398 resultados para Anticoagulant activitity


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Seaweeds are a major source of biologically active compounds . In the extracellular matrix of these organisms are sulfated polysaccharides that functions as structural components preventing it against dehydration. The fraction 0.9 (FucB) rich in sulfated fucans obtained from brown seaweed Dictyota menstrualis was chemical characterized and evaluated for pharmacological activity by testing anticoagulant activity, stimulatory action on the synthesis of an antithrombotic heparan sulfate, antioxidant activity and its effects in cell proliferation. The main components were FucB carbohydrates (49.80 ± 0.10 %) and sulfate (42.30 ± 0.015 %), with phenolic compounds ( 3.86 ± 0.016 %) and low protein contamination ( 0.58 ± 0.001 % ) . FucB showed polydisperse profile and analysis of signals in the infrared at 1262, 1074 and 930 cm -1 and 840 assigned to S = O bonds sulfate esters , CO bond presence of 3,6- anhydrogalactose , β -D- galactose non- sulfated sulfate and the axial position of fucose C4 , respectively. FucB exhibited moderate anticoagulant activity , the polysaccharides prolonged time (aPTT ) 200 ug ( > 90s ) partial thromboplastin FucB no effect on prothrombin time (PT), which corresponds to the extrinsic pathway of coagulation was observed. This stimulation promoted fraction of about 3.6 times the synthesis of heparan sulfate (HS) by endothelial cells of the rabbit aorta ( RAEC ) in culture compared with cells not treated with FucB . This has also been shown to compete for the binding site with heparin. The rich fraction sulfated fucans exhibited strong antioxidant activity assays on total antioxidant (109.7 and 89.5 % compared with BHT and ascorbic acid standards ) , reducing power ( 71 % compared to ascorbic acid ) and ferric chelation ( 71 , comparing with 5 % ascorbic acid). The fraction of algae showed cytostatic activity on the RAEC cells revealed that the increase of the synthesis of heparan sulfate is not related to proliferation. FucB showed antiproliferative action on cell lines modified as Hela and Hep G2 by MTT assay . These results suggest that FucB Dictyota menstrualis have anticoagulant , antithrombotic , antioxidant potential as well as a possible antitumor action, promoting the stimulation of the synthesis of antithrombotic HS by endothelial cells and is useful in the prevention of thrombosis, also due to its inhibitory action on species reactive oxygen ( ROS ) in some in vitro systems , being involved in promoting a hypercoagulable state

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Fucans is a name used for sulfated polysaccharides, which is most characteristic structure of the presence of sulfated L-fucose, are found in brown seaweed (Phaeophyceae) and echinoderms (sea urchins and sea cucumbers). These polysaccharides have been reported to possess anticoagulant, antitumor, anti-viral, anti-proliferative and anti-inflammatory activities. Therefore, in the present study was evaluate the effect of the fucan from the brown seaweed Spatoglossum schroederii in models of peritonitis and non-septic shock induced by zymosan, as well as in a murine model of colitis induces by DSS. So, the mice treatment by intravenous route with the fucan was able to reduce the exudate formation and the cell migration in the model of acute peritonitis induced by zymosan during the kinetic of 6, 24 and 48 hours. Similarly, in the model of non-septic shock induced by zymosan the fucan demonstrated a protector effect to inhibited the cellular migration to the peritoneo, to decrease the levels of IL-6 in the serum and in the peritoneal exudate, to attenuate the lose of weight in the mice; beside to reduce the serum levels of hepatic transaminases and as well as the liver injury. In the model of murine colitis, the treatment with the fucan reduced the lose of weight of the animals, decreased the levels of IL-17 and IFN- produced in the gut and decrease the intestinal lesion induced by DSS. In conclusion, the fucan used in this study presented a significant protector effect in the murine models of inflammation

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Seaweeds are organisms known to exhibit a variety of biomolecules with pharmacological properties. The coast of Rio Grande do Norte has over 100 species of seaweeds, most of them not yet explored for their pharmacological potential. Sugars and phenolic compounds are the most studied of these being assigned a range of biological properties, such as anticoagulant , antiinflammatory, antitumor and antioxidant activities. In this work, we obtained methanolic extracts from thirteen seaweeds of the coast of Rio Grande do Norte (Dictyota cervicornis; Dictiopterys delicatula; Dictyota menstruallis; D. mertensis; Sargassum filipendula; Spatoglossum schröederi; Acanthophora specifera; Botryocladia occidentalis; Caulerpa cupresoides; C. racemosa; C. prolifera; C. sertularioides e Codium isthmocladum). They were evaluated as anticoagulant and antioxidant drugs, as well as antiproliferative drugs against the tumor cell line HeLa. None of the methanolic extracts showed anticoagulant activity, but when they were evaluated as antioxidant drugs all of extracts showed antioxidant activity in all tests performed (total antioxidant capacity, sequestration of superoxide and hydroxyl radicals, ferric chelation and reductase activity), especially the algae D. mentrualis, D. cilliolata and C. prolifera, who had the greatest potential to donate electrons.In addition, the ability of iron ions chelation appears as the main antioxidant mechanism of the methanolic extracts of these seaweeds mainly for the extract of the C. racemosa seaweed, which reached almost 100% activity. In the MTT assay, all extracts showed inhibitory activity at different levels againts HeLa cells. Moreover, D. cilliolata (MEDC) and D. menstrualis (MEDM) extracts showed specific activity to this cell line, not inhibiting the viability of 3T3 normal cell line, so they were chosen for detailing the antiproliferative mechanism of action. Using flow cytometry, fluorescence microscopy and in vitro assays we demonstrated that MEDC and MEDM induced apoptosis in HeLa cells by activation of caspases 3 and 9 and yet, MEDC induces cell cycle arrest in S phase. Together, these results showed that the methanolic extracts of brown seaweed D. menstrualis and D. cilliolata may contain agents with potential use in combatting cells from human uterine adenocarcinoma. This study also points to the need for more in-depth research on phytochemical and biological context to enable the purification of biologically active products of these extracts

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Fucan is a term used to denominate a family of sulfated L-fucose-rich polysaccharides. The brown alga Spatoglossum schröederi (Dictyotaceae) has three heterofucans namely fucan A, B and C. The 21 kDa fucan A is composed of a core of β (1-3) glucuronic acid-containing oligosaccharide of 4.5 kDa with branches at C4 of fucose chains α (1-3) linked. The fucose is mostly substituted at C4 with a sulfate group and at C2 with chains of β (1-4) xylose. This fucan has neither anticoagulant (from from 0.1 to 100µg) nor hemorrhagic activities (from 50 to 800 µg/mL). The antithrombotic test in vivo showed the fucan A has no activity in any of the concentrations (from 0.2 to 20µg/g/day) tested 1h after polysaccharide administration. However, when fucan A was injected endovenously 24h before the ligature of the venae cavae, we observed a dose-dependent effect, reaching saturation at around 20g/g of rat weight. In addition, this effect is also time-dependent, reaching saturation around 16h after fucan administration. In addition, regardless of administration pathway, fucan A displayed antithrombotic action. The exception was the oral pathway. Of particular importance was the finding that fucan A stimulates the synthesis of an antithrombotic heparan sulfate from endothelial cells like heparin. The hypothesis has been raised that in vivo antithrombotic activity of fucan A is related to the increased production this heparan. Taken together with the fact that the compound is practically devoid of anticoagulant and hemorrhagic activity suggests that it may be an ideal antithrombotic agent in vivo

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Sulfated polysaccharides (SP) are widely distributed in animals and seaweeds tissues. These polymers have been studied in light of their important pharmacological activities, such as anticoagulant, antioxidant, antitumoral, anti-inflammatory, and antiviral properties. On other hand, SP potential to synthesize biomaterials like as nanoparticules has not yet been explored. In addition, to date, SP have only been found in six plants and all inhabit saline environments. However, the SP pharmacological plant activities have not been carrying out. Furthermore, there are no reports of SP in freshwater plants. Thus, do SP from marine plants show pharmacological activity? Do freshwater plants actually synthesize SP? Is it possible to synthesize nanoparticles using SP from seaweed? In order to understand this question, this Thesis was divided into tree chapters. In the first chapter a sulfated polysaccharide (SPSG) was successfully isolated from marine plant Halodule wrightii. The data presented here showed that the SPSG is a 11 kDa sulfated heterogalactan contains glucose and xylose. Several assays suggested that the SPSG possessed remarkable antioxidant properties in different in vitro assays and an outstanding anticoagulant activity 2.5-fold higher than that of heparin Clexane® in the aPTT test; in the next chapter using different tools such as chemical and histological analyses, energy-dispersive X-ray analysis (EDXA), gel electrophoresis and infra-red spectroscopy we confirm the presence of sulfated polysaccharides in freshwater plants for the first time. Moreover, we also demonstrate that SP extracted from E. crassipes root has potential as an anticoagulant compound; and in last chapter a fucan, a sulfated polysaccharide, extracted from the brown seaweed was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution for hydrophobic chains of 1H NMR was approximately 93%. SNFfuc-TBa125 in aqueous media had a mean diameter of 123 nm and zeta potential of -38.3 ± 0.74 mV, measured bydynamic light scattering. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by 2.0 43.7% at SNFuc concentrations of 0.05 0.5 mg/ mL and RAEC non-tumor cell line proliferation displayed inhibition of 8.0 22.0%. On the other hand, nanogel improved CHO and RAW non-tumor cell line proliferation in the same concentration range. Flow cytometric analysis revealed that this fucan nanogel inhibited 786 cell proliferation through caspase and caspaseindependent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle

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In the present study, six families of sulfated polysaccharides were obtained from seaweed Dictyopteris delicatula (Lamouroux, 1809) and their anticoagulant, antioxidant and antitumor activities were evaluated. All fractions showed anticoagulant activity on aPTT assay, but not on PT assay. Fractions also exhibited total antioxidant activity, superoxide radical scavenging capacity and ferric chelating property. Thus, six fractions (F0.5v, F0.7v, F1.0v, F1.3v, F1.5v e F2.0v) we obtained by proteolytic digestion, followed by acetone fractionation and molecular sieving on Sephadex G-100. Chemical analyses demonstrated that all polysaccharides contain heterofucans composed mainly of fucose, xylose, glucose, galactose, uronic acid, and sulfate. Any fractions changed the PT. However, all fractions were able on double the aPPT on a dose-dependent manner. The heterofucans F0.7v and F1.0v showed low anticoagulant activity while F1.5v presented the most prominent anticoagulant activity .When compared to Clexane®, a low molecular weight heparin, at same concentration F1.5v presented similar anticoagulant activity. The fucans F0.5v and F0.7v at 1.0 mg/mL showed high ferric chelating activity (~45%), whereas fucans F1.3v (0.5 mg/mL) showed considerable reducing power, about 53.2% of the activity of vitamin C. The fucan F1.5v presented the most prominent anticoagulant activity. The best antiproliferative activity was found with fucans F1.3v and F0.7v. However, F1.3v activity was much higher than F0.7v inhibiting almost 100% of HeLa cell proliferation. These fucans have been selected for further studies on structural characterization as well as in vivo experiments, which are already in progress

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The ethanol is the most overused psychoactive drug over the world; this fact makes it one of the main substances required in toxicological exams nowadays. The development of an analytical method, adaptation or implementation of a method known, involves a process of validation that estimates its efficiency in the laboratory routine and credibility of the method. The stability is defined as the ability of the sample of material to keep the initial value of a quantitative measure for a defined period within specific limits when stored under defined conditions. This study aimed to evaluate the method of Gas chromatography and study the stability of ethanol in blood samples, considering the variables time and temperature of storage, and the presence of preservative and, with that check if the conditions of conservation and storage used in this study maintain the quality of the sample and preserve the originally amount of analyte present. Blood samples were collected from 10 volunteers to evaluate the method and to study the stability of ethanol. For the evaluation of the method, part of the samples was added to known concentrations of ethanol. In the study of stability, the other side of the pool of blood was placed in two containers: one containing the preservative sodium fluoride 1% and the anticoagulant heparin and the other only heparin, was added ethanol at a concentration of 0.6 g/L, fractionated in two bottles, one being stored at 4ºC (refrigerator) and another at -20ºC (freezer), the tests were performed on the same day (time zero) and after 1, 3, 7, 14, 30 and 60 days of storage. The assessment found the difference in results during storage in relation to time zero. It used the technique of headspace associated with gas chromatography with the FID and capillary column with stationary phase of polyethylene. The best analysis of chromatographic conditions were: temperature of 50ºC (column), 150ºC (jet) and 250ºC (detector), with retention time for ethanol from 9.107 ± 0.026 and the tercbutanol (internal standard) of 8.170 ± 0.081 minutes, the ethanol being separated properly from acetaldehyde, acetone, methanol and 2-propanol, which are potential interfering in the determination of ethanol. The technique showed linearity in the concentration range of 0.01 and 3.2 g/L (0.8051 x + y = 0.6196; r2 = 0.999). The calibration curve showed the following equation of the line: y = x 0.7542 + 0.6545, with a linear correlation coefficient equal to 0.996. The average recovery was 100.2%, the coefficients of variation of accuracy and inter intra test showed values of up to 7.3%, the limit of detection and quantification was 0.01 g/L and showed coefficient of variation within the allowed. The analytical method evaluated in this study proved to be fast, efficient and practical, given the objective of this work satisfactorily. The study of stability has less than 20% difference in the response obtained under the conditions of storage and stipulated period, compared with the response obtained at time zero and at the significance level of 5%, no statistical difference in the concentration of ethanol was observed between analysis. The results reinforce the reliability of the method of gas chromatography and blood samples in search of ethanol, either in the toxicological, forensic, social or clinic

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Um estudo sobre infecção experimental foi realizado em oito suínos, com idade média de 90 dias, machos castrados, da raça Wessex, e distribuídos em dois grupos de quatro suínos cada. Durante 36 dias, foram analisadas as alterações bioquímicas nos soros dos suínos dos dois grupos. O Grupo I foi mantido como testemunho e recebeu 5,0mL de solução fisiológica estéril por via intravenosa (veia cava craniana) e, no Grupo II, os suínos foram inoculados pela mesma via com 5,0mL de cultura de Leptospira interrogans sorovar wolffi , amostra L-10 selvagem isolada de tatu (Dasypus novemcinctus), contendo 1,0 x 10(8) leptospiras/mL. A partir do terceiro dia após a inoculação e em intervalos de 72 horas até o décimo oitavo dia, foram feitas coletas de sangue, sem anticoagulante, dos animais inoculados e testemunhas. Os parâmetros bioquímicos analisados foram: bilirrubina total, direta e indireta, ácidos graxos, glicose e proteínas plasmáticas. Foi detectado um aumento da bilirrubina direta no terceiro dia e um aumento no sexto dia da bilirrubina total e indireta após a inoculação. As dosagens de glicose, ácidos graxos e proteínas plasmáticas apresentaram uma diminuição a partir do terceiro dia da inoculação. Com os resultados obtidos, pode-se concluir que o aumento das taxas de bilirrubinas levam a uma definição de um diagnóstico de hemólise aguda, e que a hipoglicemia, a hipolipidemia e a hipoproteinemia podem estar relacionadas com lesões hepáticas e a uma septcemia.Todas as dosagens em todos os animais retornaram aos seus valores normais a partir do décimo quinto dia.

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Veia cava inferior dupla é uma variação anatômica rara cuja prevalência é de 0,2-3%. O implante de filtro de veia cava, quando indicado em casos com duplicidade da veia cava inferior, pode ser realizado de diferentes formas: em ambas as veias cavas; em uma delas, embolizando a anastomose entre ambas; em somente uma delas; ou por implante supra-renal. Relatamos um caso de trombose venosa profunda no pós-operatório de implante de prótese de quadril com contra-indicação para tratamento anticoagulante e cuja cavografia evidenciou duplicidade de veia cava inferior. O implante de filtro de veia cava inferior realizado em posição supra-renal mostrou-se opção adequada e segura.

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Criança de 6 anos de idade, sexo feminino, procurou serviço médico devido a mal-formação gastrointestinal. Durante o acompanhamento médico, foi diagnosticada ausência parcial de veia cava inferior, alteração congênita rara que envolve a drenagem vascular do segmento inferior do corpo. Realizados exames de imagem, os quais contribuíram para avaliação e descrição do caso. Mantido tratamento conservador com anticoagulante oral. Paciente apresenta boa evolução após longo tempo de acompanhamento cardiovascular.

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INTRODUÇÃO: Dados da literatura sugerem que as taxas de tromboembolismo e sangramento em pacientes com próteses valvares cardíacas mecânicas podem ser muito reduzidas se a terapia anticoagulante for otimizada. OBJETIVOS: Avaliar a ocorrência de complicações em portadores de próteses valvares cardíacas mecânicas submetidos à terapêutica anticoagulante, otimizada por meio de ambulatório especializado. MÉTODOS: Estudou-se a ocorrência de complicações ao longo de 10 anos em 261 pacientes com próteses valvares cardíacas mecânicas, anticoagulados e acompanhados em ambulatório especializado. Esses pacientes foram divididos em dois grupos conforme porcentual de consultas com tempo de protrombina (RNI) dentro do intervalo desejado: G1-0% a 50,00% e G2-50,01% a 100% das consultas. Foram avaliadas as ocorrências de complicações tromboembólicas e hemorrágicas na sua totalidade, ou subdivididas em maiores e menores, de acordo com a gravidade. Os resultados estão apresentados sob forma de estudo atuarial e de frequência linearizada de ocorrência de eventos. RESULTADOS: O estudo atuarial mostrou que, ao longo do tempo, no grupo G2 (com 50,01% a 100% das consultas com a RNI no intervalo desejado) maior número de pacientes esteve livre da ocorrência de qualquer tipo de evento, de eventos hemorrágicos menores ou da elevação exacerbada da RNI. As frequências linearizadas de ocorrência, em todos os tipos eventos, também foram menores nos pacientes do grupo G2. CONCLUSÕES: O tempo de permanência dentro do intervalo de anticoagulação desejado está diretamente relacionado com a ocorrência de complicações. Entretanto, mesmo com acompanhamento otimizado por meio de ambulatório especializado, apenas cerca de um terço dos pacientes apresentaram nível de anticoagulação adequado em mais da metade das consultas.

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Foi realizado estudo experimental em ratos para avaliar o efeito do anticoagulante na consolidação óssea, conforme critérios clínicos, anatomopatológicos e biomecânicos. Manualmente, após perfuração do osso, foi produzida fratura aberta, na diáfise da tíbia direita, mantida sem imobilização, em 72 ratos machos da linhagem Wistar, com 60 dias de idade e peso médio de 242 gramas. Doze horas após a fratura, foi iniciado tratamento anticoagulante, mantido por 28 dias. Via subcutânea, um grupo recebeu heparina sódica na dose de 200UI/Kg de 12 em 12 horas, enquanto outro, recebeu enoxaparina na dose de 1mg/Kg de 12 em 12 horas, doses preconizadas para tratamento do tromboembolismo em humanos. O terceiro grupo, controle, recebeu água destilada. Durante o experimento, os animais foram avaliados clinicamente e após 28 dias, sacrificados. Nos animais dos três grupos, a evolução clínica foi semelhante. Mediante análise anatomopatológica efetuada por estudo descritivo e quantitativo, foi observada presença de fibrose, cartilagem e osso igualmente nos três grupos, sempre com predomínio de tecido ósseo. O estudo biomecânico, realizado por intermédio de ensaios de flexão, demonstrou coeficiente de rigidez e carga máxima semelhantes nos três grupos. Nenhuma diferença clínica, anatomopatológica e biomecânica foi encontrada, resultando todas as fraturas em consolidação de acordo com os critérios adotados, concluindo-se, portanto, que a heparina sódica e a enoxaparina nas doses, via e tempo de administração utilizados não interfiriram na consolidação da fratura da tíbia do rato.

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Aim. Superficial thrombophlebitis (ST) ascending the lower limbs is a common disease, which may be associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). The aim of this study was to investigate the prevalence of DVT and PE as complications of ascending ST of the lower limbs in the great saphenous vein (GSV) or SSV (SSV) and probable risk factors.Methods. For this study 60 consecutive patients were enrolled with ascending ST of the GSV or SSV, seen between 2000 and 2003 at a public hospital in Botucatu, SP, Brazil. All patients were assessed clinically, by venous Duplex scanning of the lower limbs to confirm ST and test for DVT, and by means of pulmonary scintigraphy to test for PE.Results. In 13 ST cases (21.67%) there was concomitant DVT and 17 ST patients (28.33%) also had PE. Eleven patients had a clinical status suggestive of DVT, but only in eight of these (61.5%), this clinical diagnosis was confirmed. Fourteen patients had a clinical status suggestive of PE, and this diagnosis was confirmed in six cases (35.30%). ST patients who also had DVT and/or PE were given anticoagulant treatment with heparin and warfarin. None of the variables studied was predictive of DVT or PE (P>0.05). However, the presence of varicose veins reduced the risk of patients having DVT (relative risk=9.09; 95%CI:1.75 - 50.00 and P=0.023).Conclusion. The prevalence rates of PE (28.3%) and DVT (21.6%) were elevated in this sample of ascending ST cases, indicating a need for detailed assessment of patients for signs of these complications, including for therapeutic management decision making. [Int Angiol 2009;28:400-8]

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OBJETIVO: Rever os fatores predisponentes e a evolução em série de casos de trombose venosa profunda dos membros superiores de nossa instituição. MÉTODOS: Cinqüenta e dois pacientes consecutivos, com trombose venosa profunda dos membros superiores (29 homens e 23 mulheres), idade média de 52,3 anos, documentados por mapeamento dúplex (71,1%), flebografia (11,1%) ou clinicamente (15,6%), foram incluídos no presente estudo. RESULTADOS: As manifestações clínicas foram: dor no antebraço (24 casos - 46,1%), dor no braço (27 casos - 51,9%), edema do membro superior (45 casos - 86,5%), dor à compressão do membro superior (36 casos - 70,2%) e dor à movimentação do mesmo (32 casos - 61,7%). Os principais fatores de risco foram: punção ou acesso venoso (20 casos - 39,1%) e câncer (16 casos - 32,6%). As veias envolvidas foram: umeral (n = 18), axilar (n = 27), subclávia (n = 15) e jugular (n = 11). A embolia pulmonar estava inicialmente presente em quatro casos (7,6%). O tratamento inicial foi feito com heparina não-fracionada intravenosa (64,3%), subcutânea (16,7%), ou heparina de baixo peso molecular (17,1%), seguido de varfarina. Doze pacientes morreram antes da alta, em função de causas não relacionadas à embolia pulmonar. Foram acompanhados os 40 pacientes restantes por período de 3 meses a 10 anos, sendo que dois morreram de causas não relacionadas à embolia pulmonar, um paciente desenvolveu seqüelas pós-trombóticas, como edema residual e limitações aos movimentos, e seis ficaram com discretos sintomas residuais (edema e dor). CONCLUSÕES: A trombose venosa profunda dos membros superiores foi mais freqüente em pacientes submetidos a acessos venosos e com neoplasia em atividade. Comparando com dados da literatura, a evolução dos pacientes sob tratamento exclusivo com anticoagulantes foi, no mínimo, similar a outros tratamentos propostos.

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The venom of Lonomia obliqua caterpillar may induce a hemorrhagic syndrome in humans, and blood incoagulability by afibrinogenemia when intravenously injected in laboratory animals. The possible antithrombotic and thrombolytic activities of L. obliqua caterpillar bristle extract (LOCBE) were evaluated in this study. The minimal intravenous dose of the extract necessary to induce afibrinogenemia and anticoagulation was 3.0 and 10.0 µg protein/kg body weight for rabbits and rats, respectively. In rabbits, this dose induced total blood incoagulability for at least 10 h and did not reduce the weight of preformed venous thrombi, in contrast to streptokinase (30,000 IU/kg). In rats, pretreatment with 5.0 and 10.0 µg/kg LOCBE prevented the formation of thrombi induced by venous stasis or by injury to the venous endothelium. The dose of 5.0 µg/kg LOCBE did not modify blood coagulation assay parameters but increased bleeding time and decreased plasma factor XIII concentration. When the extract was administered to rats at the dose of 10.0 µg/kg, the blood was totally incoagulable for 6 h. These data show that LOCBE was effective in preventing experimental venous thrombosis in rats, justifying further studies using purified fractions of the extract to clarify the mechanisms of this effect.