RESUMEN
BACKGROUND: (p-BthTX-I)2 K, a dimeric analog peptide derived from the C-terminal region of phospholipase A2-like bothropstoxin-I (p-BthTX-I), is resistant to plasma proteolysis and inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains with weak cytotoxic effects. Complications of SARS-CoV-2 infection include vascular problems and increased risk of thrombosis; therefore, studies to identify new drugs for treating SARS-CoV-2 infections that also inhibit thrombosis and minimize the risk of bleeding are required. OBJECTIVES: To determine whether (p-BthTX-I)2 K affects the hemostatic system. METHODS: Platelet aggregation was induced by collagen, arachidonic acid, and adenosine diphosphate (ADP) in the Chronolog Lumi-aggregometer. The coagulation activity was evaluated by determining activated partial thromboplastin clotting time (aPTT) and prothrombin time (PT) with (p-BthTX-I)2 K (5.0-434.5 µg) or 0.9% NaCl. Arterial thrombosis was induced with a 540 nm laser and 3.5-20 mg kg- 1 Rose Bengal in the carotid artery of male C57BL/6J mice using (p-BthTX-I)2 K. Bleeding time was determined in mouse tails immersed in saline at 37 °C after (p-BthTX-I)2 K (4.0 mg/kg and 8.0 mg/kg) or saline administration. RESULTS: (p-BthTX-I)2 K prolonged the aPTT and PT by blocking kallikrein and FXa-like activities. Moreover, (p-BthTX-I)2 K inhibited ADP-, collagen-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner. Further, low concentrations of (p-BthTX-I)2 K extended the time to artery occlusion by the formed thrombus. However, (p-BthTX-I)2 K did not prolong the bleeding time in the mouse model of arterial thrombosis. CONCLUSION: These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)2 K possibly by kallikrein inhibition, suggesting its strong biotechnological potential.
RESUMEN
The anti-inflammatory effects of the plant protease inhibitor BbCI (Bauhinia bauhinioides cruzipain inhibitor), which blocks elastase, cathepsin G, and L, and proteinase 3 has been demonstrated. Here, we investigated the recombinant rBbCI-His(6) (containing a histidine tail) in an experimental venous thrombosis model of vena cava (VC) ligature in rats, comparing to heparin. We evaluate the effects of the inhibitors (native or recombinant) or heparin on the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in human and rat plasmas. The rats undergoing treatment received a saline solution or increasing concentrations of rBbCI-His(6), heparin, or a mixture of both. After 4 h of ligature VC, thrombus, if present was removed and weighed. aPTT, PT, and cytokines were measured in blood collected by cardiac puncture. aPTT, PT, and bleeding time (BT) were also measured at the time of VC (vena cava) ligature. rBbCI-His(6) (0.45 or 1.40 mg/kg) does not alter aPTT, PT or BT. No differences in coagulation parameters were detected in rBbCI-His(6) treated rats at the time of VC ligature or when the thrombus was removed. There was a significant decrease in the weight of thrombus in the animals of the groups treated with the rBbCI-His(6) (1.40 mg/kg), with the rBbCI-His(6) mixture (1.40 mg/kg) + heparin (50 IU/kg) and heparin (100 IU/kg) in relation to control group (saline). The growth-related oncogene/keratinocyte chemoattractant (GRO/KC) serum levels in rats treated with rBbCI-His(6) (1.40 mg/kg) or heparin (200 IU/kg) were reduced. In the experimental model used, rBbCI-His(6) alone had an antithrombotic effect, not altering blood clotting or bleeding time.
Asunto(s)
Bauhinia/enzimología , Proteínas de Plantas/farmacología , Inhibidores de Serina Proteinasa/farmacología , Trombosis , Animales , Bauhinia/genética , Coagulación Sanguínea/efectos de los fármacos , Humanos , Masculino , Elastasa Pancreática/antagonistas & inhibidores , Elastasa Pancreática/sangre , Tiempo de Tromboplastina Parcial , Proteínas de Plantas/química , Proteínas de Plantas/genética , Ratas , Ratas Wistar , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/genética , Trombosis/sangre , Trombosis/tratamiento farmacológicoRESUMEN
Passion fruit (Passiflora edulis Sims f. flavicarpa) is popularly known for its sedative and calming properties and is consumed as a fresh fruit or as a juice. The clinical observation of blood incoagulability associated with excessive consumption of passion fruit juice, in a patient treated with warfarin, prompted the current study to investigate in vitro the presence of blood clotting inhibitors in Passiflora edulis Sims f. flavicarpa extract. After purification process, two compounds of distinct molecular weight and inhibitory action were better characterized. One is a trypsin inhibitor similar to inhibitors from Bowman-Birk family, named PeTI-I12, and other is a compound active in coagulation that prolongs aPTT and PT, but does not change TT. The aim of this study is to provide evidence that passion fruit extract's components play a role on hemostasis and therefore may be relevant in the handling of patients treated with anticoagulants or suffering hemorrhagic diseases.
Asunto(s)
Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Passiflora/química , Péptido Hidrolasas/metabolismo , Extractos Vegetales/farmacología , Inhibidores de Proteasas/farmacología , Secuencia de Aminoácidos , Anticoagulantes/química , Estabilidad de Enzimas , Frutas/química , Datos de Secuencia Molecular , Extractos Vegetales/química , Inhibidores de Proteasas/química , Tiempo de Protrombina , Inhibidor de la Tripsina de Soja de Bowman-Birk/química , Inhibidor de la Tripsina de Soja de Bowman-Birk/farmacología , Inhibidores de Tripsina/química , Inhibidores de Tripsina/farmacologíaRESUMEN
BACKGROUND: Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. AIM OF THE STUDY: To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease. METHODS: Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K(1)), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data. RESULTS: Mean age was 59 +/- 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3. CONCLUSIONS: Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease.
Asunto(s)
Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Dieta , Tiempo de Protrombina , Warfarina/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/sangre , Coagulación Sanguínea/fisiología , Análisis Factorial , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Triglicéridos/sangre , Enfermedades Vasculares/sangre , Enfermedades Vasculares/tratamiento farmacológico , Vitamina K 1/administración & dosificación , Vitamina K 1/sangreRESUMEN
This study investigates the role of cervical sympathectomy in the prevention of acute vasospasm induced by meningeal haemorrhage in rabbits. Sixteen adult English Norfolk rabbits were divided into 2 experimental groups: bilateral cervical sympathectomy of the superior sympathetic ganglion (SSSG, n=8), and bilateral SSSG and sympathectomy of the inferior sympathetic ganglion (SISG, n=8). Other 24 animals were used as controls. Basilar artery diameter was evaluated by angiography. SSSG protected the animals against developing cerebral vasospasm; SSSG associated with SISG did not increase this effect.