Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses / 中华危重病急救医学

OBJECTIVE@#To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ).@*METHODS@#Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated.@*RESULTS@#DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin.@*CONCLUSIONS@#The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.

Animais peçonhentos e sua trajetória secular para as ações de saúde: do histórico à aplicação / Venomous animals and their secular trajectory for health actions: from history to application / Los animales venenosos y su trayectoria secular para las acciones de salud: de la historia a la aplicación

O livro Os animais peçonhentos na saúde pública expõe um vasto histórico de acidentes envolvendo problemas de saúde provocados por animais peçonhentos. Os autores resgatam trabalhos e vivências, descritos por Louis Pasteur e Vital Brazil, fundamentais para o desenvolvimento de processos da ciência translacional como compreendida hoje, no século XXI. A obra é marcada pela defesa da necessidade de políticas públicas coerentes que sejam capazes de promover ações de capacitação, prevenção, diagnóstico, tratamento e reabilitação dos pacientes.

The book Os animais peçonhentos na saúde pública presents a vast history of accidents involving health problems caused by venomous animals. The authors rescue works and experiences, described by Louis Pasteur and Vital Brazil, fundamental for the development of translational science processes as understood today, in the 21st century. The work is marked by the defense of the need for coherent public policies capable of promoting training, prevention, diagnosis, treatment and rehabilitation of patients.

El libro Os animais peçonhentos na saúde pública expone una vasta historia de accidentes que involucran problemas de salud causados por animals venenosos. Los autores rescatan obras y experiencias, descritas por Louis Pasteur y Vital Brazil, fundamentales para el desarrollo de los procesos de ciencia translacional tal como se entienden hoy, en el siglo XXI. El libro está marcado por la defensa de la necesidad de políticas públicas coherentes capaces de promover la formación, la prevención, el diagnóstico, el tratamiento y la rehabilitación de los pacientes.

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.

Estudio retrospectivo de pacientes intoxicados admitidos en la unidad de cuidados intensivos pediátricos de un hospital en Chile / Retrospective study of poisoned patients admitted to a hospital's pediatric intensive care unit in Chile

Introducción. Las intoxicaciones pediátricas son un problema de salud pública a nivel mundial. El objetivo de este estudio fue caracterizar las intoxicaciones pediátricas que fueron atendidas en la unidad de cuidados intensivos pediátricos (UCIP) de un hospital en Chile. Población y métodos. Se revisaron las fichas clínicas de pacientes diagnosticados con intoxicación e ingresados a la UCIP entre los años 2013 y 2017. Resultados. Un total de 105 casos fueron identificados, lo que representa un 3 % del total de ingresos registrados en el período estudiado. La mediana de edad de los pacientes resultó ser de 10 años. El 73,3 % de los casos correspondieron a pacientes de sexo femenino. El 51 % de los casos se asociaron a intoxicaciones intencionales y el 83 % fue causado por exposición a medicamentos. Los medicamentos identificados con mayor frecuencia fueron los antidepresivos (11,2 %), analgésicos no esteroides (10,7 %). La ingesta fue la vía de exposición más común (93 %). El promedio de estadía de los pacientes en UCIP fue de 1,3 días. Dos pacientes ingresaron en la UCI: uno requirió intubación y otro hemodiálisis. Se determinaron relaciones estadísticamente significativas entre el sexo del paciente y la circunstancia de exposición, y entre la condición psiquiátrica del paciente y el número de sustancias tóxicas ingeridas. Conclusión. La mayoría de las intoxicaciones atendidas en la UCIP fueron intencionales y correspondieron a pacientes de sexo femenino, a quienes se les asoció alguna patología psiquiátrica. Los grupos de medicamentos identificados con mayor frecuencia fueron los antidepresivos y los antiinflamatorios no esteroides.

Introduction. Pediatric poisoning is a public health problem worldwide. The objective of this study was to establish the characteristics of pediatric cases of poisoning seen at the pediatric intensive care unit (PICU) of a hospital in Chile. Population and methods. The medical records of patients diagnosed with poisoning and admitted to the PICU between 2013 and 2017 were reviewed. Results. A total of 105 cases were identified, who account for 3% of all admissions recorded in the study period. Patients' median age was 10 years. In total, 73.3% of cases were female patients; 51% of cases were associated with intentional poisoning; and 83% were caused by drug exposure. The most common drugs identified were antidepressants (11.2%) and non-steroidal anti-inflammatory drugs (10.7%). Intake was the most frequent route of exposure (93%). The average length of stay in the PICU was 1.3 days. One patient required intubation and another required hemodialysis in the PICU. Statistically significant relationships were established between patient sex and the circumstance of exposure and between the patient's psychiatric condition and the number of toxic substances ingested. Conclusion. Most poisoning cases seen at the PICU were intentional and occurred in female patients, who had a psychiatric condition. The most common drugs identified were antidepressants and non-steroidal antiinflammatory drugs.

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.

Forensic Examination of Six Homicide Injection Cases / 法医学杂志

OBJECTIVES@#To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification.@*METHODS@#Six homicide cases of death after injection which were investigated by the Criminal Investigation Team of Shanghai Public Security Bureau were collected and analyzed, including case situation, scene investigation, autopsy and other materials.@*RESULTS@#The 6 cases were premeditated crimes, 5 cases took place in private spaces, and 5 cases involved the victims approached by suspects' decoy. There were no obvious abnormalities at the scene of the 6 cases. In 6 cases, the victim's body surface injury was mild or no, lividity color was abnormal, and the needlestick injury showed different manifestations from conventional medical measures.@*CONCLUSIONS@#Death after injection is a highly concealed crime and easy to be ignored. For the suspected injection injury found in autopsy, it is necessary to carefully examine, identify and analyze, be alert to the situation of injecting poison (drug) and do a good job in evidence fixation and material extraction.

Application of a modified Poisson model in identifying factors associated with prevalence of pregnancy termination among women aged 15 ­ 49 years in Uganda

Background: Abortion in Uganda is illegal, only permitted when it places the pregnant mother at risk. This study aimed to apply the modified Poisson model in identifying factors associated with the prevalence of pregnancy termination among women of reproductive age in Uganda. Methods: The 2016 Uganda Demographic Health Survey (UDHS) data were used in this study. More than 18,000 women of the age of 15 ­ 49 years participated in this study. A modified Poisson model that incorporated sampling weights was used to establish the factors associated with pregnancy termination. Results: In Uganda, 18,506 (18.1%) had ever had a pregnancy terminated. The results revealed that, the woman's age [APR = 3.15, 95% CI: 2.72-3.63], being married [APR = 1.55, 95% CI: 1.40-1.71], mass media exposure [APR = 1.18, 95% CI: 1.08-1.29], working status [APR = 1.21, 95% CI: 1.09-1.35], and having visited a health facility [APR = 1.20, 95% CI: 1.10-1.31] were positively significantly associated with likelihood of pregnancy termination. Conclusion: There exists a significant proportion of women who have had their pregnancies terminated in Uganda. It is observed that woman's age, marital status, mass media exposure, having visited a health facility in the last 12 months and working status were main predictors. Based on these results, researchers concluded that the emphasis should be put on improving access to post-abortion care, contraceptive use and media exposure

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

A retrospective review of calls to the Poisons Information Helpline of the Western Cape during the first 6 months of the COVID-19 pandemic in South Africa

Background: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, poison centres worldwide have reported an increase in exposures to chemicals used for infection prevention. Increased availability and use could lead to an increase in exposures. Potential effects on a South African Poison Information Helpline were unknown, therefore a study was performed to describe changes in call volume and profile of poison exposures. Methods: A retrospective analysis was conducted on an observational database of telephone enquiries. All human-related poisoning exposure call data collected from 01 March to 31 August during 2018, 2019 and 2020 were extracted and analyzed. Summary statistics were used to describe all variables. Results: The total number of calls were 5137, 5508, and 5181 in 2018, 2019, 2020, respectively. The monthly call number during 2020 was mostly less than in 2019. More calls were received from the public calls (39.4% vs 33.1%) and for accidental exposures (65.6% vs 62.3%) increased during 2020 compared to 2019. Exposures to pharmaceuticals decreased by 14.8% from 2019 to 2020, while exposures to eucalyptus oil more than doubled from 21 in 2019 to 43 during 2020. Exposures to antiseptics and disinfectants increased by 60.4%, mainly due to hand sanitizers exposure which showed a 26-fold increase from 2019 (n = 6) to 2020 (n = 156). Conclusion: A change in the profile of poison exposures was observed during the COVID-19 pandemic. Lockdown regulations and greater availability of antiseptics and disinfectants probably led to the increase in exposures. Although symptoms were mostly mild, the public should be educated on safe storage and proper use of all chemicals.

Report of envenomation in humans by handling a dyeing poison frog Dendrobates tinctorius (SCHNEIDER, 1799) (Anura: Dendrobatidae) in the Amazon, Brazil

Abstract We report a case of envenomation by Dendrobates tinctorius in the northwest of the Amazon Forest. The patients were two men, who presented with numbness in the right arm and slight numbness in the lower lip, respectively. Dendrobates tinctorius secretions contain pumiliotoxin, one of several toxins found in the dendrobatidis skin, which interferes with muscle contraction and causes locomotor difficulties. Although Dendrobatidae is a family of anurans known for their venom, few studies describe the symptoms of envenomation in humans.

Effects of venoms on neutrophil respiratory burst: a major inflammatory function

Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)

Proteomics, toxicity and antivenom neutralization of Sri Lankan and Indian Russell's viper (Daboia russelii) venoms

The western Russell's viper (Daboia russelii) is widely distributed in South Asia, and geographical venom variation is anticipated among distant populations. Antivenoms used for Russell's viper envenomation are, however, raised typically against snakes from Southern India. The present study investigated and compared the venom proteomes of D. russelii from Sri Lanka (DrSL) and India (DrI), the immunorecognition of Indian VINS Polyvalent Antivenom (VPAV) and its efficacy in neutralizing the venom toxicity. Methods: The venoms of DrSL and DrI were decomplexed with C18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol. Results: DrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A2 (PLA2) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately. Conclusion: Considering that a large amount of venom can be injected by Russell's viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.(AU)

Experience with veno-venous ecmo in patients with adult respiratory distress syndrome secondary to viral pneumonia. Case series / Experiencia con ecmo veno-venoso en pacientes con síndrome de dificultad respiratoria del adulto secundario a neumonía viral. Serie de casos

Abstract Introduction The use of extracorporeal membrane oxygenation (ECMO) has increased exponentially in recent years and has shown to be effective in treating adult respiratory distress syndrome (ARDS) secondary to HiNi-related pneumonia. However, evidence remains controversial. This study describes a case series of ECMO in ARDS secondary to viral pneumonia. Methods A search was conducted in the ECMO database of Fundación Cardiovascular de Colombia for the 20132017 period. A case series report was written of patients diagnosed with ARDS secondary to confirmed or suspected viral pneumonia. Results Nineteen patients with ECMO support and ARDS due to viral pneumonia were included in the study. The survival rate upon discharge was 11 patients (58%) and weaning from ECMO support was successful in 13 patients (68%). Hemorrhagic complications were the most frequent: gastrointestinal bleeding, 10 patients (53%); intracranial bleeding, 2 (10%); alveolar hemorrhage, 2 (10%);' hemothorax requiring thoracostomy with chest tube drainage, 2 (10%); cannulation site bleeding, 9 patients (47%); and surgical site bleeding in 3 patients (25%) who required tracheostomy. Other complications were: pneumothorax, 1 patient (5%); sepsis, 6 patients (32%); and growth of microorganisms in bronchial lavage, 6 patients (32%). Conclusions This study supports the use of veno-venous ECMO to achieve a higher survival rate than expected in patients with severe ARDS and refractory hypoxemia secondary to viral pneumonia. Early initiation of the therapy should improve overall results.

Resumen Introducción El uso de la oxigenación por membrana extracorpórea (ECMO) ha tenido un incremento exponencial en los últimos años y ha demostrado ser efectivo en el manejo del síndrome de dificultad respiratoria del adulto (SDRA) secundario a neumonía por H1N1, si bien la evidencia sigue siendo controvertida. En este estudio describimos una serie de casos de ECMO por SDRA secundario a neumonía viral. Métodos Se realizó una búsqueda en la base de datos de ECMO de la Fundación Cardiovascular desde el año 20132017. Reportamos una serie de casos donde se incluyeron pacientes diagnosticados con SDRA secundario a neumonía viral sospechosa o confirmada. Resultados Se incluyeron en el estudio 19 pacientes con soporte de ECMO y SDRA por neumonía viral. La sobrevida al alta fue 11 pacientes (58%) y el destete del ECMO fue exitoso en 13 pacientes (68%). Las complicaciones hemorrágicas presentadas fueron: sangrado digestivo, 10 pacientes (53%), sangrado cerebral, 2 (10%), hemorragia alveolar, 2 (10%), hemotórax con requerimiento de toracostomía a drenaje cerrado, 2 (10%), sangrado activo por sitio de canulación, 9 pacientes (53%), y 3 pacientes traqueostomizados (25%) que sangraron por el sitio quirúrgico. Otras complicaciones presentadas fueron: neumotórax, 1 paciente (5%), septicemia, 6 (32%) y crecimiento de microorganismos en lavados bronquiales 6 (32%). Conclusion El presente estudio permite indicar que el uso de la ECMO VV viabiliza una sobrevida mayor a la esperada en pacientes con SDRA severo e hipoxemia refractaria secundario a neumonía viral. Su inicio tempranamente debe mejorar los resultados globales.

Síndrome hemolítico urémico por ingesta de veneno de una serpiente del género Bothrops: Reporte de un caso / Hemolytic uremic syndrome due to ingestion of venom from a snake of the genus Bothrops: Report of a case

Resumen El síndrome hemolítico urémico (SHU) es una enfermedad que se caracteriza por la tríada anemia hemolítica no inmune, trombocitopenia e insuficiencia renal aguda, en la que las lesiones subyacentes están mediadas por un proceso de microangiopatía trombótica (MAT) sistêmica. Existen distintas causas que pueden desencadenar el proceso de la MAT que caracteriza el SHU. Se describe el caso de una mujer, con antecedentes de diabetes mellitus e hipertensión arterial, quién ingirió veneno de serpiente del género Bothrops con fines medicinales y 72 horas después debió ser hospitalizada por edema de miembros inferiores, dolor abdominal, equimosis e ictericia. Al ingreso, se le realizó analítica sanguínea que constató trombocitopenia, elevación de azoados y anemia; de igual forma se documentaron datos de falla renal aguda, por lo que se diagnosticó con SHU secundario a la ingesta de veneno de serpiente. En el artículo se describen aspectos del diagnóstico y el manejo clínico que se realizó y se estable que el compromiso renal por veneno de serpiente Bothrops es una entidad poco frecuente que si no se maneja de manera adecuada puede ser letal, y más aún si existen comorbilidades predisponentes.

Abstract Hemolytic uremic syndrome (HUS) is a disease characterized by the triad of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by a process of systemic thrombotic microangiopathy (TMA). There are different causes that can trigger the MAT process that characterizes HUS. The case of a woman with a history of diabetes mellitus and arterial hypertension is described, who ingested snake venom of the genus Bothrops for medicinal purposes, and 72 hours later she had to be hospitalized for edema of the lower limbs, abdominal pain, ecchymosis and jaundice. Upon admission, he underwent blood tests that found thrombocytopenia, elevated nitrogen levels and anemia; Similarly, data on acute kidney failure were documented, for which HUS was diagnosed secondary to the ingestion of snake venom. The article describes aspects of the diagnosis, and the clinical management that was carried out and it was established that renal involvement by Bothrops snake venom is a rare entity, which if not managed properly can be lethal, and even more so if there are predisposing comorbidities.

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.

A case of envenomation by the false fer-de-lance snake Leptodeira annulata (Linnaeus, 1758) in the department of La Guajira, Colombia / Un caso de envenenamiento por mordedura de una serpiente falsa cabeza de lanza, Leptodeira annulata (Linnaeus, 1758), en el departamento de La Guajira, Colombia

Envenomations by colubrid snakes in Colombia are poorly known, consequently, the clinical relevance of these species in snakebite accidents has been historically underestimated. Herein, we report the first case of envenomation by opisthoglyphous snakes in Colombia occurred under fieldwork conditions at the municipality of Distracción, in the department of La Guajira. A female biologist was bitten on the index finger knuckle of her right hand when she tried to handle a false fer-de-lance snake (Leptodeira annulata). Ten minutes after the snakebite, the patient started to have symptoms of mild local envenomation such as edema, itching, and pain in the wound. After 40 minutes, the edema reached its maximum extension covering the dorsal surface of the right hand and causing complete loss of mobility. The clinical treatment focused on pain and swelling control. No laboratory tests were performed. The patient showed good progress with the total regression of the edema 120 hours after the snake-bite accident and complete recovery of the movement of the limb in one week. Venomous bites of "non-venomous snakes" (opisthoglyphous colubrid snakes) must be considered as a significant public health problem because patients lose their work capability during hours or even days and they are forced to seek medical assistance to treat the envenomation manifestations.

Los envenenamientos por colúbridos en Colombia son poco conocidos, por lo que la relevancia clínica de estas especies de serpientes en los accidentes ofídicos ha sido históricamente subestimada. Se presenta el primer caso de envenenamiento por una serpiente opistoglifa en Colombia, ocurrido bajo condiciones de trabajo de campo en el municipio de Distracción, departamento de La Guajira. Una bióloga fue mordida en el nudillo del dedo índice de la mano derecha cuando trató de manipular una falsa cabeza de lanza o falsa mapanare (Leptodeira annulata). Diez minutos después de la mordedura de la serpiente, la paciente presentó síntomas de envenenamiento local leve, como edema, picazón y dolor en la herida. Después de 40 minutos, el edema alcanzó su extensión máxima, cubriendo la superficie dorsal de la mano derecha y causando la pérdida completa de la movilidad. El tratamiento clínico se centró en el control del dolor y la inflamación. No se hicieron pruebas de laboratorio. La paciente tuvo una buena evolución, con la regresión total del edema 120 horas después del accidente ofídico y la normalización de los movimientos de la extremidad a la semana. Las mordeduras venenosas de serpientes "no venenosas" (serpientes colúbridas opistoglifas) deben considerarse un problema de salud pública importante, ya que los pacientes pierden la capacidad de trabajo durante horas o días y se ven obligados a buscar asistencia médica para contrarrestar las manifestaciones locales de envenenamiento.

The coevolution between telson morphology and venom glands in scorpions (Arachnida)

As in previous contributions to the JVATiTD, the aim of this note is to bring some general information on a particular aspect of the scorpion biology. An attempt is made to explain the possible coevolution of telson morphology and venom glands, which took place during several hundred million years and in particular since scorpions migrated from aquatic to terrestrial environments. Three components can be directly associated with predation and defensive behaviours: (1) morphology of the chelae and structure of the chelae fingers granulations; (2) morphology of the metasoma and in particular of the telson; (3) evolution of tegumentary glands in the telson toward different types of venom glands. Since a number of recent contributions already treated some of these aspects, I will limit my comments to the possible evolution of the telson in relation to the evolution of venom glands. As in previous contributions, the content of this article is basically addressed to non-specialists on scorpions whose research embraces scorpions in several fields such as venom toxins and public health.(AU)

Venom peptides in association with standard drugs: a novel strategy for combating antibiotic resistance - an overview

Development of antibiotic resistance that leads to resurgence of bacterial infections poses a threat to disease-free existence for humankind and is a challenge for the welfare of the society at large. Despite research efforts directed towards treatment of pathogens, antibiotics within new improved classes have not emerged for years, a fact largely attributable to the pharmacological necessities compelling drug development. Recent reversion to the use of natural products alone or in combination with standard drugs has opened up new vistas for alternative therapeutics. The success of this strategy is evident in the sudden interest in plant extracts as additives/synergists for treatment of maladies caused by drug-resistant bacterial strains. Animal venoms have long fascinated scientists as sources of pharmacologically active components that can be exploited for the treatment of specific ailments and should be promoted further to clinical trials. In the present review, we outline the scope and possible methods for the applications of animal venoms in combination with commercial antibiotics to offer a better treatment approach against antibiotic-resistant infections.(AU)

Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B in Rats / 生物医学与环境科学（英文）

Objective@#This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats.@*Methods@#Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured.@*Results@#AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB .@*Conclusion@#Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .