Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.152
Filtrar
1.
Rev Med Suisse ; 15(668): 1934-1939, 2019 Oct 23.
Artigo em Francês | MEDLINE | ID: mdl-31643154

RESUMO

Venous thromboembolic events (VTE), defined by deep vein thrombosis or pulmonary embolism, are potentially serious complications after gynecologic surgery. Without thromboprophylaxis, they are common and can lead to significant morbidity and mortality. Conversely, poorly adapted prophylaxis can be hazardous. Risk factors related to the patients and to the types of surgery have been identified and can be used to adapt the prophylaxis. Several recommendations have been proposed; however, no clear consensus exists. This article reviews the pathophysiology and specific risk factors of post-gynecologic surgical VTE and provides comprehensive and practical recommendations for perioperative thromboprophylaxis in gynecology, based on various international recommendations.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Assistência Perioperatória/métodos , Embolia Pulmonar/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Feminino , Humanos , Fatores de Risco
2.
Biochem Med (Zagreb) ; 29(3): 030706, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31624459

RESUMO

Introduction: Failure to obtain complete blood clotting in serum is a common laboratory problem. Our aim was to determine whether snake proth-rombin activators are effective in clotting blood and producing quality serum for analyte measurement in anticoagulated patients. Materials and methods: Whole blood clotting was studied in a total of 64 blood samples (41 controls, 20 Warfarin patients, 3 anticoagulated patients using snake venom prothrombin activator (OsPA)) with plain tubes. Coagulation was analysed using a visual assay, Hyland-Clotek and thromboelastography. Healthy control blood was spiked with a range of anticoagulants to determine the effectiveness of OsPa-induced clotting. A paired analysis of a Dabigatran patient and a control investigated the effectiveness of the OsPA clotting tubes. Biochemical analytes (N = 31) were determined for 7 samples on chemistry and immunoassay analysers and compared with commercial tubes. Results: Snake venom prothrombin activators efficiently coagulated blood and plasma spiked with heparin and commonly used anticoagulants. Clotting was observed in the presence of anticoagulants whereas no clotting was observed in BDRST tubes containing 3 U/mL of heparin. Snake venom prothrombin activator enhanced heparinised blood clotting by shortening substantially the clotting time and improving significantly the strength of the clot. Comparison of 31 analytes from the blood of five healthy and two anticoagulated participants gave very good agreement between the analyte concentrations determined. Conclusions: Our results showed that the snake venom prothrombin activators OsPA and PtPA efficiently coagulated recalcified and fresh bloods with or without added anticoagulants. These procoagulants produced high quality serum for accurate analyte measurement.


Assuntos
Anticoagulantes/farmacologia , Protrombina/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Heparina/farmacologia , Humanos
3.
Fitoterapia ; 137: 104282, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381956

RESUMO

Four new polyketides, alternatains A-D (1-4), along with 17 known compounds (5-21) were obtained from the solid substrate fermentation cultures of Alternaria alternata MT-47, an endophytic fungus isolated from the medicinal plant of Huperzia serrata. Their structures were elucidated by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) method. Compounds 4, 6, 15, and 21 exhibited inhibitory activities on ATP release of thrombin-activated platelets with IC50 values in the range of 18.2-68.8 µM.


Assuntos
Alternaria/química , Anticoagulantes/farmacologia , Plaquetas/efeitos dos fármacos , Huperzia/microbiologia , Policetídeos/farmacologia , Acetilcolinesterase , Trifosfato de Adenosina , Anticoagulantes/isolamento & purificação , Butirilcolinesterase , China , Inibidores da Colinesterase , Endófitos/química , Humanos , Estrutura Molecular , Plantas Medicinais/microbiologia , Policetídeos/isolamento & purificação
4.
Pharm Res ; 36(10): 146, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396727

RESUMO

PURPOSE: CTB-001, a recently developed generic version of bivalirudin, an FDA-approved anticoagulant used for prophylaxis and treatment of cardiovascular diseases, has shown good efficacy and safety in clinical trials. We characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of CTB-001 by modeling and simulation analysis. METHODS: PK/PD data were collected from a randomized, double-blind, placebo-controlled, single-dose, dose-escalation phase 1 study conducted in 24 healthy Korean male subjects. PK/PD analysis was conducted sequentially by nonlinear mixed-effects modeling implemented in NONMEM®. Monte-Carlo simulations were conducted for PK, activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). RESULTS: The CTB-101 PK was best described by a three-compartment linear model with a saturable binding peripheral compartment. All PD endpoints showed dose-response relationship, and their changes over time paralleled those of CTB-101 concentrations. A simple maximum effect model best described the aPTT, PT in INR, PT in seconds, and TT, whereas an inhibitory simple maximum effect model best described PT in percentages. The maximum duration of effect of CTB-001 on aPTT prolongation was 52.1 s. CONCLUSIONS: The modeling and simulation analysis well-characterized the PK and PD of CTB-001 in healthy Koreans, which will be valuable for identifying optimal dosing regimens of CBT-001.


Assuntos
Anticoagulantes/farmacologia , Hirudinas/farmacologia , Modelos Biológicos , Fragmentos de Peptídeos/farmacologia , Adulto , Anticoagulantes/farmacocinética , Simulação por Computador , Relação Dose-Resposta a Droga , Método Duplo-Cego , Medicamentos Genéricos , Hirudinas/farmacocinética , Humanos , Masculino , Método de Monte Carlo , Fragmentos de Peptídeos/farmacocinética , Tempo de Protrombina , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia , Resultado do Tratamento , Adulto Jovem
5.
Medicine (Baltimore) ; 98(26): e16194, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261559

RESUMO

BACKGROUND: Atrial fibrillation (AF) is increasingly prevalent in chronic kidney disease (CKD) patients. The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in AF and CKD patients remains unknown. This systematic review and meta-analysis will mainly assess net clinical benefit (NCB) property of NOACs versus warfarin in patients with AF and CKD by a pooled-analysis. METHODS: We will search Medline, Embase, Cochrane Library, and Clinical Trials.gov Website comprehensively for eligible randomized controlled trials that report the efficacy and safety outcomes according to renal function of NOACs. Relative risks and their 95% confidence intervals will be calculated using fixed- and random-effects models. Subgroup, sensitivity, and regression analyses will be performed to evaluate intertrial heterogeneity and bias of the results. NCB that balance stroke/systemic embolism (SSE) and major bleeding will be calculated using Singer's method. RESULTS: This systemic review and meta-analysis will evaluate the NCB of NOACs versus warfarin via SSE, major bleeding and all-cause death in patients with CKD. CONCLUSIONS: This study will provide new evidence for clinical profile of NOACs on SSE, major bleeding, all-cause death, and NCB in CKD patients. PROSPERO REGISTRATION NUMBER: CRD42019116940.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Metanálise como Assunto , Insuficiência Renal Crônica/tratamento farmacológico , Revisão Sistemática como Assunto , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Fibrilação Atrial/complicações , Humanos , Insuficiência Renal Crônica/complicações , Projetos de Pesquisa , Varfarina/efeitos adversos , Varfarina/uso terapêutico
6.
Life Sci ; 231: 116522, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31158377

RESUMO

AIM: Liver fibrosis is a serious health problem which is a critical cause of morbidity and mortality worldwide. It is the main complication of untreated chronic inflammatory liver diseases which can progress to liver cirrhosis, hepatocellular carcinoma, and finally death. Coagulation cascade plays a mechanistic role in the pathogenesis of different chronic inflammatory disease including atherosclerosis, stroke, and tissue fibrosis. The current study was designed to investigate the effect of inhibition of coagulation cascade on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. MATERIAL AND METHODS: The study was conducted in rats. Rats were treated with CCl4 subcutaneously for 6 consecutive weeks to determine the onset of coagulation system activation in relation to development of fibrosis. To investigate the effects of coagulation system inhibition in CCl4-induced liver fibrosis, the anticoagulants drugs dabigatran and clopidogrel were administrated orally concurrently with CCl4 treatment. KEY FINDINGS: The results of our study revealed that during the first week, there were significant elevations of fibrin, tissue factor expressions, and prothrombin time (PT) coupled with neutropenia without significant changes in liver fibrosis markers such as TGF-ß, α-SMA and collagen deposition. Starting from the second week, tissue injury markers including the oxidative, inflammatory and fibrosis markers as well as histopathological changes became evident progressively. Intriguingly, dabigatran and clopidogrel significantly normalized the biochemical and pathological changes. SIGNIFICANCE: In conclusion, activation of coagulation cascade is a triggering stimulus in the initiation of CCl4-induced liver fibrosis and the anticoagulant drugs may exert promising anti-fibrotic effect.


Assuntos
Clopidogrel/farmacologia , Dabigatrana/farmacologia , Cirrose Hepática/tratamento farmacológico , Animais , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Biomarcadores/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Tetracloreto de Carbono/farmacologia , Clopidogrel/metabolismo , Dabigatrana/metabolismo , Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Trombina/efeitos dos fármacos , Trombina/metabolismo
7.
Yonsei Med J ; 60(7): 626-632, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31250576

RESUMO

PURPOSE: To compare the effect of apixaban and low molecular weight heparin (LMWH) in the prevention and treatment of deep venous thrombosis (DVT) after total knee arthroplasty in older adult patients. MATERIALS AND METHODS: A total of 220 patients (average age of 67.8±6.4 years) undergoing total knee arthroplasty were randomly selected as research subjects and were divided into apixaban and LMWH groups (110 in each group). RESULTS: The incidence of DVT was lower in the apixaban group than in the LMWH group (5.5% vs. 20.0%, p=0.001). Activated partial thromboplastin times (35.2±3.6 sec vs. 33.7±2.2 sec, p=0.010; 37.8±4.6 sec vs. 34.1±3.2 sec, p<0.001; 39.6±5.1 sec vs. 35.7±3.0 sec, p=0.032) and prothrombin times (14.0±1.0 sec vs. 12.8±0.9 sec, p<0.001; 14.5±1.2 sec vs. 13.0±1.1 sec, p<0.001; 15.3±1.4 sec vs. 13.2±1.3 sec, p=0.009) in the apixaban group at 1 week after surgery, 3 weeks after surgery, and the end of treatment were higher than those in the LMWH group. Platelet and fibrinogen levels in the apixaban group were lower than those of the LMWH group. Also, capillary plasma viscosity and erythrocyte aggregation in the apixaban group at 1 week after surgery, 3 weeks after surgery, and the end of treatment were lower than those in the LMWH group. CONCLUSION: Apixaban, which elicits fewer adverse reactions and is safer than LMWH, exhibited better effects in the prevention and treatment of DVT after total knee arthroplasty in older adults.


Assuntos
Anticoagulantes/farmacologia , Artroplastia do Joelho/efeitos adversos , Heparina de Baixo Peso Molecular/farmacologia , Pirazóis/farmacologia , Piridonas/farmacologia , Trombose Venosa/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Fatores de Tempo , Trombose Venosa/etiologia
8.
BMC Complement Altern Med ; 19(1): 148, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238930

RESUMO

BACKGROUND: Sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson, SBT) is a valuable plant because of its medical and therapeutic potential. Different bioactive compounds in SBT berries are of special interest to various researchers. However, not only sea buckthorn berries, but also leaves of this plant (both fresh and dried) contain a lot of nutrients and bioactive compounds, including phenolic compounds. The present study was carried out in order to investigate antioxidant and anticoagulant properties of sea buckthorn twig and leaf extracts (0.5-50 µg/mL) by using various in vitro models. Moreover, the aim of present experiments was to compare the biological activity of SBT leaf extract and SBT twig extract with selected berry extracts (a rich source of phenolic compounds): SBT berry extract (flavonoids being the dominant components), a commercial extract from the berries of Aronia melanocarpa (Aronox®), and a grape seed extract. METHODS: We determined the effect of plant extracts on the oxidative stress using selected markers of this process, i.e. the level of carbonyl groups in proteins. Additionally, we analysed the potential mechanism of modulation of hemostatic properties of human plasma (using selected coagulation times). RESULTS: SBT twig and leaf extracts were observed to exhibit an antioxidant activity against two strong biological oxidants: hydrogen peroxide (H2O2) and H2O2/Fe (the donor of hydroxyl radicals), which induced human plasma lipid peroxidation and protein carbonylation. Both extracts also showed anticoagulant properties. CONCLUSIONS: Our present results have demonstrated that extracts from different parts of SBT, especially berries and twigs, in comparison to well-known berries (aronia and grape), may also be viewed as a good source of active substances - antioxidants for pharmacological or cosmetic applications. Moreover, it is very important from an economic point of view to know that there is a possibility of obtaining phenolic compounds not only from the berries or leaves, but also from twigs, which constitute a production waste.


Assuntos
Elaeagnaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Caules de Planta/química , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Frutas/química , Humanos , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Photinia/química , Extratos Vegetais/isolamento & purificação , Tempo de Protrombina
9.
Biochem Med (Zagreb) ; 29(2): 021002, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31223268

RESUMO

Introduction: Blood coagulation tests (BCT) are very important for clinicians to diagnose bleeding or thrombotic disorders and to monitor anticoagulant therapy. Case description: On a Saturday morning, a laboratory technician noted an abrupt rise in the number of coagulation error messages on our ALC TOP analysers. Visual inspection revealed the presence of partially and/or fully clotted citrate tubes and prompted the clinical biologist to further investigate a potential preanalytical cause. Considered causes: Partially or fully clotted blood in citrate tubes can have multiple causes including improper mixing of the tube, under- or overfilling or combining blood samples from different tubes into one citrate tube. What happened: The affected citrate tubes originated mostly from the same clinical departments. Moreover, all the affected tubes shared the same lot number (1 of 7 in use at the time). Visual inspection of 7 unopened boxes of 100 citrate tubes of this lot number revealed one box with nine completely empty and two partially filled tubes and one box with two partially filled tubes. No under-filled tubes were found in the other 5 boxes. Discussion: The blood to additive ratio is crucial for BCT. A sudden rise in clot errors should trigger a thorough investigation to identify the cause. Main lesson: Laboratories should regularly monitor and evaluate the percentage of clotted samples as a quality indicator at scheduled time points. A problem with the volume of additive in citrate tubes should be considered as a possible cause.


Assuntos
Automação , Testes de Coagulação Sanguínea , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Coleta de Amostras Sanguíneas , Humanos
10.
Br J Anaesth ; 123(2): 186-195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202564

RESUMO

BACKGROUND: Andexanet alfa (andexanet) reverses the anticoagulant effects of factor Xa inhibitors, but it has not been assessed in clinical studies for apixaban reversal in trauma. This study evaluated andexanet for reversing apixaban anticoagulation in a porcine polytrauma model. METHODS: Oral apixaban (20 mg q.d., n=21) or placebo (n=7; sham group) was administered to male pigs for 4 days before blunt liver injury and bi-lateral femur fracture. After trauma, animals were randomised 1:1:1 to a single andexanet bolus (1000 mg), a bolus (1000 mg) plus infusion (1200 mg over 2 h), or vehicle (control). Haemodynamic and coagulation variables were monitored for 5 h or until death. The primary endpoint was blood loss. RESULTS: Mean blood loss in sham animals was 472 (standard deviation, 58) ml 12 min after injury and 658 (98) ml at 300 min, with 100% survival. Anticoagulation with apixaban significantly increased blood loss 12 min after injury [888 (133) ml, P<0.01]. Controls exhibited total blood loss of 3403 (766) ml, with 100% mortality. Andexanet bolus or bolus plus infusion significantly reduced blood loss to 1264 (205) and 1202 (95) ml, respectively), and increased survival to 100%. Haemodynamic parameters and markers of shock recovered to pre-trauma levels in andexanet-treated animals. CONCLUSION: Andexanet effectively reversed apixaban anticoagulation and reduced blood loss induced by severe trauma. Andexanet bolus alone had a similar impact on survival and blood loss as bolus plus infusion. Therefore, a 2 h andexanet infusion after the bolus may not be necessary to restore normal haemostatic mechanisms.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/farmacologia , Fator Xa/farmacologia , Traumatismo Múltiplo , Pirazóis/farmacologia , Piridonas/farmacologia , Proteínas Recombinantes/farmacologia , Animais , Anticoagulantes/farmacologia , Modelos Animais de Doenças , Masculino , Suínos
11.
Mar Drugs ; 17(6)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167439

RESUMO

Five new anthraquinone derivatives, auxarthrols D-H (1-5), along with two known analogues (6-7), were obtained from the culture of the marine-derived fungus Sporendonema casei. Their structures, including absolute configurations, were established on the basis of NMR, HRESIMS, and circular dichroism (CD) spectroscopic techniques. Among them, compound 4 represents the second isolated anthraquinone derivative with a chlorine atom, which, with compound 6, are the first reported anthraquinone derivatives with anticoagulant activity. Compounds 1 and 3 showed cytotoxic activities with IC50 values from 4.5 µM to 22.9 µM, while compounds 1, 3-4, and 6-7 showed promising antibacterial activities with MIC values from 12.5 µM to 200 µM. In addition, compound 7 was discovered to display potential antitubercular activity for the first time.


Assuntos
Antraquinonas/química , Antraquinonas/farmacologia , Ascomicetos/química , Antraquinonas/isolamento & purificação , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anticoagulantes/química , Anticoagulantes/farmacologia , Organismos Aquáticos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana
12.
Biochemistry (Mosc) ; 84(2): 119-136, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31216971

RESUMO

The review discusses main approaches to searching for new low-molecular-weight inhibitors of coagulation factors IIa, Xa, IXa, and XIa and the results of such studies conducted from 2015 to 2018. For each of these factors, several inhibitors with IC50 < 10 nM have been found, some of which are now tested in clinical trials. However, none of the identified inhibitors meets the requirements for an "ideal" anticoagulant, so further studies are required.


Assuntos
Anticoagulantes/farmacologia , Fatores de Coagulação Sanguínea/antagonistas & inibidores , Projeto Auxiliado por Computador , Anticoagulantes/química , Fatores de Coagulação Sanguínea/metabolismo , Humanos , Peso Molecular
13.
Res Vet Sci ; 124: 399-405, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31078787

RESUMO

Sodium dehydroacetate (Na-DHA), an antibiotic agent that combats growth of bacteria, fungi, and yeast, is used as a preservative in animal feed, food, and cosmetics. We previously reported that Na-DHA induces coagulation anomalies in Wistar rats, but the anticoagulant mechanism of Na-DHA remains to be established. Here we report that Na-DHA prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) in male and female Wistar rats. In addition, Na-DHA decreased vitamin K (VK) levels and increased the levels of protein induced by vitamin K absence/antagonist-II (PIVKA-II) in rat serum. Moreover, we found that treatment with VK not only reversed Na-DHA-decreased serum VK and -increased PIVKA-II levels, but also attenuated Na-DHA-prolonged PT and APTT, suggesting that Na-DHA-decreased serum VK level contributes to the anticoagulation due to Na-DHA. Further we found that Na-DHA inhibited vitamin K epoxide reductase complex subunit 1 (VKORC1), a key enzyme in VK recycling, in the liver tissue of Wistar rats, as evidenced by reduced mRNA and protein levels of VKORC1 following Na-DHA treatment. Taken together, our data indicate that Na-DHA inhibits liver VKORC1, resulting in a decrease of serum VK levels, leading to abnormal coagulation in rats.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fígado/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Pironas/farmacologia , Vitamina K/administração & dosagem , Animais , Feminino , Fígado/enzimologia , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Ratos Wistar , Vitamina K Epóxido Redutases
14.
Mar Drugs ; 17(5)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091758

RESUMO

(1) Background: Brown and red algal sulfated polysaccharides have been widely described as anticoagulant agents. However, data on green algae, especially on the Ulva genus, are limited. This study aimed at isolating ulvan from the green macroalga Ulva rigida using an acid- and solvent-free procedure, and investigating the effect of sulfate content on the anticoagulant activity of this polysaccharide. (2) Methods: The obtained ulvan fraction was chemically sulfated, leading to a doubling of the polysaccharide sulfate content in a second ulvan fraction. The potential anticoagulant activity of both ulvan fractions was then assessed using different assays, targeting the intrinsic and/or common (activated partial thromboplastin time), extrinsic (prothrombin time), and common (thrombin time) pathways, and the specific antithrombin-dependent pathway (anti-Xa and anti-IIa), of the coagulation cascade. Furthermore, their anticoagulant properties were compared to those of commercial anticoagulants: heparin and Lovenox®. (3) Results: The anticoagulant activity of the chemically-sulfated ulvan fraction was stronger than that of Lovenox® against both the intrinsic and extrinsic coagulation pathways. (4) Conclusion: The chemically-sulfated ulvan fraction could be a very interesting alternative to heparins, with different targets and a high anticoagulant activity.


Assuntos
Anticoagulantes/farmacologia , Fibroblastos/efeitos dos fármacos , Ulva/química , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Testes de Coagulação Sanguínea , Enoxaparina/farmacologia , Heparina/farmacologia , Humanos , Plasma/efeitos dos fármacos
15.
Mar Drugs ; 17(5)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100859

RESUMO

Therapeutic options for Alzheimer's disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer's disease-relevant ß-secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer's disease is largely precluded by its potent anticoagulant activity. Furthermore, ongoing concerns regarding the use of mammalian-sourced heparins, primarily due to prion diseases and religious beliefs hinder the deployment of alternative heparin-based therapeutics. A marine-derived, heparan sulphate-containing glycosaminoglycan extract, isolated from the crab Portunus pelagicus, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC50 = 1.85 µg mL-1 (R2 = 0.94) and 2.43 µg mL-1 (R2 = 0.93), respectively), while possessing highly attenuated anticoagulant activities. The results from several structural techniques suggest that the interactions between BACE1 and the extract from P. pelagicus are complex and distinct from those of heparin.


Assuntos
Doença de Alzheimer/enzimologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Braquiúros/química , Ativação Enzimática/efeitos dos fármacos , Glicosaminoglicanos/farmacologia , Animais , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Glicosaminoglicanos/química , Glicosaminoglicanos/isolamento & purificação
16.
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
17.
Med Sci Monit ; 25: 2649-2657, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971681

RESUMO

BACKGROUND Oral anticoagulants (OACs) such as warfarin and non-VKA oral anticoagulants (NOACs) have been recommended for patients with atrial fibrillation (AF) who are at risk for stroke. Whether NOACs have a higher persistence than warfarin is still unclear. This is especially true in China. MATERIAL AND METHODS Data from a large hospital-based cohort in China (China-AF Registry) from 2011 to 2017 were used for this study. Non-valvular AF patients with newly initiated OACs were included. A time-to-event approach was used to analyze patient persistence. The survival distributions of persistence were compared using the log-rank test. A multivariable Cox regression model was used to explore predictors of warfarin and NOACs non-persistence. RESULTS Patients with newly initiated warfarin (n=4845) or NOACs (n=854) were included in this study. Persistence rates at 1, 2, and 3 years were 93.2%, 89.4%, and 87.2% in the warfarin group and 88.8%, 84.3%, and 81.3% in the NOAC group respectively. Non-persistence was significantly higher with NOACs than with warfarin. On multivariate analysis, age <75 years old, outpatient clinic visits, asymptomatic AF, paroxysmal AF, duration of AF <3 years, history of peptic ulcer, and no previous TIA, stroke or thromboembolism were strong predictors of warfarin non-persistence, while in the NOACs group, age <75 years old, outpatient clinic visits, lower education status and no history of congestive heart failure were predictors. CONCLUSIONS Treatment persistence of NOACs was lower than that of warfarin among Chinese patients with AF. Patients with characteristics of non-persistence predictors need special attention to maintain their therapy.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Adesão à Medicação , Sistema de Registros , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Idoso , Anticoagulantes/farmacologia , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Varfarina/farmacologia
18.
Mar Drugs ; 17(4)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027312

RESUMO

Sulfated polysaccharides from marine algae have high potential as promising candidates for marine drug development. In this study, a homogeneous sulfated polysaccharide from the marine green alga Monostroma nitidum, designated MS-1, was isolated using water extraction and anion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that MS-1 mainly consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ residues, with additional branches consisting of 4-linked ß-d-xylose, 4-/6-linked d-glucose, terminal ß-d-glucuronic acid, and 3-/2-linked α-l-rhamnose. Sulfate ester groups substituted mainly at C-2/C-4 of →3)-α-l-Rhap-(1→ and C-4 of →2)-α-l-Rhap-(1→ residues, slightly at C-2 of terminal ß-d-glucuronic residues. MS-1 exhibited strong anticoagulant activity in vitro and in vivo as evaluated by the activated partial thromboplastin time and thrombin time assays, and significantly decreased platelet aggregation. The anticoagulant activity mechanism of MS-1 was mainly attributed to strong potentiation thrombin by heparin cofactor-II, and it also hastened thrombin and coagulation factor Xa inhibitions by potentiating antithrombin-III. MS-1 possessed markedly thrombolytic activity evaluated by plasminogen activator inhibitior-1, fibrin degradation products, and D-dimer levels using rats plasma, and recanalization rate by FeCl3-induced carotid artery thrombosis in mice. MS-1 exhibited strong antithrombotic activity in vitro and in vivo evaluated by the wet weighs and lengths of thrombus, and thrombus occlusion time by electrically-induced carotid artery thrombosis in rats. These results suggested that MS-1 could be a promising marine drug for prevention and therapy of thromboembolic disease.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Clorófitas/química , Fibrinolíticos/farmacologia , Polissacarídeos/farmacologia , Sulfatos/farmacologia , Animais , Trombose das Artérias Carótidas/sangue , Trombose das Artérias Carótidas/induzido quimicamente , Humanos , Masculino , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Sulfatos/química , Sulfatos/isolamento & purificação
19.
Mar Drugs ; 17(4)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934713

RESUMO

Apostichopus japonicus is one of the most economically important species in sea cucumber aquaculture in China. Fucosylated glycosaminoglycan from A. japonicus (AjFG) has shown multiple pharmacological activities. However, results from studies on the structure of AjFG are still controversial. In this study, the deaminative depolymerization method that is glycosidic bond-selective was used to prepare the depolymerized products from AjFG (dAjFG), and then a series of purified oligosaccharide fragments such as tri-, hexa-, nona-, and dodecasaccharides were obtained from dAjFG by gel permeation chromatography. The 1D/2D NMR and ESI-MS spectrometry analyses showed that these oligosaccharides had the structural formula of l-FucS-α1,3-d-GlcA-ß1,3-{d-GalNAc4S6S-ß1,4-[l-FucS-α1,3-]d-GlcA-ß1,3-}n-d-anTal-diol4S6S (n = 0, 1, 2, 3; FucS represents Fuc2S4S, Fuc3S4S, or Fuc4S). Thus, the unambiguous structure of native AjFG can be rationally deduced: it had the backbone of {-4-d-GlcA-ß1,3-d-GalNAc4S6S-ß1-}n, which is similar to chondroitin sulfate E, and each d-GlcA residue in the backbone was branched with a l-FucS monosaccharide at O-3. Bioactivity assays confirmed that dAjFG and nonasaccharides and dodecasaccharides from AjFG had potent anticoagulant activity by intrinsic FXase inhibition while avoiding side effects such as FXII activation and platelet aggregation.


Assuntos
Anticoagulantes/farmacologia , Glicosaminoglicanos/química , Glicosaminoglicanos/farmacologia , Oligossacarídeos/farmacologia , Stichopus/química , Animais , Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Sequência de Carboidratos , Fator XII/metabolismo , Humanos , Estrutura Molecular , Oligossacarídeos/química , Tempo de Tromboplastina Parcial , Agregação Plaquetária/efeitos dos fármacos , Relação Estrutura-Atividade
20.
Mar Drugs ; 17(4)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934819

RESUMO

Sulfated polysaccharides from sea cucumbers possess distinct chemical structure and various biological activities. Herein, three types of polysaccharides were isolated and purified from Pattalus mollis, and their structures and bioactivities were analyzed. The fucosylated glycosaminoglycan (PmFG) had a CS-like backbone composed of the repeating units of {-4-d-GlcA-ß-1,3-d-GalNAc4S6S-ß-1-}, and branches of a sulfated α-l-Fuc (including Fuc2S4S, Fuc3S4S and Fuc4S with a molar ratio of 2:2.5:1) linked to O-3 of each d-GlcA. The fucan sulfate (PmFS) had a backbone consisting of a repetitively linked unit {-4-l-Fuc2S-α-1-}, and interestingly, every trisaccharide unit in its backbone was branched with a sulfated α-l-Fuc (Fuc4S or Fuc3S with a molar ratio of 4:1). Apart from the sulfated polysaccharides, two neutral glycans (PmNG-1 & -2) differing in molecular weight were also obtained and their structures were similar to animal glycogen. Anticoagulant assays indicated that PmFG and PmFS possessed strong APTT prolonging and intrinsic factor Xase inhibition activities, and the sulfated α-l-Fuc branches might contribute to the anticoagulant and anti-FXase activities of both PmFG and PmFS.


Assuntos
Anticoagulantes/química , Anticoagulantes/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Pepinos-do-Mar/química , Animais , Anticoagulantes/isolamento & purificação , Coagulação Sanguínea/efeitos dos fármacos , Sequência de Carboidratos , Química Física , Cromatografia Líquida de Alta Pressão , Cisteína Endopeptidases , Humanos , Estrutura Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Ressonância Magnética Nuclear Biomolecular , Polissacarídeos/isolamento & purificação , Relação Estrutura-Atividade , Sulfatos/química , Sulfatos/isolamento & purificação , Sulfatos/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA