Acidentes com serpentes peçonhentas: prevenção, identificação, cuidados com os acidentados e soroterapia.

O trabalho fornece informações práticas para distinção entre serpentes venenosas e não venenosas, cuidados com acidentados e orientações preventivas de acidentes ofídicos.

Quantificação de citocinas na intoxicação experimental com veneno de Crotalus durissus terrificus e Bothropoides jararaca em ratos Wistar tratados com soroterapia e Mikania glomerata

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Quantificação de citocinas no soro e homogenato da pata na intoxicação experimental com veneno de Bothropoides jararaca em ratos Wistar tratados com soroterapia e Mikania glomerata

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Saúde pública e as empresas químico-farmacêuticas

O artigo trata da formação da indústria farmacêutica brasileira. Aborda algumas questões de história econômica e social, tais como o surgimento do sistema de saúde pública, as práticas de combate às doenças infecciosas, desde as desinfecções e produção de substâncias químicas pela indústria, à soroterapia e produção de soros e vacinas nas instituições de pesquisa científica públicas e nas empresas farmacêuticas privadas. Toma para análise da indústria farmacêutica privada nacional, a empresa Instituto Pinheiros - Produtos Terapêuticos S.A., enfatizando as relações entre seus cientistas, no desenvolvimento de produtos, de tecnologia e da própria discussão científica com as instituições públicas de pesquisa criadas no âmbito da política de saúde pública pelo estado de São Paulo.

Estudos estruturais com fosfolipases A2 e fosfolipases A2 homólogas isoladas no veneno de Bothrops moojeni

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito do extrato aquoso de Casearia sylvestris sobre a neutralização e regeneração da mionecrose induzida pelo veneno da Bothrops jaracussu em camundongos: estudo morfológico e funcional

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ação de compostos vegetais sobra a atividade da Piratoxina-I, isolada do veneno de Bothrops pirajai, em preparação neuromuscular de camundongos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo dos aspectos clínico, laboratorial, histopatológico e do tratamento na intoxicação experimental pelo veneno da serpente Crotalus durissus terrificus em cães

Pós-graduação em Medicina Veterinária - FMVZ

Aspectos epidemiológicos e clínicos do escorpionismo na região de Santarém, Estado do Pará, Brasil

Este trabalho é um estudo prospectivo e descritivo dos aspectos epidemiológicos e clínicos de 72 envenenamentos por escorpiões admitidos no Hospital Municipal de Santarém, Estado do Pará, Brasil, entre fevereiro de 2000 a fevereiro de 2001. Trouxeram o animal 8,3% das vítimas, os quais foram identificados como T. cambridgei. O sexo masculino foi acometido em 83,3%. A idade das vítimas e o tempo para o socorro médico foram respectivamente de 33,6±18,3 anos e 4,6±3,2 horas em média. Os membros superiores foram acometidos em 51,5% dos casos. As manifestações locais estiveram presentes em 91,7% e as sistêmicas em 98,6% dos envenenamentos. Entre os sintomas locais encontramos: parestesia em 79,2%, dor em 52,8%, e edema em 26,4% dos casos. Nas manifestações sistêmicas predominou as queixas neurológicas em 97,2% das vítimas, sendo o sintoma de sensação de "choque elétrico" pelo corpo (88,9%) o mais freqüente. No exame neurológico os sinais mais encontrados foram: mioclonias (93,0%), dismetria (86,1%), disartria (80,6%) e ataxia de marcha (70,8%). Classificou-se como moderados 76,4% dos envenenamentos, sem nenhum caso grave. Deixaram de realizar a soroterapia 32,7% dos casos moderados, por ausência de soro específico no momento do atendimento. O escorpionismo da região de Santarém mostra um comportamento clínico regional diferente daqueles descritos no Brasil e de outros locais da Amazônia e, apresenta uma clínica predominantemente neurológica, ainda não descrita na literatura brasileira.

Estudos estruturais por difração de raios X de fosfolipases A2 em presença de íons com importância funcional

Snakes from Bothrops genus are responsible for more than 90% of the ophidian accidents in Brazil. One of the main complications from this kind of accident is muscular necrosis, which is related to the action of phospholipases A2 and metalloproteases, two groups of enzymes found in the venom of these animals. Although this complication cannot be solved by serum therapy administration, a great number of studies have been performed with the attempt to know the pharmacological sites of these toxins aiming, in the future, the development of complementary treatments to serum therapy. This work proposes structural studies of bothropic phospholipases A2 (PLA2s) in the presence of ions relevant to their activity, using the X-ray crystallography technique. Recently, it was demonstrated ions, as manganese, calcium and others, interfere in the biological activity of the PLA2s. Particularly, Lys49-PLA2s in the presence of manganese ions have miotoxicity reduced. Asp49-PLA2s show catalytic activity dependent of calcium, although structural studies with a miotoxic Asp49-PLA2, BthTX-II, suggest a possible catalytic mechanism independent of calcium. Therefore, co-crystallization of BthTX-II in the presence of calcium ions and of PrTX-I in the presence of manganese ions were performed. Comparative structural studies among obtained results and others already published in the literature were performed aiming a better understanding of the structure-function relationship of these toxins. The BthTX-II with the presence of calcium do not show this ion in the loop of coordination of calcium, presence necessary to develop the catalyses. After comparison of this model with the native one, only one distortion was found, but no apparent relationship with the residues responsible for its activity. In the PrTX-I structure, regions candidates of manganese ions were also found... (Complete abstract click electronic access below)

Atividade antiofídica do decocto das folhas de jatropha gossypiifolia l. frente o veneno de bothrops jararaca

Antiophidic activity from decoct of Jatropha gossypiifolia L. leaves against Bothrops jararaca venom. Snakebites are a serious worldwide public health problem. In Latin America, about 90 % of accidents are attributed to snakes from Bothrops genus. Currently, the main available treatment is the antivenom serum therapy, which has some disadvantages such as inability to neutralize local effects, risk of immunological reactions, high cost and difficult access in some regions. In this context, the search for alternative therapies to treat snakebites is relevant. Jatropha gossypiifolia L., a medicinal plant popularly known in Brazil as “pinhão-roxo”, is very used in folk medicine as antiophidic. So, the aim of this study is to evaluate the antiophidic properties of this species against enzymatic and biological activities from Bothrops jararaca snake venom. The aqueous leaf extract of J. gossypiifolia was prepared by decoction. The inhibition studies were performed in vitro, by pre-incubation of a fixed amount of venom with different amounts of extract from J. gossypiifolia for 60 min at 37 °C, and in vivo, through oral or intraperitoneal treatment of animals, in different doses, 60 min before venom injection. The proteolytic activity upon azocasein was efficiently inhibited, indicating inhibitory action upon metalloproteinases (SVMPs) and/or serine proteases (SVSPs). The extract inhibited the fibrinogenolytic activity, which was also confirmed by zymography, where it was possible to observe that the extract preferentially inhibits fibrinogenolytic enzymes of 26 and 28 kDa. The coagulant activity upon fibrinogen and plasma were significantly inhibited, suggesting an inhibitory action upon thrombin-like enzymes (SVTLEs), as well as upon clotting factor activators toxins. The extract prolonged the activated partial thromboplastin time (aPTT), suggesting an inhibitory action toward not only to SVTLEs, but also against endogenous thrombin. The defibrinogenating activity in vivo was efficiently inhibited by the extract on oral route, confirming the previous results. The local hemorrhagic activity was also significantly inhibited by oral route, indicating an inhibitory action upon SVMPs. The phospholipase activity in vitro was not inhibited. Nevertheless, the edematogenic and myotoxic activities were efficiently inhibited, by oral and intraperitoneal route, which may indicate an inhibitory effect of the extract upon Lys49 phospholipase (PLA2) and/ or SVMPs, or also an anti-inflammatory action against endogenous chemical mediators. Regarding the possible action mechanism, was observed that the extract did not presented proteolytic activity, however, presented protein precipitating action. In addition, the extract showed significant antioxidant activity in different models, which could justify, at least partially, the antiophidic activity presented. The metal chelating action presented by extract could be correlated with SVMPs inhibition, once these enzymes are metal-dependent. The phytochemical analysis revealed the presence of sugars, alkaloids, flavonoids, tannins, terpenes and/or steroids and proteins, from which the flavonoids could be pointed as major compounds, based on chromatographic profile obtained by thin layer chromatography (TLC). In conclusion, the results demonstrate that the J. gossypiifolia leaves decoct present potential antiophidic activity, including action upon snakebite local effects, suggesting that this species may be used as a new source of bioactive molecules against bothropic venom.

Avaliação anti-inflamatória e antipeçonhenta das espécies Hancornia speciosa e Mimosa tenuiflora em modelos experimentais de inflamação e envenenamento induzidos por Bothrops jararaca e Tityus serrulatus

Accidents caused by venomous animals represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world by the frequency with which they occur and the mortality they cause. The use of plant extracts as an antidote for poisoning cases is an ancient practice used in many communities that have no access to antivenom. Medicinal plants represent an important source of obtaining bioactive compounds able to assist directly in the treatment of poisoning or indirectly supplementing serum therapy currently used. The aim of this study was to evaluate the effect of extracts, fractions and isolated compounds from M. tenuiflora and H. speciosa in the inflammatory process induced by carrageenan and the venom of B. jararaca and T. serrulatus. The results showed that both M. tenuiflora and H. speciosa were capable of inhibiting cell migration and cytokines levels in peritonitis induced by carrageenin and venom of T. serrulatus. In poisoning by B. jararaca model, mice treated with the plants in studies decreased the leukocyte influx into the peritoneal cavity. Finally the M. tenuiflora and H. speciosa had antiphlogistic activity, reducing edema formation and exerted inhibitory action of leukocyte migration in local inflammation induced by the venom of B. jararaca. Through of Thin Layer Chromatography (TLC) analysis was possible identified the presence of flavonoids ,saponins and/or terpenes in aqueous extract of M. tenuiflora. By High Performance Liquid Chromatography analysis, it was possible to identify the presence of rutin and chlorogenic acid in aqueous extract of H. speciosa. We conclude that the administration of extracts, fractions and isolated compounds of H. speciosa and M. tenuiflora resulted in inhibition of the inflammatory process in different experimental models. This study demonstrates for the first time the effect of M. tenuiflora and H. speciosa in inhibition of the inflammation caused by B. jararaca and T. serrulatus venom.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Inibição dos efeitos locais induzidos pelas peçonhas das serpentes Bothrops erythromelas e Bothrops jararaca pelo extrato aquoso das folhas de Jatropha mollissima (Pohl) Bail

Snakebites are a serious public health problem in tropical and subtropical countries and Bothrops genus is responsible for the accidents in Brazil and throughout Latin America (90% of cases). The local effects (pain, edema, hemorrhage and myonecrosis) and systemic (cardiovascular alterations, shock and blood clotting disorders) caused by the venom of Bothrops are due to the numerous protein and non-protein components, which are part of the constitution of the poison. The only form of therapy is scientifically validated antivenom serum therapy which, however, is not effective with respect to local effects produced, risk of immunological reactions, high cost and difficult access in some regions. Thus, the search for new alternatives to serum therapy becomes important, and in this context, many medicinal plants have been highlighted by the popular use as antiophidic. Among these plants, we can mention the species Jatropha mollissima (Euphorbiaceae) which has popular use in traditional medicine as antiophidic, anti-inflammatory, antimicrobial and antipyretic. Therefore, this study aims to evaluate the neutralizing potential of local effects induced by the venom of Bothrops erythromelas and Bothrops jararaca with the aqueous extract of the leaves of J. mollissima. The leaf extracts were prepared by decoction, fractionated (by liquid-liquid partition) and characterized by thin layer chromatography (TLC) and High Performance Liquid Chromatography (HPLC). Antiophidic activity of the extract was evaluated in model of paw edema, peritonitis, bleeding and myotoxicity induced by venoms of B. jararaca and B. erythromelas. In all models, the extract was evaluated by intraperitoneal route at the doses of 50, 100 and 200 mg/kg, administered 30 minutes prior to injection of the venom (pretreatment protocol). Stains suggestive of the presence of flavonoids: apigenin, luteolin, orientin, isoorientin, vitexin and vitexin-2-O-rhamnoside were detected in the extract by co-CCD. By means of HPLC were identified isoorientin, orientin, vitexin and isovitexin. All tested doses of J. mollissima extract reduced the paw edema induced by the venom with intensity similar to dexamethasone. The aqueous extract of J. mollissima leaves on all evaluated doses, inhibited cell migration induced by B. jararaca and B. erythromelas promoting inhibition of recruitment of mononuclear cells and the polymorphonuclear cells. Local bleeding induced by B. jararaca venom was significantly inhibited by the extract. Both venoms were inhibited by the extract in myotoxic activity. These results indicate that the aqueous extract of J. mollissima leaves have snakebite potential, particularly with respect to local effects, which may justify the use of this plant in traditional medicine and complementary therapy as anti-venom serum.