Zebrafish as Versatile Model for Assessing Animal Venoms and Toxins: Current Applications and Future Prospects.

Animal venoms and toxins hold promise as sources of novel drug candidates, therapeutic agents, and biomolecules. To fully harness their potential, it is crucial to develop reliable testing methods that provide a comprehensive understanding of their effects and mechanisms of action. However, traditional rodent assays encounter difficulties in mimicking venom-induced effects in human due to the impractical venom dosage levels. The search for reliable testing methods has led to the emergence of zebrafish (Danio rerio) as a versatile model organism for evaluating animal venoms and toxins. Zebrafish possess genetic similarities to humans, rapid development, transparency, and amenability to high-throughput assays, making it ideal for assessing the effects of animal venoms and toxins. This review highlights unique attributes of zebrafish and explores their applications in studying venom- and toxin-induced effects from various species, including snakes, jellyfish, cuttlefish, anemones, spiders, and cone snails. Through zebrafish-based research, intricate physiological responses, developmental alterations, and potential therapeutic interventions induced by venoms are revealed. Novel techniques such as CRISPR/Cas9 gene editing, optogenetics, and high-throughput screening hold great promise for advancing venom research. As zebrafish-based insights converge with findings from other models, the comprehensive understanding of venom-induced effects continues to expand, guiding the development of targeted interventions and promoting both scientific knowledge and practical applications.

Analysis of intra-specific variations in the venom of individual snakes based on Raman spectroscopy.

The knowledge of variations in the composition of venoms from different snakes is important from both theoretical and practical points of view, in particular, at developing and selecting an antivenom. Many studies on this topic are conducted with pooled venoms, while the existence and significance of variations in the composition of venoms between individual snakes of the same species are emphasized by many authors. It is important to study both inter- and intra-specific, including intra-population, venom variations, because intra-specific variations in the venom composition may affect the effectiveness of antivenoms as strongly as inter-specific. In this work, based on venom Raman spectroscopy with principal component analysis, we assessed the variations in venoms of individual snakes of the Vipera nikolskii species from two populations and compared these intra-specific variations with inter-specific variations (with regard to the other related species). We demonstrated intra-specific (inter- and intra-population) differences in venom compositions which are smaller than inter-specific variations. We also assessed the compositions of V. nikolskii venoms from two populations to explain inter-population differences. The method used is rapid and requires virtually no preparation of samples, used in extremely small quantities, allowing the venoms of individual snakes to be analyzed. In addition, the method is informative and capable of detecting fairly subtle differences in the composition of venoms.

A case of rotenone poisoning from ingesting Derris trifoliata Lour. (Tuba fruit/pod) in Malaysia.

Derris trifoliata is mainly found in mangrove area in tropical regions and the plant extract is traditionally used for fishing by poisoning. This is the first case report of rotenone poisoning in a child from ingesting Derris trifoliata seed. The child developed altered consciousness, vomiting, hypotension, metabolic acidosis, and acute kidney injury. Species identification of this case requires the collaborative efforts of various agencies. She survived from the poisoning with no neurological sequelae.

Toxinological profile and histopathological alterations induced by Bothrocophias campbelli venom from Colombia.

Snakebite envenomings most frequently reported in Colombia are caused by snakes of the genera Bothrops, Bothriechis, Bothrocophias, and Porthidium. Their venoms induce local and systemic pathophysiological effects, sometimes leading to permanent sequelae such as reduced mobility of the limbs, amputations, besides the risk of death. The genus Bothrocophias includes nine species, among which B. campbelli has a distribution restricted to the department of Nariño in Colombia. In this work we determined the toxinological profile its venom, by performing assays for the lethal, hemorrhagic, edematogenic, and myotoxic activities in mouse models, as well as for in vitro coagulant activity on human plasma. The lethal toxicity of the venom was 142.7 µg venom/mouse (111.4-179.8 µg/mouse; 6.6-10.6 µg/g body weight) by intraperitoneal route. Its hemorrhagic activity (minimum hemorrhagic dose: 12.7 ± 2.3 µg) is generally weaker compared to other South American vipers, but edematogenic (minimum edematogenic dose 1.0 ± 0.3 µg), and myotoxic (minimum myotoxic dose 3.9 ± 2.5 µg) activities are very potent. Histopathological examination of the injected mouse gastrocnemius muscle showed prominent disorganization of the myofibrils, myonecrosis, and an intense inflammatory leukocyte infiltrate. In vitro, the minimal coagulant dose was 12.3 ± 0.5 µg. Overall, this toxinological profile would predict that the clinical picture of envenomings by B. campbelli might be characterized by moderate disturbances in the coagulation cascade, mild local hemorrhage, and, conversely, severe myonecrosis and edema, which could potentially lead to compartment syndrome and gangrene.

Analyzing the biological traits of snakes in Avicenna's Canon of medicine and making a comparison with contemporary serpentology.

Snakes are a group of reptiles in the order of squamata that have been the subject of scientific research for years. This study aimed to determine the biological characteristics of snakes that were mentioned in Avicenna's Canon of Medicine to compare with modern serpentology. Data were obtained from the Canon of Medicine using keywords concerning snakes and also appropriate literature in PubMed, Scopus, Web of Science, Scientific Information Database (SID), and IranDoc. Our results revealed that Avicenna divided snakes into three classes including highly, moderately, and slightly venomous snakes that are comparable to modern serpontology. Moreover, Avicenna clarified physiological factors such as age, gender, size, psychological state, hunger state, physical features, the type of living climate, habitat, and the time of snakebite. Considering the snake features presented in the Canon of Medicine, even though is not feasible to make a full comparison between Avicenna's snake knowledge and modern serpentology but some characteristics can be still applicable. Conclusively, the present study suggested that the criteria used for the identification and classification of snakes have changed from the medieval ages to the nowadays.

Managing an Unidentified Jellyfish Sting with Mixed Envenomation Syndrome at a Noncoastal Hospital: Is This a New Form of Jellyfish Envenomation?

Jellyfish stings are the most common cause of marine envenomation in humans. Various species of box jellyfish have been identified around Penang Island, Malaysia, and these include multitentacled and four-tentacled box jellyfish (class Cubozoa). The typical syndrome following envenomation from these jellyfish has been poorly documented, posing a greater challenge when managing an unidentified jellyfish sting from Penang Island. We report a case of a 32-y-old man from Penang Island who was stung by an unidentified jellyfish while walking into the sea. The patient reported that he felt an immediate and severe electric current‒like pain over both thighs, left flank, and left forearm, followed by chest discomfort and breathlessness. Vinegar was applied over the affected areas, and he was rushed to a hospital, where he was treated with analgesia, steroids, and antihistamine. He refused hospitalization and was discharged against medical advice. He then presented to a noncoastal hospital 377 km away in Kuala Lumpur on the following day with severe pain over the affected sites as well as chest discomfort, shortness of breath, and abdominal cramps. The electrocardiograph demonstrated features of Wolff-Parkinson-White. Serial blood test results showed elevated creatine kinase but normal troponin I levels. The patient was managed symptomatically over a period of 4 d and was discharged with cardiology follow-up. Appropriate health-seeking behavior needs to be emphasized. This case report provides an opportunity to document the signs and symptoms of envenomation from possibly an undescribed jellyfish species near the coastal waters of Penang Island.

STRETCH: Stinging tree exposures to Cairns Hospital.

OBJECTIVES: To evaluate the burden of disease, investigate the treatment and response to treatment caused by exposure to stinging tree plants presenting to Cairns Hospital over a 3-year period. Our secondary aim was to examine the benefit from treating such exposures with topical dilute hydrochloric acid (HCl). METHODS: A retrospective chart review of all patients presenting to Cairns ED over a 3-year period because of stinging tree exposure. Symptoms, signs, treatment and outcomes were recorded. RESULTS: There were 48 presentations, all having immediate pain after contact with the stinging tree, with 87% describing the pain as moderate or severe. Nearly all were stung on limbs (96%). There were 13 different treatments prior to presentation. In hospital, 60% needed opioid analgesia and a median oral morphine dose equivalent of 15 mg. Of the 29 receiving HCl nine patients reported good relief or complete relief. CONCLUSIONS: Stinging tree exposure results in significant presentations to the Cairns ED each year. Pain is immediate and severe and there are no clear first aid or definitive treatment recommendations. Further work is needed to ascertain the best first aid and definitive treatment including a formal trial of dilute HCl.

Toxins' classification through Raman spectroscopy with principal component analysis.

The method based on the combination of Raman spectroscopy and principal component analysis (PCA) was applied to the set of peptide and protein toxins from animal venoms and to synthetic analogues of peptides. The study demonstrated the possibility of toxin classification according to their primary and secondary structures based on Raman spectroscopy. The method described here allows discrimination of snake venom three-finger toxins from predatory marine mollusks α-conotoxins. Moreover, PCA of the Raman spectra of toxins revealed differences within the group of three-finger toxins and also within the group of conotoxins, related to their spatial structure. In particular, on the basis of the developed technique it is possible to distinguish the disulfide isomers of the same peptide toxin. The results obtained have been confirmed by bioinformatic methods. So, we have proposed a method for the rapid analysis of newly discovered venom-derived protein or peptide toxins by establishing their similarity with other already studied toxins by referring to a particular class. Taking into account a low specimen consumption by Raman spectroscopy, the proposed method could represent a first step in the study of toxins from rare and/or endangered venomous animals. The ability to distinguish configuration of disulfide bonds allows to synthesize the correct isomer of the toxin.

Avian Toxins and Poisoning Mechanisms.

All around the world, there are species of birds that have developed the ability to acquire toxic chemicals in their bodies making them less palatable or even lethal when consumed or contacted. Exposure to poisonous bird species is rare among humans, yet their poisons can produce serious clinical outcomes. In this study, we conducted a literature search focusing on seven avian species: the pitohuis (Pitohui spp.), blue-capped ifrita (Ifrita kowaldi), European quail (Cortunix corturnix coturnix), spur or spoor-winged goose (Plectropterus gambensis), North American ruffed grouse (Bonasa umbellus), Brush bronzewings (Phaps elegans), and European hoopoes and woodhoopoes (Upupa epops and Phoeniculus purpureus, respectively). We present the geographic distribution of each poisonous bird, toxin physiology and origin, clinical signs and symptoms of poisoning, cases of human toxicity if available and discuss the birds' ability to prevent self-intoxication. Our results suggest that most cases of contact with toxic birds produce mild symptoms as most of these birds apart from the European quail (C. c. corturnix) and North American ruffed grouse (B. umbellus) are not commonly consumed by humans. Furthermore, we discuss several methods of toxin acquisition in these bird species, which are mostly diet acquired apart from the hoopoes and woodhoopoes (Upupa and Phoeniculus spp.) who have a symbiotic relationship with chemical-producing bacteria in their uropygial glands. In summary, our study provides a comprehensive review of the toxic physiology, clinical manifestations, and evolutionary insight to avian toxins.

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019.

BACKGROUND: There are two Food and Drug Administration (FDA)-approved antivenoms available for rattlesnake envenomations in the United States: the equine-derived F (ab')2 product sold with the brand name Anavip (F (ab')2 AV) and the ovine-derived Fab product sold with the brand name Crofab (FabAV). OBJECTIVE: To compare the clinical outcomes of rattlesnake envenomation patients treated either with FabAV or F (ab')2AV or a combination of these. METHODS: This is a retrospective chart review of all human rattlesnake envenomations requiring antivenom reported to one regional poison control center in 2019. Patients were categorized as receiving F (ab')2 AV, FabAV, or a combination of both. Baseline characteristics included demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation. RESULTS: There were a total of 123 patients requiring antivenom. Of these, 57 (46.3%) received FabAV, 53 (43.1%) received F (ab')2 AV, and 13 (10.6%) received a combination of these. Those receiving F (ab')2 AV were younger, with an average age of 40.8 (±25.0) years versus 51.3 (±19.9) years (p = 0.0161) for those receiving FabAV. Time between envenomation and antivenom administration, ASSS, and the percentage of those with coagulopathy at presentation were otherwise similar. Patients treated with F (ab')2 AV or FabAV received a similar total number of vials [16.0 vials (±6.1) vs 14.5 vials (±5.4), p = 0.189], but patients treated with F (ab')2 AV were more frequently given additional doses [31 patients (58.5%) vs. 22 FabAV patients (38.6%), p = 0.0051]. In patients with outpatient follow-up for 2 weeks, fewer patients treated with F (ab')2 AV developed late coagulopathy [5 patients (11.1%) vs 22 FabAV patients (48.9%), p = 0.0004]. Adverse events were generally mild and uncommon with no difference in frequency between patients who received either antivenom (2 F (ab')2 AV patients vs 4 FabAV patients, p = 0.6637). CONCLUSIONS: Other than patient age, we found no significant difference in the baseline demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation between patients receiving F (ab')2 AV or FabAV. Patients receiving F (ab')2 AV were more likely to be given an additional dose beyond the minimum typical treatment course, but less likely to develop late coagulopathy. Adverse events were uncommon and generally mild whether patients received either antivenom.

On the Biological Diversity of Ant Alkaloids.

Ants have outstanding capacity to mediate inter- and intraspecific interactions by producing structurally diverse metabolites from numerous secretory glands. Since Murray Blum's pioneering studies dating from the 1950s, there has been a growing interest in arthropod toxins as natural products. Over a dozen different alkaloid classes have been reported from approximately 40 ant genera in five subfamilies, with peak diversity within the Myrmicinae tribe Solenopsidini. Most ant alkaloids function as venom, but some derive from other glands with alternative functions. They are used in defense (e.g., alarm, repellants) or offense (e.g., toxins) but also serve as antimicrobials and pheromones. We provide an overview of ant alkaloid diversity and function with an evolutionary perspective. We conclude that more directed integrative research is needed. We suggest that comparative phylogenetics will illuminate compound diversification, while molecular approaches will elucidate genetic origins. Biological context, informed by natural history, remains critical not only for research about focal species, but also to guide applied research.

Unusual Sting by a Nonindigenous Caterpillar in Europe.

On the French island of Corsica, a 57-y-old woman without significant medical history was stung on the left thumb while she was taking care of an ornamental Ficus benjamina plant. Immediately, she felt intense pain in her hand. She saw a strange caterpillar, later identified by the local poison center as Acharia stimulea. The pain in her hand was evaluated as 8 of 10 using the numerical pain rating scale; only a slight erythema was visible on her skin. Symptoms disappeared within 2 h with use of local anti-inflammatory ointment and oral painkillers. Three other caterpillars emerged out of the soil of the potted plant during the following week. This sting by a saddleback caterpillar is exceptional in Corsica. French garden store owners and healthcare professionals should be informed that caterpillars can be imported across the oceans to Europe on different plants.

Caracterização bioquímica de uma serinoprotease com efeito ativador do plasminogênio do veneno de Lachesis muta rhombeata

Snake venom serine proteases (SVSPs) are chymotrypsin-like proteins found in some venoms of the Viperidae family. These enzymes affect physiological processes of their prey and victims, acting mainly in the hemostatic, fibrinolytic and kinin systems. SVSPs belong to the PA clan, PA (S) subclan, S1 family and A subfamily of proteolytic enzymes. This work, describes a SVSP (Lmr-PA) isolated from the venom of Lachesis muta rhombeata which activates plasminogen. The proteinase was purified by combination of gel filtration and anionic exchange chromatographies. Its homogeneity was demonstrated by SDS-PAGE, reverse-phase HPLC, and two-dimensional electrophoresis. Lmr-PA is a 30-kDa single chain glycoprotein. Its amino acid sequence (61%) was determined by mass spectrometry on nLC-MS/MS. Lmr-PA activates plasminogen to release plasmin and degrades the plasmin substrate S-2251 as well as dimethylcasein. PMSF, the specific inhibitor of serine proteases completely blocked Lmr-PA activity. The proteinase cleaves the Aα chain and partially the Bβ and γ chains of fibrinogen. In addition the protease degrades laminin, nidogen and type IV collagen from Matrigel. The enzyme digests fibrin in presence of plasminogen in vitro. Deglycosylated Lmr-PA loses approximately 26% of its activity. In addition, Lmr-PA activity is inhibited by α2-macroglobulin at a ratio of 2:1 (α2-M:E) and α2-antiplasmin inhibits plasmin generated from plasminogen. Lmr-PA does not induce aggregation of washed human platelets but, aggregates platelets in presence of exogenous fibrinogen and binds to the platelet receptors glycoproteins (GP) GPIb and GPVI. Our data indicate that Lmr-PA is a plasminogen activating serine protease, like to previously reported LV-PA from Lachesis muta muta venom. These results suggested that Lmr- PA play a role in the pathology of snake envenomation and could be a useful model to study hemostatic disorders caused by snake bites.

As serinoproteases do veneno de serpentes (SVSPs) são proteínas semelhantes à quimotripsina presentes encontradas em alguns venenos da família Viperidae. Essas enzimas afetam os processos fisiológicos de suas presas e vítimas, atuando principalmente nos sistemas hemostático, fibrinolítico e cinina. As SVSPs pertencem ao clã PA, subclan PA (S), família S1 e subfamília A de enzimas proteolíticas. Este trabalho descreve uma SVSP (Lmr-PA) isolada do veneno de Lachesis muta rhombeata que ativa o plasminogênio. A proteinase foi purifica por combinação de cromatografias de filtração em gel e troca aniônica. Sua homogeneidade foi demonstrada por SDS-PAGE, HPLC de fase reversa e eletroforese bidimensional. Lmr-PA é uma glicoproteína de cadeia simples de 30 kDa. A sua sequência de aminoácidos (61%) foi determinada por espectrometria de massa em nLC-MS/MS. Lmr-PA ativa o plasminogênio para liberar plasmina e degrada o substrato de plasmina S-2251, bem como a dimetilcaseína. PMSF, um inibidor específico de serinoproteases bloqueou completamente a atividade da Lmr-PA. A proteinase cliva a cadeia Aα e parcialmente as cadeias Bβ e γ do fibrinogênio. Além disso, a protease degrada laminina, nidogênio e colágeno tipo IV de Matrigel. A enzima digere a fibrina na presença de plasminogênio in vitro. Lmr-PA desglicosilada perde aproximadamente 26% da sua atividade. Além disso, a atividade da Lmr-PA é inibida pela α2-macroglobulina em uma proporção de 2:1 (α2-M:E) e a α2-antiplasmina inibe a plasmina gerada a partir do plasminogênio. Lmr-PA não induz a agregação de plaquetas humanas lavadas, mas agrega plaquetas na presença de fibrinogênio exógeno e se liga às glicoproteínas dos receptores plaquetários (GP) GPIb e GPVI. Nossos dados indicam que a Lmr-PA é uma serinoprotease ativadora do plasminogênio semelhante a LV-PA relatada anteriormente do veneno de Lachesis muta muta. Esses resultados sugerem que a Lmr-PA desempenha um papel na patologia do envenenamento por serpentes e pode ser um modelo útil para estudar distúrbios hemostáticos causados por acidentes ofídicos.

Estimation of local incidence of jellyfish envenomation in developed marine coastal areas and large populated island on the western coast of Peninsular Malaysia using case surveillance of government health facilities in Manjung, Perak and Langkawi Island.

BACKGROUND: Jellyfish stings are one of the commonest causes of marine animal related injuries in human. Despite mostly being harmless, box jellyfish species can cause major stings with fatalities or systemic envenoming symptoms. There are 15-20 species identified to be life-threatening. There are few reported cases that suggest the presence of deadly box jellyfish in the Malaysian coast. However, numbers of stings around Malaysia are still under reported. MATERIALS AND METHODS: This observational study was conducted in Manjung, Perak and Langkawi Island to look at the pattern and incidence of jellyfish stings which occur within 1 year. RESULTS: There were 45 sting incidents reported with the highest number of cases occurred in December and February. Cases mainly involved young adults aged 10 to 29 years old. The most common clinical symptom that presented was sudden and persistent pain. Vinegar was applied as first aid in 53.3% of reported stings. All patients were treated symptomatically and discharged well. Stings occurred at mean sea surface temperature of 29.38°C and the wind speed of 7.6 knots. All cases were mild and did not require antivenom. CONCLUSIONS: The study showed that the occurrence of jellyfish stings are affected by weather conditions. Jellyfish stings occur seasonally, thus making it predictable and easily preventable with public awareness, early first aid application and use of jellyfish nets.

Snakebite Envenoming Diagnosis and Diagnostics.

Snakebite envenoming is predominantly an occupational disease of the rural tropics, causing death or permanent disability to hundreds of thousands of victims annually. The diagnosis of snakebite envenoming is commonly based on a combination of patient history and a syndromic approach. However, the availability of auxiliary diagnostic tests at the disposal of the clinicians vary from country to country, and the level of experience within snakebite diagnosis and intervention may be quite different for clinicians from different hospitals. As such, achieving timely diagnosis, and thus treatment, is a challenge faced by treating personnel around the globe. For years, much effort has gone into developing novel diagnostics to support diagnosis of snakebite victims, especially in rural areas of the tropics. Gaining access to affordable and rapid diagnostics could potentially facilitate more favorable patient outcomes due to early and appropriate treatment. This review aims to highlight regional differences in epidemiology and clinical snakebite management on a global scale, including an overview of the past and ongoing research efforts within snakebite diagnostics. Finally, the review is rounded off with a discussion on design considerations and potential benefits of novel snakebite diagnostics.

Molecular Characterization and Functional Analysis of the Nattectin-like Toxin from the Venomous Fish Thalassophryne maculosa.

TmC4-47.2 is a toxin with myotoxic activity found in the venom of Thalassophryne maculosa, a venomous fish commonly found in Latin America whose envenomation produces an injury characterized by delayed neutrophil migration, production of major pro-inflammatory cytokines, and necrosis at the wound site, as well as a specific systemic immune response. However, there are few studies on the protein structure and functions associated with it. Here, the toxin was identified from the crude venom by chromatography and protein purification systems. TmC4-47.2 shows high homology with the Nattectin from Thalassophryne nattereri venom, with 6 cysteines and QPD domain for binding to galactose. We confirm its hemagglutinating and microbicide abilities independent of carbohydrate binding, supporting its classification as a nattectin-like lectin. After performing the characterization of TmC4-47.2, we verified its ability to induce an increase in the rolling and adherence of leukocytes in cremaster post-capillary venules dependent on the α5ß1 integrin. Finally, we could observe the inflammatory activity of TmC4-47.2 through the production of IL-6 and eotaxin in the peritoneal cavity with sustained recruitment of eosinophils and neutrophils up to 24 h. Together, our study characterized a nattectin-like protein from T. maculosa, pointing to its role as a molecule involved in the carbohydrate-independent agglutination response and modulation of eosinophilic and neutrophilic inflammation.

Molecular characterization and functional analysis of the nattectin-like toxin from the venomous fish thalassophryne maculosa

TmC4-47.2 is a toxin with myotoxic activity found in the venom of Thalassophryne maculosa, a venomous fish commonly found in Latin America whose envenomation produces an injury characterized by delayed neutrophil migration, production of major pro-inflammatory cytokines, and necrosis at the wound site, as well as a specific systemic immune response. However, there are few studies on the protein structure and functions associated with it. Here, the toxin was identified from the crude venom by chromatography and protein purification systems. TmC4-47.2 shows high homology with the Nattectin from Thalassophryne nattereri venom, with 6 cysteines and QPD domain for binding to galactose. We confirm its hemagglutinating and microbicide abilities independent of carbohydrate binding, supporting its classification as a nattectin-like lectin. After performing the characterization of TmC4-47.2, we verified its ability to induce an increase in the rolling and adherence of leukocytes in cremaster post-capillary venules dependent on the α5β1 integrin. Finally, we could observe the inflammatory activity of TmC4-47.2 through the production of IL-6 and eotaxin in the peritoneal cavity with sustained recruitment of eosinophils and neutrophils up to 24 h. Together, our study characterized a nattectin-like protein from T. maculosa, pointing to its role as a molecule involved in the carbohydrate-independent agglutination response and modulation of eosinophilic and neutrophilic inflammation.

KAMBÔ: an Amazonian enigma.

The secretions of the Giant Monkey Frog Phyllomedusa bicolor are used by populations in the Amazon regions (mainly the indigenous Katukinas and Kaxinawás). The so-called "toad vaccine" or "kambô" is applied as a medication for infections and to prevent diseases, and also as physical and mental invigorator, and analgesic. Since the 1980s, researchers and companies have been interested in the composition of these secretions. Phyllomedusin, phyllokinin, caerulein and sauvagine are the polypeptides in these secretions that can cause intense effects on smooth muscles, vessels provoking, nausea and vomiting, arterial hypotension, flushing, palpitations, nausea, vomiting, bile secretion and angioedema. These actions are similar to bradykinin. However, the feeling of well-being and improvement of motor skills described by the users seems to be associated with dermorphine, caerulein or deltorphin - peptides with analgesic properties - and their affinity for the opiate receptor systems. Caerulein is a peptide that increases digestive secretions. Phyllomedusin and Phyllokinin lead to blood pressure and digestive effects. Sauvagine release corticotropin and mimics the physiological reactions of exposure to stress. Deltorphins and dermorphins have high affinity for the opiate receptor system and can lead to analgesia. The fame acquired by the therapy motivated the use by individuals from urban areas worldwide, without safety considerations. While in indigenous communities, there is an entire cultural tradition that provides relative safety to the application, however, the extension of use to individuals from urban areas worldwide is a problem, with reports of severe adverse effects and deaths. Undoubtedly, the skin secretions of the Phyllomedusa genus contain substances of intense pharmacological action and that can lead to research for therapeutic uses, but control over their application in rituals outside the forest is needed due the risks presented.

Cottonmouth snake bites reported to the ToxIC North American snakebite registry 2013-2017.

Introduction: The majority of venomous snake exposures in the United States are due to snakes from the subfamily Crotalinae (pit vipers). There are three types of US pit vipers: rattlesnakes (Crotalus and Sisturus spp.) copperheads (Agkistrodon contortrix), and cottonmouths (Agkistrodon piscivorus) also known as water moccasins. Cottonmouth bites are reported less frequently than other pit viper envenomations, and data on cottonmouth envenomation are limited. Our objective was to describe the epidemiology, clinical manifestations, and management of cottonmouth envenomations using prospective data reported to the Toxicology Investigators Consortium's (ToxIC) North American Snakebite Registry (NASBR)Methods: Cottonmouth envenomation cases reported to NASBR for the period from January 1, 2013, through December 31, 2017 were reviewed. Variables collected included patient demographics, bite location, clinical manifestations, and management.Results: Thirty-one cottonmouth envenomations were reported. Most bites occurred in children aged 7-12 (39%). Most bites involved the lower extremity (72%). Intentional interaction with the snake occurred in three cases (10%). Swelling was the most reported clinical effect and occurred in all patients. Gastrointestinal symptoms were reported in 19% of patients, and 19% developed coagulopathy. Antivenom treatment was used in 84% of patients. Nineteen patients (61%) required hospital stays of >24 hours.Discussion: Our study represents the first systematic prospective data collection on cottonmouth bites. Our data demonstrate that cottonmouth envenomations cause primarily local effects and, occasionally, systemic toxicity. Our study also demonstrates that antivenom is often indicated for these envenomations per published guidelines and recommendations.Conclusions: Cottonmouth envenomations are relatively infrequent. However, they can cause significant local and systemic toxicity. Most cottonmouth envenomations in this series were treated with antivenom and were hospitalized beyond 24 hours.

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.