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Efectos locales en el envenenamiento ofídico en América Latina

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... Additionally, the increase in intracellular Ca 2+ also produces hypercontraction of myofilaments (Lomonte et al., 1994a;, overactivation of calpains (Capn) that hydrolyze essential structural components in the mechanical stability of the contractile machinery in muscles, and activation of Ca 2+ -dependent cytosolic PLA 2 , increasing phospholipid hydrolysis in plasma membrane and other intracellular membranes. Similarly, cell necrosis and its derivative products favor the release of mediators that promote cell inflammation, contributing to tissue damage, for example, the myotoxins release ATP and potassium ions from myotubes in such a way that they amplify cellular damage to neighboring cells through purinergic receptors (Gutiérrez et al., 1984b;Gutiérrez and Lomonte, 2003;Montecucco et al., 2008; (Fig. 5). ...
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Snake venoms are a complex biological mixture of proteins with or without enzymatic activity, peptides, and nucleotides, among other components. It is produced in specialized secretory glands located in the maxillary region, being the result of millions of years of evolution and whose biological functions are defense, immobilization, and digestion of prey. Venoms present intraspecific (i.e., individual, ontogenetic, geographical) and interspecific (i.e., between sympatric and allopatric species) variation, and the study of this variability has become the focus of toxinological research. Bothrops asper is responsible for highest incidence, morbimortality and severe cases of envenoming in Mesoamerica and northern South America. Given its clinical importance, its venom has been characterized and compared qualitatively and quantitatively across the species range. More than 50 years of research show that B. asper venom is endowed with an interesting intraspecific variability. Knowing this variation has allowed advances in the elucidation of the biological role of the venom, a better understanding of the clinical signs and symptoms in patients envenomed by B asper, the immunological implications in the context of antivenoms production, and the generation of new ideas that could be useful to solve different biological and evolutionary questions of one of the venomous snakes with the greatest distribution and strongest public health impact in Latin America.
... The venom of B. asper induces both local alterations at the site of venom injection (edema, hemorrhage, dermonecrosis, flictenas, myonecrosis), and systemic effects that can be life threatening (defibrination, bleeding distant from the bite site, nephrotoxicity and cardiovascular shock) (Otero et al., 2002;Gutiérrez & Lomonte, 2003;Gutiérrez, Rucavado, Chaves, Díaz, & Escalante, 2009). Snake venom is a complex mixture, which in addition to a large variety of toxins, enzymes and proteins without enzymatic activity, also contains amino acids, nucleotides, phosphorylated sugars, lipids, and metal ions. ...
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Introduction: It is estimated that 2 000 snakebites occur in Panama every year, 70 % of which are inflicted by Bothrops asper. Objective: To determine the biochemical and toxicologic effects and to assess the immunochemical characteristics of a reference pool of B. asper venom representative of Panama. Methods: The reference venom was prepared as a homogeneous mixture of the venoms obtained from 78 adult snakes collected in four geographic areas of Panama. Enzymatic and toxicological activities were assessed. The electrophoretic pattern was studied by SDS-PAGE. Immunoreactivity of various antivenoms was analyzed by Western blot. Results: B. asper reference venom has lethal, hemorrhagic, myotoxic, edema-forming, coagulant, defibrinating, proteinase and phospholipase A2 activities. SDS-PAGE showed the presence of protein bands with molecular weights ranging from 8 to 70 kDa, with the presence of predominant bands at ≈ 15 kDa and ≈ 30 to 66 kDa, which likely correspond to phospholipases A2 and metalloproteinases, respectively. Immunoblotting showed a high degree of recognition by various antivenoms, especially by antivenoms from Colombia and Costa Rica. Conclusions: Following recommendations by the World Health Organization, this reference venom of B. asper of Panama will become a useful tool for the preclinical evaluation of antivenoms distributed in this country.
... However, in the B. colombiensis venom, many bands were observed in these molecular weight locations. Important components of Bothrops genus venoms have been shown to be positioned in this gel region, such as proteins with myotoxic, (48) coagulant activity, phospholipase A2 and metalloproteases with fibrinolytic and haemorrhagic (49) actions. ...
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Objective: to describe the haemostatic characteristics of the venom as well as the potency appraisal of the polyvalent antiophidic serum against haemotoxicity from Porthidium lansbergii hutmani experimental envenomation. Methods: Evaluation was performed of the venom's lethality, haemorrhagic activity, effects on coagulation and platelet aggregation, proteolytic activity, and neutralization by the commercial antivenom available in the country. Results: Several components with haemostatic activities were found in Porthidium l. hutmanni venom when a study of fibrinogenolytic, haemorrhagic and proteolytic activities was conducted of a pool of P.l.h venom. Porthidium l. hutmanni venom lacked the coagulant and defibrinating activities that are characteristic of bothropic venoms. Porthidium l. hutmanni venom showed very high haemorrhagic and anticoagulant activities. These findings could be related to the presence of multiple metalloproteases, which was evidenced in this study, and also the possible presence of phospholipases or other anticoagulant activity proteins that were not defined here. They inhibited platelet aggregation, suggesting that the venom had some proteins with marked effects on haemostasis. The commercial antivenom proved to be of little effectiveness in neutralizing the crude venom haemorrhagic activity. Conclusions: These toxins cause many physiopathological alterations in bitten patients, creating a clinical picture characterized by oedema, local and systemic haemorrhages, and even necrosis, comparable to that seen in bothropic envenomation. Porthidium l. hutmanni venom has no in vitro procoagulant activity, typical of bothropic venoms, suggesting there are variances in its protein conformation. Porthidium l. hutmanni venom is used for horse immunization. However, in order to preserve the patient's life, it is necessary to improve the immunization process to produce antivenom containing high avidity and specificity antibodies against the major toxins present in this venom. Porthidium l. hutmanni venom has demonstrated being a venom with high lethal, haemorrhagic, proteolytic and procoagulant activities, whose description will have enormous utility among clinicians who deal with these accidents in its geographical distribution areas.
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Bothrops leucurus is the major causative agent of venomous snakebites in Northeastern Brazil. Severe pain is the most frequent symptom in these envenomings, with an important inflammatory component. This work characterized the pronociceptive effects evoked by B. leucurus venom (BLV) in mice and the role of inflammatory mediators in these responses. The nociceptive behaviors were quantified by the modified formalin test. The mechanical hyperalgesia was assessed by the digital von Frey test. Pharmacological assays were performed with different antagonists and synthesis inhibitors to investigate the involvement of inflammatory mediators in both nociceptive events. BLV (1–15 μg/paw) injection in mice evoked intense and dose-dependent nociceptive behaviors that lasted for up to 1 h. BLV (10 μg/paw) also caused sustained mechanical hyperalgesia. Histamine and serotonin played a role in the nociception, but not in the BLV-induced mechanical hyperalgesia. Nitric oxide contributed to both responses, but only to the late stages of mechanical hyperalgesia. Eicosanoids were also present in both nociceptive responses. Prostanoid synthesis by COX-1 seemed to be more relevant for the nociception, whereas COX-2 had a more prominent role in the mechanical hyperalgesia. Leukotrienes were the most relevant mediators of BLV-induced mechanical hyperalgesia, hence inhibiting lipoxygenase pathway could be an efficient therapeutic strategy for pain management during envenoming. Our behavioral data demonstrates that BLV promotes nociceptive transmission mediated by biogenic amines, nitric oxide and eicosanoids, and nociceptor sensitization through nitric oxide and eicosanoids. Moreover, phospholipases A2 (PLA2), an important class of toxins present in bothropic venoms, appear to play an important role in the nociceptive and hypernociceptive response induced by BLV.
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Symbolic constructions in traditional medicine and territory management are a cultural reference of the rural communities, no matter the ethnic group to which they belong. The knowledge and visibility of this ancestral background, the approach to its cosmogony and the traditional management of the ophidian poisonings reveals the cultural and ethnobiological wealth of diverse groups located in rural areas, however it is showed as a negative referent associated with a increased morbidity and accident rates in the Antioquia department. Description of the most common ethnoecological practices carried out in different rural areas of Antioquia allows us to understand the scenario of the ophidic accident in some remote communities as ethnic groups and peasants. We could analyze several bioecological aspects associated with the phenomenon of ophidism: land management and identification. RESUMEN Las construcciones simbólicas en medicina tradicional y manejo del territorio son un referente cultural de las comunidades rurales, independiente del grupo étnico al que pertenezcan. El conocimiento y visibilización de estos saberes ancestrales, el acercamiento a su cosmogonía y el manejo tradicional de los envenenamientos ofídicos, revela la riqueza cultural y etnobiológica de diversos grupos que habitan zonas rurales; sin embargo continúan siendo vistos como un referente negativo asociado al aumento de las cifras de morbilidad y accidentalidad en el departamento de Antioquia. La descripción de las manifestaciones etnoecologicas más comunes llevadas a cabo en diferentes zonas rurales de Antioquia, nos permiten entender el panorama del accidente ofídico en algunas comunidades étnicas y campesinas distantes. Se pueden analizar diferentes aspectos bioecológicos asociados al fenómeno del ofidismo: manejo del territorio e identificación del agente agresor, prácticas ancestrales y atención pre hospitalaria; todo esto, como medida inicial para comprender aquellos atenuantes sociales y etnoculturales que son señalados como la principal causa del aumento de las cifras de morbimortalidad ofídica en Colombia. Se correlacionan los resultados etnográficos obtenidos con los perfiles epidemiológicos reportados por el sistema de vigilancia en salud con la intención de ilustrar el panorama etnosocial, cultural y ecológico de los grupos poblacionales humanos de las zonas de mayor influencia. Esto permite visibilizar el saber ancestral y plantear un acercamiento conciliado entre la comunidad y el gremio de la salud, para promover la construcción de planes alternativos en educación y promoción de la salud integral que proyecten una mejora al bienestar de los miembros de las comunidades rurales a partir del diálogo intercultural y los programas de prevención del accidente ofídico. PALABRAS CLAVE: Construcciones simbólicas/saberes ancestrales, accidente ofídico/ofidismo, diálogo intercultural, serpiente y medicina tradicional.
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In rural communities, there are symbolic constructions that associate snakes with rituals, stories and even evil spells. Knowing these stories and their meaning allows us to understand how and why alternative practices are carried out to manage the cases of poisoning caused by the bite of these reptiles. Thus, this work mentions the most used practices, and in a context of constructive socialization, aims to approximate them to government proposals for primary health care, in order to reduce the morbidity figures in the rural populations evaluated.
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In Brazil, envenomation by snakes of the genus Bothrops is clinically relevant, particularly for the species Bothrops jararaca and B. erythromelas. The most effective treatment for envenomation by snakes is the administration of antivenoms associated with adjuvants. Novel adjuvants are required to reduce side effects and maximize the efficiency of conventional serum and vaccine formulations. The polymer chitosan has been shown to have immunoadjuvant properties, and it has been used as a platform for delivery systems. In this context, we evaluated the potential immunoadjuvant properties of chitosan nanoparticles (CNPs) loaded with B. jararaca and B. erythromelas venoms in the production of sera against these venoms. Stable CNPs were obtained by ionic gelation, and mice were immunized subcutaneously for 6 weeks with 100 µL of each snake venom at concentrations of 5.0 or 10.0% (w/w), encapsulated in CNPs or associated with aluminium hydroxide (AH). The evaluation of protein interactions with the CNPs revealed their ability to induce antibody levels equivalent to those of AH, even with smaller doses of antigen. In addition, the CNPs were less inflammatory due to their modified release of proteins. CNPs provide a promising approach for peptide/protein delivery from snake venom and will be useful for new vaccines.
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