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1.
J Photochem Photobiol B ; 204: 111782, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32062389

RESUMO

BACKGROUND: Ultraviolet (UV) fluorescent lamp (FL) was applied in mainstream riboflavin photochemical method (RPM) to inactivate pathogens in blood components. Low UV irradiance emitted by UV-FL resulted in more time to achieve effective inactivation. MATERIALS AND METHODS: A novel light emitting diode (LED) UV illumination with adjustable irradiance was developed by us. Two strains of drug-resistant bacteria (DRB), pan-drug resistant Acinetobacter baumannii (PDRAB) and methicillin-resistant Staphylococcus aureus (MRSA) were cultured and used for evaluating the inactivation effectiveness of RPM using UV-LED or UV-FL against DRB in plasma or platelets. Three plasma factors and four platelet parameters were measured after treatments. RESULTS: There was a linear relationship between UV-LED irradiance and electric current, the minimum UV irradiance was 24 mW/cm2, and the maximum was 258 mW/cm2. At the same UV dose of 15 J/cm2, inactivation effectiveness of UV-LED with 258 mW/cm2 against PDRAB in plasma or platelets were comparable to that of UV-FL with 16 mW/cm2, both above 98%. UV-FL treatment required 10-15 min, but UV-LED only required 1-2 min. However, MRSA showed a resistance to UV-LED (inactivation effectiveness was around 40%) compared with UV-FL (inactivation effectiveness was above 98%). The retention of fibrinogen, factor V, factor VII in plasma and platelet counts in platelets with UV-LED treatment were significantly higher than UV-FL at the same UV dose. CONCLUSION: The treatment of RPM using UV-LED with high UV irradiance was able to dramatically shorten inactivation time against PDRAB in plasma or platelets and improve retention of blood components compared with UV-FL.


Assuntos
Proteínas Sanguíneas/metabolismo , Riboflavina/química , Raios Ultravioleta , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/efeitos da radiação , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Farmacorresistência Bacteriana/efeitos dos fármacos , Fator V/metabolismo , Fibrinogênio/metabolismo , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Contagem de Plaquetas , Riboflavina/farmacologia
2.
Orv Hetil ; 161(7): 252-262, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-32037866

RESUMO

Introduction: During liver transplantation, haemostasis is typically assessed by means of standard laboratory tests and viscoelastic tests, while dynamic monitoring of coagulation factor specific blood losses is an unusual, yet established approach. Aim: Our aim was to evaluate the volume-based haemostasis reserves in blood product free liver transplants in the first perioperative 48 hours, in association with the Child-Pugh score. Method: Data of 59 blood product free liver transplanted patients' coagulation factor levels, viscoelastic parameters and coagulation factor specific blood losses according to Gross methodological, baseline and 'coagulopathic' trigger levels were analysed. The haemostasis reserves were estimated according to the Child-Pugh classification. Laboratory tests and the calculation of haemostasis reserves were carried out before liver transplantation (T1), at the end of the surgery (T2) and also 12-24-48 hours postoperatively (T3-T4-T5). The viscoelastic tests were performed before liver transplantation (T1) and at the end of the surgery (T2). Results: Fibrinogen levels decreased by 1.2 g/L. Factor II, V, VII, X levels decreased by 26-40%. From T2 to T4, fibrinogen increased by 0.9 ± 0.6 g/L over 24 h (p<0.001). Factor II, V, VII, X levels increased by 12-30% between T3 to T5 (p<0.001). The viscoelastic parameters remained in the normal range during liver transplantation (T1-T2). Haemostasis reserves decreased by 61% at the end of surgery (p<0.001), but reached 88% of the preoperative value on the second postoperative day. The initial reserves of Child B and C groups were 36-41% lower than Child A, nevertheless, these differences were not significant at 48 hours. Conclusion: The volume-based haemostasis approach supplements the standard laboratory and viscoelastic tests. This unusual approach dynamically indicates the actual reserve of haemostasis and shows the 'weakest link' within the system. Orv Hetil. 2020; 161(7): 252-262.


Assuntos
Hemostasia , Transplante de Fígado , Testes de Coagulação Sanguínea , Fibrinogênio/metabolismo , Humanos
4.
Equine Vet J ; 52(1): 59-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30912857

RESUMO

BACKGROUND: Acute-phase proteins may help assess the nature and severity of lesions and outcome in horses undergoing colic surgery. OBJECTIVES: To compare serum amyloid A and plasma fibrinogen concentrations ([SAA] and [fibrinogen]) in the immediate post-operative period after exploratory celiotomy and determine their value in assessment of post-operative complications and survival to discharge. STUDY DESIGN: Observational study. METHODS: This study included horses over 1 year of age undergoing exploratory celiotomy. Surgical procedures, lesions, post-operative care, complications and survival to discharge were recorded. [SAA] and [fibrinogen] were measured prior to surgery and 5 days post-operatively. Statistical analyses included Yate's Chi-square test, linear mixed effects model, Mann-Whitney U test and logistic regression. RESULTS: Of 300 horses, 52.0% developed post-operative complications and 83.7% survived to discharge, with significantly reduced chance of survival in horses that developed post-operative complications (P<0.01). Median [SAA] at days 1, 2, 3, 4 and 5 and median [fibrinogen] at days 3, 4 and 5 were significantly different between horses that did and did not develop post-operative complications (P<0.05). Median [SAA] at days 1, 4 and 5 were significantly different between horses that did and did not survive to discharge (P<0.05). Logistic regression revealed post-operative complications to be associated with strangulating lesions (OR 2.35, 95% confidence interval [CI] 1.41-3.91, P≤0.001) and higher [fibrinogen] at admission (OR 1.21, 95% CI 1.00-1.45, P<0.05), and survival to discharge to be associated with lower [SAA] at 5 days post-operatively (OR 0.965, 95% CI 0.94-0.99, P = 0.002). MAIN LIMITATIONS: A large variety of lesions and complications prevented detailed analysis of associations between inflammatory markers, lesions and complications. CONCLUSIONS: Horses that develop post-operative complications have acute-phase responses of greater magnitudes and durations compared with those that do not develop complications. This is also seen in horses that do not survive to discharge. Measuring [SAA] daily and [fibrinogen] at admission, may help predict the development of post-operative complications.


Assuntos
Cólica/veterinária , Fibrinogênio/metabolismo , Doenças dos Cavalos/cirurgia , Complicações Pós-Operatórias/veterinária , Proteína Amiloide A Sérica/metabolismo , Animais , Cólica/cirurgia , Feminino , Doenças dos Cavalos/sangue , Doenças dos Cavalos/metabolismo , Cavalos , Masculino , Complicações Pós-Operatórias/sangue , Período Pós-Operatório
5.
Infect Immun ; 88(1)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31636136

RESUMO

Streptococcus equi subsp. zooepidemicus is an important pathogen in horses that causes severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent, and contact with horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among S. equi subsp. zooepidemicus strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different S. equi subsp. zooepidemicus strains that the M-like protein SzM is crucial for the binding of fibrinogen to the bacterial surface and for survival in equine and human blood. S. equi subsp. zooepidemicus isolates of equine and human origins were compared with regard to SzM sequences and binding of equine and human fibrinogens. The N-terminal 216 amino acids of the mature SzM were found to exhibit a high degree of diversity, but the majority of human isolates grouped in three distinct SzM clusters. Plasma protein absorption assays and flow cytometry analysis revealed that pronounced binding of human fibrinogen is a common phenotype of human S. equi subsp. zooepidemicus isolates but much less so in equine S. equi subsp. zooepidemicus isolates. Furthermore, binding of human fibrinogen is associated with specific SzM types. These results suggest that SzM-mediated binding of human fibrinogen is an important virulence mechanism of zoonotic S. equi subsp. zooepidemicus isolates.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Transporte/metabolismo , Fibrinogênio/metabolismo , Interações Hospedeiro-Patógeno , Streptococcus equi/metabolismo , Fatores de Virulência/metabolismo , Animais , Antígenos de Bactérias/classificação , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/classificação , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/classificação , Proteínas de Transporte/genética , Análise por Conglomerados , Variação Genética , Cavalos , Humanos , Fenótipo , Ligação Proteica , Homologia de Sequência , Fatores de Virulência/classificação , Fatores de Virulência/genética
6.
Immunity ; 51(5): 949-965.e6, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31653482

RESUMO

Mast cells (MCs) are versatile immune cells capable of rapidly responding to a diverse range of extracellular cues. Here, we mapped the genomic and transcriptomic changes in human MCs upon diverse stimuli. Our analyses revealed broad H3K4me3 domains and enhancers associated with activation. Notably, the rise of intracellular calcium concentration upon immunoglobulin E (IgE)-mediated crosslinking of the high-affinity IgE receptor (FcεRI) resulted in genome-wide reorganization of the chromatin landscape and was associated with a specific chromatin signature, which we term Ca2+-dependent open chromatin (COC) domains. Examination of differentially expressed genes revealed potential effectors of MC function, and we provide evidence for fibrinogen-like protein 2 (FGL2) as an MC mediator with potential relevance in chronic spontaneous urticaria. Disease-associated single-nucleotide polymorphisms mapped onto cis-regulatory regions of human MCs suggest that MC function may impact a broad range of pathologies. The datasets presented here constitute a resource for the further study of MC function.


Assuntos
Cromatina/genética , Suscetibilidade a Doenças , Estudo de Associação Genômica Ampla , Genômica , Mastócitos/imunologia , Mastócitos/metabolismo , Biomarcadores , Células Cultivadas , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina , Fibrinogênio/genética , Fibrinogênio/metabolismo , Perfilação da Expressão Gênica , Genômica/métodos , Histonas/metabolismo , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/metabolismo , Imunoglobulina E/imunologia , Inflamação/etiologia , Inflamação/metabolismo , Polimorfismo de Nucleotídeo Único
7.
Radiat Res ; 192(6): 640-648, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31618122

RESUMO

In the event of a radiological or nuclear attack, advanced clinical countermeasures are needed for screening and medical management of the exposed population. Such a population will represent diverse heterogeneity in physiological response to radiation exposure. The current study seeks to compare the expression levels of five previously established proteomic biodosimetry biomarkers of radiation exposure, i.e., Flt3 ligand (FL), matrix metalloproteinase 9 (MMP9), serum amyloid A (SAA), pentraxin 3 (PTX3) and fibrinogen (FGB), across multiple murine strains and to test a multivariate dose prediction model based on a single C57BL6 strain against other murine strains. Female mice from five different murine strains (C57BL6, BALB/c, C3H/HeJ, CD2F1 and outbred CD-1 mice) received a single whole-body dose of 1-8 Gy from a Pantak X-ray source at a dose rate of 3.59 Gy/min. Plasma was collected by cardiac puncture at days 1, 2, 3 and 7 postirradiation. Plasma protein levels were determined via commercially available ELISA assay. Significant differences were found between radiation-induced expression levels of FL, MMP9, SAA, PTX3 and FGB among the C57BL6, BALB/c, C3H/HeJ, CD2F1 and CD-1 strains (P < 0.05). The overall trends of dose-dependent biomarker elevation, however, were similar between strains, with FL and PTX3 showing the highest degree of correlation. Application of a previous C57BL6 multivariate dose prediction model using additional murine strains showed the limitations of a model based on a single strain and the need for data normalization for variance generated by technical assay variables. Our findings indicate that strain specific differences do exist between expression levels of FL, MMP9, SAA, PTX3 and FGB in C57BL6, BALB/c, C3H/HeJ, CD2F1 and CD-1 murine strains and that use of multiple biomarkers for dose prediction strengthens the predictive accuracy of a model when challenged with a heterogeneous population.


Assuntos
Biomarcadores/metabolismo , Proteômica , Radiometria/métodos , Animais , Bioensaio , Proteína C-Reativa/metabolismo , Fibrinogênio/metabolismo , Ligantes , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Análise Multivariada , Proteínas do Tecido Nervoso/metabolismo , Proteína Amiloide A Sérica/metabolismo , Especificidade da Espécie
8.
Biomed Res Int ; 2019: 5476076, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531357

RESUMO

Objective: The blood of cancer patients is in a state of hypercoagulability, easily leading to thrombosis. Anemia is also a complication of tumors. Anemia and thrombosis affect the treatment of tumor patients. Methods: Ginsenosides Rb were extracted from the stems and leaves of American ginseng using water-saturated ethanol and ethyl acetate in silica gel column. Tumor mice model was established by injecting H22 hepatocellular carcinoma cells into the axilla of mice. Mice were randomly divided into 6 groups: normal control group, model control group, positive control group, low dose group (7 mg/kg), middle dose group (14 mg/kg), and high dose group (35 mg/kg). After 18 days, the blood was obtained by picking the eyeball of mice. The levels of red blood cells (RBC), hemoglobin (HGB), neutrophils/lymphocytes radio (NLR), platelets (PLT), platelet distribution width (PDW), fibrinogen (FIB), and D-Dimer (D-D) were measured and compared in each group of mice. Results: The content of obtained ginsenosides Rb reached 90.05%. This extraction process was simple and reliable. Middle dose of ginsenosides Rb could significantly increase RBC and HGB levels (P<0.05). Moreover, ginsenosides Rb could significantly reduce NLR, PLT, PDW, FIB, and D-D (P<0.01). Conclusion: ginsenosides Rb could significantly improve anaemia and hypercoagulation of blood in cancer mice. Ginsenosides Rb are a potential anticoagulant and antianemia drug in treating cancer.


Assuntos
Sangue/efeitos dos fármacos , Ginsenosídeos/farmacologia , Neoplasias/sangue , Anemia/metabolismo , Animais , Plaquetas/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Hemoglobinas/efeitos dos fármacos , Hemostáticos/metabolismo , Camundongos , Panax/química , Folhas de Planta/química , Trombose/metabolismo
9.
Anaesthesia ; 74(12): 1589-1600, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531856

RESUMO

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Fibrinogênio/uso terapêutico , Cirurgia Torácica/métodos , Anestesiologia , Consenso , Fibrinogênio/efeitos adversos , Fibrinogênio/metabolismo , Homeostase , Humanos , Monitorização Fisiológica
10.
Clin Lab ; 65(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532095

RESUMO

BACKGROUND: To some extent, albumin levels reflect patient nutritional status and fibrinogen, neutrophils, lymphocytes, and platelets reflect chronic inflammation. These markers may be used to evaluate prognosis in gastric cancer. METHODS: Four hundred gastric cancer patients who underwent treatment in our hospital between 2010 and 2012 were retrospectively analyzed. The aims of our study were to assess the association of preoperative albumin, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and albumin to fibrinogen ratio (AFR) with tumor stage and survival in gastric cancer (GC) patients. RESULTS: Albumin, PLR, and AFR impacted survival when accompanied by low serum albumin levels, high PLR, and low AFR. Universal analysis showed that CEA, CA19-9, serum albumin, T, N, and nerve invasion were significantly correlated with the overall survival of gastric cancer patients. Multivariate analysis indicated that lower serum albumin levels correlated with decreased survival in gastric cancer patients (HR: 1.785, 95% confidence interval 1.139 - 2.797, p < 0.05). Apart from serum albumin levels, patients with advanced cancer with deep invasion (T3 + 4) and lymph node metastasis (N1-3) had significantly decreased survival. Albumin, AFR, PLR, and NLR were associated with the T stage, and albumin, AFR, and PLR were associated with the N stage. Albumin, AFR, NLR, and PLR were significantly different between gastric cancer patients and healthy controls. CONCLUSIONS: Serum albumin, AFR, PLR, and NLR are associated with prognosis in gastric cancer patients, indicating that these four markers impact inflammation, tumor metastasis, and patient nutrition, and are important independent markers of gastric cancer progression and patient survival.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Fibrinogênio/análise , Albumina Sérica/análise , Neoplasias Gástricas/sangue , Plaquetas , Feminino , Fibrinogênio/metabolismo , Humanos , Inflamação/sangue , Estimativa de Kaplan-Meier , Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos , Estudos Retrospectivos , Albumina Sérica/metabolismo , Neoplasias Gástricas/patologia
11.
J Ovarian Res ; 12(1): 88, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533857

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery. METHODS: A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan-Meier method using log-rank test. RESULTS: The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan-Meier method by log-rank test (P < 0.001). CONCLUSIONS: A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery.


Assuntos
Carcinoma Epitelial do Ovário/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Fibrinogênio/metabolismo , Albumina Sérica/metabolismo , Adulto , Idoso , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Tratamento Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
12.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547303

RESUMO

Better understanding the mechanisms of Leonurus cardiaca L. extract (LCE) activity is necessary to prepare recommendations for the use of LCE-based herbal products for preventive/supportive purposes in case of infective endocarditis (IE) and other staphylococcal invasive infections. The aim of the study was to analyze molecular mechanisms of LCE effect on Staphylococcus aureus and blood platelets in the context of their interactions playing a pivotal role in such disorders. Using atomic force microscopy, we demonstrated that adhesion forces of S. aureus were markedly reduced after exposure to LCE at subinhibitory concentrations. The effect resulted from the impact of LCE on S. aureus cell morphology and the composition of phospholipids and fatty acids in bacterial membranes (assessed by HPLC), which modulated their stabilization, hydrophobicity, and charge. Moreover, using FACS we showed also that LCE significantly reduced GP IIb/IIIa expression on blood platelets, thus the disruption of platelet-fibrinogen interactions seems to explain antiplatelet effect of LCE. The obtained results prove the usefulness of LCE in the prevention of S. aureus adhesion, platelet activation, and vegetations development, however, also pointed out the necessity of excluding the cationic antibiotics from the treatment of S. aureus-associated IE and other invasive diseases, when motherwort herb is used simultaneously as an addition to the daily diet.


Assuntos
Endocardite Bacteriana/prevenção & controle , Leonurus/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/microbiologia , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Endocardite Bacteriana/microbiologia , Ácidos Graxos/metabolismo , Fibrinogênio/metabolismo , Humanos , Microscopia de Força Atômica , Fosfolipídeos/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/química , Staphylococcus aureus/patogenicidade
13.
Int J Mol Sci ; 20(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547461

RESUMO

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.


Assuntos
Fibrinogênio/metabolismo , Degeneração Hepatolenticular/metabolismo , Estresse Oxidativo , Ceruloplasmina/análise , Ceruloplasmina/metabolismo , Fibrinogênio/análise , Células Hep G2 , Degeneração Hepatolenticular/sangue , Humanos , Carbonilação Proteica , Mapas de Interação de Proteínas , Proteômica
14.
Br J Hosp Med (Lond) ; 80(9): 507-512, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31498668

RESUMO

Thrombocytopenia is defined as a platelet count under 150x109/litre. It may be found as a bystander to other pathology or directly related to an underlying haematological condition. Apart from laboratory artefact, it should be treated seriously as it often reflects serious underlying disease. This review uses short case histories to illustrate how to approach thrombocytopenia during the initial presentation of an adult patient to hospital. This article guides the general hospital physician through the narrow but potentially confusing differential diagnoses related to thrombocytopenia, with particular focus on immune thrombocytopenia, disseminated intravascular coagulation and thrombotic thrombocytopenic purpura. Thrombocytopenia in pregnancy deserves special consideration and will not be discussed in this article.


Assuntos
Coagulação Intravascular Disseminada/diagnóstico , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Doença Aguda , Diagnóstico Diferencial , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/terapia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Coeficiente Internacional Normatizado , Tempo de Tromboplastina Parcial , Transfusão de Plaquetas/métodos , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/terapia , Trombocitopenia
15.
J Microbiol Biotechnol ; 29(10): 1603-1606, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474099

RESUMO

Sortase A (SrtA), a type of transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall, is important in the virulence of gram-positive bacteria. Three compounds were isolated from marine-derived Streptomyces sp. MBTH32 using various chromatography techniques. The structures of these compounds were determined based on spectroscopic data and comparisons with previously reported data. Among the metabolites tested, lumichrome showed strong inhibitory activity against Staphylococcus aureus SrtA without affecting cell viability. The results of cell clumping activity assessment suggest the potential for using this compound to treat S. aureus infection by inhibiting SrtA activity.


Assuntos
Aminoaciltransferases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Fibrinogênio/metabolismo , Staphylococcus aureus/patogenicidade , Streptomyces/química , Aminoaciltransferases/genética , Aminoaciltransferases/metabolismo , Aderência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavinas/química , Flavinas/isolamento & purificação , Flavinas/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Mutação , Staphylococcus aureus/enzimologia , Streptomyces/metabolismo , Virulência/efeitos dos fármacos
16.
Mediators Inflamm ; 2019: 3767128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396017

RESUMO

Knowledge about the influence of inflammation on platelet function and relocation of hemostatic balance to hypercoagulable state is still unclear. We compared two groups of patients who suffer from acute vs. chronic inflammatory process and additionally present high on-treatment platelet reactivity-dual platelet resistance. We did not found any differences in platelet aggregation between both investigated groups, but patients who suffer from chronic inflammation presented stronger relocation of the hemostatic balance to the hypercoagulability. A high concentration of prothrombin fragment F1+2 together with higher activity of von Willebrand factor in critical limb ischemia shows more exaggerated fibrinogen turnover although the blood concentration of this factor was in normal range. We concluded that high on-treatment platelet reactivity-dual platelet resistance and intensified inflammation are linked with elevated platelet and fibrinogen turnover to counteract proper hemostatic balance in favor of a prothrombotic state.


Assuntos
Fibrinogênio/metabolismo , Inflamação/metabolismo , Idoso , Feminino , Hemostasia/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Agregação Plaquetária/fisiologia , Protrombina/metabolismo , Tromboelastografia , Fator de von Willebrand/metabolismo
17.
J Exp Clin Cancer Res ; 38(1): 351, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409352

RESUMO

BACKGROUND: Soluble fibrinogen-like protein 2 (sFGL2), a secretory protein expressed by regulatory T cells (Tregs) with immunosuppressive activity, is highly expressed in both the peripheral blood and tumor tissue of patients with hepatocellular carcinoma (HCC); however, sFGL2 function in HCC remains largely unknown. Here, we elucidated the potential role of sFGL2 in HCC progression. METHODS: T cells, dendritic cells (DCs), and related cytokines in the tumor microenvironment were comparatively analyzed in BALB/c and C57BL/6 mice bearing transplanted hepatomas harboring Fgl2-knockout or receiving sFGL2-antibody treatment. Additionally, the effects of sFGL2 on DCs and T cells were evaluated in vivo and ex vivo. RESULTS: The growth of both subcutaneously and orthotopically transplanted hepatomas was inhibited in Fgl2-knockout mice and those treated with the sFGL2 antibody, respectively, as compared with controls. Moreover, sFGL2 depletion enhanced the proportion and cytotoxicity of cytotoxic T cells, promoted DC maturation, and improved DC activity to proliferate T cells in the tumor microenvironment. Furthermore, we detected lower levels of interleukin (IL)-35 in both types of transplanted hepatomas and higher level of IL-6 in orthotopically transplanted hepatomas following sFGL2 depletion. Mechanistically, we found that sFGL2 impaired bone-marrow-derived DC (BMDCs) function by inhibiting phosphorylation of Akt, nuclear factor-kappaB, cAMP response element binding protein, and p38 and downregulating the expression of major histocompatibility complex II, CD40, CD80, CD86, and CD83 on BMDCs in vitro. CONCLUSIONS: Our data suggest that sFGL2 promotes hepatoma growth by attenuating DC activity and subsequent CD8+ T cell cytotoxicity, suggesting sFGL2 as a novel potential therapeutic target for HCC treatment.


Assuntos
Citotoxicidade Imunológica , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fibrinogênio/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Biomarcadores , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Fibrinogênio/antagonistas & inibidores , Fibrinogênio/genética , Fibrinogênio/farmacologia , Xenoenxertos , Humanos , Imunofenotipagem , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Int J Mol Sci ; 20(17)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438579

RESUMO

Snake venom contains large amounts of active proteins and peptides. In this study, a novel snake protein, metalloproteinase SP, was successfully isolated from the venom of Agkistrodon acutus by multi-gel chromatography. The isolated protein exhibits anti-platelet aggregation activity. Animal experiments showed that it exhibited defibration, anticoagulation, and antithrombotic effects and contributes to improved blood rheology and antiplatelet aggregation. In vivo experiments demonstrated that it prolonged clotting time, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen time and reduced fibrinogen content of mice. Also, metalloproteinase SP inhibited carrageenan-induced tail thrombosis, ADP-induced acute pulmonary embolism, and ADP, Arachidonic acid (AA), or collagen-induced platelet aggregation. In vitro experiments showed that the protein cleaved the α, ß, and γ chains of fibrinogen. Metabolomic analysis upon metalloproteinase SP treatment revealed that 14 metabolites, which are mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis, responded to metalloproteinase SP treatment. In summary, the isolated snake venom protein inhibits formation of acute pulmonary embolism probably through regulating and restoring perturbed energy, lipid, and amino acid metabolism.


Assuntos
Venenos de Crotalídeos/enzimologia , Fibrinolíticos/isolamento & purificação , Metaloproteases/isolamento & purificação , Animais , Fibrinogênio/metabolismo , Metabolômica/métodos , Camundongos
19.
J Clin Pathol ; 72(12): 817-824, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31366633

RESUMO

AIMS: Bivalent direct thrombin inhibitors (DTIs), hirudin and bivalirudin, bind to the active site and exosite 1 of thrombin irreversibly and reversibly, respectively. The present study aims to assess in vitro effects of hirudin and bivalirudin through clot waveform analysis (CWA) and enzyme kinetics in coagulation assays. METHODS: The pooled normal plasma and its dilutions were spiked with hirudin or bivalirudin. The activated partial thromboplastin time (APTT) assay and the Clauss fibrinogen assay were performed using the CS-5100 (Sysmex). The APTT-CWA data were automatically gained by the CS-5100 programme. RESULTS: In APTT-CWA, the maximum coagulation velocity, acceleration and deceleration were decreased dependently on the drug concentrations, demonstrating evidence for the blockade of thrombin-positive feedback by hirudin or bivalirudin. The Hill plot analysis was applied to the dose-dependent curves in bivalirudin. The Hill coefficients were greater than 1, showing positive anticoagulant cooperativity. Regarding the dose-dependent curves in hirudin, all the parameters dropped to almost zero without making an asymptotic line. In the Clauss fibrinogen assay, the Lineweaver-Burk plots demonstrated that both drugs exhibit mixed inhibition mimicking uncompetitive binding. The Dixon plots in bivalirudin were linear and supported the inhibition type described above. The Dixon plots in hirudin were non-linear and inappropriate to use for determination of the inhibition type. In addition, the inverse function of the clotting time appeared to drop to zero without making an asymptotic line, suggesting complete loss of thrombin activity by irreversible binding. CONCLUSIONS: The results provide insights into anticoagulation with bivalent DTIs.


Assuntos
Antitrombinas/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Hirudinas/farmacologia , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/farmacologia , Trombina/antagonistas & inibidores , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Fibrinogênio/metabolismo , Humanos , Cinética , Modelos Biológicos , Proteínas Recombinantes/farmacologia , Trombina/metabolismo
20.
Anesth Analg ; 129(3): e86-e88, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31425220

RESUMO

Agreement between estimated fibrinogen concentration via thromboelastography and traditional assays is not established in the parturient. We therefore recruited 56 parturients and performed Clauss and functional fibrinogen level (FLEV) tests. Mean difference of measurements was 36.8 mg/dL (95% CI, 21.8-51.9) with a standard deviation of 52.8 mg/dL. Calculated limits of agreement were 140.2 mg/dL (95% CI, 166.3-114.6) and -66.6 mg/dL (95% CI, -40.8 to -92.5), within the maximum allowable difference of 165 mg/dL. We therefore conclude that while most measurements fell within the limits of agreement, more work is needed to clearly define the role of this test in the obstetric population.


Assuntos
Fibrinogênio/metabolismo , Testes Imediatos , Pré-Eclâmpsia/sangue , Terceiro Trimestre da Gravidez/sangue , Biomarcadores/sangue , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez
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