Phytochemical and biological investigations of methanol extract of leaves of ziziphus mauritiana lam / Investigaciones fitoquímicas y biológicas de extractos metanólicos de hojas de ziziphus mauritiana lam

Seven compounds were isolated from the methanol extract of leaves of Ziziphus mauritiana. The structures of the isolated compounds were elucidated as y-fagarine (1), beta-sitosterol (2), stigmasterol (3), alfa-amyrin (4), lupeol (5), beta-amyrin (6) and betulin (7) by extensive spectroscopic studies and by co-TLC with authentic samples. This is the first report of isolation of compounds 1-7 from this plant species. The extractives from leaves were investigated for thrombolytic, membrane stabilizing, antimicrobial, antidiarrheal and analgesic potentials along with sleep inducing property on animal model. The thrombolytic and membrane stabilizing activities were assessed by using human erythrocyte comparing with standard streptokinase and acetylsalicylic acid, respectively. The methanolic extract reduced frequency of diarrheal faeces when compared to the standard loperamide. In castor oil induced diarrhea in mice a dose dependent decrease of gastrointestinal transits were observed. In radiant heat tail-flick method the methanol extract showed moderate antinociceptive activity, compared to standard morphine.

Siete compuestos fueron aislados del extracto metanólico de hojas de Ziziphus mauritiana. Las estructuras de los compuestos aislados fueron identificadas como y-fagarina (1), beta-sitosterol (2), estigmasterol (3), alfa-amirina (4), lupeol (5), beta-amirina (6) y betulina (7 ) por medio de extensivos estudios espectroscópicos y por co-TLC con muestras auténticas. Este es el primer informe de aislamiento de los compuestos 1-7 a partir de esta especie vegetal. Los extractos de las hojas fueron investigados por efectos trombolíticos, estabilizadores de membrana, antimicrobianos, antidiarreicos y potenciales analgésicos junto a la propiedad de inducir sueño en el modelo animal. Las actividades trombolíticos y la estabilización de la membrana se evaluaron mediante el uso de eritrocitos humanos comparando con estreptoquinasa estándar y el ácido acetilsalicílico, respectivamente. El extracto metanólico redujo la frecuencia de las heces diarreicas en comparación con el estándar de loperamida. En la inducción por aceite de ricino de diarrea en ratones, se observó una disminución dosis dependiente de los tránsitos gastrointestinales. En el método del coletazo producido por calor radiante, el extracto metabólico mostró una actividad antinociceptiva moderada, en comparación con la morfina estándar.

Antioxidant, antimicrobial, toxicity and analgesic properties of ethanol extract of Solena amplexicaulis root

BACKGROUND: This study was subjected to investigate different pharmacological properties of ethanol extract ofSolena amplexicaulis root. RESULTS: The extract contains flavonoid, alkaloid, saponin and steroid compounds. The extract exhibited excellent antioxidant activity in DPPH radical scavenging activity. The extract also showed potent activity in brine shrimp lethality bioassay. The LC50 value was found to 44.677 µg/ml. The extract showed better anti-bacterial activity against gram-negative bacteria. In antifungal assay, the maximum 79.31% of anti-mycotic activity was observed against Aspergillus ochraceus while minimum 44.2% against Rhizopus oryzae. MIC value ranged between 1500 - 3000 µg/ml. The extract was found moderately toxic with a 24-hr LD50 value of 81.47 mg/kg in Swiss albino mice. The degree of inhibition by the ethanolic extract of the root was found less than that of standard analgesic drug diclofenac sodium. The extract also showed moderate anti-inflammatory and antinociceptive activity and anti-diabetic property. Reducing power of the extract was comparable with standard ascorbic acid. Moderate in vitro thrombolytic activity, lipid peroxidation inhibition property, metal chelating ability and stress-protective activity was also observed. CONCLUSION: Ethanol extract of Solena amplexicaulis root can be valuable for treatment of different diseases.

Polyphenols content, cytotoxic, membrane stabilizing and thrombolytic activities of Sarcolobus globosus:a medicinal plant from Sundarban Forest / Contenido de polifenoles, citotoxicidad, estabilizante de membranas y actividades tromboliticas de Sarcolobus globosus: una planta medicinal de la Foresta Sundarban

The crude methanolic extract of the bark of Sarcolobus globosus (Family-apocynaceae) and its different organic soluble Kupchan fractions were screened for total phenol content (TPC), cytotoxic, membrane stabilizing and thrombolytic activities. The polyphenol content was determined colorimetrically using Folin-Ciocalteu method and expressed in gallic acid equivalent. The chloroform soluble Kupchan fraction (CSF) exhibited higher level of Total Polyphenol Contents (TPC, 54.21 gm of GAE/100 gm of dried extract). In the brine shrimp lethality bioassay, the crude methanolic extract (MEBP) exhibited significant cytotoxicity. The membrane stabilizing activity was assessed by using erythrocyte in hypotonic solution and was compared with acetyl salicylic acid. The hexane soluble Kupchan fraction (HSF) produced 52.73 percent inhibition of hemolysis of RBC as compared to 65.38 percent revealed by acetyl salicylic acid (0.10 mg/mL). In thrombolytic study screening, the crude methanolic extract demonstrated significant thrombolytic activity in human blood specimen.

El extracto crudo metanólico de la corteza de Sarcolobus globosus (Familia-apocynaceae) y sus diferentes fracciones solubles Kupchan fueron identificadas para contenido total de fenoles (CTF), actividades citotóxicas, estabilizantes de membrana y trombolíticas. El contenido de polifenoles fue determinado colorimétricamente usando el método Folin-Ciocalteu y expresados en equivalentes a ácido gálico. La fracción Kupchan soluble en cloroformo (FSC) exhibió los mayores niveles de Contenido Total de Polifenoles (CFT, 54,21 gm of GAE/100gm de extracto seco). En el bioensayo de letalidad (Artemia salina), el extracto metanólico crudo (EMC) exhibió una siginificativa citotoxicidad. La actividad estabilizadora de membrana fue estimada usando eritrocitos en un medio hipotónico y fue comparado con el ácido acetil salicílico. La fracción Kupchan soluble en hexano (FSH) produjo un 52,73 por ciento de inhibición de la hemólisis de los glóbulos rojos comparado con un 65,38 por ciento revelado por el ácido acetil salicílico (0,1 mg/mL). En las determinaciones trombolíticas, el extracto metanólico crudo demostró una significativa actividad trombolítica en una muestra de sangre humana.

Influence of thrombolytic therapy on early and long term left ventricular systolic function in patients with ST-segment elevation myocardial infarction

Left ventricular systolic dysfunction complicating acute myocardial infarction are responsible for significant morbidity and mortality. This study to assess the effect of thrombolytic therapy on the left ventricular systolic function during the first week and a year after ST-elevation myocardial infarction. In a study of 56 patients with first ST-Segment elevation myocardial infarction [42 men and 14 women; age range, 42-89 years [mean, 61 +/- 10], who had been admitted to the Coronary Care Unit at Hawler Teaching Hospital from May 2008 to May 2009. study done to assess the left ventricular systolic function during the first week and first year after ST-elevation myocardial infarction. Twenty one patients received tissue plasminogen activator [Alteplase] 12 hour after the onset of symptoms labeled as group-I, the remaining patients [35], had no chance to receive thrombolytic therapy labeled as group II. In group I the mean ejection fraction improved significantly from 51.6 +/- 9.4 during the first week to 55.14 +/- 11, P=0.034, at first year after acute myocardial infarction, while in group II there was no significant difference of mean ejection fraction during the first week [45.97 +/- 12.2] and first year of acute myocardial infarction [46.1 +/- 13.2],P=0.5. Thrombolytic therapy has a beneficial effect on left ventricular systolic function detected by echocardiography at the end of the first year of ST-elevation myocardial infarction

Estudo da ação da estreptoquinase e do alopurinol em retalhos cutâneos em ilha submetidos à isquemia prolongada: estudo experimental em ratos / Study of the effect of streptokinase and allopurinol in island skin flaps submitted to prolonged ischemia: experimental study in rats

OBJETIVO: Estabelecer relação entre a sobrevivência de retalhos cutâneos em ilha submetidos à isquemia prolongada e o uso da estreptoquinase e do alopurinol administrados após o período de isquemia prolongado. MÉTODOS: Foram utilizados 48 ratos machos da raça Wistar, com peso entre 300 e 350g, divididos em quatro grupos com 12 cada um, sendo; grupo controle, alopurinol, estreptoquinase e associação de alopurinol com estreptoquinase, submetidos à dissecção de retalho epigástrico em ilha, seguido de clampeamento do feixe vascular, por oito horas em isquemia mista normotérmica. Após este período, as pinças foram retiradas e cada animal recebeu o esquema terapêutico proposto através de injeção intravenosa. A análise da sobrevivência dos retalhos foi realizada no sétimo dia de pós-operatório. Foram realizadas análises descritivas ( por cento de área necrótica) e de variâncias, bem como comparações múltiplas de Dunnett T3 entre os quatro grupos e o teste da mediana. RESULTADOS: O grupo controle apresentou em média 79,88 por cento de necrose da área total. Aqueles que receberam alopurinol apresentaram em média 64,05 por cento de necrose e o grupo que recebeu estreptoquinase apresentou em média 55,52 por cento de necrose. Com a associação das duas drogas, os ratos apresentaram 54,30 por cento em média de necrose do retalho. Aplicando o teste Dunnett e o teste da mediana verificou-se de que o grupo estreptoquinase é o com menor percentual de necrose neste estudo. CONCLUSÃO: A administração sistêmica da estreptoquinase após oito horas de isquemia mista normotérmica resultou em aumento da sobrevivência de retalhos epigástricos em ilha em ratos, quando comparada à administração de alopurinol, associação do alopurinol e estreptoquinase e do grupo controle.

BACKGROUND: To establish a relation between the survival rate of island skin flaps submitted to prolonged ischemia and the effect of streptokinase and allopurinol administered after the ischemic period. METHODS: A total of 48 male Winstar rats, each weighing between 300 and 350 grams,were separated into four groups of twelve as follows: control, allopurinol, streptokinase and association of allopurinol and streptokinase, were submitted to an epigastric island flap dissection followed by epigastric vessel bundle clamping. Flaps remained this way for 8 hours in normothermic mixed ischemia. After the ischemic period, clamps were removed and each rat received the therapeutical scheme proposed for the group by intravenous injections. Flap survival analysis was performed on the seventh post operative day. Variance and descriptive analyses (as a percentage of the necrotic area) as well as Dunnett-T3 multiple comparisons among the 4 groups and median tests were carried out. RESULTS: Rats in the control group presented an average of 79.88 percent of necrosis in the flap total area; those which received allopurinol presented an average of 64.05 percent of necrosis whereas the group which received streptokinase showed an average of 55.52 percent of necrosis. With the association of both drugs, rats presented an average of 54.30 percent of necrosis in the flap total area. By applying Dunnet test and the median test, it could be verified that, in this study the streptokinase group had the lowest necrosis rate. CONCLUSION: The systemic administration of streptokinase after 8 hours of normothermic global ischemia resulted in an increased survival rate of epigastric island skin flaps in rats, when compared to the administration of allopurinol, association of the two drugs and the control group.

Eficacia de la tromboprofilaxis obstétrica / Efficacy of obstetrical tromboprophylaxis

Valorar la incidencia de enfermedad tromboembólica durante el embarazo, parto y puerperio en gestantes con riesgo y la efectividad de las tromboprofilaxis. Seguimiento de 2 727 gestantes con parto durante un año. Se realiza análisis descriptivo de nuestra población, de los factores de riesgo y de la duración de la tromboprofilaxis, analizando su relación con la incidencia de eventos tromboembólicos. Hospital Universitario San Cecilio de Granada, España. Nuestras gestantes tienen pocos factores de riesgo: cesárea, anemia posquirúrgica, tabaquismo, hipertensión inducida por el embarazo o previa, diabetes, cardiopatía y trombofilia, siendo la cesárea y la anemia los más frecuentes. La tromboprofilaxis postcesárea con nadroparina cálcica 0,4 diaria durante su hospitalización ha sido efectiva. No hubo ningún tromboembolismo. En nuestra población, con un adecuado control obstétrico y profilaxis con antiagregantes plaquetarios y/o heparinas de bajo peso molecular, se han evitado eventos tromboembólicos relacionados con el embarazo, parto puerperio.

Efecto antitrombótico, una característica poco conocida de las frutas y hortalizas / Antithrombotic effect, a not well known characteristic of fruits and vegetables

Cardiovascular diseases (CVD) are the leading cause of death in the world. Several risk factors for CVD, such as lipid disorders, hypertension and diabetes mellitus, are influenced by food. It is well known that fruits and vegetables contain antioxidants and its adequate consumption reduces cardiovascular risk. However, its antithrombotic effect (antiplatelet agent, anticoagulant and fibrinolytic) is little known. This review briefly describes these effects, both in vivo and in vitro, and the possible mechanisms that could explain this effect. Fruits such as black grape, pineapple, strawberry and kiwi show this effect. Among the vegetables that have antiaggregatory effect are garlic, onions, welsh onions, tomatoes and melons. On the other hand, the anticoagulant effect has only been found in fruits like pineapple, and among the vegetables in garlic and onions. The fibrinolytic effect has been described in fruits like kiwi and pineapple, and in vegetables such as garlic, onions and soybeans. Some fruits (pineapple and kiwi) and vegetables (onion and garlic) have more than one antithrombotic effect so their regular consumption certainly protects from CVD. We have begun the study, initially in vitro, of the potential antithrombotic effect of fruits and vegetables in the Maule Region. It is necessary to increase our domestic consumption and export of fruits and vegetables, both to improve the health of the population and the economy. The reasons above stated describe the importance of the contribution of knowledge due to the fact that antioxidant effects are less known.

Las enfermedades cardiovasculares (ECV) son la principal causa de mortalidad en el mundo. Varios de los factores de riesgo de las ECV, como dislipidemias, hipertensión arterial y diabetes mellitus, son influenciados por la alimentación. Es conocido que las frutas y hortalizas contienen antioxidantes, y que su consumo en una cantidad adecuada disminuye el riesgo cardiovascular. Sin embargo, su efecto antitrombótico (antiagregante plaquetario, anticoagulante y fibrinolítico) es poco conocido. En esta revisión se describen brevemente dichos efectos, tanto in vitro como in vivo, y los posibles mecanismos que podrían explicar éstos. En cuanto al efecto antiagregante plaquetario, entre las frutas que poseen dicha característica se incluyen uva negra, piña, frutilla y kiwi. Entre las hortalizas en que se ha descrito efecto antiagregante están el ajo, la cebolla, el cebollín, el tomate y el melón. Por su parte, el efecto anticoagulante, entre las frutas, sólo se ha encontrado en la piña, y entre las hortalizas en ajos y cebollas. El efecto fibrinolítico se ha descrito en frutas como el kiwi y la piña, y hortalizas como el ajo, las cebollas y la soya. Algunas frutas (piña y kiwi) y hortalizas (ajo y cebollas) presentan más de un efecto antitrombótico por lo que seguramente su consumo regular protege de las ECV. Nosotros hemos iniciado el estudio, por lo pronto in vitro, del posible efecto antitrombótico de frutas y hortalizas de la Región del Maule. Siendo necesario aumentar el consumo interno y las exportaciones de frutas y hortalizas, tanto para mejorar la salud de la población como desde el punto de vista económico, parece relevante contribuir al conocimiento de los efectos aquí descritos, los que son menos conocidos que el efecto antioxidante.

Estreptoquinase e oxigênio hiperbárico em congestão após reimplante de membro / Effects of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation in rats

OBJETIVO: Foram testados os efeitos do fármaco estreptoquinase e da terapia com oxigênio hiperbárico em modelo experimental de oclusão venosa após reimplante de membro. MÉTODOS: Foram realizadas amputações com preservação de vasos e nervos dos membros posteriores direitos de 140 ratos. Os grupos GM0, GM1, GM2, GM3 e GM4 foram submetidos a tempos de oclusão venosa de zero, uma, duas, três e quatro horas. Os grupos GE1 e GE2 foram tratados com estreptoquinase e terapia com oxigênio hiperbárico, respectivamente, após oclusão venosa de três horas. Os resultados foram analisados estatisticamente pelo teste do Qui-quadrado (p<0,05). RESULTADOS: As taxas de mortalidade transoperatórias dos grupos GM0, GM1, GM2, GM3 e GM4 foram 0 por cento, 10 por cento, 15 por cento, 30 por cento e 60 por cento e as pós-operatórias foram 5 por cento; 11,1 por cento; 11,7 por cento; 14,2 por cento e 100 por cento, respectivamente. As taxas de viabilidade dos membros isquêmicos após sete dias de avaliação foram 100 por cento, 87,5 por cento, 80 por cento e 66,67 por cento. As taxas de viabilidade dos grupos GE1 e GE2 foram 76,9 por cento e 100 por cento, respectivamente. As taxas de mortalidade transoperatórias foram diferentes estatisticamente com exceção de GM1 e GM2. As taxas de mortalidade pós-operatórias não foram diferentes com exceção de GM3 e GM4. As taxas de viabilidade dos grupos modelo foram diferentes entre si, exceto os grupos GM1 e GM2. GE1 resultou em uma viabilidade de membros sem diferença estatística e GE2 em uma viabilidade de membros maior que GM3. CONCLUSÃO: A estreptoquinase não alterou os efeitos da oclusão venosa e a terapia com oxigênio hiperbárico aumentou a viabilidade dos membros.

OBJECTIVE: The effectiveness of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation was tested in rats. METHODS: Amputation with preservation of vessels and nerves of the right hind limb was carried out in 140 rats. Groups MG0, MG1, MG2, MG3 and MG4 were submitted to 0, 1, 2, 3 and 4 hours of venous occlusion. MG3 was elected as control for the experimental groups. Groups EG1 and EG2 were submitted to 3 hours of venous occlusion and were treated with streptokinase and hyperbaric oxygen therapy. Limbs were observed for 7 days and their mortality and survival rates were studied. RESULTS: Trans-operatory mortality rates in groups MG0, MG1, MG2, MG3 and MG4 were 0, 10, 15, 30 and 60 percent respectively and the postoperatory mortality rates were 5; 11.1; 11.7; 14.2 and 100 percent respectively. The limb survival rates were 100 percent, 87.5 percent, 80 percent and 66.67 percent respectively and 76.9 percent and 100 percent in EG1 and EG2. Model groups were statistically different, except for MG1 and MG2 in trans-operatory mortality rates. There were no statistical differences in postoperatory mortality rates between model groups except for MG3 and MG4. Model groups were statistically different, with the exception of MG1 and MG2, in limb survival rates. EG1 and MG3 showed no statistical difference in limb survival and EG2 had a better limb survival than MG3. CONCLUSION: Results suggest that the administration of streptokinase does not change effects of venous occlusion and that hyperbaric oxygen therapy may decrease the effects of venous occlusion in limbs.

Efficacy of Femoral Vascular Closure Devices in Patients Treated with Anticoagulant, Abciximab or Thrombolytics during Percutaneous Endovascular Procedures

OBJECTIVE: This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab or thrombolytics (urokinase or t-PA) during the procedures. MATERIALS AND METHODS: From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1,180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-SealTM; the suture-mediated closure device was The Closer STM) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n = 94), thrombolytics only (n = 10), heparin and thrombolytics (n = 3), or abciximab and thrombolytics (n = 1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two groups. RESULTS: The immediate hemostasis rates were 92.9% (1,456/1,568) in the no-drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups (p = 0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture-mediated devices was also not statistically significant (92.9% vs. 84.8%, respectively; p = 0.21). CONCLUSION: Arterial closure of the femoral access site with using vascular closure devices is both safe and effective, even in the patients who received heparin, abciximab or thrombolytics.

Study of warm ischemia followed by reperfusion on a lower limb model in rats: effect of allopurinol and streptokinase

A isquemia prolongada dos tecidos leva a alterações na microcirculação e liberação de radicais livres do oxigênio, evento que pode resultar na morte do tecido, conhecido como fenômeno de não reperfusão. Um modelo em ratos de isquemia quente e reperfusão do membro posterior é proposto, e os efeitos dos fármacos alopurinol e estreptoquinase foram estudados. MÉTODO: Secção do membro posterior com preservação dos vasos e nervos foi realizada em 110 ratos. O pinçamento vascular e posterior reperfusão após isquemia quente de 0, 2, 4, 6 e 8 horas formou os grupos M0, M2, M4, M6 e M8 respectivamente. Outros grupos E1, E2 e E3 receberam, respectivamente, alopurinol, estreptoquinase e a combinação de ambas as drogas, após seis horas de isquemia. RESULTADOS: As taxas de viabilidade dos membros isquêmicos, observadas após sete dias foram: M0 - 100%, M2 - 80% ,M4 - 64%,M6 - 50% e M8 - 20%. As taxas de viabilidade dos grupos experimentais foram 67%(E1), 70%(E2) e 70%(E3). Os grupos M0, M2, M4, M6 e M8 foram diferentes entre si exceto os grupos M4 e M6. E1, E2 e E3 resultaram em viabilidade de membros maiores que M6(controle), mas não em relação ao M2 e M4. DISCUSSAO: Os resultados sugerem um aumento da viabilidade de membros após 6 horas de isquemia quando utilizado os fármacos alopurinol ou estreptoquinase. A associação de estreptoquinase e alopurinol não mostrou efeito adicional.

Terapia antitrombótica na síndrome coronária aguda sem supradesnivelamento do segmento ST / Antithrombotic therapy acute coronary syndrome with non-ST elevation

A síndrome coronariana aguda compreende um largo espectro de condições clínicas, abrangendo isquemia silenciosa, angina instável e infarto agudo do miocárdio e representando um dos principais problemas de saúde pública do mundo moderno. Atualmente, constitui a primeira causa de mortalidade em todo o mundo. Os novos avanços terapêuticos caminham no sentido de mudar esta realidade, reduzindo a morbidade e a mortalidade relacionadas com estas doenças. O tratamento atual da síndrome coronariana aguda estrutura-se basicamente na intervenção coronária percutânea e na utilização de fármacos seguros e eficazes para conter a trombose vascular. Esta monografia tem por objetivo rever alguns aspectos da fisiopatologia das síndromes isquêmicas agudas e estudar os medicamentos antitrombóticos utilizados no tratamento da síndrome coronariana aguda sem supradesnivelmento do segmento ST.

The anti-thrombotic activity of surfactins

Platelet aggregation was inhibited and the density of platelet-rich plasma (PRP) clots was decreased by the preincubation of PRP with surfactins, an acidic lipopeptide of Bacillus subtilis complex BC1212 isolated from soybean paste, in dose-dependent manner. Our findings suggest that surfactins are able to prevent a platelet aggregation leading to an inhibition of additional fibrin clot formation, and to enhance fibrinolysis with facilitated diffusion of fibrinolytic agents.

Long-term Effect of Plasmin on the Vitreolysis in Rabbit Eyes

The aim was to investigate the proteolytic activity of plasmin and its long-term complications. Plasmin was injected into the vitreous cavity of rabbits' eyes. Slit lamp biomicroscopy and electroretinography were performed. Rabbits were serially sacrificed at four months, and globes fixated and prepared for light and transmission electron microscopy. In both the plasmin-injected and control eyes, electroretinography showed a transient decrease in the amplitude, but this recovered to the baseline level in a week. Under the light microscope, the plasmin-treated eyes had a smooth retinal surface, implying separation of the vitreous cortex from the retina. In the control eyes, the collagen fibers remained on the retinal surface. By transmission electron microscopy, the plasmin-treated eyes showed a vitreous-free retinal surface, but no vitreoretinal separation was observed in the control eyes. Plasmin induces a cleavage between the vitreous and the internal limiting membrane, with no long-term complications, so may be a useful pharmacologic adjunct to vitrectomy.

Estratégias em química medicinal para o planejamento de fármacos / Strategies in medicinal chemistry to the discovery of new lead-compounds

Este artigo ilustra a aplicação das estratégias de hibridação molecular e bioisosterismo no planejamento estrutural de novos candidatos a protótipos de fármacos com propriedades analgésicas, antiiinflamatórias e antitrombóticas, com base no mecanismo de ação pretendido, explorando, inclusive, produto natural brasileiro abundante como padrão molecular básico...

Development of new heparin-like compounds and other antithrombotic drugs and their interaction with vascular endothelial cells

The anticlotting and antithrombotic activities of heparin, heparan sulfate, low molecular weight heparins, heparin and heparin-like compounds from various sources used in clinical practice or under development are briefly reviewed. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate from Artemia franciscana and a dermatan sulfate from tuna fish show a potent heparin cofactor II activity. A heparan sulfate derived from bovine pancreas has a potent antithrombotic activity in an arterial and venous thrombosis model with a negligible activity upon the serine proteases of the coagulation cascade. It is suggested that the antithrombotic activity of heparin and other antithrombotic agents is due at least in part to their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate.