, Guangzhou Red Cross Hospital, Medical College, Jinan University dDepartment of Emergency, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
[Ti] Título:Efficacy and safety of desmoteplase in acute ischemic stroke patients: A systematic review and meta-analysis.
[So] Source:Medicine (Baltimore);96(18):e6667, 2017 May.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain undetermined. The aim of this meta-analysis was to help evaluate desmoteplase's efficacy and safety. METHODS: A thorough search was performed of the Cochrane Library, PubMed, and Embase from the inception of electronic data to March 2017, and double-blind, multicenter, parallel-group, randomized trials were chosen. We conducted a meta-analysis of studies investigating intravenous desmoteplase treatment of acute ischemic stroke patients 3 to 9 hours after symptom onset. Asymptomatic intracerebral hemorrhage, good clinical outcome at 90 days, and reperfusion 4 to 8 hours posttreatment were variables assessing efficacy; symptomatic intracerebral hemorrhage and death rates were measures of safety. RESULTS: Six trials involving 1071 patients thrombolyzed >3 hours postonset were included (600 received intravenous desmoteplase, 471 placebo). Desmoteplase was associated with increased reperfusion (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.10-2.24; P = .01 vs control) and showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.97-1.62; P = .09 vs control), whereas there was no increase in symptomatic intracerebral hemorrhage and death rate with desmoteplase. However, there was no difference in the clinical response at 90 days (OR 1.14; 95% CI, 0.88-1.49; P = .31 vs control). Subgroup analysis showed that desmoteplase 90 µg/kg (OR 1.53; 95% CI, 1.07-2.21; P = .02 vs control) and 125 µg/kg (OR 4.07; 95% CI, 1.16-14.24; P = .03 vs control) were associated with an increase in reperfusion. Also, we found desmoteplase 90 µg/kg showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.95-1.63; P = .11 vs control). CONCLUSION: Intravenous desmoteplase is associated with a favorable reperfusion efficacy and acceptable safety in ischemic stroke treatment >3 hours after symptom onset. Well-designed randomized controlled trials with larger patient cohorts and a moderate dose of drugs are needed to further evaluate the true efficacy of desmoteplase in stroke patients. TRIAL REGISTRATION: URL: http://www.crd.york.ac.uk/PROSPERO; PROSPERO registration number: CRD42016037667).
[Mh] Termos MeSH primário: Isquemia Encefálica/tratamento farmacológico
Fibrinolíticos/administração & dosagem
Ativadores de Plasminogênio/administração & dosagem
Acidente Vascular Cerebral/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Intravenosa
Fibrinolíticos/efeitos adversos
Seres Humanos
Ativadores de Plasminogênio/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Fibrinolytic Agents); 0 (salivary plasminogen activator alpha 1, Desmodus rotundus); EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006667


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[PMID]:27863833
[Au] Autor:Meurer WJ; Barth BE; Gaddis G; Vilke GM; Lam SH
[Ad] Endereço:Departments of Emergency Medicine and Neurology, University of Michigan, Ann Arbor, Michigan.
[Ti] Título:Rapid Systematic Review: Intra-Arterial Thrombectomy ("Clot Retrieval") for Selected Patients with Acute Ischemic Stroke.
[So] Source:J Emerg Med;52(2):255-261, 2017 Feb.
[Is] ISSN:0736-4679
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality. However, precisely defining the optimal treatment for individual patients early after AIS onset remains elusive. There has recently been a surge in published studies documenting the effectiveness of mechanical intra-arterial thrombectomy for treatment of a subset of patients with AIS. This therapy has been proposed and studied for the small (<1.2%) subgroup of patients with ischemic strokes who have "large vessel" strokes or strokes that fail to improve after the administration of tissue plasminogen activator (t-PA). The current rapid systematic review provides practicing emergency physicians updated information regarding mechanical thrombectomy as a treatment option for carefully selected AIS patients. METHODS: A PubMed literature search was conducted from January 1996 to June 2016 and limited to human clinical trials written in English with relevant keywords. High-quality randomized controlled studies identified then underwent a structured review. RESULTS: In total, 179 papers fulfilling the search criteria were screened and 8 appropriate articles were rigorously reviewed in detail and recommendations given on the effectiveness and indication of mechanical intra-arterial thrombectomy for the treatment of AIS. CONCLUSIONS: Mechanical intra-arterial thrombectomy reduces long-term disability in a properly selected subset of patients who have an AIS caused by large vessel occlusion. Many of these patients will have failed to improve after intravenous administration of t-PA, and mortality is not increased when combined with t-PA. Careful screening criteria should be in place to identify the limited subset of patients to whom this therapy is delivered to derive optimal treatment benefits.
[Mh] Termos MeSH primário: Trombólise Mecânica/métodos
Trombólise Mecânica/normas
Acidente Vascular Cerebral/terapia
Trombectomia/métodos
[Mh] Termos MeSH secundário: Fibrinolíticos/farmacologia
Fibrinolíticos/uso terapêutico
Seres Humanos
Ativadores de Plasminogênio/farmacologia
Ativadores de Plasminogênio/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Fibrinolytic Agents); EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161120
[St] Status:MEDLINE


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[PMID]:27696935
[Au] Autor:Adivitiya; Khasa YP
[Ad] Endereço:a Department of Microbiology , University of Delhi South Campus , New Delhi , India.
[Ti] Título:The evolution of recombinant thrombolytics: Current status and future directions.
[So] Source:Bioengineered;8(4):331-358, 2017 07 04.
[Is] ISSN:2165-5987
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.
[Mh] Termos MeSH primário: Fibrinolíticos/administração & dosagem
Ativadores de Plasminogênio/administração & dosagem
Proteínas Recombinantes/administração & dosagem
Estreptoquinase/administração & dosagem
Trombose/tratamento farmacológico
Ativador de Plasminogênio Tecidual/administração & dosagem
Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Previsões
Seres Humanos
Engenharia de Proteínas/métodos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fibrinolytic Agents); 0 (Recombinant Proteins); EC 3.4.- (Streptokinase); EC 3.4.21.- (Plasminogen Activators); EC 3.4.21.68 (Tissue Plasminogen Activator); EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171127
[Lr] Data última revisão:
171127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161005
[St] Status:MEDLINE
[do] DOI:10.1080/21655979.2016.1229718


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[PMID]:27664152
[Au] Autor:Goktay AY; Senturk C
[Ad] Endereço:Interventional Radiology, Dokuz Eylul University Medical School Hospital, Izmir, Turkey. yigit.goktay@deu.edu.tr.
[Ti] Título:Endovascular Treatment of Thrombosis and Embolism.
[So] Source:Adv Exp Med Biol;906:195-213, 2017.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Deep venous thrombosis (DVT) is a common disorder with a significant mortality rate. Successful endovascular treatment of acute DVT is most likely to be achieved in patients with recently formed thrombus, (<10-14 days) with acute iliofemoral DVT. Endovascular treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation. Current practice shows strong clinical tendency for the use of PCDT with or without other endovascular methods and an individualized approach for each DVT patient. PMT has not received general acceptance because of the associated risk of PE and damage to venous valves caused by thrombectomy devices. PAT is most commonly used as an adjunctive endovascular technique like balloon maceration to fragment thrombus, balloon angioplasty, stent implantation and vena cava filter placement. Interventional endovascular therapies for DVT have the potential to provide PE protection and prevention of PTS. Patient centered individualized approach for endovascular DVT treatment is recommended to optimize the ideal clinical result.Acute stroke is the leading cause of death for people above the age of 60 and the fifth leading cause in people aged 15-59. Mortality during the first 30 days of ischemic stroke is 20 % and 30 % of survivors will remain permanently disabled. Acute stroke patients within the therapeutic window must receive IVrtPA unless there is a contraindication. In case of contraindication to IVrtPA or for patients out of the therapeutic window for thrombolytics, standart of care is the intraarterial treatment. Patients have to be transferred to a comprehensive stroke center with capacity of dedicated neurovascular imaging and interventional neuroradiology. Noncontrast head CT that is used to rule out hemorrhage is followed by imaging studies dedicated to show if there is reasonable penumbra to save. Intraarterial thrombolysis has the main advantage of extended therapy window, earlier and more efficient recanalization and less risk of hemorrhage due to lower doses of thrombolytics. Mechanical thrombectomy has several advantages over IV/IA fibrinolysis including faster recanalization and less risk of hemorrhage especially in large artery occlusions. ASA guidelines recommend choosing stent retrievers over other devices for mechanical thrombectomy. Better recanalization rates and less infarct volume after mechanical thrombectomy result in higher numbers of functionally independent patients compared with other treatments. Two landmark studies that were published recently, SWIFT PRIME and MR CLEAN, showed that IA treatment especially with the new stent retrievers lead to a significant increase in functional recovery and independence in daily life after an acute stroke.Cerebral venous and sinus thrombosis (CVST) comprises nearly 0.5-1 % of all stroke cases. CVST causes different neurological deficits depending on the sinus/cortical vein involved. CVST may cause death and dependency in 13.4 % of patients. CT/CT venography and MR/MR venography can be effectively used to diagnose and to follow up CVT cases. Anticoagulation with heparin is the most widely accepted therapy to prevent the expansion of the thrombus. Patients deteriorating despite heparinization and patients presenting with very severe neurological deficits must receive endovascular treatment. Endovascular methods include intrasinus infusion of thrombolytics or heparin, balloon angioplasty, mechanical thrombectomy or a combination of different techniques. There is a higher rate or recanalization with endovascular methods compared to other medical therapies.
[Mh] Termos MeSH primário: Anticoagulantes/uso terapêutico
Fibrinolíticos/uso terapêutico
Heparina/uso terapêutico
Ativadores de Plasminogênio/uso terapêutico
Trombose Venosa/terapia
[Mh] Termos MeSH secundário: Embolectomia com Balão
Cateterismo
Seres Humanos
Neuroimagem
Flebografia
Medicina de Precisão
Stents
Trombectomia
Terapia Trombolítica/métodos
Tomografia Computadorizada por Raios X
Trombose Venosa/diagnóstico por imagem
Trombose Venosa/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Fibrinolytic Agents); 9005-49-6 (Heparin); EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160925
[St] Status:MEDLINE


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[PMID]:28614640
[Au] Autor:Kit OL; Frantsiyants EM; Kozlova LS; Kolesnikov EN; Pogorelova YA; Cheryarina ND; Tavaryan IS
[Ti] Título:[[Gender Differences in Tissue Cascade of Activation of Plasminogen and PAI-1 in Esophageal Squamous Cell Carcinoma].]
[So] Source:Eksp Klin Gastroenterol;(5):16-21, 2016.
[Is] ISSN:1682-8658
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: comparative analysis of uPA-Ag, uPA-act, tPA-Ag, tPA-act, PAl--Ag and PAl-i-act in tissues of esophageal squamous cell carcinoma (ESCC) in men (M) and women (W) to clarify some pathogenesis issues. MATERIAL AND METHODS: Tumor tissue of ESCC and its perifocal area (19 M and 8 menopausal W aged 38-72 years, st 1I, G2, T,3N M0) were studied by ELISA using standard test kits. RESULTS: ESCC tissue of M showed an increase in both uPA types from the resection line (RL), while in W only uPA-act was increased. tPA-Ag was decreased in tumors of W, tPA-act - in tumors of all patients. Levels of both PAl-- types were higher in ESCC of M than in W. in M, tPA-Ag in perifocal area was lower than in RL, while in W, on the contrary, it was higher. tPA- Ag/tPA-act coefficient in M tumors was 5.7 times higher than in W; in perifocal area it was reduced in all patients, being at the same time in M lower than in W. Both PAl- types were increased in malignant tissues of all patients, prevailing in M tumors, and PAl-i-Ag in peritumoral tissue was higher in M than in W. CONCLUSIONS: Significant gender differences were found in expression of uPA, tPA and PAl-i in tissues of esophageal squamous cell carcinoma. Presence of tumor-associated uPA, PAH and tPA in men and uPA and PAl-i in women is possible in tumor tissue of esophageal squamous cell carcinoma and its perifocal area. Determination of plasminogen regulation system in tissues of esophageal squamous cell carcinoma can be used for the selection and individualization of postoperative treatments.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/metabolismo
Neoplasias Esofágicas/metabolismo
Inibidor 1 de Ativador de Plasminogênio/metabolismo
Ativadores de Plasminogênio/metabolismo
Caracteres Sexuais
[Mh] Termos MeSH secundário: Adulto
Idoso
Ensaio de Imunoadsorção Enzimática
Feminino
Imunofluorescência
Seres Humanos
Masculino
Meia-Idade
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plasminogen Activator Inhibitor 1); 0 (SERPINE1 protein, human); EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE


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[PMID]:27995263
[Au] Autor:Loh VW; Soon DT; Yeo LL
[Ad] Endereço:Division of Family Medicine, University Medicine Cluster, National University Health System, Singapore.
[Ti] Título:Outpatient management of transient ischaemic attack.
[So] Source:Singapore Med J;57(12):658-663, 2016 Dec.
[Is] ISSN:0037-5675
[Cp] País de publicação:Singapore
[La] Idioma:eng
[Ab] Resumo:Stroke is a significant cause of death and disability in Singapore; in 2014, it was the fourth most common cause of death. Transient ischaemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without evidence of acute infarction. The diagnosis of TIA/acute stroke needs to be considered in all patients who present with sudden focal neurological dysfunction. Prompt referral for assessment, neuroimaging and intervention provides the best chance for neurological recovery and/or minimising further neurological damage. Primary care physicians have a crucial role in TIA/stroke prevention and management. This includes referring patients with suspected acute TIA/stroke to hospitals with stroke treatment facilities immediately; managing the modifiable risk factors of cerebral ischaemia; continuing prescription of antiplatelet agents and/or anticoagulation where indicated; and teaching patients to recognise and respond to suspected cerebral ischaemia using the FAST (face, arm, speech, time) acronym.
[Mh] Termos MeSH primário: Ataque Isquêmico Transitório/diagnóstico
Acidente Vascular Cerebral/diagnóstico
[Mh] Termos MeSH secundário: Competência Clínica
Seres Humanos
Ataque Isquêmico Transitório/tratamento farmacológico
Anamnese
Pacientes Ambulatoriais
Educação de Pacientes como Assunto
Ativadores de Plasminogênio/uso terapêutico
Encaminhamento e Consulta
Fatores de Risco
Singapura
Acidente Vascular Cerebral/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE
[do] DOI:10.11622/smedj.2016180


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[PMID]:27936190
[Au] Autor:Dentovskaya SV; Platonov ME; Svetoch TE; Kopylov PK; Kombarova TI; Ivanov SA; Shaikhutdinova RZ; Kolombet LV; Chauhan S; Ablamunits VG; Motin VL; Uversky VN; Anisimov AP
[Ad] Endereço:State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, Russian Federation.
[Ti] Título:Two Isoforms of Yersinia pestis Plasminogen Activator Pla: Intraspecies Distribution, Intrinsic Disorder Propensity, and Contribution to Virulence.
[So] Source:PLoS One;11(12):e0168089, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of the C-terminal tail of Pla and makes this protein slightly more prone for disorder-based protein-protein interactions, suggesting that the T259 Pla could be functionally more active than the I259 Pla. This assumption was proven experimentally by assessing the coagulase and fibrinolytic activities of the two Pla isoforms in human plasma, as well as in a direct fluorometric assay with the Pla peptide substrate. The virulence testing of Pla-negative or expressing the I259 and T259 Pla isoforms Y. pestis subsp. microtus and subsp. pestis strains did not reveal any significant difference in LD50 values and dose-dependent survival assays between them by using a subcutaneous route of challenge of mice and guinea pigs or intradermal challenge of mice. However, a significant decrease in time-to-death was observed in animals infected with the epidemic T259 Pla-producing strains as compared to the parent Pla-negative variants. Survival curves of the endemic I259 Pla+ strains fit between them, but significant difference in mean time to death post infection between the Pla-strains and their I259 Pla+ variants could be seen only in the isogenic set of subsp. pestis strains. These findings suggest an essential role for the outer membrane protease Pla evolution in Y. pestis bubonic infection exacerbation that is necessary for intensification of epidemic process from endemic natural focality with sporadic cases in men to rapidly expanding epizootics followed by human epidemic outbreaks, local epidemics or even pandemics.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Isoenzimas/metabolismo
Ativadores de Plasminogênio/metabolismo
Yersinia pestis/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Proteínas de Bactérias/química
Feminino
Cobaias
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Ativadores de Plasminogênio/química
Homologia de Sequência de Aminoácidos
Especificidade da Espécie
Virulência
Yersinia pestis/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Isoenzymes); EC 3.4.21.- (Pla protease, Yersinia pestis); EC 3.4.21.- (Plasminogen Activators)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0168089



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