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Screening for target toxins of the antiophidic protein DM64 through a gel-based interactomics approach.

UNLABELLED: DM64 is a glycosylated protein with antivenom activity isolated from the serum of the opossum Didelphis aurita. It binds non-covalently to myotoxins I (Asp49) and II (Lys49) from Bothrops asper venom and inhibits their myotoxic effect. In this study, an affinity column with immobilized DM64 as bait was used to fish potential target toxins. All ten isolated myotoxins tested were able to effectively bind to the DM64 column. To better access the specificity of the inhibitor, crude venoms from Bothrops (8 species), Crotalus (2 species) and Naja naja atra were submitted to the affinity …

Neutralization of edema, hemorrhage and myonecrosis induced by North American crotalid venoms in simulated first-aid treatments.

Venoms of the broad-banded copperhead (Agkistrodon contortrix laticinctus, ACL) and the prairie rattlesnake (Crotalus viridis viridis, CVV), like other crotalid venoms, cause severe local tissue damage such as edema, hemorrhage and myonecrosis. Antivenom therapy is not very effective in neutralizing this local tissue damage, and such observations support the need for an effective first-aid regimen aimed at minimizing local tissue reactions. Some of the local tissue damage induced by these venoms is due to phospholipase A2 myotoxins, and since para-bromophenacyl bromide (p-BPB), an inhibitor of…

Characterization of anemia following rattlesnake envenomation in Arizona: a retrospective observational study.

INTRODUCTION: Rattlesnakes in the southwestern United States possess hemotoxic venom associated with coagulopathy and bleeding. While the two complications are related, they are distinct entities, and no known study has evaluated the phenomenon of venom-induced anemia. METHODS: A chart review was performed using electronic health records from the Arizona Poison and Drug Information Center between January 1st, 2017 and December 31st, 2022. Included charts were characterized by the presence or absence of anemia (hemoglobin <100 g/L), and clinical and demographic information were compared betwee

Use of polyvalent equine anti-viper serum to treat delayed coagulopathy due to suspected Sistrurus miliarius streckeri envenomation in two children.

BACKGROUND: Western Pygmy Rattlesnake (WPR) envenomation reportedly causes refractory and persistent coagulopathy when treated with CroFab® (Crotalidae Polyvalent Immune Fab). We report two cases where polyvalent equine anti-viper serum (AntivipmynTRI®) was used to treat recurrent coagulopathy in children. CASE DETAILS: The first patient was a 16-month-old male who was bitten by a confirmed WPR. The patient received a total of 18 vials of CroFab®. His labs normalized, swelling gradually improved, and the child was discharged to home. On day 5, the child returned to the emergency department wi

Use of microarrays for investigating the subtoxic effects of snake venoms: insights into venom-induced apoptosis in human umbilical vein endothelial cells.

The pathological effects of only a small percentage of the total number of protein components of snake venoms are well documented, yet this knowledge has led to a general understanding of the physiological consequences of snake venom poisoning. The aim of this study was to assess the effect of subpathological levels of Crotalus atrox (Western diamondback rattlesnake) and Bothrops jararaca (Jararaca) snake venoms on the gene expression profile of human umbilical vein endothelial cells (HUVEC) in culture. Analysis of the data demonstrated that HUVECs treated with C. atrox venom had 33 genes up-r…

Three-dimensional structure of a presynaptic neurotoxic phospholipase A2 from Daboia russelli pulchella at 2.4 A resolution.

The phospholipase A(2 )from Daboia russelli pulchella (DPLA(2)) is the only known member of subclass II of group IIA. The three-dimensional structure of this presynaptic neurotoxic DPLA(2) enzyme has been determined at 2.4 A resolution. The structure was determined by the molecular replacement method using the model Crotalus atrox, and refined using X-PLOR to a final R-factor of 18.8 % for all data in the resolution range 20.0 A-2.4 A. The final refined model comprises 1888 atoms from two crystallographically independent protein molecules and 160 water oxygen atoms. The overall folding of DPLA…

A study on the membrane depolarization of skeletal muscles caused by a scorpion toxin, sea anemone toxin II and crotamine and the interaction between toxins.

Quinquestriatus toxin (QTX) isolated from the venom of a scorpion (Leiurus quinquestriatus) and sea anemone (Anemonia sulcata) toxin II enhanced the twitch response of the rat and mouse diaphragms and like crotamine (isolated from the venom of Crotalus durissus terrificus) caused spontaneous fasciculation of the muscle. Trains of action potentials in muscles at 70-250 Hz, which could not be antagonized by (+)-tubocurarine, were triggered by single stimulation or occurred spontaneously after treatment with these toxins. QTX and toxin II prolonged the rat muscle action potential 3 to 4 fold wher…

Effects of local anaesthetics on phospholipases.

1. The effects of six local anaesthetics have been studied on the activities of soluble phospholipases A2 (EC 3.1.1.4) and lysophospholipase … ion was seen to be competitive with respect to Ca2+. 3. Phospholipase A2 activity in crude venom of Crotalus adamanteus was not affected or slightly stimulated by local anaesthetics up to 10(-2) M concentrations, when egg yolk was used as substrate. However, with sonicated radioactively-labelled phosphatidylcholine or phosphatidylethanolamine as substrate, …

Rapid evolution by positive selection and gene gain and loss: PLA(2) venom genes in closely related Sistrurus rattlesnakes with divergent diets.

Rapid evolution of snake venom genes by positive selection has been reported previously but key features of this process such as the targets of selection, rates of gene turnover, and functional diversity of toxins generated remain unclear. This is especially true for closely related species with divergent diets. We describe the evolution of PLA(2) gene sequences isolated from genomic DNA from four taxa of Sistrurus rattlesnakes which feed on different prey. We identified four to seven distinct PLA(2 )sequences in each taxon and phylogenetic analyses suggest that these sequences represent a rap

Primary structure of alboaggregin-B purified from the venom of Trimeresurus albolabris.

The complete amino acid sequences of alpha and beta subunits of alboaggregin-beta are presented. The alpha and beta subunits were separated by reversed-phase HPLC after reduction and S-pyridylethylation, and their sequences were determined by analysis of peptides generated by enzymatic or chemical digestion. The alpha and beta subunits consist of 133 and 123 amino acid residues, respectively. The sequences are highly homologous to each other (41.4% identity) and also to those of the alpha and beta subunits of botrocetin (a von Willebrand factor modulator) and the A and B chains of factor IX/X

Epidemiology and hospital course of rattlesnake envenomations cared for at a tertiary referral center in Central Arizona.

OBJECTIVE: To describe the demographics and primary inpatient treatment of victims of rattle-snake bites (RSBs) referred to a teritiary referral poison treatment center in central Arizona, and to compare the frequency of local tissue complications and hematologic toxicity during hospitalization in children with those for adults. METHODS: This was a chart review of patients diagnosed as having RSB by a toxicology service between July 1994 and April 2000. Data collected included: age, sex, date, bite location, time to and length of hospitalization, time to and amount of antivenin, serial hemato

Новые тенденции в нанобиосистемах Змей-Веном-Лоадед: всеобъемлющий обзор.

Достижения в медицинской нанобиотехнологии в значительной степени способствовали применению ядов змеиных токсинов, облегчая разработку новых методов лечения токсинов, производимых животными. Огромное разнообразие видов змей и их ядовые сложности подчеркивают необходимость продолжения исследований. Этот обзор посвящен изучению интеграции яда змеиных ядов с наночастицами, с тем чтобы они могли использоваться в лечении человека в целях разработки методов лечения. Сложная смесь яда змей не только вызывает значительные патологические последствия, но и позволяет получить ценные знания для создания н

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… Nanosystems Containing Crotalus Snake Venom Chitosan nanoparticles were developed by Glaucia-Silva et al. [ 103 ] through an ionic gelatinization method containing Crotalus durissus cascavella crude snake venom capable of inducing murine immunization, incorporating auxiliary components to enhance the … | - | Cell-penetrating ability | [ 108 ] Crotoxin | Crotalus durissus Terrificus | Liposomes | - | - | Immunostimulants | [ 110 , 111 ] Whole venom | Crotalus durissus terrificus | Liposomes | - | - | Biodistribution of free and encapsulated liposomes | [ 113 ] 6.3. …

The use of zootherapeutics in folk veterinary medicine in the district of Cubati, Paraíba State, Brazil.

BACKGROUND: The present work addresses the use of zootherapy in folk veterinary medicine (ethnoveterinary) by the residents of the municipal … medicine. Additionally, chameleons (Iguana iguana), chickens (Gallus domesticus), and rattlesnakes (Crotalus durissus) were mentioned by 75, 43.75, and 31.25% of the informants, respectively. Relatively simple animal illnesses, such as furuncles, or injuries resulting from embedded thorns or skin eruptions are responsible for the largest number of zoothera …

Structural and functional analysis of BmjMIP, a phospholipase A2 myotoxin inhibitor protein from Bothrops moojeni snake plasma.

A protein, which neutralizes the enzymatic, toxic, and pharmacological activities of various basic and acidic phospholipases A(2) from the v … ze the biological activities of crotoxin B (CB), the PLA(2) homologue associated with crotapotin in Crotalus durissus terrificus snake venom. Finally, the purified PLA(2) inhibitor was shown to protect in vivo against the toxic and pharmacological effects of a homologous PLA(2) enzyme, suggesting that PLIs or a corresponding derived peptide may prove usefu …

Structural and functional characterization of neuwiedase, a nonhemorrhagic fibrin(ogen)olytic metalloprotease from Bothrops neuwiedi snake venom.

A fibrino(geno)lytic nonhemorrhagic metalloprotease (neuwiedase) was purified from Bothrops neuwiedi snake venom by a single chromatographic … 65M166. The three-dimensional structure of neuwiedase was modeled based on the crystal structure of Crotalus adamanteus Adamalysin II. This model revealed that the zinc binding site region showed a high structural similarity with other metalloproteases. The proteolyitc specificity, using the Bbeta-chain of oxidized insulin as substrate, was shown to be dir …

Kinetic study of the action of snake venom phospholipase A2 on human serum high density lipoprotein 3.

The hydrolysis of the phospholipids of intact human serum high density lipoprotein 3 (HDL3) by pure alpha-phospholipase A2 from Crotalus adamanteus was studied by pH-stat titration. The enzyme quantitatively hydrolyzed phosphatidylcholine and phosphatidylethanolamine and left sphinogomyelin intact, yielding a stable and water-soluble modified HDL. Lysophospholipids and free fatty acids, the products of hydrolysis, remained in the lipoprotein. When 1 mol of defatted bovine serum albumin/mol of substrate phospholipids was added to the reaction mixture, up to 60% of the fatty acids and 85% of the…

Phylogenetic origins for severe acetaminophen toxicity in snake species compared to other vertebrate taxa.

While it has been known for a while that some snake species are extremely sensitive to acetaminophen, the underlying mechanism for this toxicity has not been reported. To investigate if essential detoxification enzymes are missing in snake species that are responsible for biotransformation of acetaminophen in other vertebrate species, livers were collected from a variety of snake species, together with samples from alligator, snapping turtle, cat, rat, and cattle. Subcellular fractions were analyzed for enzymatic activities of phenol-type sulfotransferase and UDP‑glucuronosyltransferase, total

Characterization of hypofibrinogenemia following rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom.

INTRODUCTION: Hemotoxicity is common following rattlesnake envenomation. Published experiences with equine-derived crotalidae immune F(ab')2 antivenom have characterized hemotoxicity as delayed, recurrent, or persistent. This study investigated recovery of hypofibrinogenemia following rattlesnake envenomation treated with equine-derived crotalidae immune F(ab')2 antivenom. METHODS: This is a retrospective analysis of human rattlesnake envenomations reported to the Arizona Poison and Drug Information Center over four years. We included rattlesnake-envenomated patients who developed hypofibrino

Prophylactic Antibiotics Are Not Needed Following Rattlesnake Bites.

BACKGROUND: Antibiotics are sometimes administered to victims of rattlesnake bites in the hope of preventing infections. Experts in the field recommend that prophylactic antibiotics not be used because secondary infections are rare. Current recommendations are based on a small number of studies conducted in the United States. We decided to reexamine the issue by taking advantage of a large database on snakebites in Arizona. This allowed us to determine how often prophylactic antibiotics were used and whether or not they were effective. METHODS: We obtained data from the Arizona Poison and Dru

Thromboelastography Utilization in Delayed Recurrent Coagulopathy after Severe Eastern Diamondback Rattlesnake Envenomation.

Venomous snakebites are fairly common in the United States and can present with a wide range of symptoms. A 48-year-old man presented after Eastern Diamondback rattlesnake envenomation. His hospital course was complicated by right leg compartment syndrome and delayed recurrent coagulopathy, requiring multiple doses of Crotalidae Polyvalent Immune Fab (CroFab) antivenom and transfusions. Thromboelastography was used as an adjunct to standard coagulation studies in monitoring his delayed recurrent coagulopathy.