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1.
J Agric Food Chem ; 68(10): 3132-3139, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32064873

RESUMO

Thrombin is currently one of the important targets for the treatment and prevention of thrombosis. At present, there are few reports on the application of lactoferrin peptides in anticoagulation. In this study, a peptide with the amino acid sequence of LRPVAAEIY (LF-LR) derived from lactoferrin was shown to possess antithrombotic activity. LF-LR (5 mM) significantly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time for 13.4, 1.7, and 5.1 s, respectively. It prolonged the coagulation time of fibrinogen from 15.3 ± 0.4 to 20.2 ± 0.5 s by affecting the conformation of thrombin. Using circular dichroism analysis, LF-LR can increase the α-helix content of thrombin from 25.6 to 56.7% and made the ß-sheet disappear. In addition, LF-LR also quenched fluorescence of thrombin at about 346 nm (λEx = 280 nm). By means of molecular docking, it was found that LF-LR could bind to both the active site and the exosite-I of thrombin, and the combined LYS60F, TRP60D, ASP189, LYS36, and ARG77A are typical amino acids in the two domains, respectively.


Assuntos
Anticoagulantes/química , Lactoferrina/química , Peptídeos/química , Trombina/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Domínio Catalítico , Bovinos , Fibrinogênio/química , Humanos , Cinética , Simulação de Acoplamento Molecular , Ligação Proteica , Tempo de Trombina
2.
World Neurosurg ; 135: e610-e615, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31870816

RESUMO

BACKGROUND: Noncontrast computed tomography hypodensities (HD) and ultraearly hematoma growth (uHG) are reliable markers for outcome prediction in patients with spontaneous intracerebral hemorrhage (sICH). The present study aimed to assess whether the combination of these 2 markers could improve the prognostic value for sICH. METHODS: We recruited 242 patients with sICH who had been admitted within 6 hours from the onset of symptoms. HD was assessed by 2 independent blinded readers, and uHG was calculated as baseline ICH volume/onset-to-imaging time. We divided the study population into 4 groups: uHG(L) HD(-) (uHG <6.16 mL/hour and HD negative), uHG(L) HD(+) (uHG<6.16 mL/hour and HD positive), uHG(H) HD(-) (uHG ≥6.16 mL/hour and HD negative), and uHG(H) HD(+) (uHG ≥6.16 mL/h and HD positive). The outcome at 90 days was evaluated by the modified Rankin Scale (mRS) score and was dichotomized as good (mRS score 0-3) and poor (mRS score 4-6). The association between the combined indicators and unfavorable outcome was investigated using multivariable logistic regression models. RESULTS: Patients with poor outcomes were more likely to have HD and higher uHG in univariate analysis. In multivariate logistic regression analysis, uHG(H) HD(+) had a higher risk of unfavorable outcomes compared with uHG(L) HD(-) (odds ratio [OR], 5.710; P < 0.001). In addition, the risk of unfavorable outcomes was increased in uHG(H) HD(-) (OR, 2.957, P = 0.044) and uHG(L) HD(+) (OR, 1.924; P = 0.232). The proportions of unfavorable prognoses were 32.6% in uHG(L) HD(-), 48.3% in uHG(L) HD(+), 72.2% in uHG(H) HD(-), and 87.5% in uHG(H) HD(+) (P < 0.001). CONCLUSIONS: The combination of uHG and HD improves the stratification of unfavorable prognoses in patients with sICH.


Assuntos
Hemorragia Cerebral/patologia , Hematoma/patologia , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Feminino , Hematoma/diagnóstico por imagem , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prognóstico , Estudos Retrospectivos , Tempo de Trombina , Fatores de Tempo , Tomografia Computadorizada por Raios X
3.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3349-3357, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602894

RESUMO

Rat model of blood stasis syndrome was prepared by subcutaneous injecting of epinephrine hydrochlorid,then the model rats were administrated by Yunnan Baiyao for 15 days. Blood rheology,coagulation function and histopathology were chosen as indicators to evaluate the successful replication of blood stasis syndrome model and the treatment effect of Yunnan Baiyao. UPLC-Q-TOF-MS was used to rapidly analyze the serum samples of blood stasis syndrome rat after 15 days Yunnan Baiyao treatment,Progenesis QI software was employed to identify the alkaloids components. The results showed that Yunnan Baiyao reduced the plasma viscosity and whole blood viscosity of rats with blood stasis syndrome,prolonged thrombin and prothrombin time,reduced fibrinogen content,and effectively improved pathological state such as inflammatory cell infiltration,blood stasis,congestion and edema of various organs in rats with blood stasis syndrome. Seven alkaloids components from Aconitum kusnezoffii,including karacolidine,senbusine B,isotalatizidine,karakoline,denudatine,talatisamine and chasmanine were found in the rat serum after Yunnan Baiyao treatment. Based on the effectiveness of Yunnan Baiyao in the treatment of blood stasis syndrome induced by epinephrine hydrochloride in rats,alkaloids components from the root of A. kusnezoffii absorbed into blood after Yunnan Baiyao treatment were clarified rapidly and accurately with the help of UPLC-Q-TOF-MS. Karacolidine,senbusine B,isotalatizidine,karakoline,denudatine,talatisamine and chasmanine are the pharmacodynamic material basis of the root of A. kusnezoffii for activating blood circulation and removing blood stasis.


Assuntos
Aconitum/química , Circulação Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Animais , Viscosidade Sanguínea , Tempo de Protrombina , Ratos , Tempo de Trombina
4.
Clin Appl Thromb Hemost ; 25: 1076029619867137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364394

RESUMO

To describe the effect of dabigatran on thrombin time (TT) reagents at different concentrations of thrombin. Pooled normal plasma enriched with dabigatran was dissolved in dimethylsulfoxide (DMSO) at concentrations of 0, 20, 50, 100, 200, 300, and 500 ng/mL. Samples with each concentration were evaluated using a semiautomatic coagulation analyzer to assess the effect of dabigatran on internal normalized ratio (INR), thromboplastin time (APTT), and TT, which were purchased from Instrument Laboratory (IL), Sysmex (SYS), and Stago (STA), respectively. Regarding INR, no reagent showed good sensitivity to increasing concentration of dabigatran, despite all reagents showing good linear response curves (P = .012). Regarding APTT, all reagents had low sensitivity to increasing dabigatran concentration, but SYS-APTT showed a better linear response curve (P = .001). Regarding TT, all reagents had a good linear response to the concentration of dabigatran; however, SYS-TT was very sensitive at low concentrations of dabigatran (0-100 ng/mL), while IL (TT-5 mL) and STA-TT were sensitive at medium concentrations of dabigatran (0-300 ng/mL), and IL (TT-2 mL) was less sensitive for a wide concentration of dabigatran (0-500 ng/mL; P = .007). Internal normalized ratio and APTT showed low sensitivity and SYS-TT showed high sensitivity to concentrations of dabigatran that were unsuitable to monitor. Both IL (TT-5 mL) and STA-TT were useful at medium concentrations of dabigatran by semiautomatic coagulation analyzer, which calculated results using the end point method of coagulation. Instrument Laboratory (TT-2 mL), which contains a higher concentration of thrombin, had better sensitivity to the concentration of dabigatran than APTT and was suitable for routine monitoring by an automatic analyzer.


Assuntos
Dabigatrana/farmacocinética , Monitoramento de Medicamentos/métodos , Tempo de Trombina , Antitrombinas/sangue , Antitrombinas/farmacocinética , Testes de Coagulação Sanguínea , Dabigatrana/sangue , Dabigatrana/normas , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Humanos , Indicadores e Reagentes/farmacologia , Tempo de Tromboplastina Parcial , Sensibilidade e Especificidade , Trombina/farmacologia
5.
Fitoterapia ; 138: 104345, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31470063

RESUMO

The present study reports the phytochemical investigation of n-butanol-soluble extracts of Glechoma longituba. Five new oleanane-type triterpenoid saponins with an 11α, 12α-epoxy unit, named glechomanosides A - E, were isolated from the n-butanol soluble fraction of G. longituba. Their chemical structures were established using HRESIMS, IR, 1D NMR, and 2D NMR techniques. The compounds were all evaluated for their antithrombus activities by monitoring thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antiplatelet aggregation assays. These results suggest that G. longituba might be a candidate plant source of an interesting antithrombotic activity.


Assuntos
Plaquetas/efeitos dos fármacos , Lamiaceae/química , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , China , Feminino , Masculino , Camundongos , Estrutura Molecular , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Tempo de Tromboplastina Parcial , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Agregação Plaquetária , Tempo de Protrombina , Coelhos , Saponinas/isolamento & purificação , Tempo de Trombina
6.
Int J Lab Hematol ; 41(5): 697-701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31424160

RESUMO

INTRODUCTION: In order to correctly manage the paediatric patients affected with haemostatic disorders, age-appropriate reference intervals should be used. The purpose of this study was to establish age-specific reference intervals for prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (aPTT) and fibrinogen (Fg). METHODS: In this study, a total of 34 234 apparently healthy children and adolescents aged 0-15 years were chosen as reference individuals. PT, TT, aPTT and Fg were performed on the STA-R coagulation analyzer. Outliers were eliminated using the Dixon D/R ratio rule. Partitioning by age was achieved using Harris and Boyd's standard normal deviate test. The lower (2.5th percentiles) and upper (97.5 percentiles) reference intervals were established using the nonparametric method. RESULTS: Compared with the adult group, the median time of PT was significantly different in the groups consisting of children aged 0-15 days, 15 days-1 month, 1-6 months and 11-15 years. The median time of APTT and TT was significantly prolonged in all paediatric age groups than in the adult group (P < .05). Compared with the adult group, the median values of Fg were significantly different in the groups consisting of children aged 0-15 days and 2-15 years. Our results showed that all coagulation assays required partitioning by age. CONCLUSION: Our results suggest that results of coagulation assays are highly dependent on age, and that age-specific reference intervals must be used to ensure proper evaluation of paediatric coagulation assays.


Assuntos
Testes de Coagulação Sanguínea/instrumentação , Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea , Transtornos Hemostáticos/sangue , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , China , Feminino , Fibrinogênio , Transtornos Hemostáticos/diagnóstico , Transtornos Hemostáticos/etnologia , Humanos , Lactente , Recém-Nascido , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Valores de Referência , Tempo de Trombina
7.
Molecules ; 24(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174390

RESUMO

Pentamidine is bis-oxybenzamidine-based antiprotozoal drug. The parenteral use of pentamidine appears to affect the processes of blood coagulation and/or fibrinolysis resulting in rare but potentially life-threatening blood clot formation. Pentamidine was also found to cause disseminated intravascular coagulation syndrome. To investigate the potential underlying molecular mechanism(s) of pentamidine's effects on coagulation and fibrinolysis, we studied its effects on clotting times in normal and deficient human plasmas. Using normal plasma, pentamidine isethionate doubled the activated partial thromboplastin time at 27.5 µM, doubled the prothrombin time at 45.7 µM, and weakly doubled the thrombin time at 158.17 µM. Using plasmas deficient of factors VIIa, IXa, XIa, or XIIa, the concentrations to double the activated partial thromboplastin time were similar to that obtained using normal plasma. Pentamidine also inhibited plasmin-mediated clot lysis with half-maximal inhibitory concentration (IC50) value of ~3.6 µM. Chromogenic substrate hydrolysis assays indicated that pentamidine inhibits factor Xa and plasmin with IC50 values of 10.4 µM and 8.4 µM, respectively. Interestingly, it did not significantly inhibit thrombin, factor XIa, factor XIIIa, neutrophil elastase, or chymotrypsin at the highest concentrations tested. Michaelis-Menten kinetics and molecular modeling studies revealed that pentamidine inhibits factor Xa and plasmin in a competitive fashion. Overall, this study provides quantitative mechanistic insights into the in vitro effects of pentamidine isethionate on coagulation and fibrinolysis via the disruption of the proteolytic activity of factor Xa and plasmin.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Pentamidina/farmacologia , Trombose/tratamento farmacológico , Testes de Coagulação Sanguínea , Fator VIIa/genética , Fator XIIa/genética , Fator XIa/genética , Fator Xa/genética , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Trombina/química , Trombina/genética , Tempo de Trombina , Trombose/sangue , Trombose/patologia
8.
Int J Biol Macromol ; 136: 579-585, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220498

RESUMO

In the present study, two polysaccharides, SVP2-1 and SVP2-2, were isolated from Patinopecten yessoensis viscera and purified by using DEAE-52 cellulose and Sepharose CL-6B. Both SVP2-1 and SVP2-2 could extend activated partial thromboplastin time (APTT) and thrombin time (TT) and inhibit the transformation of fibrinogen into fibrin (FIB) concentration-dependently, indicating they inhibited clotting and thrombin through intrinsic and common pathways. Of note, SVP2-2 had stronger anticoagulant activity than SVP2-1, and its backbone was determined as →6)-α-Manp (1 → 2)-α-Galp(1 → with Xyl or Glc substituted at C4 of Gal. Based on monosaccharide composition analysis, methylation analysis, and NMR analysis. Further comparison of their monosaccharide analysis and NMR spectra indicates SVP2-1 and SVP2-2 possess the same core structure features, so the higher sulfate content and lower molecular weight may be the possible reasons for the stronger anticoagulant capability of SVP2-2. The present study suggests acidic polysaccharides from scallop viscera as promising anticoagulant candidates.


Assuntos
Anticoagulantes/química , Anticoagulantes/farmacologia , Pectinidae , Polissacarídeos/química , Polissacarídeos/farmacologia , Vísceras/química , Animais , Fibrina/metabolismo , Fibrinogênio/metabolismo , Metilação , Peso Molecular , Monossacarídeos/análise , Tempo de Tromboplastina Parcial , Coelhos , Tempo de Trombina
9.
Biochem Med (Zagreb) ; 29(2): 020503, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31223257

RESUMO

A modern diagnostic laboratory offers wide spectrum of coagulation assays utilized in the diagnosis and management of patients with haemostatic disorders, preoperative screening and anticoagulation therapy monitoring. The recent survey conducted among Croatian medical biochemistry and transfusion laboratories showed the existence of different practice policies in particular phases of laboratory process during coagulation testing and highlighted areas that need improvement. Lack of assay standardization together with non-harmonized test results between different measurement methods, can potentially lead to incorrect decisions in patient's treatment. Consequently, patient safety could be compromised. Therefore, recommended procedures related to preanalytical, analytical and postanalytical phases of prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen and D-dimer testing are provided in this review, aiming to help laboratories to generate accurate and reliable test results.


Assuntos
Testes de Coagulação Sanguínea , Coleta de Amostras Sanguíneas , Medicina Clínica , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Coagulação Sanguínea , Técnicas de Laboratório Clínico , Humanos , Tempo de Tromboplastina Parcial , Tempo de Trombina
10.
Eur J Obstet Gynecol Reprod Biol ; 240: 36-40, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226575

RESUMO

OBJECTIVE: To explore coagulation parameters in association with polycystic ovarian syndrome (PCOS) and establish a model for predicting the risk of PCOS. STUDY DESIGN: This study included 181 outpatients with PCOS. A total of 301 women who attempted to seek pre-pregnancy consultation at the Department of Gynecology of our hospital were included in the control group, and six coagulation parameters were measured for all included subjects. A logistic regression model was built based on the training dataset using the purposeful selection method to select important predictors. The performance of the established model was validated on the test dataset. RESULTS: There were statistically significant differences found among all coagulation parameters except D-Dimer (DD, P = 0.080). The purposeful selection method selected age (odds ratio [OR] = 0.89; p = 0.008), prothrombin time (PT, OR = 0.68, p < 0.0001), thrombin time (TT, OR = 3.30; p = 0.0005), and fibrin degradation products (FDP, OR = 0.24; p = 0.0002) as important predictors of PCOS risk. The receiver operating characteristic (ROC) curve analysis indicated that the area under the ROC curve (AUC) of the model was 0.81 for the training dataset with an optimal cut-off point of the predicted probability of 0.45, leading to a sensitivity of 0.71 and a specificity of 0.82. The AUC was 0.79 for the test data. CONCLUSIONS: It was found that the coagulation parameters, including PT, TT, and FDP, are predictive of PCOS. These results highlight the potential of anti-coagulation therapies to lower the risk of adverse outcomes in women with PCOS.


Assuntos
Coagulação Sanguínea/fisiologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Síndrome do Ovário Policístico/diagnóstico , Tempo de Protrombina , Tempo de Trombina , Adulto , Fatores Etários , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Gravidez , Medição de Risco , Adulto Jovem
11.
Adv Clin Chem ; 90: 197-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31122609

RESUMO

Anticoagulant drugs directly or indirectly influence coagulation factors preventing fibrin formation, thus preventing blood clotting. They are classified into two groups according to the mode of application, namely parenteral and oral drugs. Among the latter, vitamin K antagonists (most often warfarin) were most widely used for almost a century. In recent years new oral anticoagulant drugs have become available that directly target either factor IIa or Xa (direct oral anticoagulants, DOACs). The proportion of patients to whom DOACs are prescribed is increasing because clinical studies have proved they are at least as effective and safe as vitamin K antagonists. Some of the anticoagulant drugs require regular laboratory monitoring, while others only need assessment of blood drug levels in specific clinical situations. This chapter provides an overview of appropriate laboratory tests used for either regular laboratory monitoring of therapy or occasional assessment of the anticoagulant effect of both parenteral and oral anticoagulant drugs used in clinical practice.


Assuntos
Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Monitoramento de Medicamentos , Fatores de Coagulação Sanguínea/antagonistas & inibidores , Humanos , Tempo de Trombina
12.
Anaesth Intensive Care ; 47(2): 183-188, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31116016

RESUMO

Dabigatran is an oral anticoagulant used for atrial fibrillation and venous thromboembolism. While an effective antibody reversal agent is available, its cost precludes routine use and the mainstay of preoperative management is timely dabigatran interruption. Unlike warfarin, there are no universally accepted protocols for interruption of dabigatran in the preoperative period and there is uncertainty around the interpretation of standard coagulation tests in the presence of dabigatran. We performed a prospective, observational pilot study in patients presenting for elective surgery to examine: 1) the preoperative plasma dabigatran concentrations on day of surgery associated with the local dabigatran interruption protocol, 2) the potential utility of dabigatran concentrations on day of surgery, and 3) the utility of standard coagulation tests in determining whether dabigatran concentrations were below a 'safe' threshold for surgery. We recruited patients presenting to pre-admission clinics for elective surgery. Dabigatran concentrations below 30 µg/L were considered adequate for proceeding with surgery. Data were obtained and analysed from 21 patients with a median (range) age of 70 (20-86) years. Median (range) dabigatran concentrations on the day of surgery were 5 (0-59) µg/L. Two patients had day of surgery concentrations exceeding 30 µg/L. Of the standard coagulation tests examined, only the thrombin clotting time (TCT) was abnormal for these two patients. Our interruption protocol was associated with safe dabigatran concentrations in most patients on the day of surgery. A minority of patients had dabigatran concentrations above the safe threshold, which were detectable by abnormal TCT results.


Assuntos
Anticoagulantes , Coagulação Sanguínea , Dabigatrana , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapêutico , Antitrombinas , Dabigatrana/farmacocinética , Dabigatrana/uso terapêutico , Humanos , Projetos Piloto , Estudos Prospectivos , Procedimentos Cirúrgicos Operatórios , Tempo de Trombina
13.
Thromb Haemost ; 119(6): 894-898, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30934105

RESUMO

BACKGROUND: Parturient women are healthy individuals who require special consideration. Parturient women are considered to be in a hyper-coagulable state. For example, the fibrinogen (FIB) levels are often higher than the upper limit of normal reference intervals (RIs) in parturient women than in non-parturient healthy individuals (2-4 g/L). OBJECTIVE: The aim of this study is to establish the RIs of pro-thrombin time (PT), activated partial thromboplastin time (aPTT), FIB levels and thrombin time (TT) for parturient women. MATERIALS AND METHODS: Blood levels of PT, aPTT, FIB and TT were assayed on an ACL TOP 700 automatic coagulation analyser using plasma samples from 10,472 parturient women. Outlier results were excluded by using Tukey's test. The RIs were calculated by the Clinical and Laboratory Standards Institute C28-A3 guideline. RESULTS: The RIs of PT, aPTT, FIB and TT were 8.7 to 12.1 seconds (8.7-12.2 seconds for 16-20 years old, 8.7-12.1 second for 21-25 years old, 8.6-12.0 second for 26-30 years old, 8.7-12.0 second for 31-35 years old, 8.7-12.6 second for 36-40 years old and 8.8-12.2 second for 41 years old), 22.9 to 42.3 seconds, 1.98 to 5.82 g/L and 9.9 to 16.7 seconds, respectively. PT levels were found to be positively associated with aging. CONCLUSION: The above-established age-specific RIs, defined by using a large dataset, may assist clinicians in making accurate medical decisions. This was the first study in which the RIs of PT, aPTT, FIB and TT were established for parturient women in different age groups.


Assuntos
Fatores Etários , Envelhecimento/fisiologia , Fibrinogênio/metabolismo , Tempo de Tromboplastina Parcial/métodos , Tempo de Protrombina/métodos , Tempo de Trombina/métodos , Adolescente , Adulto , Coagulação Sanguínea , Feminino , Humanos , Parto , Gravidez , Valores de Referência , Adulto Jovem
14.
Zhongguo Zhong Yao Za Zhi ; 44(5): 954-961, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989855

RESUMO

To compare the blood-cooling and hemostasis effects of Rehmanniae Radix before and after carbonizing on rats with blood heat and hemorrhage syndrome. The blood heat and hemorrhage syndrome rat model was established. Indexes including rectal temperature,whole blood viscosity,plasma viscosity,thrombin time(TT),activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen content(FIB),red blood cell(RBC),hemoglobin(Hb),hematocrit(HCT),blood platelet count(PLT),mean platelet volume(MPV),serum IL-1,serum IL-6 and lung histopathology were detected to investigate the blood-cooling and hemostasis effects of Rehmanniae Radix and its carbonized products. Compared with the blank control group,the rectal temperature was significantly increased with rise of the high,middle and low whole blood viscosities and plasma viscosity(P<0.05); both the high and low whole blood restore viscosity and the high and low whole blood relative viscosity were increased significantly(P< 0.05); TT,APTT and PT were notably prolonged with the increase in FIB content(P<0.05); RBC,Hb and HCT increased significantly(P< 0.05); concentrations of serum IL-1 and IL-6 were also increased(P< 0.05) in model group. Additionally,obvious hemorrhages in lung and stomach were observed in rats of the model group. Rehmanniae Radix and its carbonized products can significantly reduce rectal temperature,high middle and low whole blood viscosities and plasma viscosity(P<0.05). TT and APTT were shortened,with lower expression of FIB in group of Rehmannia Radix and its carbonized products. Hemorrhages of lung and stomach were improved by Rehmannia Radix and its carbonized products. The results indicated that Rehmannia Radix before and after carbonizing had the hemostasis and blood-cooling effects by promoting coagulation,improving blood rheology and inhibiting expressions of IL-1 and IL-6.


Assuntos
Coagulação Sanguínea , Medicamentos de Ervas Chinesas/farmacologia , Hemorragia/tratamento farmacológico , Hemostasia , Rehmannia/química , Animais , Viscosidade Sanguínea , Temperatura Corporal , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Tempo de Tromboplastina Parcial , Raízes de Plantas , Ratos , Tempo de Trombina
15.
Food Funct ; 10(5): 2552-2559, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-30994118

RESUMO

Casein (CN) has been regarded as an excellent protein source for preparing bioactive peptides. In this study, the casein peptides released in the mouse gastrointestinal tract were evaluated. The 10-week-old mouse was orally administered with 5 mg casein. After 0.5 h, the peptides in the stomach and small intestine of the mouse were extracted and analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). A total of 343 peptides were identified, and 98, 36, 181 and 28 peptides were derived from αs1-, αs2-, ß- and κ-CN respectively. Then, in silico methods were adopted to predict the potential anticoagulant peptide, including PeptideRanker, Innovagen. A novel anticoagulant peptide, AVPYPQR (ß-CN, fragment 177-183), was screened and its anticoagulant activity was verified. In vitro anticoagulant assay showed that the peptide AVPYPQR can observably prolong activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), which indicated that the peptide AVPYPQR exerts its anticoagulant activity in the intrinsic, extrinsic, and common pathways. Meanwhile, the cell viability of this peptide was estimated on the human umbilical vein endothelial cells (HUVECs). The physicochemical characteristics of this peptide have been assayed by PepDraw and ExPASy-ProtParam. The study indicated that casein could be a valuable source for preparing bioactive peptides by gastrointestinal (GI) tract digestion.


Assuntos
Anticoagulantes/química , Caseínas/química , Peptídeos/química , Animais , Anticoagulantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/fisiologia , Coagulação Sanguínea/efeitos dos fármacos , Bovinos , Digestão , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Camundongos , Tempo de Tromboplastina Parcial , Peptídeos/farmacologia , Espectrometria de Massas em Tandem , Tempo de Trombina
16.
APMIS ; 127(7): 515-528, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31009118

RESUMO

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin-antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin-antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D-dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS-SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.


Assuntos
Bacteriemia/complicações , Endocardite Bacteriana/etiologia , Hemostasia/fisiologia , Infecções Estafilocócicas/complicações , Tromboembolia/etiologia , Antitrombina III/metabolismo , Bacteriemia/metabolismo , Plaquetas/metabolismo , Plaquetas/fisiologia , Fator VIII/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Peptídeo Hidrolases/metabolismo , Estudos Prospectivos , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/patogenicidade , Tempo de Trombina/métodos , Tromboembolia/metabolismo
17.
Biomarkers ; 24(4): 389-393, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30907672

RESUMO

Background: There are only limited data in the literature on the thrombotic risk of patients with Clostridium difficile (CD) colitis, although this disease is widespread throughout the world. Objective: The aim of this study was to explore thrombin generation in these patients - the best way to evaluate their coagulation. Methods: A prospective observational study was conducted during 15 months on hospitalized patients with CD colitis. Thrombin generation was performed in platelet-poor plasma using a Ceveron® alpha analyzer and was compared with a group of volunteer control subjects. Results: Thirty-three patients and 51 control subjects were enrolled in the study. Two biomarkers - mean velocity index and peak thrombin - were significantly higher in patient group, compared to the control subjects (p = 0.010, respectively, p = 0.0395). This pattern of thrombin generation suggests that patients with CD colitis without septic shock have a potential thrombotic risk. The mean velocity index significantly correlated with the estimated related risk of death according to the Charlson age-comorbidity index. Conclusions: The higher values of thrombin generation suggest that CD colitis increases the thromboembolic risk. The pattern of thrombin generation could identify patients with particularly higher thromboembolic risk. They are potential candidates for thromboprophylaxis strategies and monitorization.


Assuntos
Clostridium difficile/patogenicidade , Enterocolite Pseudomembranosa/diagnóstico , Trombina/metabolismo , Trombose/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Coagulação Sanguínea , Estudos de Casos e Controles , Clostridium difficile/fisiologia , Enterocolite Pseudomembranosa/sangue , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/microbiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Projetos Piloto , Estudos Prospectivos , Tempo de Protrombina/estatística & dados numéricos , Tempo de Trombina/estatística & dados numéricos , Trombose/sangue , Trombose/complicações , Trombose/microbiologia , Tempo de Coagulação do Sangue Total/estatística & dados numéricos
18.
Food Chem Toxicol ; 125: 614-620, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30738133

RESUMO

The objective of this study is to investigate the biological effects of phenolic compounds extracted from the sea buckthorn berries on oxidative stress and hemostasis. The sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) berries are rich in flavonoids and non-polar compounds. In this study, the activity of the phenolic fraction from the sea buckthorn berries was evaluated in vitro in comparison with three phenolic compounds: isorhamnetin (compound 1) and its two new derivatives: compound 2 (isorhamnetin 3-O-beta-glucoside-7-O-alfa-rhamnoside) and compound 3 (isorhamnetin 3-O-beta-glucoside-7-O-alfa-(3"'-isovaleryl)-rhamnoside). The impact of these phenolic compounds and the phenolic fraction against the effect of the donor of hydroxyl radicals - H2O2/Fe on proteins and lipids in human plasma was measured. Additionally, the aim of the study was to determine the effect of these phenolic compounds and the phenolic fraction on various typical hemostasis parameters. Our results show that the used derivatives of isorhamnetin possess different biological properties (e.g. antioxidant, anti-platelet and anticoagulant). The tested compounds can be seen as new natural beneficial compounds to be used in prevention and treatment of cardiovascular diseases.


Assuntos
Frutas/química , Hemostasia/efeitos dos fármacos , Hippophae/química , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Humanos , Peróxido de Hidrogênio/efeitos adversos , Ferro/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/isolamento & purificação , Inibidores da Agregação de Plaquetas/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Quercetina/isolamento & purificação , Quercetina/farmacologia , Tempo de Trombina
19.
J Int Med Res ; 47(1): 44-58, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30477377

RESUMO

OBJECTIVE: This study was performed to compare the predictive performance of serum procalcitonin (PCT), N-terminal brain natriuretic propeptide (NT-proBNP), interleukin-6 (IL-6), prothrombin time (PT), thrombin time (TT), and Sequential Organ Failure Assessment (SOFA) score in the intensive care unit (ICU). METHODS: This retrospective cohort study enrolled 150 patients with sepsis and septic shock and 30 control patients without sepsis. Each patient was followed until death or 28 days. Correlations between variables were assessed with Spearman's rho test. The Kruskal-Wallis and Mann-Whitney U tests were used for between-group comparisons. RESULTS: Receiver operating characteristic curve analysis of the SOFA score, PCT, NT-proBNP, IL-6, PT, and TT showed an area under the curve of 0.872, 0.732, 0.711, 0.706, 0.806, and 0.691, respectively, for diagnosing sepsis. Binary logistic regression demonstrated that the SOFA score was an independent predictor of 28-day mortality and septic shock. The correlation coefficient (r) between SOFA and PCT, NT-proBNP and SOFA, IL-6 and SOFA, PT and SOFA, and TT and SOFA was 0.79, 0.52, 0.57, 0.56, and 0.58, respectively. CONCLUSION: While the SOFA score is the gold standard, analysis of multiple biomarkers could increase the performance capacity for diagnosis and prognosis in patients with sepsis in the ICU.


Assuntos
Interleucina-6/sangue , Peptídeo Natriurético Encefálico/sangue , Escores de Disfunção Orgânica , Fragmentos de Peptídeos/sangue , Pró-Calcitonina/sangue , Choque Séptico/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Tempo de Protrombina/estatística & dados numéricos , Curva ROC , Estudos Retrospectivos , Choque Séptico/sangue , Choque Séptico/mortalidade , Choque Séptico/patologia , Análise de Sobrevida , Tempo de Trombina/estatística & dados numéricos
20.
Carbohydr Polym ; 205: 89-97, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446153

RESUMO

Heparin, a highly sulfated linear polysaccharide, with anticoagulation function and blood compatibility is widely used as a biomaterials in medical application, but the most importance of heparin is its structure function as the macromolecular space arm. In this study, heparin as a spacer was covalently immobilized on the chloromethylated polystyrene microspheres (Ps) and then connected with l-phenylalanine forming the Ps-Hep-Phe structure, which was developed for endotoxin adsorption in hemoperfusion. The grafting density of heparin reach the maximum when the initial concentration of heparin solution was 5 mg/mL. The adsorbents with the heparin as a spacer showed the prolonged clotting times, low protein adsorption, and reduced the hemolysis rate, indicating that heparin-modified adsorbents have great blood compatibility. The adsorption capacity of Ps-Hep-Phe for endotoxin was 25.15 EU/g in dynamic adsorption, higher than that of Ps. Therefore, this study imply that heparin would be promising for modification of adsorbents in hemoperfusion.


Assuntos
Materiais Biocompatíveis/química , Heparina/química , Microesferas , Adsorção , Adulto , Materiais Biocompatíveis/síntese química , Coagulação Sanguínea/efeitos dos fármacos , Proteínas Sanguíneas/química , Endotoxinas/química , Hemólise/efeitos dos fármacos , Hemoperfusão , Heparina/síntese química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Tempo de Tromboplastina Parcial , Fenilalanina/análogos & derivados , Fenilalanina/síntese química , Ativação Plaquetária/efeitos dos fármacos , Poliestirenos/síntese química , Poliestirenos/química , Tempo de Trombina
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