Primer registro de un caso de loxoscelismo cutáneo ocasionado por mordedura de araña violinista (Loxosceles yucatana) en Yucatán, México / First record of a case of cutaneous loxoscelism caused by violin spider (Loxosceles yucatana) bite in Yucatan, Mexico

El loxoscelismo es ocasionado cuando el veneno dermonecrótico producido por las arañas del género Loxosceles, conocidas como «arañas violinistas», ingresa al organismo de una persona a través de su mordida. En México ocurre un subregistro de los casos de loxoscelismo por la ausencia de pruebas de laboratorio para su diagnóstico y la dificultad del cuadro clínico. El objetivo de este trabajo es describir un caso de loxoscelismo cutáneo ocasionado por mordedura de Loxosceles yucatana en un residente de Yucatán, México. El loxoscelismo cutáneo es el tipo más frecuente y menos severo. El presente caso se diagnosticó por medio de la sintomatología registrada en la historia clínica, la lesión inicial y la identificación de arañas L. yucatana. Este trabajo representa la primera descripción de un caso de loxoscelismo cutáneo con resolución favorable en Yucatán.

Loxoscelism occurs when the dermonecrotic venom produced by spiders of the genus Loxosceles, known as "violin spiders," enters a person's organism through their bite. In Mexico there is an underreporting of loxoscelism cases due to the absence of laboratory tests for its diagnosis and the complexity of the clinical picture. The aim of this paper is to describe a case of cutaneous loxoscelism caused by the bite of Loxosceles yucatana in a resident of Yucatan, Mexico. Cutaneous loxoscelism is the most frequent and less severe type. This case was diagnosed by means of the symptomatology registered in the medical records, the initial lesion, and the identification of L. yucatana spiders. This study represents the first description of a case of cutaneous loxoscelism with favorable outcome in Yucatan.

Manifestaciones cardiovasculares y síndrome compartimental asociado a mordedura por Phoneutria spp: Reporte de un caso / Cardiovascular manifestations and compartment syndrome associated with bite by Phoneutria spp: case report / Manifestações cardiovasculares e síndrome compartimental associadas à mordida de Phoneutria spp: Relato de caso

Se describen las características sobre el phoneutrismo a propósito de un caso. El phoneutrismo es el término con el que se conoce al accidente ocasionado por la mordedura de la araña phoneutria spp, la cual tiene una relevancia clínica dada por las características tóxicas de su veneno. Se presenta un caso de mordedura de la araña phoneutria spp de un paciente atendido en un hospital de alta complejidad de la ciudad de Medellín, Colombia, con manifestaciones cardiovasculares y hallazgos compatibles con un síndrome compartimental, lo cual es inusual en este tipo de arañas, por lo que se necesitó vigilancia en unidad de alta dependencia y fasciotomía cutánea. En Colombia este tipo de accidentes no son de reporte obligatorio, por tanto existe un alto riesgo de subregistro. Lo llamativo de este caso está en las manifestaciones cardiovasculares y la presencia de síndrome compartimental que no se ha descrito en la literatura con este subespecie de arañas.

The characteristics of phoneutrism are described in relation to a case. Phoneutrism is the term with which the accident caused by the bite of the phoneutria spp spider is known, which has clinical relevance given by the toxic characteristics of its venom. We present a case of a bite by the phoneutria spp spider in a patient treated at a high-complexity hospital in the city of Medellín, Colombia, with cardiovascular manifestations and findings compatible with compartment syndrome, which is unusual in this type of spiders, and required surveillance in a high dependency unit and cutaneous fasciotomy. In Colombia reporting this type of accident is not mandatory; therefore, there is a high risk of underreporting. What is striking about this case is the cardiovascular manifestations and the presence of compartment syndrome that has not been described in the literatura with this genre of spiders.

As características do fonutrismo são descritas em um relatório de um caso. Fonutrismo é o termo usado para descrever o acidente causado pela mordida da aranha Phoneutria spp, que é clinicamente relevante devido às características tóxicas de seu veneno. Apresentamos um caso de mordida de aranha por uma aranha Phoneutria em um paciente tratado em um hospital de alta complexidade na cidade de Medellín, Colômbia, com manifestações cardiovasculares e achados compatíveis com a síndrome compartimental, o que é incomum neste tipo de aranha, exigindo vigilância em uma unidade de alta de-pendência e fasciotomia cutânea. Na Colômbia, este tipo de acidente não é obrigatório, portanto, há um alto risco de subnotificação. O que é impressionante neste caso são as manifestações cardiovasculares e a presença da síndrome compartimental, que não foi descrita na literatura com esta subespécie de aranha.

Agkistrodon halys venom antitumor component-I inhibits vasculogenic mimicry in triple-negative breast cancer cells in vitro by down-regulating MMP2 / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of agkistrodon halys venom antitumor component-I (AHVAC-I) on vasculogenic mimicry (VM) formation in triple-negative breast cancer MDA-MB-231 cells and explore its possible mechanism.@*METHODS@#CCK8 assay was used to determine the optimal concentration of AHVAC-I for cell treatment based on its halfinhibitory concentration (IC50). MDA-MB-231 cells were treated with different concentrations of AHVAC-I or 5-Fu, and the changes in vasomimetic capacity of the cells were examined using Matrigel assay. The expression levels of matrix metalloproteinase-2 (MMP2) and MMP9 in the treated cells were detected using quantitative PCR and Western blotting.@*RESULTS@#Compared with the control treatment with culture medium, treatment with 5, 10 and 20 μg/mL AHVAC-I significantly reduced vasomimetic ability of MDA-MB-231 cells in a dose-dependent manner (P < 0.01). MMP2 supplementation obviously restored the vasomimetic ability of the cells inhibited by AHVAC-I.@*CONCLUSION@#AHVAC-I inhibits VM formation in triplenegative breast cancer cells in vitro by down-regulating MMP2 production.

Venenos de serpentes do gênero Bothrops: impacto da glicosilação na complexidade dos proteomas e função de toxinas / Bothrops snake venoms: impact of glycosylation on the complexity of proteomes and toxins function

A variabilidade estrutural é uma característica das proteínas de venenos de serpentes, e a glicosilação é uma das principais modificações pós-traducionais que contribui para a diversificação de seus proteomas. Recentes estudos de nosso grupo demonstraram que venenos do gênero Bothrops são marcadamente definidos pelo seu conteúdo de glicoproteínas, e que a maioria das estruturas de N-glicanos dos tipos híbrido e complexo identificados em oito venenos deste gênero contêm unidades de ácido siálico. Em paralelo, em glicoproteínas do veneno de B. cotiara foi identificada a presença de uma estrutura de N-acetilglicosamina bissecada. Assim, com o objetivo de investigar a variação do conteúdo de glicoproteínas, assim como os mecanismos envolvidos na geração dos diferentes venenos de Bothrops, neste estudo foram analisados comparativamente os glicoproteomas de nove venenos do gênero Bothrops (B. atrox, B. cotiara, B. erythromelas, B. fonsecai, B. insularis, B. jararaca, B. jararacussu, B. moojeni e B. neuwiedi). As abordagens glicoproteômicas envolveram cromatografia de afinidade e ensaio de pull-down utilizando, respectivamente, as lectinas SNA (aglutinina de Sambucus nigra) e MAL I (lectina de Maackia amurensis), que mostram afinidade por unidades de ácido siálico nas posições, respectivamente, α2,6 e α2,3; e cromatografia de afinidade com a lectina PHA-E (eritroaglutinina de Phaseolus vulgaris), que reconhece N-acetilglicosamina bissecada. Ainda, eletroforese de proteínas, blot de lectina, e identificação de proteínas por espectrometria de massas foram empregadas para caracterizar os glicoproteomas. As lectinas geraram frações dos venenos enriquecidas de diferentes componentes, onde as principais classes de glicoproteínas identificadas foram metaloprotease, serinoprotease, e L-amino ácido oxidase, além de outras enzimas pouco abundantes nos venenos. Os diferentes conteúdos de proteínas reconhecidas por essas lectinas, com especificidades distintas, ressaltaram novos aspectos da variabilidade dos subproteomas de glicoproteínas desses venenos, dependendo da espécie. Ainda, considerando que metaloproteases e serinoproteases são componentes abundantes nesses venenos e fundamentais no quadro de envenenamento botrópico, e que estas enzimas contêm diversos sítios de glicosilação, o papel das unidades de ácido siálico na atividade proteolítica das mesmas foi avaliado. Assim, a remoção enzimática de ácido siálico (i) alterou o padrão de gelatinólise em zimografia da maioria dos venenos, (ii) diminuiu a atividade proteolítica de alguns venenos sobre o fibrinogênio e a atividade coagulante do plasma humano de todos os venenos, e (iii) alterou o perfil de hidrólise de proteínas plasmáticas pelo veneno de B. jararaca, indicando que este carboidrato pode desempenhar um papel na interação das proteases com seus substratos proteicos. Em contraste, o perfil da atividade amidolítica dos venenos não se alterou após a remoção de ácido siálico e incubação com o substrato Bz-Arg-pNA, indicando que ácido siálico não é essencial em N-glicanos de serinoproteases atuando sobre substratos não proteicos. Em conjunto, esses resultados expandem o conhecimento sobre a variabilidade de proteomas de venenos do gênero Bothrops e apontam a importância das cadeias de carboidratos contendo ácido siálico nas atividades enzimáticas das proteases desses venenos

Structural variability is a feature of snake venom proteins, and glycosylation is one of the main post-translational modifications that contributes to the diversification of venom proteomes. Recent studies by our group have shown that Bothrops venoms are markedly defined by their glycoprotein content, and that most hybrid and complex N-glycan structures identified in eight venoms of this genus contain sialic acid units. In parallel, the presence of a bisected N-acetylglucosamine structure was identified in B. cotiara venom glycoproteins. Thus, with the aim of investigating the variation in the content of glycoproteins, as well as the mechanisms involved in the generation of different Bothrops venoms, in this study the glycoproteomes of nine Bothrops venoms (B. atrox, B. cotiara, B. erythromelas, B. fonsecai, B. insularis, B. jararaca, B. jararacussu, B. moojeni e B. neuwiedi) were comparatively analyzed. The glycoproteomic approaches involved affinity chromatography and pulldown using, respectively, the lectins SNA (Sambucus nigra agglutinin) and MAL I (Maackia amurensis lectin), which show affinity for sialic acid units at positions, respectively, α2,6 and α2,3, and affinity chromatography with PHA-E (Phaseolus vulgaris erythroagglutinin), which recognizes bisected N-acetylglucosamine. In addition, protein electrophoresis, lectin blot, and protein identification by mass spectrometry were employed for glycoproteome characterization. The lectins generated venom fractions enriched with different components, where the main classes of glycoproteins identified were metalloprotease, serine protease, and L-amino acid oxidase, in addition to other low abundant enzymes. The different contents of proteins recognized by these lectins of distinct specificities highlighted new aspects of the variability of the glycoprotein subproteomes of these venoms, depending on the species. Furthermore, considering that metalloproteases and serine proteases are abundant components of these venoms and essential in Bothrops envenomation, and that these enzymes contain several glycosylation sites, the role of sialic acid units in their proteolytic activities was evaluated. Thus, enzymatic removal of sialic acid (i) altered the pattern of gelatinolysis in zymography of most venoms, (ii) decreased the proteolytic activity of some venoms on fibrinogen and the clotting activity of human plasma of all venoms, and (iii) altered the hydrolysis profile of plasma proteins by B. jararaca venom, indicating that this carbohydrate may play a role in the interaction of proteases with their protein substrates. In contrast, the profile of amidolytic activity of the venoms did not change after removal of sialic acid and incubation with the substrate Bz-Arg-pNA, indicating that sialic acid is not essential in N-glycans of serine proteases acting on small substrates. Together, these results expand the knowledge about the variability of proteomes of Bothrops venoms and point to the importance of carbohydrate chains containing sialic acid in the enzymatic activities of venom proteases

Spiders in Brazil: from arachnidism to potential therapeutic use of their venom part 1 of 2

Spider envenomation, generically known as arachnidism, is described in many places around the world. In terms of medical importance, the following genera of animals stand out as the main origin of the morbid condition: Atrax (Sidney funnel web spider), Steatoda (false black widow), Latrodectus (black widow), Loxosceles (brown spider) and Phoneutria (armed spider), the last three causing accidents involving spiders in Brazil. This article, part 1 of 2, aims to present the main aspects of arachnidism in the country, with an emphasis on the biology and geographical distribution of spiders, biochemistry of the venom, pathogenesis and epidemiology of arachnidism, as well as prevention of the morbid condition.

Spiders in Brazil: from arachnidism to potential therapeutic use of their venom part 2 of 2

Arachnidism, spider envenomation, is an important public health issue in different parts of the world. Its clinical evolution depends on the genus involved. Symptoms and signs range from skin alterations to systemic manifestations. The success of treatment, consisting of serotherapy and other measures, depends on the patient's immediate care. In addition to the potential injury to human hosts, spider venom has been investigated for the therapy of various diseases. Based on these considerations, this article, part 2 of 2, aims to present the main aspects of spider accidents, focusing on clinical findings, diagnosis, differential diagnosis and treatment, as well as highlighting the potential of the venom of these arachnids.

Landscape of research, production, and regulation in venoms and antivenoms: a bibliometric analysis / Panorama de la investigación, la producción y la regulación de venenos y antivenenos: un análisis bibliométrico / Panorama de pesquisa, produção e regulação de venenos e antivenenos: análise bibliométrica

ABSTRACT Objectives. To assess the productivity and visibility in research, clinical studies, treatment, use and production of antivenoms against poisonous snakes, scorpions and spiders. Methods. Bibliometric analysis of research and other activities. Articles on venoms and antivenoms published between 2000 and 2020 were retrieved from the Scopus database. The records were analyzed by bibliometric indicators including number of documents per year, journals, authors, and citation frequency. VOSviewer® v.1.6.13 was used to construct bibliometric networks for country co-authorships and co-occurrence of terms. Results. Australia, Brazil, Costa Rica and India were among the six top countries with most documents and were selected for more detailed analysis. Costa Rica was the country with the largest percentage of its publications dedicated to antivenom production and venomics. Only a few papers dealt with the issues of quality, safety, and efficacy of antivenoms or the role of the national regulatory authorities. The use of VOSviewer® allowed visualization through joint publications of networking between countries. Visualization by co-occurrence of terms showed differences in the research carried out. Conclusions. Working in a collaborative and coordinated manner these four countries could have a major impact on envenoming globally. Attention should be given not only to antivenom production but also to strengthening regulatory oversight of antivenom products.

RESUMEN Objetivos. Evaluar la productividad y la visibilidad en la investigación, los estudios clínicos, el tratamiento, el uso y la producción de antivenenos contra las picaduras de serpientes, arañas y escorpiones venenosos. Métodos. Análisis bibliométrico de la investigación y de las otras actividades. Se tomaron los artículos sobre venenos y antivenenos publicados entre el 2000 y el 2020 en la base de datos de Scopus. Estos documentos se analizaron mediante indicadores bibliométricos como el número de documentos por año, revistas, autores o frecuencia en las citas. Se utilizó VOSviewer® v.1.6.13 para crear una red bibliométrica para coautorías de países y coapariciones de términos. Resultados. Australia, Brasil, Costa Rica e India estaban entre los seis primeros países con más documentos y se seleccionaron para un análisis más detallado. Costa Rica fue el país con el mayor porcentaje de sus publicaciones dedicadas a la producción de antivenenos y la venómica. Solo unos pocos artículos trataban los temas de la calidad, la seguridad y la eficacia de los antivenenos, o la función de las autoridades regulatorias nacionales. Gracias a VOSviewer® pudimos visualizar las publicaciones conjuntas de las colaboraciones entre países. La visualización por la coaparición de términos arrojó diferencias en la investigación realizada. Conclusiones. Si estos cuatro países trabajasen de forma colaborativa y coordinada, podrían tener una repercusión mayor en los envenenamientos por picaduras en el mundo. El foco no debe ponerse solo en la producción de antivenenos, sino también en fortalecer la supervisión regulatoria de estos productos.

RESUMO Objetivos. Avaliar a produtividade e visibilidade em pesquisa, estudos clínicos, tratamento, uso e produção de antivenenos contra peçonhas de serpentes, escorpiões e aranhas. Métodos. Análise bibliométrica de pesquisas e outras atividades. Artigos sobre venenos e antivenenos publicados entre 2000 e 2020 foram obtidos da base de dados Scopus. O conteúdo foi analisado segundo indicadores bibliométricos, como número de artigos por ano, periódicos, autores e frequência de citação. Utilizou-se o software VOSviewer® v.1.6.13 para construir redes bibliométricas de coautoria de países e co-ocorrência de termos. Resultados. Austrália, Brasil, Costa Rica e Índia figuraram entre os seis principais países com o maior número de artigos e, assim, foram selecionados para uma análise mais aprofundada. A Costa Rica teve a maior porcentagem de publicações dedicadas à produção de antivenenos e pesquisa em venômica. Apenas um pequeno número de artigos tratou de questões relacionadas à qualidade, segurança e eficácia dos antivenenos ou ao papel das autoridades nacionais reguladoras. O software VOSviewer® permitiu visualizar, através das publicações conjuntas, as redes formadas entre diferentes países. A visualização por co-ocorrência de termos revelou diferenças nas pesquisas realizadas. Conclusões. Trabalhando de forma colaborativa e coordenada, esses quatro países tiveram uma influência importante em nível mundial no campo de acidentes por animais peçonhentos. Deve-se atentar não apenas à produção de antivenenos, mas também ao fortalecimento da fiscalização regulatória destes.

Epidemiology of accidents involving venomous animals in the State of Ceará, Brazil (2007-2019)

Abstract INTRODUCTION: Envenomation remains a neglected public health problem in most tropical countries. Epidemiological studies on accidents caused by venomous animals are scarce in the Northeast region of Brazil, mainly in the state of Ceará. The present study aimed to describe the epidemiological features of envenomation cases involving venomous animals in the State of Ceará, Northeastern Brazil, from 2007 to 2019. METHODS: The online Notifiable Diseases Information System was consulted for data on all envenomation cases involving venomous terrestrial animals. Data collected were evaluated for the number of accidents/year, number of accidents/zoological group, antivenom therapy, zone of occurrence, sex, age-group distribution, and deaths. RESULTS: A total of 54,980 cases were recorded, with the highest incidence being that of scorpion stings (67.2%), predominantly in women (52.4%; odds ratio=3.6; 95% confidence interval=3.5-3.8), equally affecting people aged 10-19 years and 40-59 years (21.4%), in the urban areas (odds ratio=10.3; 95% confidence interval=9.9-10.8), especially in the rainy months. Snakebites (16.7%) had an incidence of 8.1/100,000 inhabitants, but the highest case-fatality rates were observed in bee stings (1.3%) and spider bites (0.5%). Regarding therapeutic variables, a small percentage of people had access to serotherapy (5.3%). CONCLUSIONS This study highlights the accidents caused by terrestrial venomous animals as a public health problem that must be monitored in Ceará. Thus, our findings suggest that preventive actions against scorpion and bee stings should be intensified during the months of higher incidence to improve public policies for patient care.

Neutralización de la actividad letal del veneno de serpiente Bothrops atrox por suero hiperinmune de llama (Lama glama) / Neutralization of the lethal activity from Bothrops atrox venom by hyperimune llama serum (Lama glama)

RESUMEN Objetivos: Evaluar la capacidad del suero hiperinmune de llama (Lama glama) para neutralizar la letalidad del veneno de la serpiente Bothrops atrox en ratones de laboratorio. Materiales y métodos: Se calculó la dosis letal media (DL50) de un pool de venenos de serpientes de Bothrops atrox de Perú, y se midieron los títulos de anticuerpos por ensayo ELISA; así como la potencia de neutralización del suero inmune por el cálculo de la dosis efectiva media (DE50) durante el periodo de inmunización. Resultados: La DL50 del veneno fue de 3,96 µg/g, similar a otros trabajos realizados en Bothrops atrox en Perú. Los títulos de anticuerpos contra el veneno se incrementan rápidamente en la llama mostrando una rápida respuesta inmune; sin embargo, la capacidad de neutralización se incrementa más lentamente y requiere de varias dosis y refuerzos de las inmunizaciones alcanzado una DE50 de 3,30 µL/g ratón y una potencia de neutralización 3,6 mg/mL después de 15 inmunizaciones. Conclusiones: El suero hiperinmune de llama es capaz de neutralizar la letalidad del veneno de la serpiente Bothrops atrox de Perú en ratones de laboratorio.

ABSTRACT Objectives: To evaluate the capacity of the hyperimmune llama serum (Lama glama) to neutralize the lethal activity of Bothrops atrox venom in laboratory mice. Materials and methods: Mean lethal dose (LD50) was calculated from a Bothrops atrox venom sample pool from Peru. The antibody titers were measured by ELISA assay; and the immune serum neutralization potency was measured by calculating the mean effective dose (ED50) during the immunization period. Results: The venom's LD50 was 3.96 μg/g; similar to what was found in other studies about Bothrops atrox carried out in Peru. The titers of antibodies against the venom increased rapidly in the llama, demonstrating a fast immune response; however, the neutralization capacity increased slowly and required several doses and immunization reinforcements, obtaining a ED50 of 3.30 μL/g mouse and a neutralization potency of 3.6 mg/mL after 15 immunizations. Conclusions: The hyperimmune llama serum is able to neutralize the lethality of the Bothrops atrox venom from Peru in laboratory mice.

Epidemiology of the injury with venomous animals in the state of Rio Grande do Norte, Northeast of Brazil / Epidemiologia dos acidentes com animais peçonhentos no estado do Rio Grande do Norte, Nordeste do Brasil

Abstract This report is an investigation of the epidemiological features of injuries with venomous animals in the Rio Grande do Norte state, Northeastern Brazil, from 2007 to 2014. A total of 30,429 cases were analyzed. Cases were distributed over all months of the period studied and occurred mainly in urban areas. Scorpion stings showed the highest percentage of cases, but the chance of death among snakebites was higher. Envenomation predominated in females with age between 20 and 49 years old. Children and elderly showed a higher chance of death. Most victims were bitten on the extremities of the limbs and received medical care within 0-1 hour after being bitten. The main local and systemic symptoms reported were pain and headache, respectively. Cases were mostly classified as mild and progressed to cure. Few victims show local and systemic complications. The high number of accidents with venomous animals shows that Rio Grande do Norte may be an important risk area for such injuries. Furthermore, this study provides data for the development of health actions to promote control and prevention of these injuries in this region.

Resumo Este estudo é uma investigação das características epidemiológicas dos acidentes com animais peçonhentos no estado do Rio Grande do Norte, Nordeste do Brasil, de 2007 a 2014. Um total de 30.429 casos foram analisados. Os casos foram distribuídos em todos os meses do período estudado e ocorreram principalmente em áreas urbanas. Os acidentes escorpiônicos representaram maior percentual de casos, entretanto, a chance de morte entre acidentes ofídicos foi maior. Os envenenamentos predominaram em mulheres com idade entre 20 e 49 anos. Crianças e idosos exibiram maiores chances de morte. A maioria das vítimas foi picada nas extremidades dos membros e recebeu assistência médica entre 0-1 hora após o incidente. Os principais sintomas locais e sistêmicos reportados foram dor e cefaléia, respectivamente. Os casos foram principalmente classificados como leves e progrediram para cura. Poucas vítimas manifestaram complicações locais e sistêmicas. O elevado número de acidentes com animais peçonhentos indica que o estado do Rio Grande do Norte pode ser uma importante área de risco para tais acidentes. Além disso, este estudo fornece dados que poderão ser utilizados para a elaboração de ações em saúde, a fim de promover o controle e a prevenção desses acidentes nesta região.

Toxinology in Colombia: contributions of ophidism/scorpionism program and other research groups / Toxinología en Colombia: contribuciones del programa de ofidismo/escorpionismo y de otros grupos de investigación

Background: Toxinology is a sub-field of toxicology dedicated to studying toxins produced by animals, plants and, microorganisms. In Colombia, during the last thirty years, this area has been mainly investigated by Ophidism/Scorpionism Program of Universidad de Antioquia. However, some other research groups have also contributed to our knowledge of venoms and toxins, as well as their related effects and treatments. Objective: to highlight the most significant findings in toxinology made by the Ophidism/Scorpionism Program and other research groups in Colombia. Methods: 119 papers dealing with the history of ophidiology and toxinology in Colombia were collected and analyzed. Results: some useful terms are described to understand toxinology and its scope. Also, a brief history of ophidiology is presented, spanning from the discovery of America until present-day findings. Finally, an overall description of several results related to toxin isolation, characterization, antivenoms, clinical trials, description of new species, proteomic and transcriptomic, among others. The nineteens were characterized by the study of snakebites, their clinic manifestations, and the use of antivenoms. In addition, the ethnopharmacological studies of medicinal plants used in snakebite treatments began to be explored. The 2000s included the newly ethnopharmacology, toxin isolation, clinical trials, inhibitor studies, scorpion venom characterization, and scorpion stings features. Finally, from 2010 until today, proteomic and transcriptomic gave the most important findings. Conclusions: Toxinology works in Colombia have contributed to our knowledge about endemic species, clinical manifestations of snakebite and scorpion stings, and the development of new therapeutic agents. However, we invite Colciencias and other funding agencies to assign more resources to support a higher number of researchers in this field, since snakebite is considered a neglected tropical disease by the World Health Organization, which needs more attention from governments and scholars. Finally, the venoms of some species and their possible mode of action are still unknown to us. Besides, given the complexity of venoms, we are not yet aware of the potential use of toxins in current biomedicine. Thus, studies in toxinology must continue.

Antecedentes: La Toxinología es el campo de la Toxicología que estudia las toxinas producidas por animales, plantas y microorganismos. En Colombia, durante los últimos treinta años, los estudios realizados en esta área han sido desarrollados principalmente por el Programa de Ofidismo/Escorpionismo de la Universidad de Antioquia. Sin embargo, otros grupos de investigación también han contribuido en el conocimiento de venenos, toxinas, efectos y tratamientos. Objetivo: Destacar los hallazgos más relevantes en toxinología realizados por el Programa de Ofidismo Escorpionismo y otros grupos de investigación en Colombia. Métodos: Se recopilaron 119 artículos referentes a la historia de la ofidiología y la toxinología en Colombia. Resultados: Se describieron algunos términos útiles para el entendimiento de la toxinología y sus alcances. Se construyó una breve historia de la ofidiología que inicia con el descubrimiento de América y finaliza con hallazgos recientes. Se realizó una amplia descripción de varios resultados relacionados con el aislamiento y caracterización de toxinas, antivenenos, ensayos clínicos, descripciones de nuevas especies, proteómica y transcriptómica, entre otras. Así, la década de los noventa se caracterizó por el estudio de las mordeduras de serpientes, sus manifestaciones clínicas, el uso de antivenenos y la exploración de la etnofarmacología asociada a las mordeduras de serpiente. La década del 2000 incluyó nuevamente etnofarmacología, el aislamiento de toxinas, ensayos clínicos, estudios sobre inhibidores de toxinas, caracterización de venenos y picaduras de escorpión. Finalmente, desde 2010 hasta hoy, la proteómica y transcriptómica aportaron los hallazgos más importantes. Conclusiones: Los estudios de Toxinología en Colombia han contribuido al conocimiento de especies endémicas, manifestaciones clínicas de mordeduras de serpientes y picaduras escorpiones, y el desarrollo de nuevos agentes terapéuticos. No obstante, se invita a Colciencias y a otras agencias de financiamiento a apoyar la investigación en este campo, ya que es considerada una enfermedad tropical desatendida por la Organización Mundial de la Salud y necesita mayor atención por parte del gobierno e instituciones académicas. Además, dada la complejidad de los venenos, se desconoce el uso potencial de las toxinas en la biomedicina actual. Así, se deben continuar realizando estudios en toxinología.

Efectos clinicos e histopatologicos agudos y subagudos del veneno de Tityus breweri en miocardio de hamsters / Clinical and histopathological effects of acute and subagude of the poison of Tityus breweri in hamsters myocardia

Resumen Los escorpiones del género Tityus presentan la mayor distribución mundial, de mayor importancia clínica, epidemiológica y más peligrosa del continente americano. Las toxinas de su veneno producen perturbación severa de los procesos de excitación y conducción del impulso nervioso. Desde el punto de vista histopatológicos se han observado cambios estructurales en diferentes tejidos de ratones, con el veneno de varias especies de Tityus venezolanos. Objetivo: Describir los efectos clínicos e histopatológicos agudos y subagudos del veneno de escorpión (Buthidae: T. breweri) en el miocardio de hámster. Método: Estudio experimental, exploratoria, descriptivo, analítica y correlacional. Se utilizaron hámsteres de ambos sexos del genero Cricetus y se obtuvo el veneno de 26 escorpiones T. breweri, se escogieron 6 hámster al azar, inyectándoles vía intraperitonial (VIP) veneno de Tityus breweri, 3 sacrificados a los 30 minutos y los otros 3 a los 60 minutos, 3 inyectados con agua destilada constituyeron el grupo control. Resultados: La mayoría de los animales expuestos presentaron manifestaciones de tipo colinérgicas y adrenérgicas. Las alteraciones histopatológicas agudas observadas fueron edema interfascicular y congestión vascular, infiltrado linfohistiocítico perivascular. Al transcurrir 12, 24, 48 y 72 horas de exposición del veneno, no se evidenciaron cambios histopatológicos, lo que hace presumir que se activaron los procesos de reparación de los tejidos dañados. Conclusión: el veneno de T. breweri produjo alteración histológicas agudas y subagudas en el tejido miocárdico en los hámsteres sin evidencia de alteración en el grupo control.

Abstract Scorpions of the genus Tityus present the largest distribution of the world, of greater clinical, epidemiological and more dangerous importance of the American continent. The toxins from its venom produce severe disturbance of the excitation and conduction processes of the nerve impulse. From the histopathological point of view structural changes have been observed in different tissues of mice, with the venom of several species of Venezuelan Tityus. Objective: To describe the acute and subacute clinical and histopathological effects of scorpion venom (Buthidae: T. breweri) on the hamster myocardium. Method: Experimental, exploratory, descriptive, analytical and correlational study. Hersters of both sexes of the genus Cricetus were obtained and venom of 26 T. breweri scorpions were obtained, 6 random hamsters were chosen, injecting intravenously (VIP) venom of Tityus breweri, 3 sacrificed at 30 minutes and the other 3 a The 60 minutes, 3 injected with distilled water constituted the control group. Results: Most of the exposed animals presented cholinergic and adrenergic type manifestations. The acute histopathological alterations observed were interfascicular edema and vascular congestion, perivascular lymphohistiocytic infiltrate. At the end of 12, 24, 48 and 72 hours of exposure of the venom, no histopathological changes were evidenced, which suggests that the repair processes of the damaged tissues were activated. Conclusion: T. breweri venom caused acute and subacute histological alterations in myocardial tissue in hamsters with no evidence of alteration in the control group.

Hiponatremia grave secundaria a la exposición a veneno de Phyllomedusa Bicolor (Rana Kambó): caso clínico / Severe hyponatremia secondary to Phyllomedusa bicolor (Kambó frog) poisoning: report of one case

Phyllomedusa bicolor or Kambo is a frog that lives in the Amazon rainforest. It can release through its skin a substance used in healing rituals that are common among South-American tribes, as well as in urban people of America and Europe. We report a 41-year-old female patient who, during a healing ritual consumed ayahuasca (a drink obtained from the mixture of Banisteriopsis caapi, Psychotria viridis and Mimosa hostilis) and 12 hours later received the poison of Kambo Frog (Phyllomedusa bicolor) on superficial right shoulder skin burns. The ritual included a minimum of six-liter water intake over a few hours period. She evolved with clouding of sensorium, motor agitation, frequent vomiting, and generalized tonic-clonic seizures. She presented lethargic to the emergency room, with a weak pupillary light reflex, generalized stiffness, moving all four limbs. Laboratory showed severe hyponatremia (120 mEq/L) and a creatine kinase level of 8,479 UI/L, that increased 107,216 IU/L within few days. An admission CT Brain scan was normal. The toxicological screening did not identify the presence of other substances. During hospitalization the patient developed severe psychomotor agitation controlled by a dexmedetomidine infusion, hyponatremia, low plasma osmolality (248 mOsm/kg), and disproportionately high urinary osmolality (448 mOsm/kg), suggestive of inappropriate antidiuretic hormone secretion syndrome (SIADH). With correction of hyponatremia, the patient gradually recovered consciousness. Rhabdomyolysis was assumed to be secondary to seizure and managed by volume and bicarbonate infusions with a positive response.

Fasciotomy in compartment syndrome from snakebite

BACKGROUND: Local symptoms and signs of snake envenomation mimic the clinical features of compartment syndrome. It is important to measure the intracompartmental pressure to diagnose compartment syndrome. In this study, we present our experiences of confirming compartment syndrome and performing fasciotomy in snakebite patients based on high intracompartmental pressure findings. METHODS: The medical records of patients who visited the trauma center of Wonju Severance Christian Hospital from January 2010 to December 2015 for the management of venomous snakebite were retrospectively reviewed. Starting in 2014, fasciotomy was performed in patients with an intracompartmental pressure of more than 40 mmHg in addition to the clinical symptoms of compartment syndrome. RESULTS: A total of 158 patients with snakebite came to the hospital within 48 hours for treatment. Most patients (110 patients) were bitten at the upper extremities (69.6%). Since 2014, 33 out of 59 patients were suspected to have compartment syndrome, and their intracompartmental pressures were measured. Seventeen of those patients had a high intracompartmental pressure (average, 49.6 mmHg; range, 37–88 mmHg), and fasciotomy was performed. CONCLUSIONS: In this study, as many as 10.8% of all cases were in need of fasciotomy when compartment syndrome was diagnosed by measuring the intracompartmental pressure. Previously, it was reported that fasciotomy was not required in many cases of compartment syndrome originating from snakebite. However, some patients may develop very severe compartment syndrome, requiring fasciotomy.

A case of hair dye-induced contact anaphylaxis

Anaphylaxis is a sudden-onset life-threatening systemic hypersensitivity reaction. Allergens, such as foods, stinging insect venoms, and drugs, are the globally important causative factors for anaphylaxis. Para-phenylenediamine (PPD), an aromatic amine, is a well-known hair dye component that can act as a skin irritant and/or a skin sensitizer. As an allergen, PPD can induce various reactions; the most common being contact dermatitis, a delayed-type hypersensitivity reaction. Anaphylaxis or other immediate hypersensitivity reactions by hair dye contact is extremely rare, with only a few cases reported worldwide. Here, we report a case of a 63-year-old female who presented to the Emergency Department with dyspnea, rash, vomiting, and diarrhea within minutes after using a hair dye product containing PPD. Her past medical history includes urticaria of unknown cause. Her total IgE antibody level was increased to 630 kU/L. Skin prick and patch tests with the hair dye she applied at the time of anaphylaxis demonstrated an immediate reaction. An additional patch test with 25 common contact allergens showed positive reaction to PPD. This is the first case report of hair dye-induced contact anaphylaxis presenting sensitization to PPD in Korea.

Síndrome de Kounis como manifestación de anafilaxia / Kounis Syndrome as a manifestation of anaphylaxis

Introducción: el síndrome de Kounis corresponde a la isquemia miocárdica aguda relacionada con la liberación de mediadores inflamatorios que llevan a vasoespasmo coronario y/o complicación de una placa ateromatosa durante una reacción alérgica. La incidencia de eventos coronarios en procesos alérgicos en Estados Unidos es de 8 casos por 100000 habitantes por año. Métodos: describimos el caso de una mujer que desarrolla síndrome de Kounis, posterior a múltiples picaduras de abeja, recibiendo manejo en una unidad de cuidado intensivo de una institución de salud de Colombia. La paciente presentó un síndrome coronario agudo tipo infarto agudo de miocardio con elevación del segmento ST, con arteriografía coronaria en la cual se evidenció ausencia de lesiones vasculares o vasoespasmo, con presencia de un trombo flotante en la arteria descendente anterior, sin evidencia de enfermedad ateroesclerótica. Resultados: el síndrome de Kounis es frecuente en los pacientes con anafilaxia, sin embargo, se informa poco en la literatura, debido a la falta de sospecha diagnostica y al poco reconocimiento clínico. Los síntomas de este síndrome pueden ser típicos como el dolor torácico opresivo de gran intensidad irradiado a miembro superior izquierdo o a cuello, o atípicos como disnea, nauseas o palpitaciones, los cuales pueden confundirse con las manifestaciones del proceso anafiláctico. Conclusiones: en la actualidad no existen guías para el tratamiento del síndrome y depende de la forma de presentación, comorbilidades y disponibilidad de un grupo médico interdisciplinar, que incluya monitoria y vigilancia en una unidad de cuidado intensivo.(AU)

Introduction: Kounis syndrome refers to the myocardial ischemia which results from the release of inflammatory-provoking mediators during an allergic reaction thereby causing coronary vasospasm and/or complication brought on by atheromatous plaque. The incidence of coronary disease induced by allergies in the United States is 8 cases per 100000 inhabitants per year. Methods: we cite the case of a woman who developed Kounis syndrome after receiving multiple bee stings. She was treated in the intensive care unit of a Colombian health institution. The patient presented with acute myocardial infarction with ST-segment elevation, and with no presence of vascular lesions or vasospasm during the coronary arteriography. It was further noted that there was a floating thrombus in the anterior descending artery without evidence of atherosclerotic disease. Results: Kounis syndrome is frequent in patients with anaphylaxis, however, only a few cases are reported in studies due to the lack of diagnostic suspicion and little clinical recognition. Symptoms suggesting this syndrome may be typical, such as oppressive chest pain which radiates to the upper left limb or neck, or atypical such as dyspnea, nausea, or palpitations which may be confused with the manifestations of the anaphylactic process. Conclusions: currently there are no directives for the treatment of the syndrome. It depends upon the manner of presentation, comorbidities, and the availability of an interdisciplinary medical group. It requires monitoring and surveillance in an intensive care unit.(AU)

Venom allergy, risk factors for systemic reactions and the knowledge levels among Turkish beekeepers

BACKGROUND: Allergic reactions developing after bee sting can be severe and life-threatening. According to epidemiological data, serious systemic reactions range between 1.2%–3%, and this is 2–3 times higher (6%) in beekeeping. In different beekeepers' populations, risk factors of systemic reactions have been investigated and diverse results have been found. OBJECTIVE: The aim of this study is to evaluate the level of knowledge of beekeepers about venom allergy, epidemiological data, systemic reaction rates, risk factors for systemic reactions, and the rate of emergency admissions after bee sting. METHODS: With the collaboration of Uludağ University Beekeeping Development Research Center and Beekeepers Association, a questionnaire consisting of 19 questions was applied to 242 beekeepers in Bursa and Yalova. Two hundred twenty-one beekeepers who completed the questionnaire were involved in the study. RESULTS: The mean age of the beekeepers was 49.9 years (range, 18–75 years). The systemic reaction to bee sting in beekeepers was 37.6%. Allergic rhinitis was found to be a risk factor for systemic reaction. Although 80% of the beekeepers recognized that bee venom could be lethal, only 60% of the beekeepers were aware of immunotherapy, and only 30% were aware of the adrenaline auto-injector drug. CONCLUSION: Similar to previous studies, we found that the systemic response to the bee sting in beekeepers was higher compared to normal population. Considering the occupational exposure to bee venom and thus higher risk, the awareness of venom allergy in this high risk population was low, and they were poorly informed about the treatment options.

Evaluation of the left venticular systolic function with the measurement of global longitudinal strain by Speckle tracking echocardiography in anaphylaxis

BACKGROUND: It is not known how cardiac functions are affected during anaphylaxis. OBJECTIVE: Our aim was to measure the cardiac functions shortly after an anaphylaxis attack using a new technique that detects subclinical left ventricular dysfunction. METHODS: Patients in our hospital who experienced anaphylaxis and urticaria (control group) due to any cause were included in the study. Tryptase levels were measured on the third hour of the reaction and 6 weeks later. Left ventricular systolic functions were evaluated with global strain measurement using echocardiography, approximately 4 hours and 6-week post reaction. RESULTS: Twelve patients were included in the anaphylaxis group (83.3% female; mean age, 43.25 ± 9.9 years). The causes of anaphylaxis were drug ingestion (n = 11) and venom immunotherapy. Eight of the anaphylactic reactions (66.7%) were severe and in 9 reactions (75%) tryptase levels increased. In the anaphylaxis group, strain values measured shortly after anaphylaxis were significantly lower than those calculated 6 weeks later (p < 0.001) and tryptase levels significantly increased (p = 0.002). The strain values measured both shortly after anaphylaxis and 6 weeks later did not differ according to severity of anaphylaxis. In severe anaphylaxis, tryptase levels during anaphylaxis and 6 weeks later were significantly higher (p = 0.019, p = 0.035). The control group evidenced no differences regarding strain and tryptase levels measured at reaction and 6 weeks later. At reaction, in the anaphylaxis group, the tryptase levels were higher and the strain values were lower than those in the urticaria group (p = 0.007, p = 0.003). CONCLUSION: Cardiac dysfunction may develop during an anaphylaxis independent of severity of reaction.

Usefulness of delta neutrophil index for early prediction of overt disseminated intravascular coagulopathy in patients with venomous snakebite

OBJECTIVE: Clinically, consumptive coagulopathy, such as disseminated intravascular coagulopathy (DIC), is the most important among the common venomous snakebite complications owing to the serious hemorrhage risk associated with this condition. We evaluated the predictive value of the delta neutrophil index (DNI)—a new indicator for immature granulocytes—for DIC diagnosis. METHODS: This retrospective observational study consecutively assessed adult patients with venomous snakebites for over 51 months. Patients were categorized into the no DIC and DIC groups. DNI values were measured within 24 hours after snakebite. RESULTS: Thirty patients (26.3%) developed DIC. The DIC group had significantly higher median initial DNI than the no DIC group (0% vs. 0.2%, P < 0.001). When the DIC group was divided into early and late groups (within and over 24 hours after snakebite, respectively), the DNI of the former was significantly higher than that of the latter and no DIC group. The late DIC group had significantly higher DNI than the no DIC group. Furthermore, DNI positively correlated with the DIC score (r=0.548, P < 0.001). The initial DNI (odds ratio, 4.449; 95% confidence interval, 1.738 to 11.388; P=0.002) was an early DIC predictor. The area under the curve based on the initial DNI’s receiver operating characteristic curve was 0.724. CONCLUSION: DNI values were significantly higher in the DIC group. Additionally, DNI was an early predictor of DIC development in patients with venomous snakebites in the emergency department.

Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent

BACKGROUND: Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. OBJECTIVE: This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. METHODS: Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. RESULTS: The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl (p=0.026) and 40 mg/100 µl (p=0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl (p=0.000) and 300 µl/100 µl (p=0.030). CONCLUSION: The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.