Cognitive effects of electro-acupuncture and pregabalin in a trigeminal neuralgia rat model induced by cobra venom

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Chen RW

2017-08-01

Full Text Available Ruo-Wen Chen,1,2 Hui Liu,2 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Yi-De Jiang,2 Doris K Cope,3 John P Williams,3 Rui Zhang,1 Li-Na Sun1 1Department of Anesthesiology, Weifang Medical University, Weifang City, Shandong, 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The objective of this study was to investigate the effects of electro-acupuncture (EA and pregabalin on cognition impairment induced by chronic trigeminal neuralgia (TN in rats. Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University. Subjects: Forty adult male Sprague Dawley rats. Methods: Rats were randomly divided into four groups. The TN model was induced by administration of cobra venom to the left infraorbital nerve. On postoperative day 14, either EA or pregabalin was administered, free behavioral activities were observed. Spatial learning and memory abilities were determined in the Morris water maze. The ultrastructural alterations of the Gasserian ganglion, medulla oblongata and hippocampus were examined by electron microscopy. The changes on long-term potentiation were investigated. Results: After treatment, the exploratory behavior increased and the grooming behavior decreased (P<0.05 for the EA group and pregabalin group compared with the cobra venom group; moreover, demyelination of neurons in Gasserian ganglion and medulla oblongata was reversed. The number of platform site crossings, the average percentages of time in the target quadrant and the field excitatory postsynaptic potential slopes increased (P<0.05 in the EA group compared to the cobra venom group. However, the pregabalin group

The protective effects of Mucuna pruriens seed extract against histopathological changes induced by Malayan cobra (Naja sputatrix) venom in rats.

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Fung, S Y; Tan, N H; Liew, S H; Sim, S M; Aguiyi, J C

2009-04-01

Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages.

Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of Pluchea indica Less. (Asteraceae).

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Gomes, A; Saha, Archita; Chatterjee, Ipshita; Chakravarty, A K

2007-09-01

We reported previously that the methanolic root extract of the Indian medicinal plant Pluchea indica Less. (Asteraceae) could neutralize viper venom-induced action [Alam, M.I., Auddy, B., Gomes, A., 1996. Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and P. indica) root extracts. Phytother. Res. 10, 58-61]. The present study reports the neutralization of viper and cobra venom by beta-sitosterol and stigmasterol isolated from the root extract of P. indica Less. (Asteraceae). The active fraction (containing the major compound beta-sitosterol and the minor compound stigmasterol) was isolated and purified by silica gel column chromatography and the structure was determined using spectroscopic analysis (EIMS, (1)H NMR, (13)C NMR). Anti-snake venom activity was studied in experimental animals. The active fraction was found to significantly neutralize viper venom-induced lethal, hemorrhagic, defibrinogenation, edema and PLA(2) activity. Cobra venom-induced lethality, cardiotoxicity, neurotoxicity, respiratory changes and PLA(2) activity were also antagonized by the active component. It potentiated commercial snake venom antiserum action against venom-induced lethality in male albino mice. The active fraction could antagonize venom-induced changes in lipid peroxidation and superoxide dismutase activity. This study suggests that beta-sitosterol and stigmasterol may play an important role, along with antiserum, in neutralizing snake venom-induced actions.

The Antinociceptive Effects of Iranian Cobra Snake Venom using Formalin Test

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Zahra Hadi Chegeni

2015-06-01

Full Text Available Abstract Background: There have been numerous reports of snake venoms being employed as analgesics in attempts to relieve severe pain associated with cancer, immune dysfunction and viral infections. This study investigates the antinociceptive effects of iranian cobra snake venom (Naja naja oxiana in comparison with morphine and lidocain on laboratorial femal mice. Materials and Methods: This study has been done on 48 NMRI female mice of 18-20 g in weight. Antinociceptive activeity of snake venom was evaluated by formalin test. In this test, the animals were divided into 6 groups (each group consisting of 8 mice: Sham, positive Control (receiving morphine at dose of 5 mg/kg, and receiving lidocain at dose of 20 mg/kg, and experimental groups receiving venom at doses of 1, 3 and 4/5 µg/mice. In all groups, the formalin test was recorded for 60 min after administration of venom and drugs in mice. Data were analyzed using one-way ANOVA and Tukey test. Results: The results showed that the venom of Naja naja oxiana decreased nociception meaningfully in both acute and chronic phases. We also showed that this venom revealed even a better analgesic activity in comparison with morphine and lidocain. Conclusion: This study showed that the antinociceptive effect of the venom was mediated through central nervous system and peripheral mechanisms. Although details of the mechanism remain unclear, and further studies should be considered to demonstrate its therapeutic effects.

Antibacterial action of a heat-stable form of L-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom.

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Lee, Mui Li; Tan, Nget Hong; Fung, Shin Yee; Sekaran, Shamala Devi

2011-03-01

The major l-amino acid oxidase (LAAO, EC 1.4.3.2) of king cobra (Ophiophagus hannah) venom is known to be an unusual form of snake venom LAAO as it possesses unique structural features and unusual thermal stability. The antibacterial effects of king cobra venom LAAO were tested against several strains of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli using broth microdilution assay. For comparison, the antibacterial effects of several antibiotics (cefotaxime, kanamycin, tetracycline, vancomycin and penicillin) were also examined using the same conditions. King cobra venom LAAO was very effective in inhibiting the two Gram-positive bacteria (S. aureus and S. epidermidis) tested, with minimum inhibitory concentration (MIC) of 0.78μg/mL (0.006μM) and 1.56μg/mL (0.012μM) against S. aureus and S. epidermidis, respectively. The MICs are comparable to the MICs of the antibiotics tested, on a weight basis. However, the LAAO was only moderately effective against three Gram-negative bacteria tested (P. aeruginosa, K. pneumoniae and E. coli), with MIC ranges from 25 to 50μg/mL (0.2-0.4μM). Catalase at the concentration of 1mg/mL abolished the antibacterial effect of LAAO, indicating that the antibacterial effect of the enzyme involves generation of hydrogen peroxide. Binding studies indicated that king cobra venom LAAO binds strongly to the Gram-positive S. aureus and S. epidermidis, but less strongly to the Gram-negative E. coli and P. aeruginosa, indicating that specific binding to bacteria is important for the potent antibacterial activity of the enzyme. Copyright © 2010 Elsevier Inc. All rights reserved.

Pharmacokinetics of Naja sumatrana (equatorial spitting cobra venom and its major toxins in experimentally envenomed rabbits.

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Michelle Khai Khun Yap

2014-06-01

Full Text Available The optimization of snakebite management and the use of antivenom depend greatly on the knowledge of the venom's composition as well as its pharmacokinetics. To date, however, pharmacokinetic reports on cobra venoms and their toxins are still relatively limited. In the present study, we investigated the pharmacokinetics of Naja sumatrana (Equatorial spitting cobra venom and its major toxins (phospholipase A2, neurotoxin and cardiotoxin, following intravenous and intramuscular administration into rabbits.The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h, terminal phase half-life (13.6 h and systemic bioavailability (41.9% of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively. Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5% compared to that of the phospholipase A2 (Fi.m.=68.6% or cardiotoxin (Fi.m.=45.6%. The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.Our results suggest that the venom neurotoxin is absorbed very rapidly and has the highest bioavailability following intramuscular injection, supporting its

Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca.

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Lauridsen, Line P; Laustsen, Andreas H; Lomonte, Bruno; Gutiérrez, José María

2017-01-06

A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1wt%), which includes post-synaptically acting α-neurotoxins. Phospholipases A 2 (PLA 2 ) were the second most abundant group of proteins (12.9wt%), followed by metalloproteinases (SVMPs) (9.7wt%), cysteine-rich secretory proteins (CRISPs) (7.6wt%), and Kunitz-type serine proteinase inhibitors (3.8wt%). A number of additional protein families comprised each <3wt% of venom proteins. A toxicity screening of the fractions, using the mouse lethality test, identified toxicity in RP-HPLC peaks 3, 4, 5 and 8, all of them containing α-neurotoxins of the 3FTx family, whereas the rest of the fractions did not show toxicity at a dose of 0.53mg/kg. Three polyspecific antivenoms manufactured in South Africa and India were tested for their immunoreactivity against crude venom and fractions of N. melanoleuca. Overall, antivenoms immunorecognized all fractions in the venom, the South African antivenom showing a higher titer against the neurotoxin-containing fractions. This toxicovenomic study identified the 3FTx group of α-neurotoxins in the venom of N. melanoleuca as the relevant targets to be neutralized. A toxicovenomic analysis of the venom of the forest cobra, also known as black cobra, Naja melanoleuca, was performed. Envenomings by this elapid species are characterized by a progressive descending paralysis which starts with palpebral ptosis and, in severe cases, ends up with respiratory arrest and death. A total of 52 different proteins were identified in this venom. The most abundant protein family was the three-finger toxin (3FTx) family, which comprises almost 57.1wt% of the venom, followed by phospholipases A 2 (PLA 2 ) (12.9wt%). In addition, several other protein families were identified in a much lower percentage in the venom. A

Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics.

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Melani, Rafael D; Skinner, Owen S; Fornelli, Luca; Domont, Gilberto B; Compton, Philip D; Kelleher, Neil L

2016-07-01

Characterizing whole proteins by top-down proteomics avoids a step of inference encountered in the dominant bottom-up methodology when peptides are assembled computationally into proteins for identification. The direct interrogation of whole proteins and protein complexes from the venom of Ophiophagus hannah (king cobra) provides a sharply clarified view of toxin sequence variation, transit peptide cleavage sites and post-translational modifications (PTMs) likely critical for venom lethality. A tube-gel format for electrophoresis (called GELFrEE) and solution isoelectric focusing were used for protein fractionation prior to LC-MS/MS analysis resulting in 131 protein identifications (18 more than bottom-up) and a total of 184 proteoforms characterized from 14 protein toxin families. Operating both GELFrEE and mass spectrometry to preserve non-covalent interactions generated detailed information about two of the largest venom glycoprotein complexes: the homodimeric l-amino acid oxidase (∼130 kDa) and the multichain toxin cobra venom factor (∼147 kDa). The l-amino acid oxidase complex exhibited two clusters of multiproteoform complexes corresponding to the presence of 5 or 6 N-glycans moieties, each consistent with a distribution of N-acetyl hexosamines. Employing top-down proteomics in both native and denaturing modes provides unprecedented characterization of venom proteoforms and their complexes. A precise molecular inventory of venom proteins will propel the study of snake toxin variation and the targeted development of new antivenoms or other biotherapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting

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Nadya Panagides

2017-03-01

Full Text Available The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for. Hooding and spitting are widely regarded as defensive adaptations, but it has hitherto been uncertain whether cytotoxicity serves a defensive purpose or is somehow useful in prey subjugation. The results of this study suggest that cytotoxicity evolved primarily as a defensive innovation and that it has co-evolved twice alongside hooding behavior: once in the Hemachatus + Naja and again independently in the king cobras (Ophiophagus. There was a significant increase of cytotoxicity in the Asian Naja linked to the evolution of bold aposematic hood markings, reinforcing the link between hooding and the evolution of defensive cytotoxic venoms. In parallel, lineages with increased cytotoxicity but lacking bold hood patterns evolved aposematic markers in the form of high contrast body banding. The results also indicate that, secondary to the evolution of venom rich in cytotoxins, spitting has evolved three times independently: once within the African Naja, once within the Asian Naja, and once in the Hemachatus genus. The evolution of cytotoxic venom thus appears to facilitate the evolution of defensive spitting behaviour. In contrast, a secondary loss of cytotoxicity and reduction of the hood occurred in the water cobra Naja annulata, which possesses streamlined neurotoxic venom similar to that of other aquatic elapid snakes (e

How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting.

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Panagides, Nadya; Jackson, Timothy N W; Ikonomopoulou, Maria P; Arbuckle, Kevin; Pretzler, Rudolf; Yang, Daryl C; Ali, Syed A; Koludarov, Ivan; Dobson, James; Sanker, Brittany; Asselin, Angelique; Santana, Renan C; Hendrikx, Iwan; van der Ploeg, Harold; Tai-A-Pin, Jeremie; van den Bergh, Romilly; Kerkkamp, Harald M I; Vonk, Freek J; Naude, Arno; Strydom, Morné A; Jacobsz, Louis; Dunstan, Nathan; Jaeger, Marc; Hodgson, Wayne C; Miles, John; Fry, Bryan G

2017-03-13

The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for. Hooding and spitting are widely regarded as defensive adaptations, but it has hitherto been uncertain whether cytotoxicity serves a defensive purpose or is somehow useful in prey subjugation. The results of this study suggest that cytotoxicity evolved primarily as a defensive innovation and that it has co-evolved twice alongside hooding behavior: once in the Hemachatus + Naja and again independently in the king cobras ( Ophiophagus ). There was a significant increase of cytotoxicity in the Asian Naja linked to the evolution of bold aposematic hood markings, reinforcing the link between hooding and the evolution of defensive cytotoxic venoms. In parallel, lineages with increased cytotoxicity but lacking bold hood patterns evolved aposematic markers in the form of high contrast body banding. The results also indicate that, secondary to the evolution of venom rich in cytotoxins, spitting has evolved three times independently: once within the African Naja , once within the Asian Naja , and once in the Hemachatus genus. The evolution of cytotoxic venom thus appears to facilitate the evolution of defensive spitting behaviour. In contrast, a secondary loss of cytotoxicity and reduction of the hood occurred in the water cobra Naja annulata , which possesses streamlined neurotoxic venom similar to that of other aquatic elapid snakes (e.g., hydrophiine

Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca

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Lauridsen, Line P.; Laustsen, Andreas Hougaard; Lomonte, Bruno

2017-01-01

A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1 wt%), which includes post-synaptically acting α-neurotoxins........ This toxicovenomic study identified the 3FTx group of α-neurotoxins in the venom of N. melanoleuca as the relevant targets to be neutralized....

[Sequencing and analysis of the complete mitochondrial genome of the King Cobra, Ophiophagus hannah (Serpents: Elapidae)].

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Chen, Nian; Lai, Xiao-Ping

2010-07-01

We obtained the complete mitochondrial genome of King Cobra(GenBank accession number: EU_921899) by Ex Taq-PCR, TA-cloning and primer-walking methods. This genome is very similar to other vertebrate, which is 17 267 bp in length and encodes 38 genes (including 13 protein-coding, 2 ribosomal RNA and 23 transfer RNA genes) and two long non-coding regions. The duplication of tRNA-Ile gene forms a new mitochondrial gene rearrangement model. Eight tRNA genes and one protein genes were transcribed from L strand, and the other genes were transcribed genes from H strand. Genes on the H strand show a fairly similar content of Adenosine and Thymine respectively, whereas those on the L strand have higher proportion of A than T. Combined rDNA sequence data (12S+16S rRNA) were used to reconstruct the phylogeny of 21 snake species for which complete mitochondrial genome sequences were available in the public databases. This large data set and an appropriate range of outgroup taxa demonstrated that Elapidae is more closely related to colubridae than viperidae, which supports the traditional viewpoints.

Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

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Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke

2011-01-01

with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...

Venomous snakes of Costa Rica: biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics.

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Lomonte, Bruno; Fernández, Julián; Sanz, Libia; Angulo, Yamileth; Sasa, Mahmood; Gutiérrez, José María; Calvete, Juan J

2014-06-13

In spite of its small territory of ~50,000km(2), Costa Rica harbors a remarkably rich biodiversity. Its herpetofauna includes 138 species of snakes, of which sixteen pit vipers (family Viperidae, subfamily Crotalinae), five coral snakes (family Elapidae, subfamily Elapinae), and one sea snake (Family Elapidae, subfamily Hydrophiinae) pose potential hazards to human and animal health. In recent years, knowledge on the composition of snake venoms has expanded dramatically thanks to the development of increasingly fast and sensitive analytical techniques in mass spectrometry and separation science applied to protein characterization. Among several analytical strategies to determine the overall protein/peptide composition of snake venoms, the methodology known as 'snake venomics' has proven particularly well suited and informative, by providing not only a catalog of protein types/families present in a venom, but also a semi-quantitative estimation of their relative abundances. Through a collaborative research initiative between Instituto de Biomedicina de Valencia (IBV) and Instituto Clodomiro Picado (ICP), this strategy has been applied to the study of venoms of Costa Rican snakes, aiming to obtain a deeper knowledge on their composition, geographic and ontogenic variations, relationships to taxonomy, correlation with toxic activities, and discovery of novel components. The proteomic profiles of venoms from sixteen out of the 22 species within the Viperidae and Elapidae families found in Costa Rica have been reported so far, and an integrative view of these studies is hereby presented. In line with other venomic projects by research groups focusing on a wide variety of snakes around the world, these studies contribute to a deeper understanding of the biochemical basis for the diverse toxic profiles evolved by venomous snakes. In addition, these studies provide opportunities to identify novel molecules of potential pharmacological interest. Furthermore, the

The status of taxonomy and venom in sea snakes

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Redsted Rasmussen, Arne; Sanders, Kate L.

2017-01-01

The status of taxonomy and venom in sea snakesArne R Rasmussen1, Kate L Sanders21 The Royal Danish Academy of Fine Arts, School of Architecture, Design & Conservation, Copenhagen, Denmark2 School of Earth and Environmental Sciences, University of Adelaide, Adelaide, South Australia 5000, AustraliaSea...... snakes form two aquatic groups of snakes with a flat vertically paddle-form tail (sea kraits and viviparous sea snakes). Sea snakes belong to the same family Elapidae, which also includes the terrestrial mambas, cobra, kraits, taipan and brown snake. All elapids are characterized by the anterior position...... of the poison-fangs on the maxillary bone (proteroglyphous). Globally there are some 70 species of sea snake found in the tropical and subtropical waters of the Indian Ocean and the Pacific Ocean. Most species are found in the Indo-Malayan Archipelago, the China Sea, Indonesia, and the Australian region...

Protein Characterization of Javan Cobra (Naja sputatrix) Venom Following Sun Exposure and Photo-Oxidation Treatment

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Sulistiyani; Biki, R. S.; Andrianto, D.

2017-03-01

Snake venom has always been known for its toxicity that can cause fatality, however, it is also one of the important biological resources to be used for disease treatment. In Indonesia, snake venom previously expose under the sun has been used for alternative treatment of some diseases such as dengue fever, atherosclerosis, cancer, and diabetes. There has been very little scientific evidence on the use of snake venom of Indonesia origin as well as its protein characteristic. Thus, the objective of this research is to characterize the protein content and the specific activity of the venom of Javan Cobra (N.sputatrix) when treated with sun exposure in comparison with photo-oxidation by ultraviolet. Qualitative analysis of protein contents was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). The L-amino acid oxidase activity (LAAO) and the phospholipase A2 (PLA2) activities were determined using spectrophotometry. The venom’s protein was separated into 5 main protein bands with molecular weight ranging from 14 to 108 kDa. A time course study showed that the venom lost 91% of its LAAO activity and 96% of PLA2 activity after 6 hours of sun exposure. UV photo-oxidation carried out for 3 hours decreased 91% of LAAO activity, and almost diminished all of PLA2 activity (99.8%). These findings suggest that the exposure of N. sputatrix venom under the sun and UV photo-oxidation decreased its toxicity as shown by the significant reduction of the enzymes activity, but did not affect the protein’s integrity. Therefore, these approaches produced N.sputatrix venom with less toxicity but still withheld other characters of intact proteins.

In Vitro and In Vivo Evaluation of Polyherbal Formulation against Russell's Viper and Cobra Venom and Screening of Bioactive Components by Docking Studies

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Sakthivel, G.; Dey, Amitabha; Nongalleima, Kh.; Chavali, Murthy; Rimal Isaac, R. S.; Singh, N. Surjit; Deb, Lokesh

2013-01-01

The present study emphasizes to reveal the antivenom activity of Aristolochia bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which were evaluated against venoms of Daboia russelli russelli (Russell's viper) and Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above-mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200 mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and 0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro antioxidant activities sample extracts showed free radical scavenging effects in dose dependent manner. Computational drug design and docking studies were carried out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from Indian common krait venom. This confirmed that aristolochic acid and leucasin can neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a source of natural antioxidants and common antidote for snake bite. However, further studies are needed to identify the lead molecule responsible for antidote activity. PMID:23533518

In vivo studies on detoxifying actions of aqueous bark extract of Prosopis cineraria against crude venom from Indian cobra (Naja naja

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Thirunavukkarasu Sivaraman

2013-12-01

Full Text Available Detoxification effect of aqueous, methanol and petroleum ether extracts of medicinal plants such as Aristolochia bracteolata, Mucuna pruriens, Prosopis cineraria and Rauvolfia tetraphylla was systematically screened against lethality of crude venom of Naja naja using Swiss albino mice as animal models. We have herein demonstrated that aqueous bark extract of P. cineraria has substantial anti-venom potential vis-à-vis other extracts used in the present study. The aqueous extract at the dose of 14 mg/kg b.w. was able to almost completely neutralize the lethal activity of 3LD50 (1.12 mg/kg b.w. of the cobra venom and the extract did not cause any types of adverse side-effects to the animal models. The investigation justifies not only the veraciousness of the extract used by traditional healers of Asian subcontinent as antidotes to snake venoms and also suggests that the aqueous extract should contain specific inhibitors to most principle toxic components of the crude venom.

Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom.

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He, Ying-Ying; Liu, Shu-Bai; Lee, Wen-Hui; Qian, Jin-Qiao; Zhang, Yun

2008-10-01

Snake venom Kunitz/BPTI members are good tools for understanding of structure-functional relationship between serine proteases and their inhibitors. A novel dual Kunitz/BPTI serine proteinase inhibitor named OH-TCI (trypsin- and chymotrypsin-dual inhibitor from Ophiophagus hannah) was isolated from king cobra venom by three chromatographic steps of gel filtration, trypsin affinity and reverse phase HPLC. OH-TCI is composed of 58 amino acid residues with a molecular mass of 6339Da. Successful expression of OH-TCI was performed as the maltose-binding fusion protein in E. coli DH5alpha. Much different from Oh11-1, the purified native and recombinant OH-TCI both had strong inhibitory activities against trypsin and chymotrypsin although the sequence identity (74.1%) between them is very high. The inhibitor constants (K(i)) of recombinant OH-TCI were 3.91 x 10(-7) and 8.46 x10(-8)M for trypsin and chymotrypsin, respectively. To our knowledge, it was the first report of Kunitz/BPTI serine proteinase inhibitor from snake venom that had equivalent trypsin and chymotrypsin inhibitory activities.

Discovery Of Human Antibodies Against Spitting Cobra Toxins

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Bojsen-Møller, Laura; Lohse, Brian; Harrison, Robert

Current snakebite envenoming treatment options consist of animal-derived antisera and are associated with severe adverse reactions due to the heterologous nature of the animal-derived antibodies present in these antisera, and the presence of therapeutically irrelevant antibodies. The African...... spitting cobras are among the most medically important snakes in sub-Saharan regions due to the severity of the clinical outcomes caused by their cytotoxic venom, which is derived from cytotoxins of the 3FTx toxin family and PLA2. Here we report the results of our progress in identifying human antibodies...... targeting relevant toxins from the venom of the black necked spitting cobra (Naja nigricolis)....

Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

DEFF Research Database (Denmark)

Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke

2011-01-01

with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...... slightly affects the C5-CVF interface, explaining the IgA dependence for SSL7-mediated inhibition of C5 cleavage. CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. A general model...

An in-depth snake venom proteopeptidome characterization: Benchmarking Bothrops jararaca.

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Nicolau, Carolina A; Carvalho, Paulo C; Junqueira-de-Azevedo, Inácio L M; Teixeira-Ferreira, André; Junqueira, Magno; Perales, Jonas; Neves-Ferreira, Ana Gisele C; Valente, Richard H

2017-01-16

A large-scale proteomic approach was devised to advance the understanding of venom composition. Bothrops jararaca venom was fractionated by OFFGEL followed by chromatography, generating peptidic and proteic fractions. The latter was submitted to trypsin digestion. Both fractions were separately analyzed by reversed-phase nanochromatography coupled to high resolution mass spectrometry. This strategy allowed deeper and joint characterizations of the peptidome and proteome (proteopeptidome) of this venom. Our results lead to the identification of 46 protein classes (with several uniquely assigned proteins per class) comprising eight high-abundance bona fide venom components, and 38 additional classes in smaller quantities. This last category included previously described B. jararaca venom proteins, common Elapidae venom constituents (cobra venom factor and three-finger toxin), and proteins typically encountered in lysosomes, cellular membranes and blood plasma. Furthermore, this report is the most complete snake venom peptidome described so far, both in number of peptides and in variety of unique proteins that could have originated them. It is hypothesized that such diversity could enclose cryptides, whose bioactivities would contribute to envenomation in yet undetermined ways. Finally, we propose that the broad range screening of B. jararaca peptidome will facilitate the discovery of bioactive molecules, eventually leading to valuable therapeutical agents. Our proteopeptidomic strategy yielded unprecedented insights into the remarkable diversity of B. jararaca venom composition, both at the peptide and protein levels. These results bring a substantial contribution to the actual pursuit of large-scale protein-level assignment in snake venomics. The detection of typical elapidic venom components, in a Viperidae venom, reinforces our view that the use of this approach (hand-in-hand with transcriptomic and genomic data) for venom proteomic analysis, at the specimen

Snake venom instability | Willemse | African Zoology

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Egyptian cobra Naja haje haje) and puffadder (Bills arietans). Considerable differences in electrophoretic characteristics were found between fresh venom and commercial venom samples from the same species of snake. These differences could be attributed partly to the instability of snake venom under conditions of drying ...

Inhibition of vitamin D2-induced arteriosclerosis in rats by depletion of complement with cobra venom factor.

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Pang, A S; Minta, J O

1980-01-01

Widespread calcerous deposits developed in the aorta, heart and kidneys of rats fed for 4 days with purina chow and high doses of vitamin D2 (200,000 IU/kg body wt/day). Decomplementation of rats with highly purified cobra venom factor (CoF) prior to vitamin D2 feeding, almost completely prevented calcium deposition in the aorta and arteritis. The mortality rate in the CoF-treated vitamin D2-fed rats was much lower than in untreated rats. These findings suggest that the complement system may be recruited in the pathogenesis of vitamin D2-induced arteriosclerosis.

Venomic Analysis of the Poorly Studied Desert Coral Snake, Micrurus tschudii tschudii, Supports the 3FTx/PLA₂ Dichotomy across Micrurus Venoms.

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Sanz, Libia; Pla, Davinia; Pérez, Alicia; Rodríguez, Yania; Zavaleta, Alfonso; Salas, Maria; Lomonte, Bruno; Calvete, Juan J

2016-06-07

The venom proteome of the poorly studied desert coral snake Micrurus tschudii tschudii was unveiled using a venomic approach, which identified ≥38 proteins belonging to only four snake venom protein families. The three-finger toxins (3FTxs) constitute, both in number of isoforms (~30) and total abundance (93.6% of the venom proteome), the major protein family of the desert coral snake venom. Phospholipases A₂ (PLA₂s; seven isoforms, 4.1% of the venom proteome), 1-3 Kunitz-type proteins (1.6%), and 1-2 l-amino acid oxidases (LAO, 0.7%) complete the toxin arsenal of M. t. tschudii. Our results add to the growing evidence that the occurrence of two divergent venom phenotypes, i.e., 3FTx- and PLA₂-predominant venom proteomes, may constitute a general trend across the cladogenesis of Micrurus. The occurrence of a similar pattern of venom phenotypic variability among true sea snake (Hydrophiinae) venoms suggests that the 3FTx/PLA₂ dichotomy may be widely distributed among Elapidae venoms.

Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis

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Ebrahim, Karim; Shirazi, Farshad H.; Vatanpour, Hosein; zare, Abas; Kobarfard, Farzad; Rabiei, Hadi

2014-01-01

Purpose Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against...

Comparison of proteomic profiles of the venoms of two of the 'Big Four' snakes of India, the Indian cobra (Naja naja) and the common krait (Bungarus caeruleus), and analyses of their toxins.

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Choudhury, Manisha; McCleary, Ryan J R; Kesherwani, Manish; Kini, R Manjunatha; Velmurugan, Devadasan

2017-09-01

Snake venoms are mixtures of biologically-active proteins and peptides, and several studies have described the characteristics of some of these toxins. However, complete proteomic profiling of the venoms of many snake species has not yet been done. The Indian cobra (Naja naja) and common krait (Bungarus caeruleus) are elapid snake species that are among the 'Big Four' responsible for the majority of human snake envenomation cases in India. As understanding the composition and complexity of venoms is necessary for successful treatment of envenomation in humans, we utilized three different proteomic profiling approaches to characterize these venoms: i) one-dimensional SDS-PAGE coupled with in-gel tryptic digestion and electrospray tandem mass spectrometry (ESI-LC-MS/MS) of individual protein bands; ii) in-solution tryptic digestion of crude venoms coupled with ESI-LC-MS/MS; and iii) separation by gel-filtration chromatography coupled with tryptic digestion and ESI-LC-MS/MS of separated fractions. From the generated data, 81 and 46 different proteins were identified from N. naja and B. caeruleus venoms, respectively, belonging to fifteen different protein families. Venoms from both species were found to contain a variety of phospholipases A 2 and three-finger toxins, whereas relatively higher numbers of snake venom metalloproteinases were found in N. naja compared to B. caeruleus venom. The analyses also identified less represented venom proteins including L-amino acid oxidases, cysteine-rich secretory proteins, 5'-nucleotidases and venom nerve growth factors. Further, Kunitz-type serine protease inhibitors, cobra venom factors, phosphodiesterases, vespryns and aminopeptidases were identified in the N. naja venom, while acetylcholinesterases and hyaluronidases were found in the B. caeruleus venom. We further analyzed protein coverage (Lys/Arg rich and poor regions as well as potential glycosylation sites) using in-house software. These studies expand our

Protein profile analysis of Malaysian snake venoms by two-dimensional gel electrophoresis

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J Vejayan

2010-01-01

Full Text Available Snake venoms comprise a highly complex mixture of proteins, which requires for their characterization the use of versatile two-dimensional electrophoresis techniques. In the present study, venoms obtained from eight snakes (Ophiophagus hannah, Naja kaouthia, Naja sumatrana, Bungarus fasciatus, Trimeresurus sumatranus, Tropidolaemus wagleri, Enhydrina schistosa and Calloselasma rhodostoma commonly found in Malaysia were separated based on two independent properties, isoelectric point (pI and molecular weight (MW. Many differences in snake venoms at the inter-family, inter-subfamily, inter-genus and inter-species levels were revealed. Notably, proteins from individuals of the Viperidae family - Trimeresurus sumatranus, Tropidolaemus wagleri and Calloselasma rhodostoma - were found to be numerous and scattered by the two-dimensional gel electrophoresis (2DE specifically in regions between 37 and 100 kDa compared to the Elapidae venom proteins. The latter were clustered at the basic and lower molecular mass region (less than 20 kDa. Trains of spots were commonly observed, indicating that these proteins may be derived from post-translational modifications. Ophiophagus hannah (Elapidae revealed a great amount of protein spots in the higher molecular mass range when compared to Enhydrina schistosa, Naja kaouthia, Naja sumatrana and Bungarus fasciatus. Overall 2DE showed large differences in the venom profile of each species, which might be employed as an ancillary tool to the identification of venomous snake species.

Inhibitory and enzyme-kinetic investigation of chelerythrine and lupeol isolated from Zanthoxylum rhoifolium against krait snake venom acetylcholinesterase

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Ahmad, Mustaq, E-mail: mushtaq213@yahoo.com [University of Science and Technology, Bannu, (Pakistan). Department of Biotechnology; Weber, Andrea D.; Zanon, Graciane; Tavares, Luciana de C.; Ilha, Vinicius; Dalcol, Ionara I.; Morel, Ademir F., E-mail: ademirfariasm@gmail.com [Universidade Federal de Santa Maria, RS (Brazil). Dept. de Quimica

2014-01-15

The in vitro activity of chelerythrine and lupeol, two metabolites isolated from Zanthoxylum rhoifolium were studied against the venom of the snake Bungarus sindanus (Elapidae). The venom, which is highly toxic to humans, consists mainly by the enzyme acetylcholinesterase (AChE). Both compounds showed activity against the venom, and the alkaloid chelerythrine presented higher activity than did triterpene lupeol. (author)

The Crystal Structure of Cobra Venom Factor, a Cofactor for C3- and C5-Convertase CVFBb

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Krishnan, Vengadesan; Ponnuraj, Karthe; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V.L.; (Madras); (UAB)

2009-05-26

Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. Unlike the latter, CVFBb is a stable complex and an efficient C5 convertase. We solved the crystal structure of CVF, isolated from Naja naja kouthia venom, at 2.6 {angstrom} resolution. The CVF crystal structure, an intermediate between C3b and C3c, lacks the TED domain and has the CUB domain in an identical position to that seen in C3b. The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B.

Inhibition of the nicotinic acetylcholine receptors by cobra venom α-neurotoxins: is there a perspective in lung cancer treatment?

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Angela Alama

Full Text Available Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated.We determined the activity of α-neurotoxins from Naja atra (short-chain neurotoxin, α-cobrotoxin and Naja kaouthia (long-chain neurotoxin, α-cobratoxin in vitro by cytotoxicity measurements in 5 lung cancer cell lines, by colony formation assay with α7nAChRs expressing and non-expressing cell lines and in vivo by assessing tumor growth in an orthotopic Non-Obese Diabetic/Severe Combined Immunodeficient (NOD/SCID mouse model system utilizing different treatment schedules and dosages.No statistically significant reduction in tumor growth was observed in the treatment arms in comparison to the control for both toxins. Paradoxically α-cobrotoxin from Naja atra showed the tendency to enhance tumor growth although, even in this case, the statistical significance was not reached.In conclusion our results show that, in contrast with other reports, the nAChR inhibitors α-cobratoxin from N. kaouthia and α-cobrotoxin from N. atra neither suppressed tumor growth nor prolonged the survival of the treated animals.

Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

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Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

2004-08-01

Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at

[Spitting cobras: description of 2 cases in Djibouti].

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Rouvin, B; Kone, M; N'diaye, M; Seck, M; Diatta, B

2010-02-01

The purpose of this report is to describe two cases involving ophthalmic exposure to venom from spitting cobras. Based on these cases, readers are reminded that eye injury can be prevented by low-cost treatment consisting of prompt, prolonged saline irrigation. This treatment also reduces pain.

The protective effect of Mucuna pruriens seeds against snake venom poisoning.

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Tan, Nget Hong; Fung, Shin Yee; Sim, Si Mui; Marinello, Enrico; Guerranti, Roberto; Aguiyi, John C

2009-06-22

The seed, leaf and root of Mucuna pruriens have been used in traditional medicine for treatments of various diseases. In Nigeria, the seed is used as oral prophylactics for snakebite. To study the protective effects of Mucuna pruriens seed extract against the lethalities of various snake venoms. Rats were pre-treated with Mucuna pruriens seed extract and challenged with various snake venoms. The effectiveness of anti-Mucuna pruriens (anti-MPE) antibody to neutralize the lethalities of snake venoms was investigated by in vitro neutralization. In rats, MPE pre-treatment conferred effective protection against lethality of Naja sputatrix venom and moderate protection against Calloselasma rhodostoma venom. Indirect ELISA and immunoblotting studies showed that there were extensive cross-reactions between anti-MPE IgG and venoms from many different genera of poisonous snakes, suggesting the involvement of immunological neutralization in the protective effect of MPE pre-treatment against snake venom poisoning. In vitro neutralization experiments showed that the anti-MPE antibodies effectively neutralized the lethalities of Asiatic cobra (Naja) venoms, but were not very effective against other venoms tested. The anti-MPE antibodies could be used in the antiserum therapy of Asiatic cobra (Naja) bites.

Stabilising the Integrity of Snake Venom mRNA Stored under Tropical Field Conditions Expands Research Horizons.

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Gareth Whiteley

2016-06-01

Full Text Available Snake venoms contain many proteinaceous toxins that can cause severe pathology and mortality in snakebite victims. Interestingly, mRNA encoding such toxins can be recovered directly from venom, although yields are low and quality is unknown. It also remains unclear whether such RNA contains information about toxin isoforms and whether it is representative of mRNA recovered from conventional sources, such as the venom gland. Answering these questions will address the feasibility of using venom-derived RNA for future research relevant to biomedical and antivenom applications.Venom was extracted from several species of snake, including both members of the Viperidae and Elapidae, and either lyophilized or immediately added to TRIzol reagent. TRIzol-treated venom was incubated at a range of temperatures (4-37°C for a range of durations (0-48 hours, followed by subsequent RNA isolation and assessments of RNA quantity and quality. Subsequently, full-length toxin transcripts were targeted for PCR amplification and Sanger sequencing. TRIzol-treated venom yielded total RNA of greater quantity and quality than lyophilized venom, and with quality comparable to venom gland-derived RNA. Full-length sequences from multiple Viperidae and Elapidae toxin families were successfully PCR amplified from TRIzol-treated venom RNA. We demonstrated that venom can be stored in TRIzol for 48 hours at 4-19°C, and 8 hours at 37°C, at minimal cost to RNA quality, and found that venom RNA encoded multiple toxin isoforms that seemed homologous (98-99% identity to those found in the venom gland.The non-invasive experimental modifications we propose will facilitate the future investigation of venom composition by using venom as an alternative source to venom gland tissue for RNA-based studies, thus obviating the undesirable need to sacrifice snakes for such research purposes. In addition, they expand research horizons to rare, endangered or protected snake species and provide

Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae Venom in Vitro

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Alejandro Carbajal-Saucedo

2014-01-01

Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom.

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Nekaris, K Anne-Isola; Moore, Richard S; Rode, E Johanna; Fry, Bryan G

2013-09-27

Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom's primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras.

Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

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Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

2012-06-01

Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

Influence of hirudin and cobra venom factor on the release of 14C-serotonin and 51chromium from human platelets induced by thrombin, collagen, aggregate gammaglobulin and HLA antibody

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Hagemeyer, G.M.

1982-01-01

The present work investigates the influence of hirudin and cobra venom factor on thrombin, collagen, aggregate gammaglobulin and HLA-antibody-induced release of 14 C-serotonin and 51 chromium from human platelets. Besides the platelet-specific release reaction ( 14 C-serotonin) the extent of platelet lysis was determined by measurement of the loss of 51 chromium from the platelets. The results showed the thrombin, collagen and aggregate-gammaglobulin-induced platelet alteration to be a non-complement-dependent reaction of the platelets with release of 14 C-serotonin. Following long-term incubation small quantities of 51 chromium are also released. As this release of 51 chromium cannot be inhibited using cobra venom factor and does not occur in washed platelets either, it is most probably a non-complement-dependent reaction. The HLA-antibody-induced, specific platelet alteration is both complement-dependent and complement-independent. Differentiation is possible by inhibition of the complement-dependent lysis. On the other hand thrombin is of no relevance to the collagen, aggregate gammaglobulin, and HLA-antibody-induced platelet alteration as the interactions of these substances with platelets are not inhibited by hirudin. The above results are confirmed by investigation of the 51 chromium uptake capacity of washed platelets treated previously with thrombin, collagen and HLA antibody. (orig./MG) [de

Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution.

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Modahl, Cassandra M; Mackessy, Stephen P

2016-06-01

Envenomation of humans by snakes is a complex and continuously evolving medical emergency, and treatment is made that much more difficult by the diverse biochemical composition of many venoms. Venomous snakes and their venoms also provide models for the study of molecular evolutionary processes leading to adaptation and genotype-phenotype relationships. To compare venom complexity and protein sequences, venom gland transcriptomes are assembled, which usually requires the sacrifice of snakes for tissue. However, toxin transcripts are also present in venoms, offering the possibility of obtaining cDNA sequences directly from venom. This study provides evidence that unknown full-length venom protein transcripts can be obtained from the venoms of multiple species from all major venomous snake families. These unknown venom protein cDNAs are obtained by the use of primers designed from conserved signal peptide sequences within each venom protein superfamily. This technique was used to assemble a partial venom gland transcriptome for the Middle American Rattlesnake (Crotalus simus tzabcan) by amplifying sequences for phospholipases A2, serine proteases, C-lectins, and metalloproteinases from within venom. Phospholipase A2 sequences were also recovered from the venoms of several rattlesnakes and an elapid snake (Pseudechis porphyriacus), and three-finger toxin sequences were recovered from multiple rear-fanged snake species, demonstrating that the three major clades of advanced snakes (Elapidae, Viperidae, Colubridae) have stable mRNA present in their venoms. These cDNA sequences from venom were then used to explore potential activities derived from protein sequence similarities and evolutionary histories within these large multigene superfamilies. Venom-derived sequences can also be used to aid in characterizing venoms that lack proteomic profiles and identify sequence characteristics indicating specific envenomation profiles. This approach, requiring only venom, provides

Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (king cobra).

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Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Dieter; Foo, Chun Shin; Rajagopalan, Nandhakishore; Nirthanan, Selvanayagam; Bertrand, Daniel; Sivaraman, J; Kini, R Manjunatha

2010-03-12

Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.

The venom-gland transcriptome of the eastern coral snake (Micrurus fulvius) reveals high venom complexity in the intragenomic evolution of venoms

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2013-01-01

Background Snake venom is shaped by the ecology and evolution of venomous species, and signals of positive selection in toxins have been consistently documented, reflecting the role of venoms as an ecologically critical phenotype. New World coral snakes (Elapidae) are represented by three genera and over 120 species and subspecies that are capable of causing significant human morbidity and mortality, yet coral-snake venom composition is poorly understood in comparison to that of Old World elapids. High-throughput sequencing is capable of identifying thousands of loci, while providing characterizations of expression patterns and the molecular evolutionary forces acting within the venom gland. Results We describe the de novo assembly and analysis of the venom-gland transcriptome of the eastern coral snake (Micrurus fulvius). We identified 1,950 nontoxin transcripts and 116 toxin transcripts. These transcripts accounted for 57.1% of the total reads, with toxins accounting for 45.8% of the total reads. Phospholipases A2 and three-finger toxins dominated expression, accounting for 86.0% of the toxin reads. A total of 15 toxin families were identified, revealing venom complexity previously unknown from New World coral snakes. Toxins exhibited high levels of heterozygosity relative to nontoxins, and overdominance may favor gene duplication leading to the fixation of advantageous alleles. Phospholipase A2 expression was uniformly distributed throughout the class while three-finger toxin expression was dominated by a handful of transcripts, and phylogenetic analyses indicate that toxin divergence may have occurred following speciation. Positive selection was detected in three of the four most diverse toxin classes, suggesting that venom diversification is driven by recurrent directional selection. Conclusions We describe the most complete characterization of an elapid venom gland to date. Toxin gene duplication may be driven by heterozygote advantage, as the frequency of

The venom-gland transcriptome of the eastern coral snake (Micrurus fulvius) reveals high venom complexity in the intragenomic evolution of venoms.

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Margres, Mark J; Aronow, Karalyn; Loyacano, Jacob; Rokyta, Darin R

2013-08-02

Snake venom is shaped by the ecology and evolution of venomous species, and signals of positive selection in toxins have been consistently documented, reflecting the role of venoms as an ecologically critical phenotype. New World coral snakes (Elapidae) are represented by three genera and over 120 species and subspecies that are capable of causing significant human morbidity and mortality, yet coral-snake venom composition is poorly understood in comparison to that of Old World elapids. High-throughput sequencing is capable of identifying thousands of loci, while providing characterizations of expression patterns and the molecular evolutionary forces acting within the venom gland. We describe the de novo assembly and analysis of the venom-gland transcriptome of the eastern coral snake (Micrurus fulvius). We identified 1,950 nontoxin transcripts and 116 toxin transcripts. These transcripts accounted for 57.1% of the total reads, with toxins accounting for 45.8% of the total reads. Phospholipases A(2) and three-finger toxins dominated expression, accounting for 86.0% of the toxin reads. A total of 15 toxin families were identified, revealing venom complexity previously unknown from New World coral snakes. Toxins exhibited high levels of heterozygosity relative to nontoxins, and overdominance may favor gene duplication leading to the fixation of advantageous alleles. Phospholipase A(2) expression was uniformly distributed throughout the class while three-finger toxin expression was dominated by a handful of transcripts, and phylogenetic analyses indicate that toxin divergence may have occurred following speciation. Positive selection was detected in three of the four most diverse toxin classes, suggesting that venom diversification is driven by recurrent directional selection. We describe the most complete characterization of an elapid venom gland to date. Toxin gene duplication may be driven by heterozygote advantage, as the frequency of polymorphic toxin loci was

Secreted Phospholipases A₂ from Animal Venoms in Pain and Analgesia.

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Zambelli, Vanessa O; Picolo, Gisele; Fernandes, Carlos A H; Fontes, Marcos R M; Cury, Yara

2017-12-19

Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted phospholipases A₂ (sPLA₂s). These PLA₂ belong to distinct PLA₂s groups. For example, snake venom sPLA₂s from Elapidae and Viperidae families, the most important families when considering envenomation, belong, respectively, to the IA and IIA/IIB groups, whereas bee venom PLA₂ belongs to group III of sPLA₂s. It is well known that PLA₂, due to its hydrolytic activity on phospholipids, takes part in many pathophysiological processes, including inflammation and pain. Therefore, secreted PLA₂s obtained from animal venoms have been widely used as tools to (a) modulate inflammation and pain, uncovering molecular targets that are implicated in the control of inflammatory (including painful) and neurodegenerative diseases; (b) shed light on the pathophysiology of inflammation and pain observed in human envenomation by poisonous animals; and, (c) characterize molecular mechanisms involved in inflammatory diseases. The present review summarizes the knowledge on the nociceptive and antinociceptive actions of sPLA₂s from animal venoms, particularly snake venoms.

Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

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Suntravat, Montamas; Nuchprayoon, Issarang; Pérez, John C

2010-09-15

Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

Plastic surgical management of a cobra bite – a case study

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Kuhbier, Jörn W.

2017-02-01

Full Text Available Cobra bites are quite rare in European countries as these snakes are not native there. Toxins are devastating for tissue resulting in massive necrosis, thus plastic surgery might play a role in reconstruction of the lost tissue. A case of a male patient bitten by a thai cobra in the left index finger is presented. Antitoxin administration was delayed due to secondary patient admission. Progressive tissue necrosis made radical debridement necessary, resulting in the need for plastic surgical defect coverage with a flap. While a radical debridement to prevent toxic necrosis due to lytic enzymes in cobra venom has been favoured beforehand, large case studies led to a more restrained initial surgical intervention. However, antitoxin administration should be first line therapy in management of these cases. If severe necrosis is present as it might occur in delayed admission, a plastic surgical management of the patient might be advantageous.

Snake venoms components with antitumor activity in murine melanoma cells

International Nuclear Information System (INIS)

Queiroz, Rodrigo Guimaraes

2012-01-01

Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

Preparation of cobra (Naja naja) venom toxoid using gamma-radiations. Part I

International Nuclear Information System (INIS)

Gaitonde, B.B.; Kankonkar, S.R.

1975-01-01

Detoxification of venom by radiation was investigated. Two concentrations i.e. 0.01% of venom solution were irradiated with different doses of gamma-radiations from cobalt-60 source. The results obtained indicate that the toxicity of venom is markedly attenuated by gamma-radiation. (author)

Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

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Zambelli, Vanessa O.; Picolo, Gisele; Fernandes, Carlos A. H.

2017-01-01

Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted phospholipases A2 (sPLA2s). These PLA2 belong to distinct PLA2s groups. For example, snake venom sPLA2s from Elapidae and Viperidae families, the most important families when considering envenomation, belong, respectively, to the IA and IIA/IIB groups, whereas bee venom PLA2 belongs to group III of sPLA2s. It is well known that PLA2, due to its hydrolytic activity on phospholipids, takes part in many pathophysiological processes, including inflammation and pain. Therefore, secreted PLA2s obtained from animal venoms have been widely used as tools to (a) modulate inflammation and pain, uncovering molecular targets that are implicated in the control of inflammatory (including painful) and neurodegenerative diseases; (b) shed light on the pathophysiology of inflammation and pain observed in human envenomation by poisonous animals; and, (c) characterize molecular mechanisms involved in inflammatory diseases. The present review summarizes the knowledge on the nociceptive and antinociceptive actions of sPLA2s from animal venoms, particularly snake venoms. PMID:29311537

Molecular mechanism of cell death induced by king cobra (Ophiophagus hannah) venom l-amino acid oxidase.

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Fung, Shin Yee; Lee, Mui Li; Tan, Nget Hong

2015-03-01

Snake venom LAAOs have been reported to exhibit a wide range of pharmacological activities, including cytotoxic, edema-inducing, platelet aggregation-inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities. A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity against human tumorigenic cells but not in their non-tumorigenic counterparts, and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In this work, the molecular mechanism of cell death induced by OH-LAAO was investigated. The enzyme exerts its apoptosis-inducing effect presumably via both intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9 activities. Oligonucleotide microarray analysis showed that the expression of a total of 178 genes was significantly altered as a result of oxidative stress induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at least 27 genes are involved in apoptosis and cell death. These alterations of gene expression was presumably caused by the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidative modifications of signaling molecules that eventually lead to apoptosis and cell death. The very substantial up-regulation of cytochrome P450 genes may also contribute to the potent cytotoxic action of OH-LAAO by producing excessive reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidation of signalling molecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Coral snake venoms: mode of action and pathophysiology of experimental envenomation

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Oswald Vital Brazil

1987-06-01

Full Text Available Coral snakes, the New World Elapidae, are included in the genera Micniroides and Micrurus. The genus Mlcrurus comprises nearly all coral snake species and those which are responsible for human snake-bite accidents. The following generalizations concerning the effects induced by their venoms, and their venom-properties can be made. Coral snake venoms are neurotoxic, producing loss of muscle strenght and death by respiratory paralysis. Local edema and necrosis are not induced nor blood coagulation or hemorrhages. Proteolysis activity is absent or of very low grade. They display phospholipase A2 activity. Nephrotoxic effects are not evoked. The main toxins from elapid venoms are postsynaptic and presynaptic neurotoxins and cardiotoxins. Phospholipases A2 endowed with myonecrotic or cardiotoxin-like properties are important toxic components from some elapid venoms. The mode of action of Micrurus frontalis, M. lemniscatus, M. corallinus and M. fulvius venoms has been investigated in isolated muscle preparations and is here discussed. It is shown that while M. frontalis and M. lemniscatus venoms must contain only neurotoxins that act at the cholinergic end-plate receptor (postsynaptic neurotoxins, M. corallinus venom also inhibits evoked acetylcholine release by the motor nerve endings (presynaptic neurotoxin-like effect and M. fulvius induces muscle fiber membrane depolarization (cardiotoxin-like effect. The effects produced by M. corallinus and M. fulvius venoms in vivo in dogs and M. frontalis venom in dogs and monkeys are also reported.

An Alternative Inactivant for Rift Valley Fever Virus using Cobra Venom-derived L-Amino Oxidase, which is Related to its Immune Potential

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Ebtesam M Al-Olayan

Full Text Available ABSTRACT Vaccine improvement depends on the formulation, adjuvant type and inactivant used. The type of formulation may interfere with immunogenicity. The present work aimed to evaluate the inactivation activity and related immune potential of the Cobra venom-derived LAO enzyme compared to the currently used inactivants (BPL and formalin for both animal and human vaccines. The RVF virus was completely inactivated within 6 hrs, 4 hrs and 2 hrs after treatment with Formalin, LAO and BPL, respectively. The vaccine potency [ED50] was arranged in a descending order from formalin (0.016 to BPL (0.005 and LAO (0.002. The total IgG levels, Neutralizing Index (NI and Interferon levels were significantly increased compared to those detected after immunization with the BPL- and Formalin-inactivated vaccine candidates.

Rapid Radiations and the Race to Redundancy: An Investigation of the Evolution of Australian Elapid Snake Venoms

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Jackson, Timothy N. W.; Koludarov, Ivan; Ali, Syed A.; Dobson, James; Zdenek, Christina N.; Dashevsky, Daniel; op den Brouw, Bianca; Masci, Paul P.; Nouwens, Amanda; Josh, Peter; Goldenberg, Jonathan; Cipriani, Vittoria; Hay, Chris; Hendrikx, Iwan; Dunstan, Nathan; Allen, Luke; Fry, Bryan G.

2016-01-01

Australia is the stronghold of the front-fanged venomous snake family Elapidae. The Australasian elapid snake radiation, which includes approximately 100 terrestrial species in Australia, as well as Melanesian species and all the world’s true sea snakes, may be less than 12 million years old. The incredible phenotypic and ecological diversity of the clade is matched by considerable diversity in venom composition. The clade’s evolutionary youth and dynamic evolution should make it of particular interest to toxinologists, however, the majority of species, which are small, typically inoffensive, and seldom encountered by non-herpetologists, have been almost completely neglected by researchers. The present study investigates the venom composition of 28 species proteomically, revealing several interesting trends in venom composition, and reports, for the first time in elapid snakes, the existence of an ontogenetic shift in the venom composition and activity of brown snakes (Pseudonaja sp.). Trends in venom composition are compared to the snakes’ feeding ecology and the paper concludes with an extended discussion of the selection pressures shaping the evolution of snake venom. PMID:27792190

Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins

DEFF Research Database (Denmark)

Laustsen, Andreas Hougaard; Gutiérrez, José María; Lohse, Brian

2015-01-01

/cardiotoxins. IgGs isolated from a person who had repeatedly self-immunized with a variety of snake venoms were immunoprofiled by ELISA against all venom fractions. Stronger responses against larger toxins, but lower against the most critical α-neurotoxins were obtained. As expected, no neutralization potential...

The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom.

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Dhananjaya, Bhadrapura Lakkappa; Sudarshan, Shivalingaiah; Dongol, Yashad; More, Sunil S

2016-05-01

The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 μg/ml concentration. Further, M. indica extract (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent.

Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

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Aird, Steven D; Aggarwal, Shikha; Villar-Briones, Alejandro; Tin, Mandy Man-Ying; Terada, Kouki; Mikheyev, Alexander S

2015-08-28

While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown. Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation. Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive

Snake oil and venoms for medical research

Science.gov (United States)

Wolpert, H. D.

2011-04-01

Some think that using derivatives of snake venom for medical purposes is the modern version of snake oil but they are seriously misjudging the research potentials of some of these toxins in medicines of the 2000's. Medical trials, using some of the compounds has proven their usefulness. Several venoms have shown the possibilities that could lead to anticoagulants, helpful in heart disease. The blood clotting protein from the taipan snake has been shown to rapidly stop excessive bleeding. The venom from the copperhead may hold an answer to breast cancer. The Malaysian pit viper shows promise in breaking blood clots. Cobra venom may hold keys to finding cures for Parkinson's disease and Alzheimer's. Rattlesnake proteins from certain species have produced blood pressure medicines. Besides snake venoms, venom from the South American dart frog, mollusks (i.e. Cone Shell Snail), lizards (i.e. Gila Monster & Komodo Dragon), some species of spiders and tarantulas, Cephalopods, mammals (i.e. Platypus & Shrews), fish (i.e. sting rays, stone fish, puffer fish, blue bottle fish & box jelly fish), intertidal marine animals (echinoderms)(i.e. Crown of Thorn Star Fish & Flower Urchin) and the Honeybee are being investigated for potential medical benefits.

A Review and Database of Snake Venom Proteomes.

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Tasoulis, Theo; Isbister, Geoffrey K

2017-09-18

Advances in the last decade combining transcriptomics with established proteomics methods have made possible rapid identification and quantification of protein families in snake venoms. Although over 100 studies have been published, the value of this information is increased when it is collated, allowing rapid assimilation and evaluation of evolutionary trends, geographical variation, and possible medical implications. This review brings together all compositional studies of snake venom proteomes published in the last decade. Compositional studies were identified for 132 snake species: 42 from 360 (12%) Elapidae (elapids), 20 from 101 (20%) Viperinae (true vipers), 65 from 239 (27%) Crotalinae (pit vipers), and five species of non-front-fanged snakes. Approximately 90% of their total venom composition consisted of eight protein families for elapids, 11 protein families for viperines and ten protein families for crotalines. There were four dominant protein families: phospholipase A₂s (the most common across all front-fanged snakes), metalloproteases, serine proteases and three-finger toxins. There were six secondary protein families: cysteine-rich secretory proteins, l-amino acid oxidases, kunitz peptides, C-type lectins/snaclecs, disintegrins and natriuretic peptides. Elapid venoms contained mostly three-finger toxins and phospholipase A₂s and viper venoms metalloproteases, phospholipase A₂s and serine proteases. Although 63 protein families were identified, more than half were present in <5% of snake species studied and always in low abundance. The importance of these minor component proteins remains unknown.

Micrurus snake venoms activate human complement system and generate anaphylatoxins

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Tanaka Gabriela D

2012-01-01

Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

Isolation and cloning of a metalloproteinase from king cobra snake venom.

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Guo, Xiao-Xi; Zeng, Lin; Lee, Wen-Hui; Zhang, Yun; Jin, Yang

2007-06-01

A 50 kDa fibrinogenolytic protease, ohagin, from the venom of Ophiophagus hannah was isolated by a combination of gel filtration, ion-exchange and heparin affinity chromatography. Ohagin specifically degraded the alpha-chain of human fibrinogen and the proteolytic activity was completely abolished by EDTA, but not by PMSF, suggesting it is a metalloproteinase. It dose-dependently inhibited platelet aggregation induced by ADP, TMVA and stejnulxin. The full sequence of ohagin was deduced by cDNA cloning and confirmed by protein sequencing and peptide mass fingerprinting. The full-length cDNA sequence of ohagin encodes an open reading frame of 611 amino acids that includes signal peptide, proprotein and mature protein comprising metalloproteinase, disintegrin-like and cysteine-rich domains, suggesting it belongs to P-III class metalloproteinase. In addition, P-III class metalloproteinases from the venom glands of Naja atra, Bungarus multicinctus and Bungarus fasciatus were also cloned in this study. Sequence analysis and phylogenetic analysis indicated that metalloproteinases from elapid snake venoms form a new subgroup of P-III SVMPs.

Minor snake venom proteins: Structure, function and potential applications.

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Boldrini-França, Johara; Cologna, Camila Takeno; Pucca, Manuela Berto; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Anjolette, Fernando Antonio Pino; Cordeiro, Francielle Almeida; Wiezel, Gisele Adriano; Cerni, Felipe Augusto; Pinheiro-Junior, Ernesto Lopes; Shibao, Priscila Yumi Tanaka; Ferreira, Isabela Gobbo; de Oliveira, Isadora Sousa; Cardoso, Iara Aimê; Arantes, Eliane Candiani

2017-04-01

Snake venoms present a great diversity of pharmacologically active compounds that may be applied as research and biotechnological tools, as well as in drug development and diagnostic tests for certain diseases. The most abundant toxins have been extensively studied in the last decades and some of them have already been used for different purposes. Nevertheless, most of the minor snake venom protein classes remain poorly explored, even presenting potential application in diverse areas. The main difficulty in studying these proteins lies on the impossibility of obtaining sufficient amounts of them for a comprehensive investigation. The advent of more sensitive techniques in the last few years allowed the discovery of new venom components and the in-depth study of some already known minor proteins. This review summarizes information regarding some structural and functional aspects of low abundant snake venom proteins classes, such as growth factors, hyaluronidases, cysteine-rich secretory proteins, nucleases and nucleotidases, cobra venom factors, vespryns, protease inhibitors, antimicrobial peptides, among others. Some potential applications of these molecules are discussed herein in order to encourage researchers to explore the full venom repertoire and to discover new molecules or applications for the already known venom components. Copyright © 2016. Published by Elsevier B.V.

Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism.

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Ashis K Mukherjee

Full Text Available The monocled cobra (Naja kaouthia is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4 is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da and Nk-PLA2β (13282.38 Da purified from the venom of N. kaouthia.By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM and thrombin (Ki = 8.3 nM, respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their "pharmacological target(s" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation.In order to develop peptide-based superior anticoagulant therapeutics, future application of Nk-PLA2

Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

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Witchuda Danpaiboon

2014-05-01

Full Text Available Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase. N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv.

Science.gov (United States)

Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

2014-05-13

Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

Efficacy of tannins from Mimosa pudica and tannic acid in neutralizing cobra (Naja kaouthia venom

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FY Sia

2011-01-01

Full Text Available In the present study, the effectiveness of Mimosa pudica tannins (MPT in neutralizing the lethality of Naja kaouthia venom was compared with commercially derived tannins. Preincubation of MPT with N. kaouthia venom maintained 100% survival of mice after 24 hours. The mouse group in which there was no preincubation, no protection against the effects of the venom was observed. M. pudica tannin was found to be more effective in neutralizing the lethality of N. kaouthia venom when compared to commercial tannic acid. Two protein spots were missing in the two-dimensional gel electrophoresis (2-DE of the MPT treated mouse indicating the down-regulation of venom proteins. The results from this study indicated that tannins obtained from M. pudica are better than tannic acid in neutralizing the lethality of N. kaouthia venom in vitro. However, further investigations are required to establish that M. pudica has potential for treating N. kaouthia snakebites.

Snake Venom PLA2, a Promising Target for Broad-Spectrum Antivenom Drug Development

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Huixiang Xiao

2017-01-01

Full Text Available Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae. Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.

Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom.

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Rey-Suárez, Paola; Núñez, Vitelbina; Fernández, Julián; Lomonte, Bruno

2016-03-16

In Colombia, nearly 2.8% of the 4200 snakebite accidents recorded annually are inflicted by coral snakes (genus Micrurus). Micrurus dumerilii has a broad distribution in this country, especially in densely populated areas. The proteomic profile of its venom was here studied by a bottom-up approach combining RP-HPLC, SDS-PAGE and MALDI-TOF/TOF. Venom proteins were assigned to eleven families, the most abundant being phospholipases A2 (PLA2; 52.0%) and three-finger toxins (3FTx; 28.1%). This compositional profile shows that M. dumerilii venom belongs to the 'PLA2-rich' phenotype, in the recently proposed dichotomy for Micrurus venoms. Enzymatic and toxic venom activities correlated with protein family abundances. Whole venom induced a conspicuous myotoxic, cytotoxic and anticoagulant effect, and was mildly edematogenic and proteolytic, whereas it lacked hemorrhagic activity. Some 3FTxs and PLA2s reproduced the lethal effect of venom. A coral snake antivenom to Micrurus nigrocinctus demonstrated significant cross-recognition of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect. The combined compositional, functional, and immunological data here reported for M. dumerilii venom may contribute to a better understanding of these envenomings, and support the possible use of anti-M. nigrocinctus coral snake antivenom in their treatment. Coral snakes represent a highly diversified group of elapids in the New World, with nearly 70 species within the genus Micrurus. Owing to their scarce yields, the biochemical composition and toxic activities of coral snake venoms have been less well characterized than those of viperid species. In this work, an integrative view of the venom of M. dumerilii, a medically relevant coral snake from Colombia, was obtained by a combined proteomic, functional, and immunological approach. The venom contains proteins from at least eleven families, with a predominance of phospholipases A2 (PLA2), followed by three

Antivenom Cross-Neutralization of the Venoms of Hydrophis schistosus and Hydrophis curtus, Two Common Sea Snakes in Malaysian Waters

Directory of Open Access Journals (Sweden)

Choo Hock Tan

2015-02-01

Full Text Available Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV. NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking. The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4% and H. curtus (70.4%. These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.

Background simulation for the COBRA-experiment

Energy Technology Data Exchange (ETDEWEB)

Quante, Thomas [TU Dortmund, Institut fuer Physik (Germany); Collaboration: COBRA-Collaboration

2015-07-01

COBRA is a next-generation experiment searching for neutrinoless double beta (0νββ) decay using CdZnTe semiconductor detectors. The main focus is on {sup 116}Cd, with a Q-value of 2813.5 keV well above the highest dominant naturally occurring gamma lines. By measuring the half-life of the 0νββ decay, it is possible to clarify the nature of the neutrino as either Dirac or Majorana particle and furthermore to determine the effective Majorana mass. COBRA is currently in the demonstrator phase to study possible background contributions and gain information about the longterm stability of the used detectors. For this purpose a demonstrator array made up of 64 Cadmium-Zinc-Telluride (CdZnTe) semiconductor detectors in coplanar grid configuration was designed and realised at the Gran Sasso Underground laboratory (LNGS) in Italy. Simulations of the whole demonstrator setup are ongoing to reproduce the measured spectra for each detector. This is done in two steps. The first uses the Geant4 based framework VENOM for tracking and energy deposition inside each detector. Detector effects like the energy resolution and electron trapping have to be applied in the second step. The used detector geometry has to be verified against calibration measurements. This talk gives an overview of the current simulation status.

Cost-utility of COBRA-light versus COBRA therapy in patients with early rheumatoid arthritis: the COBRA-light trial

NARCIS (Netherlands)

ter Wee, Marieke M.; Coupé, Veerle M. H.; den Uyl, Debby; Blomjous, Birgit S.; Kooijmans, Esmee; Kerstens, Pit J. S. M.; Nurmohamed, Mike T.; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E.; Boers, Maarten; Lems, Willem F.

2017-01-01

To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy. This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164

Australian elapid snake envenomation in cats: Clinical priorities and approach.

Science.gov (United States)

Mcalees, Trudi J; Abraham, Linda A

2017-11-01

Practical relevance: No fewer than 140 species of terrestrial snakes reside in Australia, 92 of which possess venom glands. With the exception of the brown tree snake, the venom-producing snakes belong to the family Elapidae. The venom of a number of elapid species is more toxic than that of the Indian cobra and eastern diamondback rattle snake, which has earned Australia its reputation for being home to the world's most venomous snakes. Clinical challenges: The diagnosis of elapid snake envenomation is not always easy. Identification of Australian snakes is not straightforward and there are no pathognomonic clinical signs. In cats, diagnosis of envenomation is confounded by the fact that, in most cases, there is a delay in seeking veterinary attention, probably because snake encounters are not usually witnessed by owners, and also because of the tendency of cats to hide and seek seclusion when unwell. Although the administration of antivenom is associated with improved outcomes, the snake venom detection kit and antivenom are expensive and so their use may be precluded if there are financial constraints. Evidence base: In providing comprehensive guidance on the diagnosis and treatment of Australian elapid snake envenomation in cats, the authors of this review draw on the published veterinary, medical and toxicology literature, as well as their professional experience as specialists in medicine, and emergency medicine and critical care.

[A case of favourable outcome of severe acute intoxication with an animal poison after a bite by the monocled cobra].

Science.gov (United States)

Livanov, G A; Batotsyrenkov, B V; Lodiagin, A N; Andrianov, A Iu; Kuznetsov, O A; Loladze, A T; Baranov, D V

2014-01-01

This paper reports a case of severe acute intoxication with an animal poison after a bite by the monocled cobra. Combined treatment including artificial lung ventilation, infusion-detoxication and desensitizing (hormonal) therapy, hemosorption, correction of metabolic disorders with cytoflavin, antibacterial therapy had positive effect on the patient's condition and ensured the favourable outcome ofpotentially lethal poisoning without the use ofa specific anti-snake venom serum.

Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake)

International Nuclear Information System (INIS)

Sanchez, Elda E.; Galan, Jacob A.; Russell, William K.; Soto, Julio G.; Russell, David H.; Perez, John C.

2006-01-01

Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983, the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be only neurotoxic; however, now there is evidence that these snakes can contain venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from the venom of a Mohave rattlesnake collected in central Arizona (Pinal County), were isolated and characterized. The disintegrins in these venoms were identified by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their amino acid sequences are similar to crotratroxin, a disintegrin isolated from the venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in whole human blood both having IC 5 s of 13.8 nM, but were not effective in inhibiting the binding of human urinary bladder carcinoma cells (T24) to fibronectin

In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom.

Science.gov (United States)

Degueldre, Michel; Echterbille, Julien; Smargiasso, Nicolas; Damblon, Christian; Gouin, Charlotte; Mourier, Gilles; Gilles, Nicolas; De Pauw, Edwin; Quinton, Loïc

2017-11-18

Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA), the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS) and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S -cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR) experiments.

In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom

Directory of Open Access Journals (Sweden)

Michel Degueldre

2017-11-01

Full Text Available Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA, the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S-cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR experiments.

Snake venoms components with antitumor activity in murine melanoma cells; Componentes derivados de venenos de serpentes com acao antitumoral em celulas de melanoma murino

Energy Technology Data Exchange (ETDEWEB)

Queiroz, Rodrigo Guimaraes

2012-07-01

Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

Keeping venomous snakes in the Netherlands: a harmless hobby or a public health threat?

Science.gov (United States)

van Genderen, P J J; Slobbe, L; Koene, H; Mastenbroek, R D L; Overbosch, D

2013-10-01

To describe the incidence of venomous snakebites and the hospital treatment thereof (if any) amongst private individuals who keep venomous snakes as a hobby. Descriptive study. Private keepers of venomous snakes were invited via the social media Facebook, Hyves, Twitter, Google Plus, Linked In and two large discussion forums to fill in an online questionnaire on a purely voluntary and anonymous basis. In the period from 1 September 2012 to 31 December 2012, 86 questionnaires were completed by individuals who keep venomous snakes as a hobby. One-third of the venomous snake keepers stated that they had at some point been bitten by a venomous snake. Out of those, two-thirds needed hospital treatment and one-third of those bitten required at least one, sometimes more, doses of antiserum. The chances of being bitten increased the more venomous snakes a person kept. An inventory of the collections of venomous snakes being kept further revealed that no antiserum exists for 16 of the species, including for the most commonly held venomous snake, the coral cobra. Keeping venomous snakes as a hobby is not without danger. Although in the majority of snakebite cases no antiserum had to be administered, there is nevertheless a significant risk of morbidity and sequelae. Preventing snakebites in the first place remains the most important safety measure since there are no antiserums available for a substantial number of venomous snakes.

Transcriptomic basis for an antiserum against Micrurus corallinus (coral snake venom

Directory of Open Access Journals (Sweden)

Ho Paulo L

2009-03-01

Full Text Available Abstract Background Micrurus corallinus (coral snake is a tropical forest snake belonging to the family Elapidae. Its venom shows a high neurotoxicity associated with pre- and post-synaptic toxins, causing diaphragm paralysis, which may result in death. In spite of a relatively small incidence of accidents, serum therapy is crucial for those bitten. However, the adequate production of antiserum is hampered by the difficulty in obtaining sufficient amounts of venom from a small snake with demanding breeding conditions. In order to elucidate the molecular basis of this venom and to uncover possible immunogens for an antiserum, we generated expressed sequences tags (ESTs from its venom glands and analyzed the transcriptomic profile. In addition, their immunogenicity was tested using DNA immunization. Results A total of 1438 ESTs were generated and grouped into 611 clusters. Toxin transcripts represented 46% of the total ESTs. The two main toxin classes consisted of three-finger toxins (3FTx (24% and phospholipases A2 (PLA2s (15%. However, 8 other classes of toxins were present, including C-type lectins, natriuretic peptide precursors and even high-molecular mass components such as metalloproteases and L-amino acid oxidases. Each class included an assortment of isoforms, some showing evidence of alternative splicing and domain deletions. Five antigenic candidates were selected (four 3FTx and one PLA2 and used for a preliminary study of DNA immunization. The immunological response showed that the sera from the immunized animals were able to recognize the recombinant antigens. Conclusion Besides an improvement in our knowledge of the composition of coral snake venoms, which are very poorly known when compared to Old World elapids, the expression profile suggests abundant and diversified components that may be used in future antiserum formulation. As recombinant production of venom antigens frequently fails due to complex disulfide arrangements, DNA

An update on potential molecular mechanisms underlying the actions of snake venom L-amino acid oxidases (LAAOs).

Science.gov (United States)

Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan

2017-11-08

LAAOs (EC 1.4.3.2) are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Background analysis for the beta-spectrum of the isotope 113Cd in the COBRA experiment

Energy Technology Data Exchange (ETDEWEB)

Platzek, Stephan [Technische Universitaet Dresden (Germany); Collaboration: COBRA-Collaboration

2016-07-01

The COBRA experiment uses Cadmium-Zinc-Telluride as detector material. This semiconductor contains several isotopes that are candidates for neutrinoless double beta-decay. Due to the natural abundance of the detector material various other isotopes are present as well. One of them is {sup 113}Cd with an abundance of about 12%. The fourfold forbidden non-unique beta-decay of {sup 113}Cd is a rare process with a half-life of about 8.10{sup 15} years. The shape of the spectrum is still topic of scientific discussions because of various forecasts given by theoretical models. The signal related to this decay is by far the most prominent in the COBRA setup causing more than 98% of the total rate. In this talk potential background components contributing to the {sup 113}Cd beta-spectrum are discussed with the aim to develop a detailed background simulation with the program VENOM (based on Geant4), that includes background sources originating from cosmic activation as well as natural radioactivity and detector specific effects.

Assessment of the toxicity level of gamma-irradiated snake (Naja naja oxiana) venom by photoacoustic spectroscopy

International Nuclear Information System (INIS)

Vidyasagar, P.B.; Pal, Saumen

1991-01-01

Immunization is the only answer to the challenge of the diseases for which it is extremely difficult to institute timely and proper treatment following the inset. Various antigenic agents responsible for such diseases are used for the purpose of immunization to overcome this difficulty. To make safe use of the antigens it is required to reduce their toxicity level keeping the antigenicity intact and develop a suitable way to detect it. To ensure this, toxoids are produced from the toxic antigens by using different physical and chemical methods. Snake venoms are some important antigens which deserve more attention to be used for immunization because bites by poisonous snakes require instant treatment which is difficult to install. Toxoids used in the present study were produced by irradiating oxus cobra (Naja naja oxiana) venom under cobalt-60 gamma-ray source. The toxocity level of thus produced venom toxoid was assessed by photoacoustic (PA) spectroscopy. In support of the PA observations, optical absorption and fluorescence spectra of the venom in solution were also studied. Percentile change in PA signal intensity was taken as the parameter for toxocity level which was then correlated to the percentile residual toxocity of the venom obtained by direct method of injecting the venom in mice. Efforts were also made to find out the possible effects of the radiation on the venom. (author). 29 refs., 7 figs

Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

Science.gov (United States)

Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N W; Casewell, Nicholas R; Undheim, Eivind A B; Vidal, Nicolas; Ali, Syed A; King, Glenn F; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

2013-01-01

Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

Biological effects of Naja haje crude venom on the hepatic and renal tissues of mice

Directory of Open Access Journals (Sweden)

Amany A. Tohamy

2014-07-01

Full Text Available Snake venoms are known to cause different metabolic disorders, altering cellular and enzymatic activities in animals and releasing pharmacological substances. In this study, the lethality as well as biochemical and histopathological effect of Egyptian cobra (Naja haje; N. haje crude venom at a sublethal dose have been investigated on liver and kidney of male mice. Venom injected intramuscularly in mice with 1/2 LD50 (approximately 0.0115 μg/g body weight of mice and the animals were sacrificed 6 days post injection. Results indicated that the injection of crude venom of the N. haje induced a significant disturbance in liver and kidney functions. In addition, results revealed that N. haje venom has a potent oxidative activity by increasing the level of reactive oxygen species with concomitant significant increase in hydrogen peroxide, lipid peroxidation, carbonyl protein and nitric oxide levels in hepatic and renal tissues. This activity was extended to decrease non-enzymatic and enzymatic antioxidant defense components such as glutathione, superoxide dismutase and catalase. Additionally, the biochemical alternations induced in hepatic and renal tissues were associated with significant alternations in the histological architecture of liver and kidney of injected mice. From this study, we can conclude that such injury could be considered among the factors that lead to death caused by N. haje venom.

COBRA-WC: a version of COBRA for single-phase multiassembly thermal hydraulic transient analysis

International Nuclear Information System (INIS)

George, T.L.; Basehore, K.L.; Wheeler, C.L.; Prather, W.A.; Masterson, R.E.

1980-07-01

The objective of this report is to provide the user of the COBRA-WC (Whole Core) code a basic understanding of the code operation and capabilities. Included in this manual are the equations solved and the assumptions made in their derivations, a general description of the code capabilities, an explanation of the numerical algorithms used to solve the equations, and input instructions for using the code. Also, the auxiliary programs GEOM and SPECSET are described and input instructions for each are given. Input for COBRA-WC sample problems and the corresponding output are given in the appendices. The COBRA-WC code has been developed from the COBRA-IV-I code to analyze liquid Metal Fast Breeder Reactor (LMFBR) assembly transients. It was specifically developed to analyze a core flow coastdown to natural circulation cooling

Elapid Snake Venom Analyses Show the Specificity of the Peptide Composition at the Level of Genera Naja and Notechis

Directory of Open Access Journals (Sweden)

Aisha Munawar

2014-02-01

Full Text Available Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms—that of the African cobra, N. m. mossambica (genus Naja, and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis. A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F cytotoxins, bradykinin-potentiating peptides (BPPs and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467 from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes.

Culturable Aerobic and Facultative Anaerobic Intestinal Bacterial Flora of Black Cobra (Naja naja karachiensis) in Southern Pakistan

Science.gov (United States)

Iqbal, Junaid; Sagheer, Mehwish; Tabassum, Nazneen; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

2014-01-01

Using morphological analysis and biochemical testing, here for the first time, we determined the culturable gut bacterial flora (aerobes and facultative anaerobes) in the venomous Black Cobra (Naja naja karachiensis) from South Asia. The findings revealed that these snakes inhabit potentially pathogenic bacteria including Serratia marcescens, Pseudomonas aeruginosa, Shewanella putrefaciens, Aeromonas hydrophila, Salmonella sp., Moraxella sp., Bacillus sp., Ochrobactrum anthropi, and Providencia rettgeri. These findings are of concern, as injury from snake bite can result in wound infections and tissue necrosis leading to sepsis/necrotizing fasciitis and/or expose consumers of snake meat/medicine in the community to infections. PMID:25002979

Studies on Impact of Irradiation Treatment on Certain Pharmacological and Biochemical Responses of Naja nigricollis Snake Venom

International Nuclear Information System (INIS)

Abd El Hamid, F.Y.A.

2015-01-01

Snakebite is a serious medical problem worldwide, especially in the tropics. In Egypt, the Black-neck Spitting Cobra; Naja nigricollis is one of the most venomous snakes distributed in the south part of Egypt. The lethality as well as the immunological, biochemical and histological effects of Naja nigricollis venom at a sublethal dose has been investigated before and after exposure to gamma radiation (1.5 KGy and 3 KGy). The toxicity of irradiated venom decreased as compared to that of the native one. There was no change in the antigenic reactivity between both native and irradiated venom. The effect of ½ LD 50 of native or irradiated (1.5 KGy) was studied on the activities of heart enzymes: CPK, CK-MB, LDH and AST after (1, 2, 4, 24 hours) of envenomation. The present study showed that snake venom envenomation caused significant (p ≤ 0.05) elevation in serum CPK, CK-MB, LDH and AST levels. In contrast, the 1.5 KGy gamma-irradiated venom recorded no significant changes compared to that of normal rats. Histopathological study of heart confirmed these findings. The 1.5 KGy and 3 KGy gamma irradiation decrease the phospholipase activity of the venom. Anticoagulant activity was prominent when re calcification time was tested on human plasma using each venom (native, γ- irradiated venoms) as a test solution. Naja nigricollis venom detoxified by gamma irradiation (1.5 KGy or 3 KGy) was used as toxoid for active immunization of rabbits following a short schedule of immunization with complete Freund's adjuvant. Effective neutralization of venom toxin by immune sera of rabbits was observed.

ABSENCE OF LECITHIN FROM THE STROMATA OF THE RED CELLS OF CERTAIN ANIMALS (RUMINANTS), AND ITS RELATION TO VENOM HEMOLYSIS

Science.gov (United States)

Turner, Joseph C.

1957-01-01

Lipide extracts of the red cells of several animal species have been analyzed chromatographically. Genetically determined differences in phospholipide composition were found. Lecithin is absent from the cells of ox, sheep, and goat. Cells containing lecithin are susceptible to the direct hemolysin of cobra venom while cells not containing lecithin are resistant. The facts indicate that the direct hemolysin is a lecithinase. PMID:13406178

Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

Directory of Open Access Journals (Sweden)

Kartik Sunagar

Full Text Available Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF, brain-derived neurotrophic factors (BDNF and neurotrophin-3 (NT-3, which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74% and on the molecular surface of the protein (92%, while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf

Science.gov (United States)

Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N. W.; Casewell, Nicholas R.; Undheim, Eivind A. B.; Vidal, Nicolas; Ali, Syed A.; King, Glenn F.; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

2013-01-01

Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. PMID:24312363

Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches.

Science.gov (United States)

Liu, Chien-Chun; You, Chen-Hsien; Wang, Po-Jung; Yu, Jau-Song; Huang, Guo-Jen; Liu, Chien-Hsin; Hsieh, Wen-Chin; Lin, Chih-Chuan

2017-12-01

In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom-freeze-dried neurotoxic antivenom (FNAV)-against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two 'true' cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites.

Evolution of an arsenal: structural and functional diversification of the venom system in the advanced snakes (Caenophidia).

Science.gov (United States)

Fry, Bryan G; Scheib, Holger; van der Weerd, Louise; Young, Bruce; McNaughtan, Judith; Ramjan, S F Ryan; Vidal, Nicolas; Poelmann, Robert E; Norman, Janette A

2008-02-01

Venom is a key innovation underlying the evolution of advanced snakes (Caenophidia). Despite this, very little is known about venom system structural diversification, toxin recruitment event timings, or toxin molecular evolution. A multidisciplinary approach was used to examine the diversification of the venom system and associated toxins across the full range of the approximately 100 million-year-old advanced snake clade with a particular emphasis upon families that have not secondarily evolved a front-fanged venom system ( approximately 80% of the 2500 species). Analysis of cDNA libraries revealed complex venom transcriptomes containing multiple toxin types including three finger toxins, cobra venom factor, cysteine-rich secretory protein, hyaluronidase, kallikrein, kunitz, lectin, matrix metalloprotease, phospholipase A(2), snake venom metalloprotease/a disintegrin and metalloprotease, and waprin. High levels of sequence diversity were observed, including mutations in structural and functional residues, changes in cysteine spacing, and major deletions/truncations. Morphological analysis comprising gross dissection, histology, and magnetic resonance imaging also demonstrated extensive modification of the venom system architecture in non-front-fanged snakes in contrast to the conserved structure of the venom system within the independently evolved front-fanged elapid or viperid snakes. Further, a reduction in the size and complexity of the venom system was observed in species in which constriction has been secondarily evolved as the preferred method of prey capture or dietary preference has switched from live prey to eggs or to slugs/snails. Investigation of the timing of toxin recruitment events across the entire advanced snake radiation indicates that the evolution of advanced venom systems in three front-fanged lineages is associated with recruitment of new toxin types or explosive diversification of existing toxin types. These results support the role of venom

COBRA compliance: how employers can successfully meet today's complexities.

Science.gov (United States)

Trimble, Jim

2003-03-01

Although the architects of COBRA had sound and compassionate motivations in place, administration of and compliance with this law are far from easy. COBRA assists employees that lose their jobs by allowing them to purchase insurance benefits from their former employer. Outsourcing COBRA administration can be the best way for some employers to cope with COBRA regulations, contingencies and paperwork and avoid legal fees and penalties. But look for COBRA providers that have a sound track record.

Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the "bivalent" Sea Snake Antivenom.

Science.gov (United States)

Tan, Choo Hock; Tan, Kae Yi; Tan, Nget Hong

2016-07-20

beaked sea snake (Hydrophis schistosus) and N. scutatus. However, it is surprising to note that bioCSL Sea Snake Antivenom neutralized N. scutatus venom much more effectively compared to the targeted sea snake venom by a marked difference in potency of approximately 6-fold. This phenomenon may be explained by the main difference in the proteomes of the two venoms, where H. schistosus venom is dominated by short-neurotoxins in high abundance - this is a poorly immunogenic toxin group that has been increasingly recognized in the venoms of a few cobras. Further investigations should be directed toward strategies to improve the neutralization of short-neurotoxins, in line with the envisioned production of an effective pan-regional elapid antivenom. Copyright © 2016 Elsevier B.V. All rights reserved.

COBRA1 inhibits AP-1 transcriptional activity in transfected cells

International Nuclear Information System (INIS)

Zhong Hongjun; Zhu Jianhua; Zhang Hao; Ding Lihua; Sun Yan; Huang Cuifen; Ye Qinong

2004-01-01

Mutations in the breast cancer susceptibility gene (BRCA1) account for a significant proportion of hereditary breast and ovarian cancers. Cofactor of BRCA1 (COBRA1) was isolated as a BRCA1-interacting protein and exhibited a similar chromatin reorganizing activity to that of BRCA1. However, the biological role of COBRA1 remains largely unexplored. Here, we report that ectopic expression of COBRA1 inhibited activator protein 1 (AP-1) transcriptional activity in transfected cells in a dose-dependent manner, whereas reduction of endogenous COBRA1 with a small interfering RNA significantly enhanced AP-1-mediated transcriptional activation. COBRA1 physically interacted with the AP-1 family members, c-Jun and c-Fos, and the middle region of COBRA1 bound to c-Fos. Lack of c-Fos binding site in the COBRA1 completely abolished the COBRA1 inhibition of AP-1 trans-activation. These findings suggest that COBRA1 may directly modulate AP-1 pathway and, therefore, may play important roles in cell proliferation, differentiation, apoptosis, and oncogenesis

Assessment of the computer code COBRA/CFTL

International Nuclear Information System (INIS)

Baxi, C.B.; Burhop, C.J.

1981-07-01

The COBRA/CFTL code has been developed by Oak Ridge National Laboratory (ORNL) for thermal-hydraulic analysis of simulated gas-cooled fast breeder reactor (GCFR) core assemblies to be tested in the core flow test loop (CFTL). The COBRA/CFTL code was obtained by modifying the General Atomic code COBRA*GCFR. This report discusses these modifications, compares the two code results for three cases which represent conditions from fully rough turbulent flow to laminar flow. Case 1 represented fully rough turbulent flow in the bundle. Cases 2 and 3 represented laminar and transition flow regimes. The required input for the COBRA/CFTL code, a sample problem input/output and the code listing are included in the Appendices

Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms.

Science.gov (United States)

Pla, Davinia; Bande, Benjamin W; Welton, Ronelle E; Paiva, Owen K; Sanz, Libia; Segura, Álvaro; Wright, Christine E; Calvete, Juan J; Gutiérrez, José María; Williams, David J

2017-01-06

The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA 2 s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2.3%) 1-3 l-amino acid oxidase (LAAO) molecules (1.6%). Probing of a P. papuanus cDNA library with specific primers resulted in the elucidation of the full-length nucleotide sequences of six new toxins, including vespryn and NGF not found in the venom proteome, and a calglandulin protein involved in toxin expression with the venom glands. Intravenous injection of P. papuanus venom in mice induced lethality, intravascular haemolysis, pulmonary congestion and oedema, and anticoagulation after intravenous injection, and these effects are mainly due to the action of PLA 2 s. This study also evaluated the in vivo preclinical efficacy of Australian black snake and polyvalent Seqirus antivenoms. These antivenoms were effective in neutralising the lethal, PLA 2 and anticoagulant activities of P. papuanus venom in mice. On the other hand, all of the Seqirus antivenoms tested using an antivenomic approach exhibited strong immunorecognition of all the venom components. These preclinical results suggest that Australian Seqirus 1 antivenoms may provide paraspecific protection against P. papuanus venom in humans. The toxicological profile and proteomic composition of the venom of the Papuan black snake, Pseudechis papuanus, a large diurnal snake endemic to the southern coast of New Guinea and a handful of close offshore islands, were investigated. Intravenous injection of P. papuanus venom in mice induced intravascular hemolysis, pulmonary congestion and edema

COBRA-Seq: Sensitive and Quantitative Methylome Profiling

Directory of Open Access Journals (Sweden)

Hilal Varinli

2015-10-01

Full Text Available Combined Bisulfite Restriction Analysis (COBRA quantifies DNA methylation at a specific locus. It does so via digestion of PCR amplicons produced from bisulfite-treated DNA, using a restriction enzyme that contains a cytosine within its recognition sequence, such as TaqI. Here, we introduce COBRA-seq, a genome wide reduced methylome method that requires minimal DNA input (0.1–1.0 mg and can either use PCR or linear amplification to amplify the sequencing library. Variants of COBRA-seq can be used to explore CpG-depleted as well as CpG-rich regions in vertebrate DNA. The choice of enzyme influences enrichment for specific genomic features, such as CpG-rich promoters and CpG islands, or enrichment for less CpG dense regions such as enhancers. COBRA-seq coupled with linear amplification has the additional advantage of reduced PCR bias by producing full length fragments at high abundance. Unlike other reduced representative methylome methods, COBRA-seq has great flexibility in the choice of enzyme and can be multiplexed and tuned, to reduce sequencing costs and to interrogate different numbers of sites. Moreover, COBRA-seq is applicable to non-model organisms without the reference genome and compatible with the investigation of non-CpG methylation by using restriction enzymes containing CpA, CpT, and CpC in their recognition site.

Catching COBRAs

NARCIS (Netherlands)

Muntinga, D.G.

2013-01-01

With social media usage increasingly widespread and influential, companies face the challenge of inspiring and cultivating Consumers’ Online Brand-Related Activities (COBRAs). This dissertation argues that they can do so effectively only when they have a good understanding of consumers’ willingness

The detection of hemorrhagic proteins in snake venoms using monoclonal antibodies against Virginia opossum (Didelphis virginiana) serum.

Science.gov (United States)

Sánchez, E E; García, C; Pérez, J C; De La Zerda, S J

1998-10-01

, reacted with all the hemorrhagic venoms except for the venom of the King cobra (Ophiophagus hannah) and did not react with the non-hemorrhagic venoms. The hemorrhagic binding site of CAH monoclonal antibody and the antihemorrhagin in Virginia opossum are different binding sites. The five-step western blot will be a very useful assay for determining hemorrhagic activity without using live animals.

ASSERT and COBRA predictions of flow distribution in vertical bundles

International Nuclear Information System (INIS)

Tahir, A.; Carver, M.B.

1983-01-01

COBRA and ASSERT are subchannel codes which compute flow and enthalpy distributions in rod bundles. COBRA is a well known code, ASSERT is under development at CRNL. This paper gives a comparison of the two codes with boiling experiments in vertical seven rod bundles. ASSERT predictions of the void distribution are shown to be in good agreement with reported experimental results, while COBRA predictions are unsatisfactory. The mixing models in both COBRA and ASSERT are briefly discussed. The reasons for the failure of COBRA-IV and the success of ASSERT in simulating the experiments are highlighted

HYMENOPTERA ALLERGENS: FROM VENOM TO VENOME

Directory of Open Access Journals (Sweden)

Edzard eSpillner

2014-02-01

Full Text Available In Western Europe hymenoptera venom allergy primarily relates to venoms of the honeybee and the common yellow jacket. In contrast to other allergen sources, only a few major components of hymenoptera venoms had been characterized until recently. Improved expression systems and proteomic detection strategies have allowed the identification and characterization of a wide range of additional allergens. The field of hymenoptera venom allergy research has moved rapidly from focusing on venom extract and single major allergens to a molecular understanding of the entire venome as a system of unique and characteristic components. An increasing number of such components has been identified, characterized regarding function and assessed for allergenic potential. Moreover, advanced expression strategies for recombinant production of venom allergens allow selective modification of molecules and provide insight into different types of IgE reactivities and sensitization patterns. The obtained information contributes to an increased diagnostic precision in hymenoptera venom allergy and may serve for monitoring, reevaluation and improvement of current therapeutic strategies.

78 FR 13662 - Cobra Pipeline Ltd.; Notice of Petition

Science.gov (United States)

2013-02-28

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. PR13-32-000; PR13-33-000] Cobra Pipeline Ltd.; Notice of Petition Take notice that on February 4, 2013, Cobra Pipeline Ltd. (Cobra... Docket No. PR13-11-000, as more fully detailed in the petitions. Any person desiring to participate in...

Squeezers and leaf-cutters: differential diversification and degeneration of the venom system in toxicoferan reptiles.

Science.gov (United States)

Fry, Bryan G; Undheim, Eivind A B; Ali, Syed A; Jackson, Timothy N W; Debono, Jordan; Scheib, Holger; Ruder, Tim; Morgenstern, David; Cadwallader, Luke; Whitehead, Darryl; Nabuurs, Rob; van der Weerd, Louise; Vidal, Nicolas; Roelants, Kim; Hendrikx, Iwan; Gonzalez, Sandy Pineda; Koludarov, Ivan; Jones, Alun; King, Glenn F; Antunes, Agostinho; Sunagar, Kartik

2013-07-01

Although it has been established that all toxicoferan squamates share a common venomous ancestor, it has remained unclear whether the maxillary and mandibular venom glands are evolving on separate gene expression trajectories or if they remain under shared genetic control. We show that identical transcripts are simultaneously expressed not only in the mandibular and maxillary glands, but also in the enigmatic snake rictal gland. Toxin molecular frameworks recovered in this study were three-finger toxin (3FTx), CRiSP, crotamine (beta-defensin), cobra venom factor, cystatin, epididymal secretory protein, kunitz, L-amino acid oxidase, lectin, renin aspartate protease, veficolin, and vespryn. We also discovered a novel low-molecular weight disulfide bridged peptide class in pythonid snake glands. In the iguanian lizards, the most highly expressed are potentially antimicrobial in nature (crotamine (beta-defensin) and cystatin), with crotamine (beta-defensin) also the most diverse. However, a number of proteins characterized from anguimorph lizards and caenophidian snakes with hemotoxic or neurotoxic activities were recruited in the common toxicoferan ancestor and remain expressed, albeit in low levels, even in the iguanian lizards. In contrast, the henophidian snakes express 3FTx and lectin toxins as the dominant transcripts. Even in the constricting pythonid and boid snakes, where the glands are predominantly mucous-secreting, low-levels of toxin transcripts can be detected. Venom thus appears to play little role in feeding behavior of most iguanian lizards or the powerful constricting snakes, and the low levels of expression argue against a defensive role. However, clearly the incipient or secondarily atrophied venom systems of these taxa may be a source of novel compounds useful in drug design and discovery.

Squeezers and Leaf-cutters: Differential Diversification and Degeneration of the Venom System in Toxicoferan Reptiles*

Science.gov (United States)

Fry, Bryan G.; Undheim, Eivind A.B.; Ali, Syed A.; Jackson, Timothy N. W.; Debono, Jordan; Scheib, Holger; Ruder, Tim; Morgenstern, David; Cadwallader, Luke; Whitehead, Darryl; Nabuurs, Rob; van der Weerd, Louise; Vidal, Nicolas; Roelants, Kim; Hendrikx, Iwan; Gonzalez, Sandy Pineda; Koludarov, Ivan; Jones, Alun; King, Glenn F.; Antunes, Agostinho; Sunagar, Kartik

2013-01-01

Although it has been established that all toxicoferan squamates share a common venomous ancestor, it has remained unclear whether the maxillary and mandibular venom glands are evolving on separate gene expression trajectories or if they remain under shared genetic control. We show that identical transcripts are simultaneously expressed not only in the mandibular and maxillary glands, but also in the enigmatic snake rictal gland. Toxin molecular frameworks recovered in this study were three-finger toxin (3FTx), CRiSP, crotamine (beta-defensin), cobra venom factor, cystatin, epididymal secretory protein, kunitz, l-amino acid oxidase, lectin, renin aspartate protease, veficolin, and vespryn. We also discovered a novel low-molecular weight disulfide bridged peptide class in pythonid snake glands. In the iguanian lizards, the most highly expressed are potentially antimicrobial in nature (crotamine (beta-defensin) and cystatin), with crotamine (beta-defensin) also the most diverse. However, a number of proteins characterized from anguimorph lizards and caenophidian snakes with hemotoxic or neurotoxic activities were recruited in the common toxicoferan ancestor and remain expressed, albeit in low levels, even in the iguanian lizards. In contrast, the henophidian snakes express 3FTx and lectin toxins as the dominant transcripts. Even in the constricting pythonid and boid snakes, where the glands are predominantly mucous-secreting, low-levels of toxin transcripts can be detected. Venom thus appears to play little role in feeding behavior of most iguanian lizards or the powerful constricting snakes, and the low levels of expression argue against a defensive role. However, clearly the incipient or secondarily atrophied venom systems of these taxa may be a source of novel compounds useful in drug design and discovery. PMID:23547263

Popsicle-Stick Cobra Wave.

Science.gov (United States)

Boucher, Jean-Philippe; Clanet, Christophe; Quéré, David; Chevy, Frédéric

2017-08-25

The cobra wave is a popular physical phenomenon arising from the explosion of a metastable grillage made of popsicle sticks. The sticks are expelled from the mesh by releasing the elastic energy stored during the weaving of the structure. Here we analyze both experimentally and theoretically the propagation of the wave front depending on the properties of the sticks and the pattern of the mesh. We show that its velocity and its shape are directly related to the recoil imparted to the structure by the expelled sticks. Finally, we show that the cobra wave can only exist for a narrow range of parameters constrained by gravity and rupture of the sticks.

COBRA-IV wire wrap data comparisons

International Nuclear Information System (INIS)

Donovan, T.E.; George, T.L.; Wheeler, C.L.

1979-02-01

Thermal hydraulic analyses of hexagonally packed wire-wrapped fuel assemblies are complicated by the induced crossflow between adjacent subchannels. The COBRA-IV computer code simultaneously solves the hydrodynamics and thermodynamics of fuel assemblies. The modifications and the results are presented which are predicted by the COBRA-IV calculation. Comparisons are made with data measured in five experimental models of a wire-wrapped fuel assembly

Venomics-Accelerated Cone Snail Venom Peptide Discovery

Science.gov (United States)

Himaya, S. W. A.

2018-01-01

Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads. PMID:29522462

Venomics-Accelerated Cone Snail Venom Peptide Discovery

Directory of Open Access Journals (Sweden)

S. W. A. Himaya

2018-03-01

Full Text Available Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads.

Steady state thermal hydraulic analysis of LMR core using COBRA-K code

Energy Technology Data Exchange (ETDEWEB)

Kim, Eui Kwang; Kim, Young Gyun; Kim Young In; Kim Young Cheol

1997-02-01

A thermal hydraulics analysis code COBRA-K is being developed by the KAERI LMR core design technology development team. COBRA-K is a part of the integrated computation system for LMR core design and analysis, the K-CORE system. COBRA-K is supposed to predict the flow and temperature distributions in LMR core. COBRA-K is an extension of the previously published COBRA-IV-I code with several functional improvements. Specially COBRA-K has been improved to analyze single and multi-assembly, and whole-core in the transient condition. This report describes the overall features of COBRA-K and gives general input descriptions. The 19 pin assembly experimental data of ORNL were used to verify the accuracy of this code for the steady state analysis. The comparative results show good agreements between the calculated and the measured data. And COBRA-K can be used to predict flow and temperature distributions for the LMR core design. (author). 7 refs., 6 tabs., 13 figs.

In vivo studies on detoxifying actions of aqueous bark extract of Prosopis cineraria against crude venom from Indian cobra (Naja naja)

OpenAIRE

Thirunavukkarasu Sivaraman; Sivarathri Siva Rajesh; Veerayan Elango

2013-01-01

Detoxification effect of aqueous, methanol and petroleum ether extracts of medicinal plants such as Aristolochia bracteolata, Mucuna pruriens, Prosopis cineraria and Rauvolfia tetraphylla was systematically screened against lethality of crude venom of Naja naja using Swiss albino mice as animal models. We have herein demonstrated that aqueous bark extract of P. cineraria has substantial anti-venom potential vis-à-vis other extracts used in the present study. The aqueous extract at the dose of...

Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

Science.gov (United States)

von Reumont, Bjoern Marcus; Campbell, Lahcen I.; Jenner, Ronald A.

2014-01-01

Venomics research is being revolutionized by the increased use of sensitive -omics techniques to identify venom toxins and their transcripts in both well studied and neglected venomous taxa. The study of neglected venomous taxa is necessary both for understanding the full diversity of venom systems that have evolved in the animal kingdom, and to robustly answer fundamental questions about the biology and evolution of venoms without the distorting effect that can result from the current bias introduced by some heavily studied taxa. In this review we draw the outlines of a roadmap into the diversity of poorly studied and understood venomous and putatively venomous invertebrates, which together represent tens of thousands of unique venoms. The main groups we discuss are crustaceans, flies, centipedes, non-spider and non-scorpion arachnids, annelids, molluscs, platyhelminths, nemerteans, and echinoderms. We review what is known about the morphology of the venom systems in these groups, the composition of their venoms, and the bioactivities of the venoms to provide researchers with an entry into a large and scattered literature. We conclude with a short discussion of some important methodological aspects that have come to light with the recent use of new -omics techniques in the study of venoms. PMID:25533518

Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

Directory of Open Access Journals (Sweden)

Bjoern Marcus von Reumont

2014-12-01

Full Text Available Venomics research is being revolutionized by the increased use of sensitive -omics techniques to identify venom toxins and their transcripts in both well studied and neglected venomous taxa. The study of neglected venomous taxa is necessary both for understanding the full diversity of venom systems that have evolved in the animal kingdom, and to robustly answer fundamental questions about the biology and evolution of venoms without the distorting effect that can result from the current bias introduced by some heavily studied taxa. In this review we draw the outlines of a roadmap into the diversity of poorly studied and understood venomous and putatively venomous invertebrates, which together represent tens of thousands of unique venoms. The main groups we discuss are crustaceans, flies, centipedes, non-spider and non-scorpion arachnids, annelids, molluscs, platyhelminths, nemerteans, and echinoderms. We review what is known about the morphology of the venom systems in these groups, the composition of their venoms, and the bioactivities of the venoms to provide researchers with an entry into a large and scattered literature. We conclude with a short discussion of some important methodological aspects that have come to light with the recent use of new -omics techniques in the study of venoms.

COBRA-IV-I: an interim version of COBRA for thermal-hydraulic analysis of rod bundle nuclear fuel elements and cores

Energy Technology Data Exchange (ETDEWEB)

Wheeler, C.L.; Stewart, C.W.; Cena, R.J.; Rowe, D.S.; Sutey, A.M.

1976-03-01

The COBRA-IV-I computer code uses the subchannel analysis approach to determine the enthalpy and flow distribution in rod bundles for both steady-state and transient conditions. The steady-state and transient solution schemes used in COBRA-IIIC are still available in COBRA-IV-I as the implicit solution scheme option. In addition to these techniques, a new explicit solution scheme is now available which allows the calculation of severe transients involving flow reversals, recirculations, expulsion and reentry flows, with a pressure or flow boundary condition specified. Significant storage compaction and reduced running times have been achieved to allow the calculation of problems involving hundreds of subchannels.

Development and assessment of the COBRA/RELAP5 code

Energy Technology Data Exchange (ETDEWEB)

Jeong, Jae Jun; Ha, Kwi Seok; Sim, Seok Ku

1997-04-01

The COBRA/RELAP5 code, a merged version of the COBRA-TF and RELAP5/MOD3.2 codes, has been developed to combine the realistic three-dimensional reactor vessel model of COBRA-TF with RELAP5/MOD3, thus to produce an advanced system analysis code with a multidimensional thermal-hydraulic module. This report provides the integration scheme of the two codes and the results of developmental assessments. These includes single channel tests, manometric flow oscillation problem, THTF Test 105, and LOFT L2-3 large-break loss-of-coolant experiment. From the single channel tests the integration scheme and its implementation were proven to be valid. Other simulation results showed good agreement with the experiments. The computational speed was also satisfactory. So it is confirmed that COBRA/RELAP5 can be a promising tool for analysis of complicated, multidimensional two-phase flow transients. The area of further improvements in the code integration are also identified. This report also serves as a user`s manual for the COBRA/RELAP5 code. (author). 6 tabs., 20 figs., 20 refs.

New and already known acanthocephalans from amphibians and reptiles in Vietnam, with keys to species of Pseudoacanthocephalus Petrochenko, 1956 (Echinorhynchidae) and Sphaerechinorhynchus Johnston and Deland, 1929 (Plagiorhynchidae).

Science.gov (United States)

Amin, Omar M; Ha, Ngyuen Van; Heckmann, Richard A

2008-02-01

Adults of 2 new species in 2 orders of acanthocephalans obtained from the intestines of terrestrial amphibians and reptiles collected between 1998 and 2004 in Vietnam are described here. Pseudoacanthocephalus nguyenthileae n. sp. (Palaeacnthocephala: Echinorhynchidae) was collected from 5 species of terrestrial amphibians: (1) the common Sunda toad Bufo melanostictus Schneider (Bufonidae); (2) Paa verucospinosa (Bourret); (3) Gunther's Amoy frog Rana guentheri Boulenger; (4) Taipei frog R. taipehensis Denburgh (Ranidae), and (5) the Burmese whipping frog Polypedates mutus (Smith) (Racophoridae); as well as from the Chinese cobra Naja atra Cantor (Reptilia: Elapidae) and house gecko Hemidactylus frenatus Dumeril and Bibron (Reptilia: Gekkonidae). Sphaerechinorhynchus maximesospinus n. sp. (Plagiorhynchidae: Sphaerechinorhynchinae) was isolated from a king cobra Ophiophagus hannah (cantor) (Reptilia: Elapidae). Cystacanths of Porrorchis houdemeri (Joyeux and Baer, 1935) Schmidt and Kuntz, 1967 (Plagiorhynchidae: Porrorchinae) obtained from the mesenteries of banded krait Bungarus fasciatus (Schneider) (Reptilia: Elapidae), a paratenic host, are reported for the first time. Keys to the species of Pseudoacanthocephalus and Sphaerechinorhynchus are included. Characteristic features distinguishing the new species from related taxa include: P. nguyenthileae has 15-19 (usually 16-18) proboscis hook rows, each with 5-6 hooks that progressively increase in length and size posteriorly. The largest, intermediate, and smallest proboscis hooks of S. maximesospinus are the middle, anterior, and posterior hooks, respectively; the proboscis and neck are enclosed in a membrane. Morphometric characteristics of P. nguyenthileae show host-related variability.

Delineating residues for haemolytic activities of snake venom cardiotoxin 1 from Naja naja as probed by molecular dynamics simulations and in vitro validations.

Science.gov (United States)

Gorai, Biswajit; Sivaraman, Thirunavukkarasu

2017-02-01

Cardiotoxins (CTXs) are single polypeptide chain consisting of 59-62 amino acids with four disulfide bridges and globular proteins of simple β-sheet folds. The CTXs are one of principal toxic components causing haemolysis and damaging various cells and belong to three-finger toxin (TFT) superfamily of snake venoms. However, there is no natural or synthetic small molecular inhibitor to the protein toxins to date. In the present study, modes of interaction of cardiotoxin 1 (CTX1) from Indian cobra (Naja naja) with heterogeneous erythrocyte membrane (EM) model system have been extensively examined by using all-atom molecular dynamics (MD) simulations in near physiological conditions and comprehensive analyses of the MD data revealed two distinct principal regions ('head groove' and 'loop groove') of the protein toxin for establishing structural interactions with the EM system. Moreover, combined analyses of data from high-throughput virtual screening of NCI small molecular database, in vitro haemolytic assays for top-hits of the chemical compounds against crude venom of Naja naja and as well CTXs purified from the venom and pharmacokinetic examinations on the chemical compounds retarding haemolytic activities of CTXs suggested that Etidronic acid and Zoledronic acid are promising prototypic chemical inhibitors to CTXs of snake venoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of the unified version of COBRA/RELAP5

Energy Technology Data Exchange (ETDEWEB)

Jeong, J J; Ha, K S; Chung, B D; Lee, W J; Sim, S K [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1998-12-31

The COBRA/RELAP5 code, an integrated version of the COBRA-TF and RELAP5/MOD3 codes, has been developed for the realistic simulations of complicated, multi-dimensional, two-phase, thermal-hydraulic system transients in light water reactors. Recently, KAERI developed an unified version of the COBRA/RELAP5 code, which can run in serial mode on both workstations and personal computers. This paper provides the brief overview of the code integration scheme, the recent code modifications, the developmental assessments, and the future development plan. 13 refs., 5 figs., 2 tabs. (Author)

Development of the unified version of COBRA/RELAP5

Energy Technology Data Exchange (ETDEWEB)

Jeong, J. J.; Ha, K. S.; Chung, B. D.; Lee, W. J.; Sim, S. K. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1997-12-31

The COBRA/RELAP5 code, an integrated version of the COBRA-TF and RELAP5/MOD3 codes, has been developed for the realistic simulations of complicated, multi-dimensional, two-phase, thermal-hydraulic system transients in light water reactors. Recently, KAERI developed an unified version of the COBRA/RELAP5 code, which can run in serial mode on both workstations and personal computers. This paper provides the brief overview of the code integration scheme, the recent code modifications, the developmental assessments, and the future development plan. 13 refs., 5 figs., 2 tabs. (Author)

Cobra Fiber-Optic Positioner Upgrade

Science.gov (United States)

Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.

2013-01-01

A prime focus spectrometer (PFS), along with corrective optics, will mount in place of the secondary mirror of the Subaru telescope on Mauna Kea, Hawaii. This will allow simultaneous observations of cosmologic targets. It will enable large-scale galactic archeology and dark energy surveys to help unlock the secrets of the universe. To perform these cosmologic surveys, an array of 2,400 optical fibers needs to be independently positioned within the 498-mm-diameter focal plane of the PFS instrument to collect light from galaxies and stars for spectrographic analyses. To allow for independent re-positioning of the fibers, a very small positioner (7.7 mm in diameter) is required. One hundred percent coverage of the focal plane is also required, so these small actuators need to cover a patrol region of 9.5 mm in diameter. To optimize the amount of light that can be collected, the fibers need to be placed within 5 micrometers of their intended target (either a star or galaxy). The Cobra Fiber Positioner was designed to meet the size and accuracy requirements stated above. Cobra is a two-degrees-of-freedom mechanism that can position an optical fiber in the focal plane of the PFS instrument to a precision of 5 micrometers. It is a theta-phi style positioner containing two rotary piezo tube motors with one offset from the other, which enables the optic fibers to be placed anywhere in a small circular patrol region. The patrol region of the actuator is such that the array of 2,400 positioners allows for full coverage of the instrument focal plane by overlapping the patrol areas. A second-generation Cobra positioner was designed based on lessons learned from the original prototype built in 2009. Improvements were made to the precision of the ceramic motor parts, and hard stops were redesigned to minimize friction and prevent jamming. These changes resulted in reducing the number of move iterations required to position the optical fiber within 5 micrometers of its target. At

Comparison of MATRA-S and COBRA-SFS for Low Flow Subchannel Analysis

Energy Technology Data Exchange (ETDEWEB)

Seo, Kyong Won; Kwon, Hyuk; Kim, Seong Jin; Hwang, Dae Hyun [KAERI, Daejeon (Korea, Republic of)

2016-05-15

In this study, we compared the MATRA-S with COBRA-SFS for the PNL test because the COBRASFS is believed to be superior to MATRA-S for the low flow conditions. COBRA-SFS code was developed for subchannel analysis of spent fuel storage system based on COBRA-3C, COBRA-4I, and COBRA-WC. As the code was designed to predict temperature and flow distributions in spent fuel storage system, it can analyze thermal hydraulic fields of natural convection as well as radiation and conduction heat transfer. In the way of improving XSHCME of MATRA-S to be applicable to low flow problems, we compared MATRA-S XSCHEM and COBRA-SFS RECIRC for steady state and flow transient. Both methods use similar algorithms to solve pressure, axial flow and cross flow. MATRA-S XSCHEM predicted flow velocity profile well even negative flow in recirculation flow.

Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its central analgesic effects under red light

Directory of Open Access Journals (Sweden)

Yang Q

2017-05-01

Full Text Available Qian Yang, Chuang Zhao, Jun Zhao, Yong Ye Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: Cobra neurotoxin (CNT, a peptide isolated from snake venom of Naja naja atra, shows central analgesic effects in our previous research. In order to help CNT pass through blood–brain barrier (BBB and improve its central analgesic effects, a new kind of CNT nanocapsules were prepared by double emulsification with soybean lecithin and cholesterol as the shell, and pheophorbide as the photosensitizer added to make it photoresponsive. The analgesic effects were evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT nanocapsules had an average particle size of 229.55 nm, zeta potential of -53.00 mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly distributed in outer layer of the CNT nanocapsules and increased the release of the CNT nanocapsules after 650 nm illumination. The central analgesic effects were improved after intraperitoneal injection of CNT at 25 and 50 µg·kg-1 under 650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by red light generated reactive oxygen species which opened the nanocapsules and BBB and helped the CNT enter the brain. This research provides a new drug delivery for treatment of central pain. Keywords: cobra neurotoxin, nanocapsules, photoresponsive, central analgesic effects, red light, drug delivery, photosensitizer

Verification and validation of COBRA-SFS transient analysis capability

International Nuclear Information System (INIS)

Rector, D.R.; Michener, T.E.; Cuta, J.M.

1998-05-01

This report provides documentation of the verification and validation testing of the transient capability in the COBRA-SFS code, and is organized into three main sections. The primary documentation of the code was published in September 1995, with the release of COBRA-SFS, Cycle 2. The validation and verification supporting the release and licensing of COBRA-SFS was based solely on steady-state applications, even though the appropriate transient terms have been included in the conservation equations from the first cycle. Section 2.0, COBRA-SFS Code Description, presents a capsule description of the code, and a summary of the conservation equations solved to obtain the flow and temperature fields within a cask or assembly model. This section repeats in abbreviated form the code description presented in the primary documentation (Michener et al. 1995), and is meant to serve as a quick reference, rather than independent documentation of all code features and capabilities. Section 3.0, Transient Capability Verification, presents a set of comparisons between code calculations and analytical solutions for selected heat transfer and fluid flow problems. Section 4.0, Transient Capability Validation, presents comparisons between code calculations and experimental data obtained in spent fuel storage cask tests. Based on the comparisons presented in Sections 2.0 and 3.0, conclusions and recommendations for application of COBRA-SFS to transient analysis are presented in Section 5.0

Computational and in vitro insights on snake venom phospholipase A2 inhibitor of phytocompound ikshusterol3-O-glucoside of Clematis gouriana Roxb. ex DC.

Science.gov (United States)

Muthusamy, Karthikeyan; Chinnasamy, Sathishkumar; Nagarajan, Subbiah; Sivaraman, Thirunavukkarasu

2017-12-14

Ikshusterol3-O-glucoside was isolated from Clematis gouriana Roxb. ex DC. root. A structure of the isolated compound was determined on the basis of various spectroscopic interpretations (UV, NMR, FTIR, and GC-MS-EI). This structure was submitted in the PubChem compound database (SID 249494133). SID 249494133 was carried out by density functional theory calculation to observe the chemical stability and electrostatic potential of this compound. The absorption, distribution, metabolism, and excretion property of this compound was predicted to evaluate the drug likeness and toxicity. In addition, molecular docking, quantum polarized ligand docking, prime MMGBSA calculation, and induced fit docking were performed to predict the binding status of SID 249494133 with the active site of phospholipase A 2 (PLA 2 ) (PDB ID: 1A3D). The stability of the compound in the active site of PLA 2 was carried out using molecular dynamics simulation. Further, the anti-venom activity of the compound was assessed using the PLA 2 assay against Naja naja (Indian cobra) crude venom. The results strongly show that Ikshusterol3-O-glucoside has a potent snake-venom neutralizing capacity and it might be a potential molecule for the therapeutic treatment for snakebites.

26 CFR 54.4980B-5 - COBRA continuation coverage.

Science.gov (United States)

2010-04-01

... employee and spouse who have no children divorce on May 1, 2001, and the spouse elects COBRA continuation... divorce on June 1, 2001, and one of the children remains with the employee. The spouse elects COBRA... other reference in §§ 54.4980B-1 through 54.4980B-10 to coverage in effect immediately before (or on the...

VALIDATION OF SIMBAT-PWR USING STANDARD CODE OF COBRA-EN ON REACTOR TRANSIENT CONDITION

Directory of Open Access Journals (Sweden)

Muhammad Darwis Isnaini

2016-03-01

Full Text Available The validation of Pressurized Water Reactor typed Nuclear Power Plant simulator developed by BATAN (SIMBAT-PWR using standard code of COBRA-EN on reactor transient condition has been done. The development of SIMBAT-PWR has accomplished several neutronics and thermal-hydraulic calculation modules. Therefore, the validation of the simulator is needed, especially in transient reactor operation condition. The research purpose is for characterizing the thermal-hydraulic parameters of PWR1000 core, which be able to be applied or as a comparison in developing the SIMBAT-PWR. The validation involves the calculation of the thermal-hydraulic parameters using COBRA-EN code. Furthermore, the calculation schemes are based on COBRA-EN with fixed material properties and dynamic properties that calculated by MATPRO subroutine (COBRA-EN+MATPRO for reactor condition of startup, power rise and power fluctuation from nominal to over power. The comparison of the temperature distribution at nominal 100% power shows that the fuel centerline temperature calculated by SIMBAT-PWR has 8.76% higher result than COBRA-EN result and 7.70% lower result than COBRA-EN+MATPRO. In general, SIMBAT-PWR calculation results on fuel temperature distribution are mostly between COBRA-EN and COBRA-EN+MATPRO results. The deviations of the fuel centerline, fuel surface, inner and outer cladding as well as coolant bulk temperature in the SIMBAT-PWR and the COBRA-EN calculation, are due to the value difference of the gap heat transfer coefficient and the cladding thermal conductivity.

AN/FPS-108 COBRA DANE Space Surveillance Mission Evolution

Science.gov (United States)

Chorman, P.; Boggs, J.

2013-09-01

It has been ten years since the COBRA DANE radar was restored to continuous full power operations in a more dedicated role of space debris tracking. Over this time, the satellite catalog population has grown and the overall average RCS value of cataloged objects has decreased dramatically, due to a combination of breakups and collisions together with the increased sensitivity offered by COBRA DANE's support to the network. This shift in catalog composition places new challenges on COBRA DANE and other debris tracking radars (PARCS and Eglin/FPS-85) to consistently track the ever-increasing number of small objects. Space Surveillance Network radars now operate at the limits of their detection performance, tracking several thousand new objects in a size category that only the most powerful and sensitive radars can observe (i.e., COBRA DANE's inherent Spacetrack mission software functionality remained better tuned for its original support role against the larger (known) orbital objects than for its more modern role in acquiring and reporting small debris in an appreciable number -- that is, until now. Several newly-identified software changes offer promise of significantly increased data yield that will make COBRA DANE an even more important asset for this evolving mission. In the course of assisting JSpOC, AFSPC, and USSTRATCOM with the ongoing challenges of lost satellite management, it was discovered that the radar's performance is being artificially restricted by mission software, rather than by the system's overall architectural design (power-aperture envelope and radar resources). This paper captures specific opportunities to improve COBRA DANE's Spacetrack mission performance, several of which are currently implemented and slated to become operational with the next two software releases. With one of the more prominent enhancements, COBRA DANE will be capable of autonomously 'fence tasking' all newly acquired small objects. Under the current operating paradigm

Detecting surface events at the COBRA experiment

Energy Technology Data Exchange (ETDEWEB)

Tebruegge, Jan [Exp. Physik IV, TU Dortmund (Germany); Collaboration: COBRA-Collaboration

2015-07-01

The aim of the COBRA experiment is to prove the existence of neutrinoless double-beta-decay and to measure its half-life. For this purpose the COBRA demonstrator, a prototype for a large-scale experiment, is operated at the Gran Sasso Underground Laboratory (LNGS) in Italy. The demonstrator is a detector array made of 64 Cadmium-Zinc-Telluride (CdZnTe) semiconductor detectors in the coplanar grid anode configuration. Each detector is 1**1 ccm in size. This setup is used to investigate the experimental issues of operating CdZnTe detectors in low background mode and identify potential background components. As the ''detector=source'' principle is used, the neutrinoless double beta decay COBRA searches for happens within the whole detector volume. Consequently, events on the surface of the detectors are considered as background. These surface events are a main background component, stemming mainly from the natural radioactivity, especially radon. This talk explains to what extent surface events occur and shows how these are recognized and vetoed in the analysis using pulse shape discrimination algorithms.

The venom optimization hypothesis revisited.

Science.gov (United States)

Morgenstern, David; King, Glenn F

2013-03-01

Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. Copyright © 2012 Elsevier Ltd. All rights reserved.

Venom On-a-Chip: A Fast and Efficient Method for Comparative Venomics.

Science.gov (United States)

Zancolli, Giulia; Sanz, Libia; Calvete, Juan J; Wüster, Wolfgang

2017-05-28

Venom research has attracted an increasing interest in disparate fields, from drug development and pharmacology, to evolutionary biology and ecology, and rational antivenom production. Advances in "-omics" technologies have allowed the characterization of an increasing number of animal venoms, but the methodology currently available is suboptimal for large-scale comparisons of venom profiles. Here, we describe a fast, reproducible and semi-automated protocol for investigating snake venom variability, especially at the intraspecific level, using the Agilent Bioanalyzer on-chip technology. Our protocol generated a phenotype matrix which can be used for robust statistical analysis and correlations of venom variation with ecological correlates, or other extrinsic factors. We also demonstrate the ease and utility of combining on-chip technology with previously fractionated venoms for detection of specific individual toxin proteins. Our study describes a novel strategy for rapid venom discrimination and analysis of compositional variation at multiple taxonomic levels, allowing researchers to tackle evolutionary questions and unveiling the drivers of the incredible biodiversity of venoms.

Molecular evidence for the first records of facultative parthenogenesis in elapid snakes.

Science.gov (United States)

Allen, L; Sanders, K L; Thomson, V A

2018-02-01

Parthenogenesis is a form of asexual reproduction by which embryos develop from unfertilized eggs. Parthenogenesis occurs in reptiles; however, it is not yet known to occur in the widespread elapid snakes (Elapidae), which include well-known taxa such as cobras, mambas, taipans and sea snakes. Here, we describe the production of viable parthenogens in two species of Australo-Papuan elapids with divergent reproductive modes: the oviparous coastal/Papuan taipan ( Oxyuranus scutellatus ) and the viviparous southern death adder ( Acanthophis antarcticus ). Analyses of nuclear SNP data excluded paternity for putative fathers and convincingly demonstrated asexual reproduction, thus representing the first evidence of facultative parthenogenesis in Elapidae. Our finding has broad implications for understanding the evolution of reproductive diversity in snakes, as well as managing the conservation of genetic diversity in wild and captive populations.

Structure of N-Terminal Sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-Peptide with Phospholipase A2 from Venom of Andaman Cobra Sub-Species Naja naja sagittifera at 2.0 Å Resolution

Directory of Open Access Journals (Sweden)

Zeenat Mirza

2014-03-01

Full Text Available Alzheimer’s disease (AD is one of the most significant social and health burdens of the present century. Plaques formed by extracellular deposits of amyloid β (Aβ are the prime player of AD’s neuropathology. Studies have implicated the varied role of phospholipase A2 (PLA2 in brain where it contributes to neuronal growth and inflammatory response. Overall contour and chemical nature of the substrate-binding channel in the low molecular weight PLA2s are similar. This study involves the reductionist fragment-based approach to understand the structure adopted by N-terminal fragment of Alzheimer’s Aβ peptide in its complex with PLA2. In the current communication, we report the structure determined by X-ray crystallography of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser (DAEFRHDS of Aβ-peptide with a Group I PLA2 purified from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution (Protein Data Bank (PDB Code: 3JQ5. This is probably the first attempt to structurally establish interaction between amyloid-β peptide fragment and hydrophobic substrate binding site of PLA2 involving H bond and van der Waals interactions. We speculate that higher affinity between Aβ and PLA2 has the therapeutic potential of decreasing the Aβ–Aβ interaction, thereby reducing the amyloid aggregation and plaque formation in AD.

Use of immunoturbidimetry to detect venom-antivenom binding using snake venoms.

Science.gov (United States)

O'Leary, M A; Maduwage, K; Isbister, G K

2013-01-01

Immunoturbidimetry studies the phenomenon of immunoprecipitation of antigens and antibodies in solution, where there is the formation of large, polymeric insoluble immunocomplexes that increase the turbidity of the solution. We used immunoturbidimetry to investigate the interaction between commercial snake antivenoms and snake venoms, as well as cross-reactivity between different snake venoms. Serial dilutions of commercial snake antivenoms (100μl) in water were placed in the wells of a microtitre plate and 100μl of a venom solution (50μg/ml in water) was added. Absorbance readings were taken at 340nm every minute on a BioTek ELx808 plate reader at 37°C. Limits imposed were a 30minute cut-off and 0.004 as the lowest significant maximum increase. Reactions with rabbit antibodies were carried out similarly, except that antibody dilutions were in PBS. Mixing venom and antivenom/antibodies resulted in an immediate increase in turbidity, which either reached a maximum or continued to increase until a 30minute cut-off. There was a peak in absorbance readings for most Australian snake venoms mixed with the corresponding commercial antivenom, except for Pseudonaja textilis venom and brown snake antivenom. There was cross-reactivity between Naja naja venom from Sri Lanka and tiger snake antivenom indicated by turbidity when they were mixed. Mixing rabbit anti-snake antibodies with snake venoms resulted in increasing turbidity, but there was not a peak suggesting the antibodies were not sufficiently concentrated. The absorbance reading at pre-determined concentrations of rabbit antibodies mixed with different venoms was able to quantify the cross-reactivity between venoms. Indian antivenoms from two manufacturers were tested against four Sri Lankan snake venoms (Daboia russelli, N. naja, Echis carinatus and Bungarus caeruleus) and showed limited formation of immunocomplexes with antivenom from one manufacturer. The turbidity test provides an easy and rapid way to compare

Echidna venom gland transcriptome provides insights into the evolution of monotreme venom.

Directory of Open Access Journals (Sweden)

Emily S W Wong

Full Text Available Monotremes (echidna and platypus are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna "venom" may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.

Data package addendum for COBRA-1A2 life extension to 400 EFPD

International Nuclear Information System (INIS)

Hecht, S.L.; Ermi, A.M.

1994-01-01

The COBRA-1A experiment was originally designed for irradiations up to 350 effective full power days (EFPD) in EBR-II. Three of the seven B7A test capsules were discharged after 88.6 EFPD (COBRA-1A1; EBR-II designation X516), while the remaining four capsules continued to be irradiated to a goal exposure of 300 EFPD (COBRA-1A2; EBR-II designation X516A). However, it was recently decided that COBRA-1A2 was to remain in the reactor during Run 170, giving and nominal end-of-life (EOL) exposure of 375 EFPD. Since the revised test exposure exceeds the design basis given in supporting analyses, amended analyses are provided herein, giving the technical bases for the extended irradiation. This report describes the safety analysis for the extension of the COBRA-1A2 test (X516A) to 400 effective full power days in FBR-II

Local morbidity from red-bellied black snake (Pseudechis porphyriacus, Elapidae) envenoming: Two cases and a brief review of management.

Science.gov (United States)

Weinstein, Scott A; Mirtschin, Peter J; Tristram, Hamish; Lawton, Luke; White, Julian

2018-02-01

The red-bellied black snake (Pseudechis porphyriacus, Elapidae) is one of several species of venomous snakes most commonly implicated in human and domestic animal envenoming in Australia. Human systemic envenoming can present with myotoxicity that may include myoglobinuria; hemoglobinuria and intravascular hemolysis; thrombocytopenia, anticoagulant coagulopathy, and, rarely, mild cranial nerve palsies. Pseudechis porphyriacus envenoming can also feature significant local morbidity such as ecchymoses, bleeding, pain and necrosis. Some envenomed patients may develop progressive thickness necrosis independent of secondary infection, and occasionally require surgical debridement. Uncommonly, some digital envenoming may cause more severe deeper tissue pathology that justifies dermotomy and/or distal phalangeal amputation. Presented are two patients with significant local morbidity from P. porphyriacus envenoming. An 18-month old girl received a protracted envenoming on her right foot, while a 38-year old male professional zoologist was envenomed on the third digit of his right hand. Each patient experienced myotoxicity, one had anticoagulant coagulopathy, and both developed clinically significant local morbidity including persistent bleeding, ecchymoses, local necrosis and pain; each required extensive treatment and variably prolonged admission. Noted also were transiently elevated D-dimer with low-normal or normal fibrinogen levels. The progressive necrosis and subsequent chronic pathologic changes with ischemia of the latter patient's digit eventually required a dermotomy and amputation of the distal phalanx. The pediatric patient did not require extensive wound debridement, but experienced prolonged difficulty in ambulation because of slowly resolving wound discomfort. Factors that may contribute to the severity of local morbidity of P. porphyriacus envenoming are considered, and management of envenoming by this taxon is briefly reviewed. Crown Copyright © 2017

Transcriptomics-guided bottom-up and top-down venomics of neonate and adult specimens of the arboreal rear-fanged Brown Treesnake, Boiga irregularis, from Guam.

Science.gov (United States)

Pla, Davinia; Petras, Daniel; Saviola, Anthony J; Modahl, Cassandra M; Sanz, Libia; Pérez, Alicia; Juárez, Elena; Frietze, Seth; Dorrestein, Pieter C; Mackessy, Stephen P; Calvete, Juan J

2018-03-01

The Brown Treesnake (Boiga irregularis) is an arboreal, nocturnal, rear-fanged venomous snake native to northern and eastern regions of Australia, Papua New Guinea and the Solomon Islands. It was inadvertently introduced onto the island of Guam during the late 1940's to early 1950's, and it has caused massive declines and extirpations of the native bird, lizard, and mammal populations. In the current study, we report the characterization of the venom proteome of an adult and a neonate B. irregularis specimens from Guam by a combination of venom gland transcriptomic and venomic analyses. Venom gland transcriptomic analysis of an adult individual identified toxins belonging to 18 protein families, with three-finger toxin isoforms being the most abundantly expressed transcripts, comprising 94% of all venom protein transcript reads. Transcripts for PIII-metalloproteinases, C-type lectins, cysteine-rich secretory proteins, acetylcholinesterases, natriuretic peptides, ficolins, phospholipase A 2 (PLA 2 ) inhibitors, PLA 2 s, vascular endothelial growth factors, Kunitz-type protease inhibitors, cystatins, phospholipase Bs, cobra venom factors, waprins, SVMP inhibitors, matrix metalloproteinases, and hyaluronidases were also identified, albeit, at very low abundances ranging from 0.05% to 1.7% of the transcriptome. The venom proteomes of neonate and adult B. irregularis were also both overwhelmingly (78 and 84%, respectively) dominated by monomeric and dimeric 3FTxs, followed by moderately abundant (21% (N) and 13% (A)) CRISPs, low abundance (1% (N), 3% (A)) PIII-SVMPs, and very low abundance (blot analysis showed that all venom proteins were recognized by anti-BTS IgGs, and cross-reactivity with other rear-fanged snake venoms was also observed. Incubation of anti-BTS venom IgGs with crude B. irregularis venom resulted in a significant decrease in proteolytic (SVMP) activity against azocasein. These results provide the first comparative venomic and anti-venomic analysis of

Why are Dutch rheumatologists reluctant to use the COBRA treatment strategy in early rheumatoid arthritis?

Science.gov (United States)

van Tuyl, Lilian H D; Plass, Anne Marie C; Lems, Willem F; Voskuyl, Alexandre E; Dijkmans, Ben A C; Boers, Maarten

2007-01-01

Background The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow‐up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. Objective To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. Methods A short structured questionnaire based on social–psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). Results The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high‐dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. Conclusion The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient‐related consequences of the therapy. PMID:17392349

VenomKB, a new knowledge base for facilitating the validation of putative venom therapies.

Science.gov (United States)

Romano, Joseph D; Tatonetti, Nicholas P

2015-11-24

Animal venoms have been used for therapeutic purposes since the dawn of recorded history. Only a small fraction, however, have been tested for pharmaceutical utility. Modern computational methods enable the systematic exploration of novel therapeutic uses for venom compounds. Unfortunately, there is currently no comprehensive resource describing the clinical effects of venoms to support this computational analysis. We present VenomKB, a new publicly accessible knowledge base and website that aims to act as a repository for emerging and putative venom therapies. Presently, it consists of three database tables: (1) Manually curated records of putative venom therapies supported by scientific literature, (2) automatically parsed MEDLINE articles describing compounds that may be venom derived, and their effects on the human body, and (3) automatically retrieved records from the new Semantic Medline resource that describe the effects of venom compounds on mammalian anatomy. Data from VenomKB may be selectively retrieved in a variety of popular data formats, are open-source, and will be continually updated as venom therapies become better understood.

Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction.

Science.gov (United States)

Sunagar, Kartik; Johnson, Warren E; O'Brien, Stephen J; Vasconcelos, Vítor; Antunes, Agostinho

2012-07-01

mechanism employed by the organism. CRISPs in Elapidae, which mostly employ neurotoxins, have experienced less positive selection pressure (ω = 2.86) compared with the "nonvenomous" colubrids (ω = 4.10) that rely on grip and constriction to capture the prey, and the Viperidae, a lineage that mostly employs haemotoxins (ω = 4.19). Relatively lower omega estimates in Anguimorph lizards (ω = 2.33) than snakes (ω = 3.84) suggests that lizards probably depend more on pace and powerful jaws for predation than venom.

Bothrops fonsecai snake venom activities and cross-reactivity with commercial bothropic venom.

Science.gov (United States)

Collaço, Rita de Cássia O; Randazzo-Moura, Priscila; Tamascia, Mariana L; da Silva, Igor Rapp F; Rocha, Thalita; Cogo, José C; Hyslop, Stephen; Sanny, Charles G; Rodrigues-Simioni, Léa

2017-01-01

In this work, we examined some biochemical and biological activities of Bothrops fonsecai venom, a pitviper endemic to southeastern Brazil, and assessed their neutralization by commercial bothropic antivenom (CAv). Cross-reactivity of venom with CAv was also assessed by immunoblotting and size-exclusion high performance chromatography (SE-HPLC). Bothrops fonsecai venom had PLA 2 , proteolytic and esterase activities that were neutralized to varying extents by venom:antivenom ratios of 5:1 and 5:2 (PLA 2 and esterase activities) or not significantly by either venom:antivenom ratio (proteolytic activity). The minimum hemorrhagic dose (69.2μg) was totally neutralized by both ratios. Clotting time in rat citrated plasma was 33±10.5s (mean±SD; n=5) and was completely neutralized by a 5:2 ratio. Edema formation was dose-dependent (1-30μg/site) and significantly inhibited by both ratios. Venom (10-300μg/mL) caused neuromuscular blockade in extensor digitorum longus preparations; this blockade was inhibited best by a 5:2 ratio. Venom caused myonecrosis and creatine kinase release in vivo (gastrocnemius muscle) and in vitro (extensor digitorum longus) that was effectively neutralized by both venom:antivenom ratios. Immunoblotting showed that venom components of ~25-100kDa interacted with CAv. SE-HPLC profiles for venom incubated with CAv or specific anti-B. fonsecai antivenom raised in rabbits (SAv) indicated that CAv had a higher binding capacity than SAv, whereas SAv had higher affinity than CAv. These findings indicate that B. fonsecai venom contains various activities that are neutralized to different extents by CAv and suggest that CAv could be used to treat envenoming by B. fonsecai. Copyright © 2016. Published by Elsevier Inc.

Kinins in ant venoms--a comparison with venoms of related Hymenoptera

NARCIS (Netherlands)

Piek, T.; Schmidt, J. O.; de Jong, J. M.; Mantel, P.

1989-01-01

1. Venom preparations have been made of six ant, one pompilid wasp, two mutillid wasp, and four social wasp species. 2. The venoms were analysed pharmacologically in order to detect kinin-like activity. 3. Due to the small amounts of venoms available only a cascade of smooth muscle preparation could

Hemostatic properties of Venezuelan Bothrops snake venoms with special reference to Bothrops isabelae venom.

Science.gov (United States)

Rodríguez-Acosta, Alexis; Sánchez, Elda E; Márquez, Adriana; Carvajal, Zoila; Salazar, Ana M; Girón, María E; Estrella, Amalid; Gil, Amparo; Guerrero, Belsy

2010-11-01

In Venezuela, Bothrops snakes are responsible for more than 80% of all recorded snakebites. This study focuses on the biological and hemostatic characteristics of Bothrops isabelae venom along with its comparative characteristics with two other closely related Bothrops venoms, Bothrops atrox and Bothrops colombiensis. Electrophoretic profiles of crude B. isabelae venom showed protein bands between 14 and 100 kDa with the majority in the range of 14-31 kDa. The molecular exclusion chromatographic profile of this venom contains five fractions (F1-F5). Amidolytic activity evaluation evidenced strong thrombin-like followed by kallikrein-like activities in crude venom and in fractions F1 and F2. The fibrinogenolytic activity of B. isabelae venom at a ratio of 100:1 (fibrinogen/venom) induced a degradation of A alpha and B beta chains at 15 min and 2 h, respectively. At a ratio of 100:10, a total degradation of A alpha and B beta chains at 5 min and of gamma chains at 24 h was apparent. This current study evidences one of rarely reported for Bothrops venoms, which resembles the physiologic effect of plasmin. B. isabelae venom as well as F2 and F3 fractions, contain fibrinolytic activity on fibrin plate of 36, 23.5 and 9.45 mm(2)/microg, respectively using 25 microg of protein. Crude venom and F1 fraction showed gelatinolytic activity. Comparative analysis amongst Venezuelan bothropoid venoms, evidenced that the LD(50) of B. isabelae (5.9 mg/kg) was similar to B. atrox-Puerto Ayacucho 1 (6.1 mg/kg) and B. colombiensis-Caucagua (5.8 mg/kg). B. isabelae venom showed minor hemorrhagic activity, whereas B. atrox-Parguasa (Bolivar state) was the most hemorrhagic. In this study, a relative high thrombin-like activity was observed in B. colombiensis venoms (502-568 mUA/min/mg), and a relative high factor Xa-like activity was found in B. atrox venoms (126-294 mUA/min/mg). Fibrinolytic activity evaluated with 10 microg protein, showed that B. isabelae venom contained higher

Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms.

Science.gov (United States)

Debono, Jordan; Cochran, Chip; Kuruppu, Sanjaya; Nouwens, Amanda; Rajapakse, Niwanthi W; Kawasaki, Minami; Wood, Kelly; Dobson, James; Baumann, Kate; Jouiaei, Mahdokht; Jackson, Timothy N W; Koludarov, Ivan; Low, Dolyce; Ali, Syed A; Smith, A Ian; Barnes, Andrew; Fry, Bryan G

2016-07-08

Central and South American pitvipers, belonging to the genera Bothrops and Bothriechis, have independently evolved arboreal tendencies. Little is known regarding the composition and activity of their venoms. In order to close this knowledge gap, venom proteomics and toxin activity of species of Bothriechis, and Bothrops (including Bothriopsis) were investigated through established analytical methods. A combination of proteomics and bioactivity techniques was used to demonstrate a similar diversification of venom composition between large and small species within Bothriechis and Bothriopsis. Increasing our understanding of the evolution of complex venom cocktails may facilitate future biodiscoveries.

Performance Evaluation of the COBRA GEM for the Application of the TPC

Science.gov (United States)

Terasaki, Kohei; Hamagaki, Hideki; Gunji, Taku; Yamaguchi, Yorito

2014-09-01

Suppression of the back-drifting ions from avalanche region to drift space (IBF: Ion Backflow) is the key for a Time Projection Chamber (TPC) since IBF easily distorts the drift field. To suppress IBF, Gating Grid system is widely used for the TPC but this limits the data taking rate. Gas Electron Multiplier (GEM) has advantages in the reduction of IBF and high rate capability. By adopting GEM, it is possible to run a TPC continuously under high rate and high multiplicity conditions. Motivated by the study of IBF reduction for RICH with Thick COBRA, which has been developed by F. A. Amero et al., we developed COBRA GEMs for the application of a TPC. With a stack configuration, IBF reaches about 0.1 ~ 0.5%, which is ×5--10 better IBF than the standard GEMs. However, the measured energy resolution with COBRA is 20% (σ) and this is much worse than the resolution with standard GEMs. Measurement of long-time stability of gain indicates that gain of COBRA varies significantly due to charging up effect. Simulation studies based on Garfield++ are performed for understanding quantitatively the reasons of worse energy resolution and instability of gain. In this presentation, we will report the simulation studies together with the measured performance of the COBRA GEM.

Immunology of Bee Venom.

Science.gov (United States)

Elieh Ali Komi, Daniel; Shafaghat, Farzaneh; Zwiener, Ricardo D

2017-01-20

Bee venom is a blend of biochemicals ranging from small peptides and enzymes to biogenic amines. It is capable of triggering severe immunologic reactions owing to its allergenic fraction. Venom components are presented to the T cells by antigen-presenting cells within the skin. These Th2 type T cells then release IL-4 and IL-13 which subsequently direct B cells to class switch to production of IgE. Generating venom-specific IgE and crosslinking FcεR1(s) on the surface of mast cells complete the sensitizing stage in allergic individuals who are most likely to experience severe and even fatal allergic reactions after being stung. Specific IgE for bee venom is a double-edged sword as it is a powerful mediator in triggering allergic events but is also applied successfully in diagnosis of the venom allergic patient. The healing capacity of bee venom has been rediscovered under laboratory-controlled conditions using animal models and cell cultures. The potential role of enzymatic fraction of bee venom including phospholipase A2 in the initiation and development of immune responses also has been studied in numerous research settings. Undoubtedly, having insights into immunologic interactions between bee venom components and innate/specific immune cells both locally and systematically will contribute to the development of immunologic strategies in specific and epitope-based immunotherapy especially in individuals with Hymenoptera venom allergy.

Cobra-Gruppens besøg i Bregnerød

DEFF Research Database (Denmark)

Baumeister, Ruth

2014-01-01

This article describes the Cobra-meeting in Bregnerød. It exemplifies the interior painting of the weekend retreat of the Royal academy´s architecture students and contextualizes the event within the European postwar discourse of a synthesis of the arts.......This article describes the Cobra-meeting in Bregnerød. It exemplifies the interior painting of the weekend retreat of the Royal academy´s architecture students and contextualizes the event within the European postwar discourse of a synthesis of the arts....

Coiled Brine Recovery Assembly (CoBRA) Project

Data.gov (United States)

National Aeronautics and Space Administration — The Coiled Brine Recovery Assembly (CoBRA) project will result in a proof-of-concept demonstration for a lightweight, compact, affordable, regenerable and disposable...

Venomics of New World pit vipers: genus-wide comparisons of venom proteomes across Agkistrodon.

Science.gov (United States)

Lomonte, Bruno; Tsai, Wan-Chih; Ureña-Diaz, Juan Manuel; Sanz, Libia; Mora-Obando, Diana; Sánchez, Elda E; Fry, Bryan G; Gutiérrez, José María; Gibbs, H Lisle; Sovic, Michael G; Calvete, Juan J

2014-01-16

We report a genus-wide comparison of venom proteome variation across New World pit vipers in the genus Agkistrodon. Despite the wide variety of habitats occupied by this genus and that all its taxa feed on diverse species of vertebrates and invertebrate prey, the venom proteomes of copperheads, cottonmouths, and cantils are remarkably similar, both in the type and relative abundance of their different toxin families. The venoms from all the eleven species and subspecies sampled showed relatively similar proteolytic and PLA2 activities. In contrast, quantitative differences were observed in hemorrhagic and myotoxic activities in mice. The highest myotoxic activity was observed with the venoms of A. b. bilineatus, followed by A. p. piscivorus, whereas the venoms of A. c. contortrix and A. p. leucostoma induced the lowest myotoxic activity. The venoms of Agkistrodon bilineatus subspecies showed the highest hemorrhagic activity and A. c. contortrix the lowest. Compositional and toxicological analyses agree with clinical observations of envenomations by Agkistrodon in the USA and Central America. A comparative analysis of Agkistrodon shows that venom divergence tracks phylogeny of this genus to a greater extent than in Sistrurus rattlesnakes, suggesting that the distinct natural histories of Agkistrodon and Sistrurus clades may have played a key role in molding the patterns of evolution of their venom protein genes. A deep understanding of the structural and functional profiles of venoms and of the principles governing the evolution of venomous systems is a goal of venomics. Isolated proteomics analyses have been conducted on venoms from many species of vipers and pit vipers. However, making sense of these large inventories of data requires the integration of this information across multiple species to identify evolutionary and ecological trends. Our genus-wide venomics study provides a comprehensive overview of the toxic arsenal across Agkistrodon and a ground for

Venomics of New World pit vipers: Genus-wide comparisons of venom proteomes across Agkistrodon

Science.gov (United States)

Lomonte, Bruno; Tsai, Wan-Chih; Ureña-Diaz, Juan Manuel; Sanz, Libia; Mora-Obando, Diana; Sánchez, Elda E.; Fry, Bryan G.; Gutiérrez, José María; Gibbs, H. Lisle; Sovic, Michael G.; Calvete, Juan J.

2015-01-01

We report a genus-wide comparison of venom proteome variation across New World pit vipers in the genus Agkistrodon. Despite the wide variety of habitats occupied by this genus and that all its taxa feed on diverse species of vertebrates and invertebrate prey, the venom proteomes of copperheads, cottonmouths, and cantils are remarkably similar, both in the type and relative abundance of their different toxin families. The venoms from all the eleven species and subspecies sampled showed relatively similar proteolytic and PLA2 activities. In contrast, quantitative differences were observed in hemorrhagic and myotoxic activities in mice. The highest myotoxic activity was observed with the venoms of A. b. bilineatus, followed by A. p. piscivorus, whereas the venoms of A. c. contortrix and A. p. leucostoma induced the lowest myotoxic activity. The venoms of Agkistrodon bilineatus subspecies showed the highest hemorrhagic activity and A. c. contortrix the lowest. Compositional and toxicological analyses agree with clinical observations of envenomations by Agkistrodon in the USA and Central America. A comparative analysis of Agkistrodon shows that venom divergence tracks phylogeny of this genus to a greater extent than in Sistrurus rattlesnakes, suggesting that the distinct natural histories of Agkistrodon and Sistrurus clades may have played a key role in molding the patterns of evolution of their venom protein genes. Biological significance A deep understanding of the structural and functional profiles of venoms and of the principles governing the evolution of venomous systems is a goal of venomics. Isolated proteomics analyses have been conducted on venoms from many species of vipers and pit vipers. However, making sense of these large inventories of data requires the integration of this information across multiple species to identify evolutionary and ecological trends. Our genus-wide venomics study provides a comprehensive overview of the toxic arsenal across

Black Bear Reactions to Venomous and Non-venomous Snakes in Eastern North America

Science.gov (United States)

Rogers, Lynn L; Mansfield, Susan A; Hornby, Kathleen; Hornby, Stewart; Debruyn, Terry D; Mize, Malvin; Clark, Rulon; Burghardt, Gordon M

2014-01-01

Bears are often considered ecological equivalents of large primates, but the latter often respond with fear, avoidance, and alarm calls to snakes, both venomous and non-venomous, there is sparse information on how bears respond to snakes. We videotaped or directly observed natural encounters between black bears (Ursus americanus) and snakes. Inside the range of venomous snakes in Arkansas and West Virginia, adolescent and adult black bears reacted fearfully in seven of seven encounters upon becoming aware of venomous and non-venomous snakes; but in northern Michigan and Minnesota where venomous snakes have been absent for millennia, black bears showed little or no fear in four encounters with non-venomous snakes of three species. The possible roles of experience and evolution in bear reactions to snakes and vice versa are discussed. In all areas studied, black bears had difficulty to recognize non-moving snakes by smell or sight. Bears did not react until snakes moved in 11 of 12 encounters with non-moving timber rattlesnakes (Crotalus horridus) and four species of harmless snakes. However, in additional tests in this study, bears were repulsed by garter snakes that had excreted pungent anal exudates, which may help explain the absence of snakes, both venomous and harmless, in bear diets reported to date. PMID:25635152

Venom evolution widespread in fishes: a phylogenetic road map for the bioprospecting of piscine venoms.

Science.gov (United States)

Smith, William Leo; Wheeler, Ward C

2006-01-01

Knowledge of evolutionary relationships or phylogeny allows for effective predictions about the unstudied characteristics of species. These include the presence and biological activity of an organism's venoms. To date, most venom bioprospecting has focused on snakes, resulting in six stroke and cancer treatment drugs that are nearing U.S. Food and Drug Administration review. Fishes, however, with thousands of venoms, represent an untapped resource of natural products. The first step involved in the efficient bioprospecting of these compounds is a phylogeny of venomous fishes. Here, we show the results of such an analysis and provide the first explicit suborder-level phylogeny for spiny-rayed fishes. The results, based on approximately 1.1 million aligned base pairs, suggest that, in contrast to previous estimates of 200 venomous fishes, >1,200 fishes in 12 clades should be presumed venomous. This assertion was corroborated by a detailed anatomical study examining potentially venomous structures in >100 species. The results of these studies not only alter our view of the diversity of venomous fishes, now representing >50% of venomous vertebrates, but also provide the predictive phylogeny or "road map" for the efficient search for potential pharmacological agents or physiological tools from the unexplored fish venoms.

High-resolution proteomic profiling of spider venom: expanding the toxin diversity of Phoneutria nigriventer venom.

Science.gov (United States)

Liberato, Tarcísio; Troncone, Lanfranco Ranieri Paolo; Yamashiro, Edson T; Serrano, Solange M T; Zelanis, André

2016-03-01

Here we present a proteomic characterization of Phoneutria nigriventer venom. A shotgun proteomic approach allowed the identification, for the first time, of O-glycosyl hydrolases (chitinases) in P. nigriventer venom. The electrophoretic profiles under nonreducing and reducing conditions, and protein identification by mass spectrometry, indicated the presence of oligomeric toxin structures in the venom. Complementary proteomic approaches allowed for a qualitative and semi-quantitative profiling of P. nigriventer venom complexity, expanding its known venom proteome diversity.

Polymerized soluble venom--human serum albumin

International Nuclear Information System (INIS)

Patterson, R.; Suszko, I.M.; Grammer, L.C.

1985-01-01

Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. 125 I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom

Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis.

NARCIS (Netherlands)

Tuyl, L.H.D. van; Plass, A.M.C.; Lems, W.F.; Voskuyl, A.E.; Kerstens, P.J.S.M.; Dijkmans, B.A.C.; Boers, M.

2008-01-01

Objective. The COBRA therapy (combination therapy in early rheumatoid arthritis) has proven to be an effective treatment for early RA, but is rarely prescribed. A survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early RA. The present qualitative study was carried out to

Polymerized soluble venom--human serum albumin

Energy Technology Data Exchange (ETDEWEB)

Patterson, R.; Suszko, I.M.; Grammer, L.C.

1985-03-01

Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

Use of gamma irradiated viper venom as the toxoid against viper venom poisoning in mice and rabbits

International Nuclear Information System (INIS)

Hati, A.K.; Mandal, M.; Hati, R.N.; Das, S.

1995-01-01

The present paper deals with detoxification of the crude viper (Vipera russelli) venom by gamma irradiation and its effective immunogenic role in Balb/C mice, used as a toxoid. The successful immunization of rabbits with irradiated viper venom toxoid is also reported. Certain biochemical changes of the venom due to radiation exposure and neutralization capacity of the immune sera against phosphodiesterase and protease activity of the crude viper venom have also been studied. The neutralizing potency of Russell's viper venom (RVV) toxoid anti venom (anti venom raised in rabbits against γ-irradiated RVV toxoid adsorbed on aluminium phosphate), in comparison with a commercial bivalent anti venom (as a standard reference) with reference to haemorrhagic, necrotic and lethal effects of Russell's viper envenomation are reported. 25 refs

Experimental Study on the comparison of antibacterial and antioxidant effects between the Bee Venom and Sweet Bee Venom

Directory of Open Access Journals (Sweden)

Joong chul An

2006-12-01

Full Text Available Objectives : This study was conducted to compare antibacterial activities and free radical scavenging activity between the Bee Venom and Sweet Bee Venom in which the allergy-causing enzyme is removed. Methods : To evaluate antibacterial activities of the test samples, gram negative E. coli and gram positive St. aureus were compared using the paper disc method. For comparison of the antioxidant effects, DPPH (1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and Thiobarbituric Acid Reactive Substances (TBARS assay were conducted. Results : 1. Antibacterial activity against gram negative E. coli was greater in the Sweet Bee Venom group than the Bee Venom group. 2. Antibacterial activity against gram positive St. aureus was similar between the Bee Venom and Sweet Bee Venom groups. 3. DPPH free radical scavenging activity of the Bee Venom group showed 2.8 times stronger than that of the Sweet Bee Venom group. 4. Inhibition of lipid peroxidation of the Bee Venom group showed 782 times greater than that of the Sweet Bee Venom group. Conclusions : The Bee Venom group showed outstanding antibacterial activity against gram positive St. aureus, and allergen-removed Sweet Bee Venom group showed outstanding antibacterial activity against both gram negative E. coli and gram positive St. aureus. For antioxidant effects, the Bee Venom was superior over the Sweet Bee Venom and the superiority was far more apparent for lipid peroxidation.

Combined Venom Gland Transcriptomic and Venom Peptidomic Analysis of the Predatory Ant Odontomachus monticola

Directory of Open Access Journals (Sweden)

Kohei Kazuma

2017-10-01

Full Text Available Ants (hymenoptera: Formicidae have adapted to many different environments and have become some of the most prolific and successful insects. To date, 13,258 ant species have been reported. They have been classified into 333 genera and 17 subfamilies. Except for a few Formicinae, Dolichoderinae, and members of other subfamilies, most ant species have a sting with venom. The venoms are composed of formic acid, alkaloids, hydrocarbons, amines, peptides, and proteins. Unlike the venoms of other animals such as snakes and spiders, ant venoms have seldom been analyzed comprehensively, and their compositions are not yet completely known. In this study, we used both transcriptomic and peptidomic analyses to study the composition of the venom produced by the predatory ant species Odontomachus monticola. The transcriptome analysis yielded 49,639 contigs, of which 92 encoded toxin-like peptides and proteins with 18,106,338 mapped reads. We identified six pilosulin-like peptides by transcriptomic analysis in the venom gland. Further, we found intact pilosulin-like peptide 1 and truncated pilosulin-like peptides 2 and 3 by peptidomic analysis in the venom. Our findings related to ant venom peptides and proteins may lead the way towards development and application of novel pharmaceutical and biopesticidal resources.

Venom Evolution

Indian Academy of Sciences (India)

IAS Admin

Therefore, the platypus sequence was studied to quantify the role of gene duplication in the evolution of venom. ... Platypus venom is present only in males and is used for asserting dominance over com- petitors during the ... Certain toxin gene families are known to re- peatedly evolve through gene duplications. The rapidly ...

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa.

Science.gov (United States)

Aird, Steven D; da Silva, Nelson Jorge; Qiu, Lijun; Villar-Briones, Alejandro; Saddi, Vera Aparecida; Pires de Campos Telles, Mariana; Grau, Miguel L; Mikheyev, Alexander S

2017-06-08

Venom gland transcriptomes and proteomes of six Micrurus taxa ( M. corallinus , M. lemniscatus carvalhoi , M. lemniscatus lemniscatus , M. paraensis , M. spixii spixii , and M. surinamensis ) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2-6 toxin classes that account for 91-99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A₂ (PLA₂s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA₂s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1-2.0%) are found in all venoms except that of M. s. spixii . Other toxin families are present in all six venoms at trace levels (venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6-9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three

Immunoreactivity between venoms and commercial antiserums in four Chinese snakes and venom identification by species-specific antibody.

Science.gov (United States)

Gao, Jian-Fang; Wang, Jin; Qu, Yan-Fu; Ma, Xiao-Mei; Ji, Xiang

2013-01-31

We studied the immunoreactivity between venoms and commercial antiserums in four Chinese venomous snakes, Bungarus multicinctus, Naja atra, Deinagkistrodon acutus and Gloydius brevicaudus. Venoms from the four snakes shared common antigenic components, and most venom components expressed antigenicity in the immunological reaction between venoms and antiserums. Antiserums cross-reacted with heterologous venoms. Homologous venom and antiserum expressed the highest reaction activity in all cross-reactions. Species-specific antibodies (SSAbs) were obtained from four antiserums by immunoaffinity chromatography: the whole antiserum against each species was gradually passed through a medium system coated with heterologous venoms, and the cross-reacting components in antiserum were immunoabsorbed by the common antigens in heterologous venoms; the unbound components (i.e., SSAbs) were collected, and passed through Hitrap G protein column and concentrated. The SSAbs were found to have high specificity by western blot and enzyme-linked immunosorbent assay (ELISA). A 6-well ELISA strip coated with SSAbs was used to assign a venom sample and blood and urine samples from the envenomed rats to a given snake species. Our detections could differentiate positive and negative samples, and identify venoms of a snake species in about 35 min. The ELISA strips developed in this study are clinically useful in rapid and reliable identification of venoms from the above four snake species. Copyright © 2012 Elsevier B.V. All rights reserved.

Synchronization and an application of a novel fractional order King Cobra chaotic system

Energy Technology Data Exchange (ETDEWEB)

Muthukumar, P., E-mail: muthukumardgl@gmail.com; Balasubramaniam, P., E-mail: balugru@gmail.com [Department of Mathematics, Gandhigram Rural Institute‐Deemed University, Gandhigram 624 302, Tamilnadu (India); Ratnavelu, K., E-mail: kuru052001@gmail.com [Faculty of Science, Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

2014-09-01

In this paper, we design a new three dimensional King Cobra face shaped fractional order chaotic system. The multi-scale synchronization scheme of two fractional order chaotic systems is described. The necessary conditions for the multi-scale synchronization of two identical fractional order King Cobra chaotic systems are derived through feedback control. A new cryptosystem is proposed for an image encryption and decryption by using synchronized fractional order King Cobra chaotic systems with the supports of multiple cryptographic assumptions. The security of the proposed cryptosystem is analyzed by the well known algebraic attacks. Numerical simulations are given to show the effectiveness of the proposed theoretical results.

A review of neogene and quaternary snakes of Central and Eastern Europe. Part 11: natricinae, elapidae, viperidae

Directory of Open Access Journals (Sweden)

Szyndlar, Z.

1991-08-01

Full Text Available Remains of Neogene and Quaternary "natricine" colubrids, elapids and viperids, including snakes previously described and those undescribed yet, coming from Poland, Ukraine, Moldavia, Czechoslovakia, Austria, Hungary, Romania, Bulgaria, and Greece are discussed. The following taxa, including 11 extinct species, were recognized: "Natricinae": Neonatrix nova, Neonatrix sp., Palaeonatrix silesiaca, Palaeonatrix lehmani, Natrix longivertebrata, Natrix cf. N. longivertebrata, Natrix natrix, Natrix tesselata, Natrix cf. N. tesselata, Natrix sp., "Natricinae" indet.; Elapidae: Naja romani, Naja sp., cf. Naja sp.; Viperidae: Vipera platyspondyla, Vipera sarmatica, Vipera burgenlandica, Vipera gedulyi, Vipera kuchurganica, Vipera antiqua, Vipera cf. V. ammodytes, Vipera berus, Vipera sp ('Oriental vipers' group, Vipera sp. ('aspis' group, Vipera sp. ('berus' group, Vipera sp. . (status unknown. Taxonomic status of two other extinct species, Natrix parva and Laophis crotaloides, is uncertain. Modern species appeared fírst in Central and East Europe in the middle Pliocene (MN 15. Older snakes belonged to extinct species of either extinct or extant genera; taxonomic distinction of most extinct genera is, however, not fully demonstrated. Best recognized oldest snakes from the area (Elapidae, Viperidae, and sorne Colubridae are clearly referable to modern genera and intrageneric subdivisions occurring today are observed in oldest (Iower Miocene remains; closest living relatives of these fossils are presently distributed in the Oriental Realm.Se revisan y estudian los restos neógenos y cuaternarios de colúbridos «natricinos», elápidos y vipéridos, incluyendo tanto serpientes previamente descritas como- otras inéditas. Los materiales analizados proceden de Polonia, Ukrania, Moldavia, Checoslovaquia, Austria, Hungría, Rumania, Bulgaria y Grecia. Se reconocen los siguientes taxones, incluyendo 11 especies extinguidas: Natricinae: Neonatrix nova

Pharmacokinetics of Snake Venom

Directory of Open Access Journals (Sweden)

Suchaya Sanhajariya

2018-02-01

Full Text Available Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present and Medline (1946–present. For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans.

MagLev Cobra: Test Facilities and Operational Experiments

Science.gov (United States)

Sotelo, G. G.; Dias, D. H. J. N.; de Oliveira, R. A. H.; Ferreira, A. C.; De Andrade, R., Jr.; Stephan, R. M.

2014-05-01

The superconducting MagLev technology for transportation systems is becoming mature due to the research and developing effort of recent years. The Brazilian project, named MagLev-Cobra, started in 1998. It has the goal of developing a superconducting levitation vehicle for urban areas. The adopted levitation technology is based on the diamagnetic and the flux pinning properties of YBa2Cu3O7-δ (YBCO) bulk blocks in the interaction with Nd-Fe-B permanent magnets. A laboratory test facility with permanent magnet guideway, linear induction motor and one vehicle module is been built to investigate its operation. The MagLev-Cobra project state of the art is presented in the present paper, describing some construction details of the new test line with 200 m.

Vintage venoms: proteomic and pharmacological stability of snake venoms stored for up to eight decades.

Science.gov (United States)

Jesupret, Clémence; Baumann, Kate; Jackson, Timothy N W; Ali, Syed Abid; Yang, Daryl C; Greisman, Laura; Kern, Larissa; Steuten, Jessica; Jouiaei, Mahdokht; Casewell, Nicholas R; Undheim, Eivind A B; Koludarov, Ivan; Debono, Jordan; Low, Dolyce H W; Rossi, Sarah; Panagides, Nadya; Winter, Kelly; Ignjatovic, Vera; Summerhayes, Robyn; Jones, Alun; Nouwens, Amanda; Dunstan, Nathan; Hodgson, Wayne C; Winkel, Kenneth D; Monagle, Paul; Fry, Bryan Grieg

2014-06-13

For over a century, venom samples from wild snakes have been collected and stored around the world. However, the quality of storage conditions for "vintage" venoms has rarely been assessed. The goal of this study was to determine whether such historical venom samples are still biochemically and pharmacologically viable for research purposes, or if new sample efforts are needed. In total, 52 samples spanning 5 genera and 13 species with regional variants of some species (e.g., 14 different populations of Notechis scutatus) were analysed by a combined proteomic and pharmacological approach to determine protein structural stability and bioactivity. When venoms were not exposed to air during storage, the proteomic results were virtually indistinguishable from that of fresh venom and bioactivity was equivalent or only slightly reduced. By contrast, a sample of Acanthophis antarcticus venom that was exposed to air (due to a loss of integrity of the rubber stopper) suffered significant degradation as evidenced by the proteomics profile. Interestingly, the neurotoxicity of this sample was nearly the same as fresh venom, indicating that degradation may have occurred in the free N- or C-terminus chains of the proteins, rather than at the tips of loops where the functional residues are located. These results suggest that these and other vintage venom collections may be of continuing value in toxin research. This is particularly important as many snake species worldwide are declining due to habitat destruction or modification. For some venoms (such as N. scutatus from Babel Island, Flinders Island, King Island and St. Francis Island) these were the first analyses ever conducted and these vintage samples may represent the only venom ever collected from these unique island forms of tiger snakes. Such vintage venoms may therefore represent the last remaining stocks of some local populations and thus are precious resources. These venoms also have significant historical value as

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

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Steven D. Aird

2017-06-01

Full Text Available Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs and phospholipases A2 (PLA2s comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0% are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%. Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen

Computational Studies of Snake Venom Toxins

OpenAIRE

Paola G. Ojeda; David Ramírez; Jans Alzate-Morales; Julio Caballero; Quentin Kaas; Wendy González

2017-01-01

Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics t...

Production of effective antivenin to treat cobra snake (Naja naja oxiana envenoming

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Akbari, A.

2010-01-01

Full Text Available Conventional treatment of Naja naja oxiana (NNO envenoming requires large volumes of equine antivenin raised against NNO crude venom. The poor efficiency of this antivenin is assumed to be due to the high molecular weight non-toxic proteins, a strong immunogen, present in the crude venom. These proteins cause depression of antibody formation against the low molecular weight toxic components of venom. In the present study the low molecular weight lethal components were isolated from crude venom of NNO venom by sephadex G50 get filtration chromatography. A sera was prepared by immunizing horses with toxic fraction. One milliliter of this serum neutralized 1.8mg of NNO crude venom. This high titer antivenin is thus 2.2 times more potent than the sera obtained against NNO crude venom.

Functional and proteomic comparison of Bothrops jararaca venom from captive specimens and the Brazilian Bothropic Reference Venom.

Science.gov (United States)

Farias, Iasmim Baptista de; Morais-Zani, Karen de; Serino-Silva, Caroline; Sant'Anna, Sávio S; Rocha, Marisa M T da; Grego, Kathleen F; Andrade-Silva, Débora; Serrano, Solange M T; Tanaka-Azevedo, Anita M

2018-03-01

Snake venom is a variable phenotypic trait, whose plasticity and evolution are critical for effective antivenom production. A significant reduction of the number of snake donations to Butantan Institute (São Paulo, Brazil) occurred in recent years, and this fact may impair the production of the Brazilian Bothropic Reference Venom (BBRV). Nevertheless, in the last decades a high number of Bothrops jararaca specimens have been raised in captivity in the Laboratory of Herpetology of Butantan Institute. Considering these facts, we compared the biochemical and biological profiles of B. jararaca venom from captive specimens and BBRV in order to understand the potential effects of snake captivity upon the venom composition. Electrophoretic analysis and proteomic profiling revealed few differences in venom protein bands and some differentially abundant toxins. Comparison of enzymatic activities showed minor differences between the two venoms. Similar cross-reactivity recognition pattern of both venoms by the antibothropic antivenom produced by Butantan Institute was observed. Lethality and neutralization of lethality for B. jararaca venom from captive specimens and BBRV showed similar values. Considering these results we suggest that the inclusion of B. jararaca venom from captive specimens in the composition of BBRV would not interfere with the quality of this reference venom. Snakebite envenomation is a neglected tropical pathology whose treatment is based on the use of specific antivenoms. Bothrops jararaca is responsible for the majority of snakebites in South and Southeastern Brazil. Its venom shows individual, sexual, and ontogenetic variability, however, the effect of animal captivity upon venom composition is unknown. Considering the reduced number of wild-caught snakes donated to Butantan Institute in the last decades, and the increased life expectancy of the snakes raised in captivity in the Laboratory of Herpetology, this work focused on the comparative

Anaphylaxis to Insect Venom Allergens

DEFF Research Database (Denmark)

Ollert, Markus; Blank, Simon

2015-01-01

available for diagnostic measurement of specific IgE in venom-allergic patients. These recombinant venom allergens offer several promising possibilities for an improved diagnostic algorithm. Reviewed here are the current status, recent developments, and future perspectives of molecular diagnostics of venom...

Ecological venomics: How genomics, transcriptomics and proteomics can shed new light on the ecology and evolution of venom.

Science.gov (United States)

Sunagar, Kartik; Morgenstern, David; Reitzel, Adam M; Moran, Yehu

2016-03-01

Animal venom is a complex cocktail of bioactive chemicals that traditionally drew interest mostly from biochemists and pharmacologists. However, in recent years the evolutionary and ecological importance of venom is realized as this trait has direct and strong influence on interactions between species. Moreover, venom content can be modulated by environmental factors. Like many other fields of biology, venom research has been revolutionized in recent years by the introduction of systems biology approaches, i.e., genomics, transcriptomics and proteomics. The employment of these methods in venom research is known as 'venomics'. In this review we describe the history and recent advancements of venomics and discuss how they are employed in studying venom in general and in particular in the context of evolutionary ecology. We also discuss the pitfalls and challenges of venomics and what the future may hold for this emerging scientific field. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of reflood heat transfer model of COBRA-TIF against ABB-CE evaluation model

Energy Technology Data Exchange (ETDEWEB)

Lee, S. I.; Lee, S. Y.; Park, C. E.; Choi, H. R.; Choi, C. J. [Korea Power Engineering Company Inc., Taejon (Korea, Republic of)

2000-05-01

According to 10 CFR 50 Appendix K, ECCS performance evaluation model should be based on the experimental data of FLECHT and have the conservatism compared with experimental data. To meet this requirement ABB-CE has the complicate code structure as follows: COMPERC-II calculates three reflood rates, and FLELAPC and HTCOF calculate the reflood heat transfer coefficients, and finally STRIKIN-II calculates the cladding temperature using the reflood heat transfer calculated in previous stage. In this paper, to investigate whether or not COBRA-TF satisfies the requirement of Appendix K, the reflood heat transfer coefficient of COBRA-TF was assessed against ABB-CE MOD-2C model. It was found out that COBRA-TF predicts properly the experimental data and has more conservatism than the results of ABB-CE MOD-2C model. Based on these results, it can be concluded that the reflood heat transfer coefficients calculated by COBRA-TF meet the requirement of Appendix K.

The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

Directory of Open Access Journals (Sweden)

Min-Ki Kim

2007-12-01

Full Text Available Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Venom and Sweet Bee Venom according to the dosage dependent variation are investigated the histologic changes after injection of these Pharmacopuncture. Result : Following results were obtained from the preadipocyte proliferation and lipolysis of adipocyte and histologic investigation of fat tissue. 1. Bee Venom and Sweet Bee Venom showed the effect of decreased preadipocyte proliferation depend on concentration. 2. Bee Venom and Sweet Bee Venom showed the effect of decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH significantly. 3. Bee Venom was not showed the effect of lipolysis, but Sweet Bee Venom was increased in low dosage and decreased in high dosage. 4. Investigated the histologic changes in porcine fat tissue after treated Bee Venom and Sweet Bee Venom, we knew that these Pharmacopuncture was activated nonspecific lysis of cell membranes depend on concentration. Conclusion : These results suggest that Bee Venom and Sweet Bee Venom efficiently induces decreased proliferation of preadipocyte and lipolysis in adipose tissue

Quantitative Proteomic Analysis of Venoms from Russian Vipers of Pelias Group: Phospholipases A₂ are the Main Venom Components.

Science.gov (United States)

Kovalchuk, Sergey I; Ziganshin, Rustam H; Starkov, Vladislav G; Tsetlin, Victor I; Utkin, Yuri N

2016-04-12

Venoms of most Russian viper species are poorly characterized. Here, by quantitative chromato-mass-spectrometry, we analyzed protein and peptide compositions of venoms from four Vipera species (V. kaznakovi, V. renardi, V. orlovi and V. nikolskii) inhabiting different regions of Russia. In all these species, the main components were phospholipases A₂, their content ranging from 24% in V. orlovi to 65% in V. nikolskii. Altogether, enzyme content in venom of V. nikolskii reached ~85%. Among the non-enzymatic proteins, the most abundant were disintegrins (14%) in the V. renardi venom, C-type lectin like (12.5%) in V. kaznakovi, cysteine-rich venom proteins (12%) in V. orlovi and venom endothelial growth factors (8%) in V. nikolskii. In total, 210 proteins and 512 endogenous peptides were identified in the four viper venoms. They represented 14 snake venom protein families, most of which were found in the venoms of Vipera snakes previously. However, phospholipase B and nucleotide degrading enzymes were reported here for the first time. Compositions of V. kaznakovi and V. orlovi venoms were described for the first time and showed the greatest similarity among the four venoms studied, which probably reflected close relationship between these species within the "kaznakovi" complex.

MagLev Cobra: Test Facilities and Operational Experiments

International Nuclear Information System (INIS)

Sotelo, G G; Dias, D H J N; De Oliveira, R A H; Ferreira, A C; De Andrade, R Jr; Stephan, R M

2014-01-01

The superconducting MagLev technology for transportation systems is becoming mature due to the research and developing effort of recent years. The Brazilian project, named MagLev-Cobra, started in 1998. It has the goal of developing a superconducting levitation vehicle for urban areas. The adopted levitation technology is based on the diamagnetic and the flux pinning properties of YBa 2 Cu 3 O 7−δ (YBCO) bulk blocks in the interaction with Nd-Fe-B permanent magnets. A laboratory test facility with permanent magnet guideway, linear induction motor and one vehicle module is been built to investigate its operation. The MagLev-Cobra project state of the art is presented in the present paper, describing some construction details of the new test line with 200 m.

BEE VENOM TRAP DESIGN FOR PRODUCE BEE VENOM OF APIS MELLIFERA L. HONEY BEES

OpenAIRE

Budiaman

2015-01-01

Bee venom is one honey bee products are very expensive and are required in the pharmaceutical industry and as an anti-cancer known as nanobee, but the production technique is still done in the traditional way. The purpose of this study was to design a bee venom trap to produce bee venom of Apis mellifera L honey bees. The method used is to design several models of bee venom apparatus equipped weak current (DC current) with 3 variations of voltage, ie 12 volts, 15 volts and 18 volts coupled...

Colubrid Venom Composition: An -Omics Perspective.

Science.gov (United States)

Junqueira-de-Azevedo, Inácio L M; Campos, Pollyanna F; Ching, Ana T C; Mackessy, Stephen P

2016-07-23

Snake venoms have been subjected to increasingly sensitive analyses for well over 100 years, but most research has been restricted to front-fanged snakes, which actually represent a relatively small proportion of extant species of advanced snakes. Because rear-fanged snakes are a diverse and distinct radiation of the advanced snakes, understanding venom composition among "colubrids" is critical to understanding the evolution of venom among snakes. Here we review the state of knowledge concerning rear-fanged snake venom composition, emphasizing those toxins for which protein or transcript sequences are available. We have also added new transcriptome-based data on venoms of three species of rear-fanged snakes. Based on this compilation, it is apparent that several components, including cysteine-rich secretory proteins (CRiSPs), C-type lectins (CTLs), CTLs-like proteins and snake venom metalloproteinases (SVMPs), are broadly distributed among "colubrid" venoms, while others, notably three-finger toxins (3FTxs), appear nearly restricted to the Colubridae (sensu stricto). Some putative new toxins, such as snake venom matrix metalloproteinases, are in fact present in several colubrid venoms, while others are only transcribed, at lower levels. This work provides insights into the evolution of these toxin classes, but because only a small number of species have been explored, generalizations are still rather limited. It is likely that new venom protein families await discovery, particularly among those species with highly specialized diets.

Expression of venom gene homologs in diverse python tissues suggests a new model for the evolution of snake venom.

Science.gov (United States)

Reyes-Velasco, Jacobo; Card, Daren C; Andrew, Audra L; Shaney, Kyle J; Adams, Richard H; Schield, Drew R; Casewell, Nicholas R; Mackessy, Stephen P; Castoe, Todd A

2015-01-01

Snake venom gene evolution has been studied intensively over the past several decades, yet most previous studies have lacked the context of complete snake genomes and the full context of gene expression across diverse snake tissues. We took a novel approach to studying snake venom evolution by leveraging the complete genome of the Burmese python, including information from tissue-specific patterns of gene expression. We identified the orthologs of snake venom genes in the python genome, and conducted detailed analysis of gene expression of these venom homologs to identify patterns that differ between snake venom gene families and all other genes. We found that venom gene homologs in the python are expressed in many different tissues outside of oral glands, which illustrates the pitfalls of using transcriptomic data alone to define "venom toxins." We hypothesize that the python may represent an ancestral state prior to major venom development, which is supported by our finding that the expansion of venom gene families is largely restricted to highly venomous caenophidian snakes. Therefore, the python provides insight into biases in which genes were recruited for snake venom systems. Python venom homologs are generally expressed at lower levels, have higher variance among tissues, and are expressed in fewer organs compared with all other python genes. We propose a model for the evolution of snake venoms in which venom genes are recruited preferentially from genes with particular expression profile characteristics, which facilitate a nearly neutral transition toward specialized venom system expression. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Benchmarking of LOFT LRTS-COBRA-FRAP safety analysis model

International Nuclear Information System (INIS)

Hanson, G.H.; Atkinson, S.A.; Wadkins, R.P.

1982-05-01

The purpose of this work was to check out the LOFT LRTS/COBRA-IV/FRAP-T5 safety-analysis models against test data obtained during a LOFT operational transient in which there was a power and fuel-temperature rise. LOFT Experiment L6-3 was an excessive-load-increase anticipated transient test in which the main steam-flow-control valve was driven from its operational position to full-open in seven seconds. The resulting cooldown and reactivity-increase transients provide a good benchmark for the reactivity-and-power-prediction capability of the LRTS calculations, and for the fuel-bundle and fuel-rod temperature-response analysis capability of the LOFT COBRA-IV and FRAP-T5 models

Cobra: A content-based video retrieval system

NARCIS (Netherlands)

Petkovic, M.; Jonker, W.; Jensen, C.S.; Jeffery, K.G.; Pokorny, J.; Saltenis, S.; Bertino, E.; Böhm, K.; Jarke, M.

2002-01-01

An increasing number of large publicly available video libraries results in a demand for techniques that can manipulate the video data based on content. In this paper, we present a content-based video retrieval system called Cobra. The system supports automatic extraction and retrieval of high-level

Three-Fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of Snake Venom Toxins

Science.gov (United States)

Sunagar, Kartik; Jackson, Timothy N. W.; Undheim, Eivind A. B.; Ali, Syed. A.; Antunes, Agostinho; Fry, Bryan G.

2013-01-01

Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they are theorised to undergo adaptive evolution, the underlying diversification mechanisms remain elusive. Here, we report the molecular evolution of different 3FTx functional forms and show that positively selected point mutations have driven the rapid evolution and diversification of 3FTx. These diversification events not only correlate with the evolution of advanced venom delivery systems (VDS) in Caenophidia, but in particular the explosive diversification of the clade subsequent to the evolution of a high pressure, hollow-fanged VDS in elapids, highlighting the significant role of these toxins in the evolution of advanced snakes. We show that Type I, II and III α-neurotoxins have evolved with extreme rapidity under the influence of positive selection. We also show that novel Oxyuranus/Pseudonaja Type II forms lacking the apotypic loop-2 stabilising cysteine doublet characteristic of Type II forms are not phylogenetically basal in relation to other Type IIs as previously thought, but are the result of secondary loss of these apotypic cysteines on at least three separate occasions. Not all 3FTxs have evolved rapidly: κ-neurotoxins, which form non-covalently associated heterodimers, have experienced a relatively weaker influence of diversifying selection; while cytotoxic 3FTx, with their functional sites, dispersed over 40% of the molecular surface, have been extremely constrained by negative selection. We show that the a previous theory of 3FTx molecular evolution (termed ASSET) is evolutionarily implausible and cannot account for the considerable variation observed in very short segments of 3FTx. Instead, we propose a theory of

Toxin synergism in snake venoms

DEFF Research Database (Denmark)

Laustsen, Andreas Hougaard

2016-01-01

Synergism between venom toxins exists for a range of snake species. Synergism can be derived from both intermolecular interactions and supramolecular interactions between venom components, and can be the result of toxins targeting the same protein, biochemical pathway or physiological process. Few...... simple systematic tools and methods for determining the presence of synergism exist, but include co-administration of venom components and assessment of Accumulated Toxicity Scores. A better understanding of how to investigate synergism in snake venoms may help unravel strategies for developing novel...

Allergen-specific immunotherapy of Hymenoptera venom allergy

DEFF Research Database (Denmark)

Schiener, Maximilian; Graessel, Anke; Ollert, Markus

2017-01-01

Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms...... by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy......, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses...

Pharmacokinetics of Snake Venom

OpenAIRE

Suchaya Sanhajariya; Stephen B. Duffull; Geoffrey K. Isbister

2018-01-01

Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present) and Medline (1946–present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, ...

Conversion of the COBRA-IV-I code from CDC CYBER to HP 9000/700 version

International Nuclear Information System (INIS)

Sohn, D. S.; Yoo, Y. J.; Nahm, K. Y.; Hwang, D. H.

1996-01-01

COBRA-IV-I is a multichannel analysis code for the thermal-hydraulic analysis of rod bundle nuclear fuel elements and cores based on the subchannel approach. The existing COBRA-IV-I code is the control data corporation (CDC) CYBER version, which has limitations on the computer core storage and gives some inconvenience to the user interface. To solve these problems, we have converted the COBRA-IV-I code form the CDC CYBER mainframe to an Hewlett Packard (HP) 9000/700-series workstation version, and have verified the converted code. as a result, we have found almost no difference between the two versions in their calculation results. Therefore we expect the HP 9000/700 version of the COBRA-IV-I code to be the basis for the future development of an improved multichannel analysis code under the more convenient user environment. (author). 3 tabs., 2 figs., 8 refs

Snake venomics across genus Lachesis. Ontogenetic changes in the venom composition of Lachesis stenophrys and comparative proteomics of the venoms of adult Lachesis melanocephala and Lachesis acrochorda.

Science.gov (United States)

Madrigal, Marvin; Sanz, Libia; Flores-Díaz, Marietta; Sasa, Mahmood; Núñez, Vitelbina; Alape-Girón, Alberto; Calvete, Juan J

2012-12-21

We report the proteomic analysis of ontogenetic changes in venom composition of the Central American bushmaster, Lachesis stenophrys, and the characterization of the venom proteomes of two congeneric pitvipers, Lachesis melanocephala (black-headed bushmaster) and Lachesis acrochorda (Chochoan bushmaster). Along with the previous characterization of the venom proteome of Lachesis muta muta (from Bolivia), our present outcome enables a comparative overview of the composition and distribution of the toxic proteins across genus Lachesis. Comparative venomics revealed the close kinship of Central American L. stenophrys and L. melanocephala and support the elevation of L. acrochorda to species status. Major ontogenetic changes in the toxin composition of L. stenophrys venom involves quantitative changes in the concentration of vasoactive peptides and serine proteinases, which steadily decrease from birth to adulthood, and age-dependent de novo biosynthesis of Gal-lectin and snake venom metalloproteinases (SVMPs). The net result is a shift from a bradykinin-potentiating and C-type natriuretic peptide (BPP/C-NP)-rich and serine proteinase-rich venom in newborns and 2-years-old juveniles to a (PI>PIII) SVMP-rich venom in adults. Notwithstanding minor qualitative and quantitative differences, the venom arsenals of L. melanocephala and L. acrochorda are broadly similar between themselves and also closely mirror those of adult L. stenophrys and L. muta venoms. The high conservation of the overall composition of Central and South American bushmaster venoms provides the ground for rationalizing the "Lachesis syndrome", characterized by vagal syntomatology, sensorial disorders, hematologic, and cardiovascular manifestations, documented in envenomings by different species of this wide-ranging genus. This finding let us predict that monospecific Lachesic antivenoms may exhibit paraspecificity against all congeneric species. Copyright © 2012 Elsevier B.V. All rights reserved.

COBRA: a Bayesian approach to pulsar searching

Science.gov (United States)

Lentati, L.; Champion, D. J.; Kramer, M.; Barr, E.; Torne, P.

2018-02-01

We introduce COBRA, a GPU-accelerated Bayesian analysis package for performing pulsar searching, that uses candidates from traditional search techniques to set the prior used for the periodicity of the source, and performs a blind search in all remaining parameters. COBRA incorporates models for both isolated and accelerated systems, as well as both Keplerian and relativistic binaries, and exploits pulse phase information to combine search epochs coherently, over time, frequency or across multiple telescopes. We demonstrate the efficacy of our approach in a series of simulations that challenge typical search techniques, including highly aliased signals, and relativistic binary systems. In the most extreme case, we simulate an 8 h observation containing 24 orbits of a pulsar in a binary with a 30 M⊙ companion. Even in this scenario we show that we can build up from an initial low-significance candidate, to fully recovering the signal. We also apply the method to survey data of three pulsars from the globular cluster 47Tuc: PSRs J0024-7204D, J0023-7203J and J0024-7204R. This final pulsar is in a 1.6 h binary, the shortest of any pulsar in 47Tuc, and additionally shows significant scintillation. By allowing the amplitude of the source to vary as a function of time, however, we show that we are able to obtain optimal combinations of such noisy data. We also demonstrate the ability of COBRA to perform high-precision pulsar timing directly on the single pulse survey data, and obtain a 95 per cent upper limit on the eccentricity of PSR J0024-7204R of εb < 0.0007.

Bioactive Components in Fish Venoms

Science.gov (United States)

Ziegman, Rebekah; Alewood, Paul

2015-01-01

Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

Application of the subchannel analysis code COBRA III C for liquid sodium

International Nuclear Information System (INIS)

Nissen, K.L.

1981-01-01

The subchannel-analysis code COBRA III C was developed to gain knowledge of mass flow and temperature distribution in rod bundles of light water reactors. A comparison of experimental results for the temperature distribution in a 19 rod bundle with calculations done by the computer program shows the capability of COBRA III C to handle liquid sodium cooling. The code needs sodium properties as well as changed correlations for turbulent mixing and heat transfer at the rod. (orig.) [de

Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Japanese patients with bipolar disorder.

Science.gov (United States)

Toyoshima, Kuniyoshi; Fujii, Yutaka; Mitsui, Nobuyuki; Kako, Yuki; Asakura, Satoshi; Martinez-Aran, Anabel; Vieta, Eduard; Kusumi, Ichiro

2017-08-01

In Japan, there are currently no reliable rating scales for the evaluation of subjective cognitive impairment in patients with bipolar disorder. We studied the relationship between the Japanese version of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and objective cognitive assessments in patients with bipolar disorder. We further assessed the reliability and validity of the COBRA. Forty-one patients, aged 16-64, in a remission period of bipolar disorder were recruited from Hokkaido University Hospital in Sapporo, Japan. The COBRA (Japanese version) and Frankfurt Complaint Questionnaire (FCQ), the gold standard in subjective cognitive assessment, were administered. A battery of neuropsychological tests was employed to measure objective cognitive impairment. Correlations among the COBRA, FCQ, and neuropsychological tests were determined using Spearman's correlation coefficient. The Japanese version of the COBRA had high internal consistency, good retest reliability, and concurrent validity-as indicated by a strong correlation with the FCQ. A significant correlation was also observed between the COBRA and objective cognitive measurements of processing speed. These findings are the first to demonstrate that the Japanese version of the COBRA may be clinically useful as a subjective cognitive impairment rating scale in Japanese patients with bipolar disorder. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Black Bear Reactions to Venomous and Non-venomous Snakes in Eastern North America

OpenAIRE

Rogers, Lynn L; Mansfield, Susan A; Hornby, Kathleen; Hornby, Stewart; Debruyn, Terry D; Mize, Malvin; Clark, Rulon; Burghardt, Gordon M

2014-01-01

Bears are often considered ecological equivalents of large primates, but the latter often respond with fear, avoidance, and alarm calls to snakes, both venomous and non-venomous, there is sparse information on how bears respond to snakes. We videotaped or directly observed natural encounters between black bears (Ursus americanus) and snakes. Inside the range of venomous snakes in Arkansas and West Virginia, adolescent and adult black bears reacted fearfully in seven of seven encounters upon b...

Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom

Science.gov (United States)

2013-01-01

Background Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. Objective We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. Methods Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. Results Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). Conclusions Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the

Fossilized venom: the unusually conserved venom profiles of Heloderma species (beaded lizards and gila monsters).

Science.gov (United States)

Koludarov, Ivan; Jackson, Timothy N W; Sunagar, Kartik; Nouwens, Amanda; Hendrikx, Iwan; Fry, Bryan G

2014-12-22

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation.

Fossilized Venom: The Unusually Conserved Venom Profiles of Heloderma Species (Beaded Lizards and Gila Monsters)

Science.gov (United States)

Koludarov, Ivan; Jackson, Timothy N. W.; Sunagar, Kartik; Nouwens, Amanda; Hendrikx, Iwan; Fry, Bryan G.

2014-01-01

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation. PMID:25533521

Enzymatic analysis of Hemiscorpius lepturus scorpion venom using zymography and venom-specific antivenin.

Science.gov (United States)

Seyedian, Ramin; Pipelzadeh, Mohammad Hassan; Jalali, Amir; Kim, Euikyung; Lee, Hyunkyoung; Kang, Changkeun; Cha, Mijin; Sohn, Eun-Tae; Jung, Eun-Sun; Rahmani, Ali Hassan; Mirakabady, Abbas Zare

2010-09-15

Hemiscorpius lepturus envenomation exhibits various pathological changes in the affected tissues, including skin, blood cells, cardiovascular and central nervous systems. The enzymatic activity and protein component of the venom have not been described previously. In the present study, the electrophoretic profile of H. lepturus venom was determined by SDS-PAGE (12 and 15%), resulting in major protein bands at 3.5-5, 30-35 and 50-60 kDa. The enzymatic activities of the venom was, for the first time, investigated using various zymography techniques, which showed the gelatinolytic, caseinolytic, and hyaluronidase activities mainly at around 50-60 kDa, 30-40 kDa, and 40-50 kDa, respectively. Among these, the proteolytic activities was almost completely disappeared in the presence of a matrix metalloproteinase inhibitor, 1, 10-phenanthroline. Antigen-antibody interactions between the venom and its Iranian antivenin was observed by Western blotting, and it showed several antigenic proteins in the range of 30-160 kDa. This strong antigen-antibody reaction was also demonstrated through an enzyme-linked immunosorbent assay (ELISA). The gelatinase activity of the venom was suppressed by Razi institute polyvalent antivenin, suggesting the inhibitory effect of the antivenin against H. lepturus venom protease activities. Prudently, more extensive clinical studies are necessary for validation of its use in envenomed patients. Copyright 2010 Elsevier Ltd. All rights reserved.

COBRA-Bee Carpal-Wrist Gimbal for Astrobee, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — TUI proposes to develop a carpal-wrist gimbal payload for the Astrobee free-flier, called 'COBRA-Bee' to satisfy Astrobee mission needs for a lightweight, integrated...

In-vitro diagnostics of Hymenoptera venom allergy

NARCIS (Netherlands)

Rueff, F.; Vos, B.; Przybilla, B.

In-vitro diagnostics of Hymenoptera venom allergy Patients with a history of anaphylactic sting reactions require an allergological work-up (history, in-vitro tests, and skin tests) to clarify indications on venom immunotherapy and on the type of venom to be used. To demonstrate a venom

COBRA-3M: a digital computer code for analyzing thermal-hydraulic behavior in pin bundles

International Nuclear Information System (INIS)

Marr, W.W.

1975-03-01

The COBRA-3M computer program is a modification of the thermal-hydraulic subchannel-analysis program COBRA-III. It includes detailed thermal models of fuel pin and duct wall. It is especially suitable for analyzing small pin bundles used in in-reactor or out-of-reactor experiments. (U.S.)

Computational Studies of Snake Venom Toxins.

Science.gov (United States)

Ojeda, Paola G; Ramírez, David; Alzate-Morales, Jans; Caballero, Julio; Kaas, Quentin; González, Wendy

2017-12-22

Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

Cardiovascular-Active Venom Toxins: An Overview.

Science.gov (United States)

Rebello Horta, Carolina Campolina; Chatzaki, Maria; Rezende, Bruno Almeida; Magalhães, Bárbara de Freitas; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Ribeiro Oliveira-Mendes, Bárbara Bruna; do Carmo, Anderson Oliveira; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

2016-01-01

Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses.

Computational Studies of Snake Venom Toxins

Directory of Open Access Journals (Sweden)

Paola G. Ojeda

2017-12-01

Full Text Available Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

The popsicle-stick cobra wave

OpenAIRE

Boucher , Jean-Philippe; Clanet , Christophe; Quéré , David; Chevy , Frédéric

2017-01-01

The cobra wave is a popular physical phenomenon arising from the explosion of a metastable grillage made of popsicle sticks. The sticks are expelled from the mesh by releasing the elastic energy stored during the weaving of the structure. Here we analyse both experimentally and theoretically the propagation of the wave-front depending on the properties of the sticks and the pattern of the mesh. We show that its velocity and its shape are directly related to the recoil imparted to the structur...

Mastocytosis and insect venom allergy.

Science.gov (United States)

Bonadonna, Patrizia; Zanotti, Roberta; Müller, Ulrich

2010-08-01

To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases. In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful. In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 microg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation.

Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution.

Science.gov (United States)

Skejic, Jure; Steer, David L; Dunstan, Nathan; Hodgson, Wayne C

2015-11-06

This study demonstrates a direct role of venom protein expression alteration in the evolution of snake venom toxicity. Avian skeletal muscle contractile response to exogenously administered acetylcholine is completely inhibited upon exposure to South Australian and largely preserved following exposure to Queensland eastern brown snake Pseudonaja textilis venom, indicating potent postsynaptic neurotoxicity of the former and lack thereof of the latter venom. Label-free quantitative proteomics reveals extremely large differences in the expression of postsynaptic three-finger α-neurotoxins in these venoms, explaining the difference in the muscle contractile response and suggesting that the type of toxicity induced by venom can be modified by altered expression of venom proteins. Furthermore, the onset of neuromuscular paralysis in the rat phrenic nerve-diaphragm preparation occurs sooner upon exposure to the venom (10 μg/mL) with high expression of α-neurotoxins than the venoms containing predominately presynaptic β-neurotoxins. The study also finds that the onset of rat plasma coagulation is faster following exposure to the venoms with higher expression of venom prothrombin activator subunits. This is the first quantitative proteomic study that uses extracted ion chromatogram peak areas (MS1 XIC) of distinct homologous tryptic peptides to directly show the differences in the expression of venom proteins.

COBRA-SFS predictions of single assembly spent fuel heat transfer data

International Nuclear Information System (INIS)

Lombardo, N.J.; Michener, T.E.; Wheeler, C.L.; Rector, D.R.

1986-04-01

The study reported here is one of several efforts to evaluate and qualify the COBRA-SFS computer code for use in spent fuel storage system thermal analysis. The ability of COBRA-SFS to predict the thermal response of two single assembly spent fuel heat transfer tests was investigated through comparisons of predictions with experimental test data. From these comparisons, conclusions regarding the computational treatment of the physical phenomena occurring within a storage system can be made. This objective was successfully accomplished as reasonable agreement between predictions and data were obtained for the 21 individual test cases of the two experiments

Assessment of immunogenic characteristics of Hemiscorpius lepturus venom and its cross-reactivity with venoms from Androctonus crassicauda and Mesobuthus eupeus.

Science.gov (United States)

Khanbashi, Shahin; Khodadadi, Ali; Assarehzadegan, Mohammad-Ali; Pipelzadeh, Mohammad Hassan; Vazirianzadeh, Babak; Hosseinzadeh, Mohsen; Rahmani, Ali Hassan; Asmar, Akbar

2015-01-01

Hemiscorpius lepturus (H. lepturus), one of the most venomous scorpions in tropical and sub-tropical areas, belongs to the Hemiscorpiidae family. Studies of antibodies in sera against the protein component of the venom from this organism can be of great use for the development of engineered variants of proteins for eventual use in the diagnosis/treatment of, and prevention of reactions to, stings. In the present in vitro study, the proteins of H. lepturus venom, which could specifically activate the production of immunoglobulin G (IgG) in victims accidently exposed to the venom from this scorpion, were evaluated and their cross-reactivity with venoms from two other important scorpion species including Androctonus crassicauda and Mesobuthus eupeus assessed. H. lepturus venom was analyzed with respect to its protein composition and its antigenic properties against antibodies found in sera collected from victims exposed to the venom of this scorpion within a previous 2-month period. The cross-reactivity of the H. lepturus venom with those from A. crassicauda and M. eupeus was assessed using ELISA and immunoblotting. Electrophoretic analysis of the venom of H. lepturus revealed several protein bands with weights of 8-116 KDa. The most frequent IgG-reactive bands in the test sera had weights of 34, 50, and 116 kDa. A weak cross-reactivity H. lepturus of venom with venoms from A. crassicauda and M. eupeus was detected. The results of immunoblotting and ELISA experiments revealed that H. lepturus venom activated the host immune response, leading to the production of a high titer of antibodies. Clearly, a determination of the major immunogenic components of H. lepturus venom could be valuable for future studies and ultimately of great importance for the potential production of recombinant or hypo-venom variants of these proteins.

THE USE OF THE ANTI-VENOM SPECIFIC ANTIBODIES ISOLATED FROM DUCK EGGS FOR INACTIVATION OF THE VIPER VENOM

Directory of Open Access Journals (Sweden)

ADRIANA CRISTE

2008-05-01

Full Text Available The activity of specific anti-venom can be demonstrated using protection test in laboratory mice. Our study aimed to emphasize the possibility of viper venom inactivation by the antibodies produced and isolated from duck eggs and also to the activation concentration of these antibodies. The venom used for inoculation was harvested from two viper species (Vipera ammodytes and Vipera berus. The immunoglobulin extract had a better activity on the venom from Vipera berus compared to the venom from Vipera ammodytes. This could be the result of a better immunological response, as consequence of the immunization with this type of venom, compared to the response recorded when the Vipera ammodytes venom was used. Besides the advantages of low cost, high productivity and reduced risk of anaphylactic shock, the duck eggs also have high activity up to dilutions of 1/16, 1/32, respectively, with specific activity and 100 surviving in individuals which received 3 x DL50.

[Bites of venomous snakes in Switzerland].

Science.gov (United States)

Plate, Andreas; Kupferschmidt, Hugo; Schneemann, Markus

2016-06-08

Although snake bites are rare in Europe, there are a constant number of snake bites in Switzerland. There are two domestic venomous snakes in Switzerland: the aspic viper (Vipera aspis) and the common European adder (Vipera berus). Bites from venomous snakes are caused either by one of the two domestic venomous snakes or by an exotic venomous snake kept in a terrarium. Snake- bites can cause both a local and/or a systemic envenoming. Potentially fatal systemic complications are related to disturbances of the hemostatic- and cardiovascular system as well as the central or peripheral nervous system. Beside a symptomatic therapy the administration of antivenom is the only causal therapy to neutralize the venomous toxins.

Analysis of Fang Puncture Wound Patterns in Isfahan Province’s, Iran, Venomous and Non-Venomous Snakes

Directory of Open Access Journals (Sweden)

Dehghani R.1 PhD,

2015-01-01

Full Text Available Aims Venomous snake bites are public health problems in different parts of the world. The most specific mainstay in the treatment of envenomation is anti-venom. To treat the envenomation, it is very important to identify the offending species. This study was designed to determine the penetrating pattern of fangs and teeth of some viper snakes. Materials & Methods This descriptive study was performed on live venomous and nonvenomous snakes from 2010 till 2011. All 47 sample snakes were collected from different regions of Isfahan province such as Kashan City, Ghamsar, Niasar, Mashhad Ardehal, Taher- Abad and Khozagh. Their mouths were inspected every two weeks and development of their fangs and teeth were recorded by taking clear digital photos. Fangs and teeth patterns of samples were drawn and the results were compared. Findings One or two wounds appeared as typical fang marks at the bite site of venomous snakes while non-venomous snakes had two carved rows of small teeth. Three different teeth and fang patterns were recognized in venomous snakes which were completely different. Conclusion The fang marks of venomous snakes do not always have a common and classic pattern and there are at least 3 different patterns in Isfahan province, Iran.

Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom

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Khin Than Yee

2016-12-01

Full Text Available Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs: RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation.

The Biochemical Toxin Arsenal from Ant Venoms

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Axel Touchard

2016-01-01

Full Text Available Ants (Formicidae represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents.

The Biochemical Toxin Arsenal from Ant Venoms

Science.gov (United States)

Touchard, Axel; Aili, Samira R.; Fox, Eduardo Gonçalves Paterson; Escoubas, Pierre; Orivel, Jérôme; Nicholson, Graham M.; Dejean, Alain

2016-01-01

Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents. PMID:26805882

Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy.

Science.gov (United States)

Gawlik, Radoslaw; Glück, Joanna; Jawor, Barbara; Rogala, Barbara

2015-01-01

Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn't correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.

Radiating sterilization of the venom of snake

International Nuclear Information System (INIS)

Abiyev, H.A.; Topchiyeva, Sh.A.; Rustamov, V.R.

2006-01-01

Full text: Water solutions of venoms are unstable and they lose toxicity in some day. Snake venoms inactivate under action of some physical factors: the UV-irradiation, x-rays beams. The purpose of the present work was sterilization of venom Vipera lebetina obtusa under influence of small dozes γ-radiations. Object of research was integral venom of adult individuals. Transcaucasian viper, and also the water solutions of venom irradiated with small dozes scale of radiation. An irradiation of venom carried out to radioisotope installation 60NI. For experiment tests of dry venom, and also their water solutions have been taken. Water solutions of venom have been subjected -radiation up to dozes 1.35, 2.7, 4.05, 5.4 kGr simultaneously dry venom of vipers was exposed -radiation before absorption of a doze 5.4 kGr. In comparative aspect action scale of radiation on ultra-violet spectra of absorption of venom was studied. Ultra-violet spectra venom have been taken off on device Specord UV-VIS. In 12 months after an irradiation spectra of absorption of venom have been repeatedly taken off. In spectra irradiated dry and solutions of venom new maxima of absorption have been revealed in the field of 285 nm and 800 nm describing change of toxicity. It is shown, that the increase in absorption of a doze of radiation occurs decrease of intensity of strips of absorption reduction of intensity of absorption.It is revealed at 260 and 300 nm testifying to course of biochemical reactions of separate enzymes zootoxins. It is necessary to note, that at comparison of intensity of absorption of control samples of poison with irradiated up to dozes 1.35 kGr it has not been revealed essential changes. The subsequent increase in a doze scale of radiation up to 2.7, 4.05, 5.4 kGr promotes proportional reduction of intensity of the absorption, describing toxicity of snake venom. At repeated (later 12 months) measurement of the irradiated water solutions of venom are not revealed changes in

Snake venomics of Crotalus tigris: the minimalist toxin arsenal of the deadliest Nearctic rattlesnake venom. Evolutionary Clues for generating a pan-specific antivenom against crotalid type II venoms [corrected].

Science.gov (United States)

Calvete, Juan J; Pérez, Alicia; Lomonte, Bruno; Sánchez, Elda E; Sanz, Libia

2012-02-03

We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7-8 gene products from 6 toxin families; the presynaptic β-neurotoxic heterodimeric PLA(2), Mojave toxin, and two serine proteinases comprise, respectively, 66 and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1-2 PIII-SVMPs each represent 0.1-5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend toward neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by pedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, Crotalus horridus , Crotalus oreganus helleri, Crotalus scutulatus scutulatus, and Sistrurus catenatus catenatus indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South and North American Crotalus species.

Low cost venom extractor based on Arduino(®) board for electrical venom extraction from arthropods and other small animals.

Science.gov (United States)

Besson, Thomas; Debayle, Delphine; Diochot, Sylvie; Salinas, Miguel; Lingueglia, Eric

2016-08-01

Extracting venom from small species is usually challenging. We describe here an affordable and versatile electrical venom extractor based on the Arduino(®) Mega 2560 Board, which is designed to extract venom from arthropods and other small animals. The device includes fine tuning of stimulation time and voltage. It was used to collect venom without apparent deleterious effects, and characterized for the first time the venom of Zoropsis spinimana, a common spider in French Mediterranean regions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Treating autoimmune disorders with venom-derived peptides.

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Shen, Bingzheng; Cao, Zhijian; Li, Wenxin; Sabatier, Jean-Marc; Wu, Yingliang

2017-09-01

The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

Isolation and characterization of bioactive compounds of Clematis gouriana Roxb. ex DC against snake venom phospholipase A2 (PLA2) computational and in vitro insights.

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Muthusamy, Karthikeyan; Chinnasamy, Sathishkumar; Nagarajan, Subbiah; Sivaraman, Thirunavukkarasu; Chinnasamy, Selvakumar

2017-07-01

Bioactive compounds were isolated from Clematis gouriana Roxb. ex DC. The compounds were separated, characterized, the structures elucidated and submitted to the PubChem Database. The PubChem Ids SID 249494134 and SID 249494135 were tested against phospholipases A 2 (PLA 2 ) of Naja naja (Indian cobra) venom for PLA 2 activity. Both the compounds showed promising inhibitory activity; computational data also substantiated the results. The two compounds underwent density functional theory calculation to observe the chemical stability and electrostatic potential profile. Molecular interactions between the compounds and PLA 2 were observed at the binding pocket of the PLA 2 protein. Further, this protein-ligand complexes were simulated for a timescale of 100 ns of molecular dynamics simulation. Experimental and computational results showed significant PLA 2 inhibition activity.

Transcriptome analysis of the venom gland of the scorpion Scorpiops jendeki: implication for the evolution of the scorpion venom arsenal

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Wu Yingliang

2009-07-01

Full Text Available Abstract Background The family Euscorpiidae, which covers Europe, Asia, Africa, and America, is one of the most widely distributed scorpion groups. However, no studies have been conducted on the venom of a Euscorpiidae species yet. In this work, we performed a transcriptomic approach for characterizing the venom components from a Euscorpiidae scorpion, Scorpiops jendeki. Results There are ten known types of venom peptides and proteins obtained from Scorpiops jendeki. Great diversity is observed in primary sequences of most highly expressed types. The most highly expressed types are cytolytic peptides and serine proteases. Neurotoxins specific for sodium channels, which are major groups of venom components from Buthidae scorpions, are not detected in this study. In addition to those known types of venom peptides and proteins, we also obtain nine atypical types of venom molecules which haven't been observed in any other scorpion species studied to date. Conclusion This work provides the first set of cDNAs from Scorpiops jendeki, and one of the few transcriptomic analyses from a scorpion. This allows the characterization of a large number of venom molecules, belonging to either known or atypical types of scorpion venom peptides and proteins. Besides, our work could provide some clues to the evolution of the scorpion venom arsenal by comparison with venom data from other scorpion lineages.

The first venomous crustacean revealed by transcriptomics and functional morphology: remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin.

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von Reumont, Björn M; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A

2014-01-01

Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.

Animal venoms as antimicrobial agents.

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Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

2017-06-15

Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

Parallelized preconditioned BiCGStab solution of sparse linear system equations in F-COBRA-TF

International Nuclear Information System (INIS)

Geemert, Rene van; Glück, Markus; Riedmann, Michael; Gabriel, Harry

2011-01-01

Recently, the in-house development of a preconditioned and parallelized BiCGStab solver has been pursued successfully in AREVA’s advanced sub-channel code F-COBRA-TF. This solver can be run either in a sequential computation mode on a single CPU, or in a parallel computation mode on multiple parallel CPUs. The developed procedure enables the computation of several thousands of successive sparse linear system solutions in F-COBRA-TF with acceptable wall clock run times. The current paper provides general information about F-COBRA-TF in terms of modeling capabilities and application areas, and points out where the relevance arises for the efficient iterative solution of sparse linear systems. Furthermore, the preconditioning and parallelization strategies in the developed BiCGStab iterative solution approach are discussed. The paper is concluded with a number of verification examples. (author)

Pharmacological screening technologies for venom peptide discovery.

Science.gov (United States)

Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

2017-12-01

Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunochemical studies of yellowjacket venom proteins.

Science.gov (United States)

King, T P; Alagon, A C; Kuan, J; Sobotka, A K; Lichtenstein, L M

1983-03-01

The major proteins of yellowjacket venoms have been isolated and characterized immuno-chemically. They consist of hyaluronidase, phospholipase, and antigen 5. Venoms from three species of yellowjacket were studied. Vespula germanica, V. maculifrons, and V. vulgaris. The phospholipases could be isolated in good yield only when affinity chromatography was used to minimize limited proteolysis. A kallikrein-like peptidase was found present in the yellowjacket venom. Phospholipases from these three species were immunochemically indistinguishable from each other, as were their antigen 5s. Sera from individuals sensitive to yellowjacket venom contained IgE and IgG specific for antigen 5 and phospholipase.

Inactivation of complement by Loxosceles reclusa spider venom.

Science.gov (United States)

Gebel, H M; Finke, J H; Elgert, K D; Cambell, B J; Barrett, J T

1979-07-01

Zymosan depletion of serum complement in guinea pigs rendered them highly resistant to lesion by Loxosceles reclusa spider venom. Guinea pigs deficient in C4 of the complement system are as sensitive to the venom as normal guinea pigs. The injection of 35 micrograms of whole recluse venom intradermally into guinea pigs lowered their complement level by 35.7%. Brown recluse spider venom in concentrations as slight as 0.02 micrograms protein/ml can totally inactivate one CH50 of guinea pig complement in vitro. Bee, scorpion, and other spider venoms had no influence on the hemolytic titer of complement. Fractionation of recluse spider venom by Sephadex G-200 filtration separated the complement-inactivating property of the venom into three major regions which could be distinguished on the basis of heat stability as well as size. None was neutralized by antivenom. Polyacrylamide gel electrophoresis of venom resolved the complement inactivators into five fractions. Complement inactivated by whole venom or the Sephadex fractions could be restored to hemolytic activity by supplements of fresh serum but not by heat-inactivated serum, pure C3, pure C5, or C3 and C5 in combination.

Comparison of Vespula germanica venoms obtained from different sources.

Science.gov (United States)

Sanchez, F; Blanca, M; Miranda, A; Carmona, M J; Garcia, J; Fernandez, J; Torres, M J; Rondon, M C; Juarez, C

1994-08-01

This study was carried out to compare the allergenic potency of Vespula germanica (VG) venoms extracted by different methods and commercially available venoms from Vespula species currently used for in vivo and in vitro studies including immunotherapy. Pure VG venom was used as the reference material. Protein content and enzymatic and allergenic properties of all venoms studied were determined by dye stain reagent, hyaluronidase and phospholipase A1B enzyme activities, and radioallergosorbent test inhibition studies, respectively. Radioallergosorbent test discs sensitized with commercial and pure VG venom were compared using specific IgE antibodies from subjects allergic to VG venom. The data obtained indicate that there were important differences in the allergenic potency between the Vespula species venoms employed for in vivo and/or in vitro assays, VG venom obtained by sac dissection, and pure VG venom. These results indicate that venoms from Vespula species used for in vitro and in vivo tests have a lower concentration of allergens and contain nonvenom proteins. These data should be taken into account when these vespid venoms are used for diagnostic purposes and also when evaluating immunotherapy studies.

Bioinformatics-Aided Venomics

Directory of Open Access Journals (Sweden)

Quentin Kaas

2015-06-01

Full Text Available Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future.

Cobra-TF simulation of BWR bundle dry out experiments

Energy Technology Data Exchange (ETDEWEB)

Frepoli, C.; Ireland, A.; Hochreiter, L.; Ivanov, K. [Penn State Univ., Dept. of Mechanical and Nuclear Engineering, University Park, PA (United States); Velten, R. [Siemens Nuclear Power GmbH, Erlangen (Germany)

2001-07-01

The COBRA-TF computer code uses a two-fluid, three-field and three-dimensional formulation to model a two-phase flow field in a specific geometry. The liquid phase is divided in a continuous liquid field and a separate dispersed field, which is used to describe the entrained liquid drops. For each space dimension, the code solves three momentum equations, three mass conservation equations and two energy conservation equations. Entrainment and depositions models are implemented into the code to model the mass transfer between the two liquid fields. This study presents the results obtained with COBRA-TF for the simulation of the Siemens 9-9Q BWR Bundle Dryout experiments. The model includes 20 channels and 34 axial nodes in the heated section. The predicted critical power and dryout location is compared with the measured values. An assessment of the code entrainment and de-entrainment models is presented. (authors)

Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) against Russell's viper venom: characterization of piperine as active principle.

Science.gov (United States)

Shenoy, P A; Nipate, S S; Sonpetkar, J M; Salvi, N C; Waghmare, A B; Chaudhari, P D

2013-05-20

Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. To examine the ability of ethanolic extract of fruits of Piper longum L., Piperaceae (PLE) and piperine, one of the main active principles of Piper longum, to inhibit the Russell's viper (Doboia russelii, Viperidae) snake venom activities. Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine against Russell's viper venom was studied in embryonated fertile chicken eggs, mice and rats by using various models as follows: inhibition of venom lethal action, inhibition of venom haemorrhagic action (in vitro), inhibition of venom haemorrhagic action (in vivo), inhibition of venom necrotizing action, inhibition of venom defibrinogenating action, inhibition of venom induced paw edema, inhibition of venom induced mast cell degranulation, creatine kinase assay and assay for catalase activity. PLE was found to inhibit the venom induced haemorrhage in embryonated fertile chicken eggs. Administration of PLE and piperine significantly (p<0.01) inhibited venom induced lethality, haemorrhage, necrosis, defibrinogenation and inflammatory paw edema in mice in a dose dependent manner. PLE and piperine also significantly (p<0.01) reduced venom induced mast cell degranulation in rats. Venom induced decrease in catalase enzyme levels in mice kidney tissue and increase in creatine kinase enzyme levels in mice serum were significantly (p<0.01) reversed by administration of both PLE and piperine. PLE possesses good anti-snake venom properties and piperine is one of the compounds responsible for the effective venom neutralizing ability of the plant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Studies on Bee Venom and Its Medical Uses

Science.gov (United States)

Ali, Mahmoud Abdu Al-Samie Mohamed

2012-07-01

Use of honey and other bee products in human treatments traced back thousands of years and healing properties are included in many religious texts including the Veda, Bible and Quran. Apitherapy is the use of honey bee products for medical purposes, this include bee venom, raw honey, royal jelly, pollen, propolis, and beeswax. Whereas bee venom therapy is the use of live bee stings (or injectable venom) to treat various diseases such as arthritis, rheumatoid arthritis, multiple sclerosis (MS), lupus, sciatica, low back pain, and tennis elbow to name a few. It refers to any use of venom to assist the body in healing itself. Bee venom contains at least 18 pharmacologically active components including various enzymes, peptides and amines. Sulfur is believed to be the main element in inducing the release of cortisol from the adrenal glands and in protecting the body from infections. Contact with bee venom produces a complex cascade of reactions in the human body. The bee venom is safe for human treatments, the median lethal dose (LD50) for an adult human is 2.8 mg of venom per kg of body weight, i.e. a person weighing 60 kg has a 50% chance of surviving injections totaling 168 mg of bee venom. Assuming each bee injects all its venom and no stings are quickly removed at a maximum of 0.3 mg venom per sting, 560 stings could well be lethal for such a person. For a child weighing 10 kg, as little as 93.33 stings could be fatal. However, most human deaths result from one or few bee stings due to allergic reactions, heart failure or suffocation from swelling around the neck or the mouth. As compare with other human diseases, accidents and other unusual cases, the bee venom is very safe for human treatments.

Tears of Venom: Hydrodynamics of Reptilian Envenomation

Science.gov (United States)

Young, Bruce A.; Herzog, Florian; Friedel, Paul; Rammensee, Sebastian; Bausch, Andreas; van Hemmen, J. Leo

2011-05-01

In the majority of venomous snakes, and in many other reptiles, venom is conveyed from the animal’s gland to the prey’s tissue through an open groove on the surface of the teeth and not through a tubular fang. Here we focus on two key aspects of the grooved delivery system: the hydrodynamics of venom as it interacts with the groove geometry, and the efficiency of the tooth-groove-venom complex as the tooth penetrates the prey’s tissue. We show that the surface tension of the venom is the driving force underlying the envenomation dynamics. In so doing, we explain not only the efficacy of the open groove, but also the prevalence of this mechanism among reptiles.

Allergen-specific immunotherapy of Hymenoptera venom allergy

DEFF Research Database (Denmark)

Schiener, Maximilian; Graessel, Anke; Ollert, Markus

2017-01-01

by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy...

Optimization of antiscorpion venom production

Directory of Open Access Journals (Sweden)

O. Ozkan

2006-01-01

Full Text Available The present study was carried out to produce highly efficient antivenom from a small number of telsons in a short time. Venom solution was prepared through maceration of telsons from Androctonus crassicauda (Olivier, 1807 collected in the Southeastern Anatolia Region, Turkey. Lethal dose 50% (LD50 of the venom solution injected into mice was 1 ml/kg (95% confidence interval; 0.8-1.3, according to probit analysis. Different adjuvants (Freund's Complete Adjuvant, Freund's Incomplete Adjuvant, and 0.4% aluminium phosphate, at increasing doses and combined with venom, were subcutaneously injected into horses on days 0, 14, 21, 28, 35, and 42 of the experiment. Antivenom was collected from the immunized horses on days 45, 48, and 51 using the pepsin digestive method. The antivenom effective dose 50% (ED50 in mice was 0.5 ml (95% confidence interval; 0.40-0.58, according to probit analysis. It was concluded that 0.5 ml antivenom neutralized a venom dose 35-fold higher than the venom LD50. Thus, highly potent antivenom could be produced from about 238 telsons in 51 days.

Snake Venom Metalloproteinases

OpenAIRE

Gâz Florea Şerban Andrei; Gâz Florea Adriana; Kelemen Hajnal; Muntean Daniela-Lucia

2016-01-01

As more data are generated from proteome and transcriptome analysis revealing that metalloproteinases represent most of the Viperid and Colubrid venom components authors decided to describe in a short review a classification and some of the multiple activities of snake venom metalloproteinases. SVMPs are classified in three major classes (P-I, P-II and P-III classes) based on the presence of various domain structures and according to their domain organization. Furthermore, P-II and P-III clas...

Tracing Monotreme Venom Evolution in the Genomics Era

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Camilla M. Whittington

2014-04-01

Full Text Available The monotremes (platypuses and echidnas represent one of only four extant venomous mammalian lineages. Until recently, monotreme venom was poorly understood. However, the availability of the platypus genome and increasingly sophisticated genomic tools has allowed us to characterize platypus toxins, and provides a means of reconstructing the evolutionary history of monotreme venom. Here we review the physiology of platypus and echidna crural (venom systems as well as pharmacological and genomic studies of monotreme toxins. Further, we synthesize current ideas about the evolution of the venom system, which in the platypus is likely to have been retained from a venomous ancestor, whilst being lost in the echidnas. We also outline several research directions and outstanding questions that would be productive to address in future research. An improved characterization of mammalian venoms will not only yield new toxins with potential therapeutic uses, but will also aid in our understanding of the way that this unusual trait evolves.

Tracing monotreme venom evolution in the genomics era.

Science.gov (United States)

Whittington, Camilla M; Belov, Katherine

2014-04-02

The monotremes (platypuses and echidnas) represent one of only four extant venomous mammalian lineages. Until recently, monotreme venom was poorly understood. However, the availability of the platypus genome and increasingly sophisticated genomic tools has allowed us to characterize platypus toxins, and provides a means of reconstructing the evolutionary history of monotreme venom. Here we review the physiology of platypus and echidna crural (venom) systems as well as pharmacological and genomic studies of monotreme toxins. Further, we synthesize current ideas about the evolution of the venom system, which in the platypus is likely to have been retained from a venomous ancestor, whilst being lost in the echidnas. We also outline several research directions and outstanding questions that would be productive to address in future research. An improved characterization of mammalian venoms will not only yield new toxins with potential therapeutic uses, but will also aid in our understanding of the way that this unusual trait evolves.

Tc 99m - scorpion venom: labelling, biodistribution and scintiimaging

International Nuclear Information System (INIS)

Murugesan, S.; Noronha, O.P.D.; Samuel, A.M.; Murthy, K. Radha Krishna

1999-01-01

Labelling of scorpion (Mesobuthus tamulus concanesis Pocock) venom was successfully achieved with Tc 99m using direct tin reduction procedure. Biodistribution studies were carried out in Wistar rats at different time intervals after i.v. administration of the labelled venom. Scintiimages were obtained after scorpion envenoming using a large field of view gamma camera to ascertain the pharmacological action of venom in the body. Within 5 min of administration, labelled venom was found in the blood (27.7%), muscle (30.11%), bone (13.3%), kidneys (11.5%), liver (10.4%) and other organs. The level of venom in the kidneys was higher than in the liver. The labelled venom was excreted through renal and hepatobiliary pathways. An immunoreactivity study was carried out in rabbits after i.v. injection of labelled scorpion venom followed by the injection of the species specific antivenom. A threefold increase in uptake by the kidneys ss was observed compared with that seen with scorpion venom alone. the neutralisation of the venom in the kidneys was higher than in the liver. (author)

The effects of hybridization on divergent venom phenotypes: Characterization of venom from Crotalus scutulatus scutulatus × Crotalus oreganus helleri hybrids.

Science.gov (United States)

Smith, Cara Francesca; Mackessy, Stephen P

2016-09-15

Hybridization between divergent species can be analyzed to elucidate expression patterns of distinct parental characteristics, as well as to provide information about the extent of reproductive isolation between species. A known hybrid cross between two rattlesnakes with highly divergent venom phenotypes provided the opportunity to examine occurrence of parental venom characteristics in the F1 hybrids as well as ontogenetic shifts in the expression of these characters as the hybrids aged. Although venom phenotypes of adult rattlesnake venoms are known for many species, the effect of hybridization on phenotype inheritance is not well understood, and effects of hybridization on venom ontogeny have not yet been investigated. The current study investigates both phenomena resulting from the hybridization of a male snake with type I degradative venom, Crotalus oreganus helleri (Southern Pacific Rattlesnake), and a female snake with type II highly toxic venom, Crotalus scutulatus scutulatus (Mojave Rattlesnake). SDS-PAGE, enzymology, Western blot and reversed phase HPLC (RP-HPLC) were used to characterize the venom of the C. o. helleri male, the C. s. scutulatus female and their two hybrid offspring as they aged. In general, Crotalus o. helleri × C. s. scutulatus hybrid venoms appeared to exhibit overlapping parental venom profiles, and several different enzyme activity patterns. Both hybrids expressed C. o. helleri father-specific myotoxins as well as C. s. scutulatus mother-specific Mojave toxin. Snake venom metalloprotease activity displayed apparent sex-influenced expression patterns, while hybrid serine protease activities were intermediate to parental activities. The C. s. scutulatus × C. o. helleri hybrid male's venom profile provided the strongest evidence that type I and type II venom characteristics are expressed simultaneously in hybrid venoms, as this snake contained distinctive characteristics of both parental species. However, the possibility of

Human antibody fragments specific for Bothrops jararacussu venom reduce the toxicity of other Bothrops sp. venoms.

Science.gov (United States)

Roncolato, Eduardo Crosara; Pucca, Manuela Berto; Funayama, Jaqueline Carlos; Bertolini, Thaís Barboza; Campos, Lucas Benício; Barbosa, José Elpidio

2013-01-01

Approximately 20,000 snakebites are registered each year in Brazil. The classical treatment for venomous snakebite involves the administration of sera obtained from immunized horses. Moreover, the production and care of horses is costly, and the use of heterologous sera can cause hypersensitivity reactions. The production of human antibody fragments by phage display technology is seen as a means of overcoming some of these disadvantages. The studies here attempted to test human monoclonal antibodies specific to Bothrops jararacussu against other Bothrops sp. venoms, using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Using the Griffin.1 phage antibody library, this laboratory previously produced scFvs capable of inhibiting the phospholipase and myotoxic activities of Bothrops jararacussu venom. The structural and functional similarities of the various forms of phospholipase A2 (PLA₂) in Bothrops venom served as the basis for the present study wherein the effectiveness of those same scFvs were evaluated against B. jararaca, B. neuwiedi, and B. moojeni venoms. Each clone was found to recognize all three Bothrops venoms, and purified scFvs partially inhibited their in vitro phospholipase activity. In vivo assays demonstrated that the scFv clone P2B7 reduced myotoxicity and increased the survival of animals that received the test venoms. The results here indicate that the scFv P2B7 is a candidate for inclusion in a mixture of specific antibodies to produce a human anti-bothropic sera. This data demonstrates that the human scFv P2B7 represents an alternative therapeutic approach to heterologous anti-bothropic sera available today.

An overview of Bothrops erythromelas venom

OpenAIRE

Nery,Neriane Monteiro; Luna,Karla Patrícia; Fernandes,Carla Freire Celedônio; Zuliani,Juliana Pavan

2016-01-01

Abstract This review discusses studies on the venom of Bothrops erythromelas published over the past 36 years. During this period, many contributions have been made to understand the venomous snake, its venom, and its experimental and clinical effects better. The following chronological overview is based on 29 articles that were published between 1979 and 2015, with emphasis on diverse areas. The complexity of this task demands an integration of multidisciplinary research tools to study toxin...

Snake Venom Metalloproteinases

Directory of Open Access Journals (Sweden)

Gâz Florea Şerban Andrei

2016-03-01

Full Text Available As more data are generated from proteome and transcriptome analysis revealing that metalloproteinases represent most of the Viperid and Colubrid venom components authors decided to describe in a short review a classification and some of the multiple activities of snake venom metalloproteinases. SVMPs are classified in three major classes (P-I, P-II and P-III classes based on the presence of various domain structures and according to their domain organization. Furthermore, P-II and P-III classes were separated in subclasses based on distinctive post-translational modifications. SVMPs are synthesized in a latent form, being activated through a Cys-switch mechanism similar to matrix metalloproteinases. Most of the metalloproteinases of the snake venom are responsible for the hemorrhagic events but also have fibrinogenolytic activity, poses apoptotic activity, activate blood coagulation factor II and X, inhibit platelet aggregation, demonstrating that SVMPs have multiple functions in addition to well-known hemorrhagic function.

Tityus serrulatus venom--A lethal cocktail.

Science.gov (United States)

Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

2015-12-15

Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

Fibrin(ogen)olytic activity of bumblebee venom serine protease

International Nuclear Information System (INIS)

Qiu Yuling; Choo, Young Moo; Yoon, Hyung Joo; Jia Jingming; Cui Zheng; Wang Dong; Kim, Doh Hoon; Sohn, Hung Dae; Jin, Byung Rae

2011-01-01

Bee venom is a rich source of pharmacologically active components; it has been used as an immunotherapy to treat bee venom hypersensitivity, and venom therapy has been applied as an alternative medicine. Here, we present evidence that the serine protease found in bumblebee venom exhibits fibrin(ogen)olytic activity. Compared to honeybee venom, bumblebee venom contains a higher content of serine protease, which is one of its major components. Venom serine proteases from bumblebees did not cross-react with antibodies against the honeybee venom serine protease. We provide functional evidence indicating that bumblebee (Bombus terrestris) venom serine protease (Bt-VSP) acts as a fibrin(ogen)olytic enzyme. Bt-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products. However, Bt-VSP is not a plasminogen activator, and its fibrinolytic activity is less than that of plasmin. Taken together, our results define roles for Bt-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings offer significant insight into the allergic reaction sequence that is initiated by bee venom serine protease and its potential usefulness as a clinical agent in the field of hemostasis and thrombosis. - Graphical abstract: Display Omitted Highlights: → Bumblebee venom serine protease (Bt-VSP) is a fibrin(ogen)olytic enzyme. → Bt-VSP activates prothrombin. → Bt-VSP directly degrades fibrinogen into fibrin degradation products. → Bt-VSP is a hemostatically active protein that is a potent clinical agent.

The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

OpenAIRE

Min-Ki Kim; Si Hyeong, Lee; Jo Young Shin; Kang San Kim; Nam Guen Cho; Ki Rok Kwon; Tae Jin Rhim

2007-01-01

Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Ve...

Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy.

Science.gov (United States)

Yoshida, Naruo; Hirata, Hirokuni; Watanabe, Mineaki; Sugiyama, Kumiya; Arima, Masafumi; Fukushima, Yasutsugu; Ishii, Yoshiki

2015-07-01

Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P venom (R = 0.78) in improvement testing and conventional testing. To determine specificity, 20 volunteers who had never experienced a Hymenoptera sting were all negative for sIgE against these venoms in both improvement and conventional testing. Improved sensitivity was seen in 8 patients negative for sIgE against both venoms in conventional testing, while improvement testing revealed sIgE against hornet or paper wasp venom in 5 (total 38 (92.7%)) patients. The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Snake antivenom for snake venom induced consumption coagulopathy

OpenAIRE

Maduwage, Kalana; Buckley, Nick A.; Janaka de Silva, H.; Lalloo, David; Isbister, Geoffrey K.

2015-01-01

Background\\ud \\ud Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that antivenom improves outcomes for venom induced consumption coagulopathy in some snakebites and not others. However, the effectiveness of snake antivenom in all cases of venom induced consumption coagulopathy is controversial.\\ud \\ud Objectives\\ud \\ud To assess the effect of snake antivenom as a treatment for venom induced consumption coagulopathy in people...

Centipede Venoms and Their Components: Resources for Potential Therapeutic Applications

Directory of Open Access Journals (Sweden)

Md Abdul Hakim

2015-11-01

Full Text Available Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components.

Radioactive elements definition in composition of snake venom

International Nuclear Information System (INIS)

Mekhrabova, M.A.; Topchieva, Sh.F.; Abiev, G.A.; Nagiev, Dj.A.

2010-11-01

Full text: The given article presents questions concerned to usage of snake venom in medicine and pharmacy for medicinal drugs production, zootoxin base antidotes, thorough treatment of many deseases, especially onkological, also have a widespread in biology as a specific test-material for biological sistem analises. It is experimentally proved that certain amount of snake venom can replace morphine drugs, taking into acount that snake venom solutions make longer prolonged influence than other drugs, vithout causing an accustoming. It is also marked about possibility of usage of snake venom for cancer treatment. Many expeditions had been conducted with the purpose to research snake venom crytals on the territory of Azerbaijan. During these expeditions snakes capturing had been made with the purpose of taking the venom and also soil samples had been taken in order to research the quantity of radioactive elements. Measurements made with the help of electronic microscope C anberra . Revealed uranium activity in spectrum of venom as a result of radiation background, which appears under influence of ionizing radiation on the environment. On the base of analises data it can be ascertained that snake venom can be used for production of medicinal and also other necessary drugs. [ru

Guillain-Barré syndrome following bee venom acupuncture.

Science.gov (United States)

Lee, Hyun Jo; Park, In Seok; Lee, Jon-In; Kim, Joong-Seok

2015-01-01

Bee venom acupuncture has been widely used in Oriental medicine with limited evidence of effectiveness. Most of the complications due to bee venom acupuncture are local or systemic allergic reactions. However, serious medical and neurological complications have also been reported. We herein describe the treatment of a 68-year-old woman who developed progressive quadriplegia 10 days after receiving multiple honeybee venom sting acupuncture treatments. The electrophysiological findings were consistent with Guillain-Barré syndrome (GBS). The temporal relationship between the development of GBS and honeybee venom sting acupuncture is suggestive of a cause-and-effect relationship, although the precise pathophysiology and causative components in honeybee venom need to be verified.

Determination of the NPP Krsko reactor core safety limits using the COBRA-III-C code

International Nuclear Information System (INIS)

Lajtman, S.; Feretic, D.; Debrecin, N.

1989-01-01

This paper presents the NPP Krsko reactor core safety limits determined by the COBRA-III-C code, along with the methodology used. The reactor core safety limits determination is a part of reactor protection limits procedure. The results obtained were compared to safety limits presented in NPP Krsko FSAR. The COBRA-III-C NPP Krsko design core steady state thermal hydraulics calculation, used as the basis for the safety limits calculation, is presented as well. (author)

Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Perú and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism.

Science.gov (United States)

Núñez, Vitelbina; Cid, Pedro; Sanz, Libia; De La Torre, Pilar; Angulo, Yamileth; Lomonte, Bruno; Gutiérrez, José María; Calvete, Juan J

2009-11-02

The venom proteomes of Bothrops atrox from Colombia, Brazil, Ecuador, and Perú were characterized using venomic and antivenomic strategies. Our results evidence the existence of two geographically differentiated venom phenotypes. The venom from Colombia comprises at least 26 different proteins belonging to 9 different groups of toxins. PI-metalloproteinases and K49-PLA(2) molecules represent the most abundant toxins. On the other hand, the venoms from Brazilian, Ecuadorian, and Peruvian B. atrox contain predominantly PIII-metalloproteinases. These toxin profiles correlate with the venom phenotypes of adult and juvenile B. asper from Costa Rica, respectively, suggesting that paedomorphism represented a selective trend during the trans-Amazonian southward expansion of B. atrox through the Andean Corridor. The high degree of crossreactivity of a Costa Rican polyvalent (Bothrops asper, Lachesis stenophrys, Crotalus simus) antivenom against B. atrox venoms further evidenced the close evolutionary kinship between B. asper and B. atrox. This antivenom was more efficient immunodepleting proteins from the venoms of B. atrox from Brazil, Ecuador, and Perú than from Colombia. Such behaviour may be rationalized taking into account the lower content of poorly immunogenic toxins, such as PLA(2) molecules and PI-SVMPs in the paedomorphic venoms. The immunological profile of the Costa Rican antivenom strongly suggests the possibility of using this antivenom for the management of snakebites by B. atrox in Colombia and the Amazon regions of Ecuador, Perú and Brazil.

Introducing COBRAs: exploring motivations for brand-related social media use

NARCIS (Netherlands)

Muntinga, D.G.; Moorman, M.; Smit, E.G.

2011-01-01

The article examines the use of social media by Internet users related to advertising and marketing, called "consumers' online brand-related activities (COBRA)." Interviews are conducted with such Internet users through instant messaging as to their motivations for engaging with brands and brand

Simplification of intradermal skin testing in Hymenoptera venom allergic children.

Science.gov (United States)

Cichocka-Jarosz, Ewa; Stobiecki, Marcin; Brzyski, Piotr; Rogatko, Iwona; Nittner-Marszalska, Marita; Sztefko, Krystyna; Czarnobilska, Ewa; Lis, Grzegorz; Nowak-Węgrzyn, Anna

2017-03-01

The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. We reviewed the medical records of 91 children and 121 adults. Bee venom allergy was exposure dependent, regardless of age (P bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kU A /L; interquartile range, 11.30-66.30 kU A /L) compared with adults (5.10 kU A /L; interquartile range, 2.03-8.30 kU A /L) (P venom were higher in bee venom allergic children compared with the wasp venom allergic children (P venom. At concentrations lower than 0.1 μg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Cysteine-free peptides in scorpion venom: geographical distribution ...

African Journals Online (AJOL)

GRACE

2006-12-29

Dec 29, 2006 ... In 1993, the first cysteine-free peptide was isolated from scorpion venom. ..... Venom is produced by 2 venom glands in the tail and stored in 2 ... The resistance of a variety of bacterial micro-organisms .... Biopolymers 55: 4-30.

Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®.

Science.gov (United States)

Aramadhaka, Lavakumar Reddy; Prorock, Alyson; Dragulev, Bojan; Bao, Yongde; Fox, Jay W

2013-07-01

Like most natural product libraries animal venoms have long been recognized as potentially rich source of biologically active molecules with the potential to be mined for the discovery of drugs, drug leads and/or biosimilars. In this work we demonstrate as a proof of concept a novel approach to explore venoms for potential biosimilarity to other drugs based on their ability to alter the transcriptomes of test cell lines followed by informatic searches and Connectivity Mapping to match the action of the venom on the cell gene expression to that of other drugs in the Connectivity Map (C-Map) database. As our test animal venom we chose Heloderma suspectum venom (Gila monster) since exendin-4, a glucagon-like peptide 1 receptor agonist, isolated from the venom is currently on the market to treat type 2 diabetes. The action of Byetta(®) (exentide, synthetic exendin-4), was also used in transcriptome studies. Analysis of transcriptomes from cells treated with the venom or the drug showed similarities as well as differences. The former case was primarily attributed to the fact that Gila monster venom likely contains a variety of biologically active molecules that could alter the MCF7 cell transcriptome compared to that of the single perturbant Byetta(®). Using Ingenuity Pathway Analysis software, insulin-like growth factor 1 signaling was identified in the category of "Top Canonical Pathways" for both the venom and Byetta(®). In the category of "Top Molecules" up-regulated, both venom and Byetta(®) shared IL-8, cyclic AMP-dependent transcription factor 3 (ATF-3), neuron-derived orphan receptor 1 (NR4A3), dexamethasone-induced Ras-related protein 1 (RASD1) and early growth response protein 1, (EGR-1) all with potential relevance in diabetes. Using Connectivity Mapping, Gila monster venom showed positive correlation with 1732 instances and negative correlation with 793 instances in the Connectivity database whereas Byetta(®) showed positive correlation with 1692

Accelerated proteomic visualization of individual predatory venoms of Conus purpurascens reveals separately evolved predation-evoked venom cabals.

Science.gov (United States)

Himaya, S W A; Marí, Frank; Lewis, Richard J

2018-01-10

Cone snail venoms have separately evolved for predation and defense. Despite remarkable inter- and intra-species variability, defined sets of synergistic venom peptides (cabals) are considered essential for prey capture by cone snails. To better understand the role of predatory cabals in cone snails, we used a high-throughput proteomic data mining and visualisation approach. Using this approach, the relationship between the predatory venom peptides from nine C. purpurascens was systematically analysed. Surprisingly, potentially synergistic levels of κ-PVIIA and δ-PVIA were only identified in five of nine specimens. In contrast, the remaining four specimens lacked significant levels of these known excitotoxins and instead contained high levels of the muscle nAChR blockers ψ-PIIIE and αA-PIVA. Interestingly, one of nine specimens expressed both cabals, suggesting that these sub-groups might represent inter-breeding sub-species of C. purpurascens. High throughput cluster analysis also revealed these two cabals clustered with distinct groups of venom peptides that are presently uncharacterised. This is the first report showing that the cone snails of the same species can deploy two separate and distinct predatory cabals for prey capture and shows that the cabals deployed by this species can be more complex than presently realized. Our semi-automated proteomic analysis facilitates the deconvolution of complex venoms to identify co-evolved families of peptides and help unravel their evolutionary relationships in complex venoms.

Quercetin modulates activities of Taiwan cobra phospholipase A 2 ...

Indian Academy of Sciences (India)

Home; Journals; Journal of Biosciences; Volume 37; Issue 2. Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects on membrane structure and membrane-bound mode of phospholipase A2. Yi-Ling Chiou Shinne-Ren Lin Wan-Ping Hu Long-Sen Chang. Articles Volume 37 Issue 2 June 2012 pp ...

Effects of gamma radiation on bee venom: preliminary studies

International Nuclear Information System (INIS)

Costa, H.; Boni-Mitake, M.; Souza, C.F.; Rogero, J.R.

1999-01-01

Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. several works utilizing ionizing radiation showed that it is able to modify protein structures, and successfully detoxify snake venoms toxins, although maintaining its immunological properties. The main objective of this paper was to study the effects of gamma radiation on bee venom, regarding some biochemical and toxicological aspects. Africanized Apis melllifera whole venom (2 mg/ml) in 0.15 M Na Cl solution was irradiated with 2 kGy in a 60 Co source. Preliminary studies has been carried out in order to identify some biochemical changes after irradiation. Concerning this, irradiated and native venom were submitted to a molecular exclusion chromatography (Sephadex G-100), UV absorption spectrum and protein concentration analysis. It could be seen that irradiated bee venom spectrum presented differences when compared to native bee venom, suggesting that some structural alterations has occurred. Protein concentration and chromatography profiles were not changes after irradiation. In order to evaluate the toxicity a lethality assay (L D 50 ) has been performed with both venoms, and irradiated venom showed to be less toxic than native one. (author)

Intoxicação por veneno de cobra: necrose symetrica da cortex renal: uremia

Directory of Open Access Journals (Sweden)

A. Penna de Azevedo

1938-01-01

Full Text Available Em um caso fatal de ophidismo, em individuo de 15 annos de edade, picado por uma cobra jararaca (Bothrops jararaca na face externa da perna direita e que veio a fallecer 26 dias apoz o accidente, os A.A, descrevem as lesões anatomo-pathologicas encontradas e as modificações do metabolismo, evidenciadas pelos exames chimicos do sangue. As principaes alterações existentes, acham-se localisadas nos rins os quaes apresentam lesões de glomerulonephrite diffusa e o aspecto typico da necrose cortical symmetrica. Como alterações de maior significação observam-se ainda lesões vasculares de grande intensidade e constituidas essencialmente por processo de endoarterite productiva. A necrose symmetrica da cortex renal, a vista das intensas alterações vasculares (endoarterite productiva que acarretaram a obliteração das arterías, é considerada como a consequencia immediata de taes lesões vasculares. Os vasos renaes, séde do processo inflammatorio, são as arterias interlobar, arciforme e interlobular, mas principalmente as arteriolares da camada cortical. O processo de endoarterite assume sempre o carater progressivo, de modo que a luz vascular vae sendo aos poucos, totalmente obstruida. Ao contrario do que se tem observado nos casos de necrose cortical symmetrica, citados na literatura, em que as alterações parenchymatosas são consequentes a thrombose dos vasos reanes, no caso presente esse aspecto não foi verificado mas tão sómente a existencia da endoarterite productiva obliterante. Consideram os A.A. as lesões renaes no caso que estudaram, como a resultante da actuação lenta e prolongada do veneno de cobra sobre as estructuras renaes, baseados nos seguintes factos já conhecidos e admittidos: eliminação do veneno de cobra pelos rins; capacidade do mesmo veneno, determinar a glomerulo-nephrite diffusa e acção do veneno de cobra sobre o endothelio vascular, facilitada essencialmente pela funcção especifica do orgão. As

Pharmacological evaluation of bee venom and melittin

Directory of Open Access Journals (Sweden)

Camila G. Dantas

Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

Role of the inflammasome in defense against venoms

Science.gov (United States)

Palm, Noah W.; Medzhitov, Ruslan

2013-01-01

Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1–dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1–deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1–dependent immune response can protect against the damaging effects of envenomation. PMID:23297192

Important biological activities induced by Thalassophryne maculosa fish venom.

Science.gov (United States)

Sosa-Rosales, Josefina Ines; Piran-Soares, Ana Amélia; Farsky, Sandra H P; Takehara, Harumi Ando; Lima, Carla; Lopes-Ferreira, Mônica

2005-02-01

The accidents caused by Thalassophryne maculosa fish venoms are frequent and represent a public health problem in some regions of Venezuela. Most accidents occur in the fishing communities and tourists. The clinical picture is characterized by severe pain, dizziness, fever, edema, and necrosis. Due to the lack of efficient therapy it may take weeks, or even months for complete recovery of the victims. The investigations presented here were undertaken to assess the eletrophoretical profile and principal biological properties of the T. maculosa venom. Venom obtained from fresh captured specimens of this fish was tested in vitro or in animal models for a better characterization of its toxic activities. In contrast to other fish venoms, T. maculosa venom showed relative low LD50. The injection of venom in the footpad of mice reproduced a local inflammatory lesion similar to that described in humans. Significant increase of the nociceptive and edematogenic responses was observed followed within 48 h by necrosis. Pronounced alterations on microvascular hemodynamics were visualized after venom application. These alterations were represented by fibrin depots and thrombus formation followed by complete venular stasis and transient arteriolar contraction. T. maculosa venom is devoid of phospholipase A2 activity, but the venom showed proteolytic and myotoxic activities. SDS-Page analysis of the crude venom showed important bands: one band located above 97 M(w), one band between 68 and 97 M(w), one major band between 29 and 43 M(w) and the last one located below 18.4 M(w) Then, the results presented here support that T. maculosa venom present a mixture of bioactive toxins involved in a local inflammatory lesion.

Bee venom therapy: Potential mechanisms and therapeutic applications.

Science.gov (United States)

Zhang, Shuai; Liu, Yi; Ye, Yang; Wang, Xue-Rui; Lin, Li-Ting; Xiao, Ling-Yong; Zhou, Ping; Shi, Guang-Xia; Liu, Cun-Zhi

2018-04-11

Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Venom ophthalmia caused by venoms of spitting elapid and other snakes: Report of ten cases with review of epidemiology, clinical features, pathophysiology and management.

Science.gov (United States)

Chu, Edward R; Weinstein, Scott A; White, Julian; Warrell, David A

2010-09-01

Venom ophthalmia caused by venoms of spitting elapid and other snakes: report of ten cases with review of epidemiology, clinical features, pathophysiology and management. Chu, ER, Weinstein, SA, White, J and Warrell, DA. Toxicon XX:xxx-xxx. We present ten cases of ocular injury following instillation into the eye of snake venoms or toxins by spitting elapids and other snakes. The natural history of spitting elapids and the toxinology of their venoms are reviewed together with the medical effects and management of venom ophthalmia in humans and domestic animals including both direct and allergic effects of venoms. Although the clinical features and management of envenoming following bites by spitting elapids (genera Naja and Hemachatus) are well documented, these snakes are also capable of "spraying" venom towards the eyes of predators, a defensive strategy that causes painful and potentially blinding ocular envenoming (venom ophthalmia). Little attention has been given to the detailed clinical description, clinical evolution and efficacy of treatment of venom ophthalmia and no clear management guidelines have been formulated. Knowledge of the pathophysiology of ocular envenoming is based largely on animal studies and a limited body of clinical information. A few cases of ocular exposure to venoms from crotaline viperids have also been described. Venom ophthalmia often presents with pain, hyperemia, blepharitis, blepharospasm and corneal erosions. Delay or lack of treatment may result in corneal opacity, hypopyon and/or blindness. When venom is "spat" into the eye, cranial nerve VII may be affected by local spread of venom but systemic envenoming has not been documented in human patients. Management of venom ophthalmia consists of: 1) urgent decontamination by copious irrigation 2) analgesia by vasoconstrictors with weak mydriatic activity (e.g. epinephrine) and limited topical administration of local anesthetics (e.g. tetracaine) 3) exclusion of corneal abrasions

In vitro neutralization of the scorpion, Buthus tamulus venom toxicity.

Science.gov (United States)

Venkateswarlu, Y; Janakiram, B; Reddy, G R

1988-01-01

Scorpion (Buthus tamulus) venom was subjected to neutralization by treating the venom with various chemicals such as hydrochloric acid, sodium hydroxide, thiourea, formaldehyde, zinc sulphate, acetic acid and trichloroacetic acid. The venom was also subjected to heat treatment. The levels of total protein, free amino acids and protease activity in neutralized venom decreased significantly. The decrease in venom protein and free amino acids was in proportion to the duration of the heat treatment and the concentration of chemicals used except zinc sulphate, sodium hydroxide and thiourea. Protease activity of neutralized venom samples also showed a decrease except with zinc sulphate which enhanced the enzyme activity. Intramuscular injection of formaldehyde, trichlcroacetic acid and heat treated venoms into albino rats produced low mortality while thiourea and zinc sulphate were not effective in reducing the mortality. Hydrochloric acid and acetic acid treated venoms reduced the mortality by 50% with a decrease in the symptoms of envenomation. The changes were attributed to the denaturing of venom protein by chemical and heat treatments.

COBRA 9121: Federal liability for patient screening and transfer.

Science.gov (United States)

Frew, S A

1988-01-01

Health care is no longer a simple cottage industry of individual providers. Increases in competition and government regulation have transformed the old structure of health care into a fend-for-yourself marketplace dominated by multi-institutional corporations. In order to accomplish this change, health care providers have had to alter their locus of attention from the patient to the bottom line. As a result, it is not surprising to find corporate business practices interspersed among the traditional health care practices. On March 1, 1987, the federal government began an assault on a casualty of this new market oriental philosophy, patient transfers or "dumping". COBRA 9121 is an "anti-dumping" law designed to prevent hospitals from continuing this practice. The vehicle for ensuring that the statute's broad provisions are followed is a set of "sudden death" probations. For example, under COBRA, hospitals found guilty of knowing or negligent violations may be suspended or terminated from receiving all Medicare reimbursement. One way to avoid these "sudden death" probations is to understand the implications of this law.

COBRA-SFS [Spent Fuel Storage]: A thermal-hydraulic analysis computer code: Volume 2, User's manual

International Nuclear Information System (INIS)

Rector, D.R.; Cuta, J.M.; Lombardo, N.J.; Michener, T.E.; Wheeler, C.L.

1986-11-01

COBRA-SFS (Spent Fuel Storage) is a general thermal-hydraulic analysis computer code used to predict temperatures and velocities in a wide variety of systems. The code was refined and specialized for spent fuel storage system analyses for the US Department of Energy's Commercial Spent Fuel Management Program. The finite-volume equations governing mass, momentum, and energy conservation are written for an incompressible, single-phase fluid. The flow equations model a wide range of conditions including natural circulation. The energy equations include the effects of solid and fluid conduction, natural convection, and thermal radiation. The COBRA-SFS code is structured to perform both steady-state and transient calculations; however, the transient capability has not yet been validated. This volume contains the input instructions for COBRA-SFS and an auxiliary radiation exchange factor code, RADX-1. It is intended to aid the user in becoming familiar with the capabilities and modeling conventions of the code

Comparison of the air-Q intubating laryngeal airway and the cobra perilaryngeal airway as conduits for fiber optic-guided intubation in pediatric patients.

Science.gov (United States)

Girgis, Karim K; Youssef, Maha M I; ElZayyat, Nashwa S

2014-10-01

One of the methods proposed in cases of difficult airway management in children is using a supraglottic airway device as a conduit for tracheal intubation. The aim of this study was to compare the efficacy of the Air-Q Intubating Laryngeal Airway (Air-Q) and the Cobra Perilaryngeal Airway (CobraPLA) to function as a conduit for fiber optic-guided tracheal intubation in pediatric patients. A total of 60 children with ages ranging from 1 to 6 years, undergoing elective surgery, were randomized to have their airway managed with either an Air-Q or CobraPLA. Outcomes recorded were the success rate, time and number of attempts required for fiber optic-guided intubation and the time required for device removal after intubation. We also recorded airway leak pressure (ALP), fiber optic grade of glottic view and occurrence of complications. Both devices were successfully inserted in all patients. The intubation success rate was comparable with the Air-Q and the CobraPLA (96.7% vs. 90%), as was the first attempt success rate (90% vs. 80%). The intubation time was significantly longer with the CobraPLA (29.5 ± 10.9 s vs. 23.2 ± 9.8 s; P fiber optic grade of glottic view was comparable with the two devices. The CobraPLA was associated with a significantly higher incidence of blood staining of the device on removal and post-operative sore throat. Both the Air-Q and CobraPLA can be used effectively as a conduit for fiber optic-guided tracheal intubation in children. However, the Air-Q proved to be superior due to a shorter intubation time and less airway morbidity compared with the CobraPLA.

Cross reactivity between European hornet and yellow jacket venoms.

Science.gov (United States)

Severino, M G; Caruso, B; Bonadonna, P; Labardi, D; Macchia, D; Campi, P; Passalacqua, G

2010-08-01

Cross-reactions between venoms may be responsible for multiple diagnostic positivities in hymenoptera allergy. There is limited data on the cross-reactivity between Vespula spp and Vespa crabro, which is an important cause of severe reactions in some parts of Europe. We studied by CAP-inhibition assays and immunoblotting the cross-reactivity between the two venoms. Sera from patients with non discriminative skin/CAP positivity to both Vespula and Vespa crabro were collected for the analyses. Inhibition assays were carried out with a CAP method, incubating the sera separately with both venoms and subsequently measuring the specific IgE to venoms themselves. Immunoblotting was performed on sera with ambiguous results at the CAP-inhibition. Seventeen patients had a severe reaction after Vespa crabro sting and proved skin and CAP positive also to vespula. In 11/17 patients, Vespula venom completely inhibited IgE binding to VC venom, whereas VC venom inhibited binding to Vespula venom only partially (Vespula germanica, thus indicating a true sensitisation to crabro. In the case of multiple positivities to Vespa crabro and Vespula spp the CAP inhibition is helpful in detecting the cross-reactivities.

Wasp venom proteins: phospholipase A1 and B.

Science.gov (United States)

King, T P; Kochoumian, L; Joslyn, A

1984-04-01

Three major venom proteins from different species of wasps have been isolated and characterized. They are hyaluronidase, phospholipase, and antigen 5 of as yet unknown biochemical function. These three proteins are allergens in wasp venom-sensitive persons. The species of wasps studied, of the genus Polistes, were annularis, carolina, exclamans, fuscatus, and instabilis. Antigen 5 and phospholipase from wasp venoms were shown to be antigenically distinct from homologous proteins of yellowjacket venoms. The venom phospholipase from wasp, as well as that from yellowjacket (Vespula germanica), appears to have dual enzymatic specificities of the A1 and B types. That is, hydrolysis takes place at the 1-acyl residue of phosphatidylcholine and at the 1- or 2-acyl residue of lysophosphatidylcholine.

Effects of gamma radiation on bee venom: preliminary studies

Energy Technology Data Exchange (ETDEWEB)

Costa, H.; Boni-Mitake, M.; Souza, C.F.; Rogero, J.R. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Div. de Radiobiologia

1999-11-01

Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. several works utilizing ionizing radiation showed that it is able to modify protein structures, and successfully detoxify snake venoms toxins, although maintaining its immunological properties. The main objective of this paper was to study the effects of gamma radiation on bee venom, regarding some biochemical and toxicological aspects. Africanized Apis melllifera whole venom (2 mg/ml) in 0.15 M Na Cl solution was irradiated with 2 kGy in a {sup 60} Co source. Preliminary studies has been carried out in order to identify some biochemical changes after irradiation. Concerning this, irradiated and native venom were submitted to a molecular exclusion chromatography (Sephadex G-100), UV absorption spectrum and protein concentration analysis. It could be seen that irradiated bee venom spectrum presented differences when compared to native bee venom, suggesting that some structural alterations has occurred. Protein concentration and chromatography profiles were not changes after irradiation. In order to evaluate the toxicity a lethality assay (L D{sub 50}) has been performed with both venoms, and irradiated venom showed to be less toxic than native one. (author) 23 refs., 3 figs., 1 tab.

Snake Venom As An Effective Tool Against Colorectal Cancer.

Science.gov (United States)

Uzair, Bushra; Atlas, Nagina; Malik, Sidra Batool; Jamil, Nazia; Salaam, Temitope Ojuolape; Rehman, Mujaddad Ur; Khan, Barkat Ali

2018-06-13

Cancer is considered one of the most predominant causes of morbidity and mortality all over the world and colorectal cancer is the most common fatal cancers, triggering the second cancer related death. Despite progress in understanding carcinogenesis and development in chemotherapeutics, there is an essential need to search for improved treatment. More than the half a century, cytotoxic and cytostatic agents have been examined as a potential treatment of cancer, among these agents; remarkable progresses have been reported by the use of the snake venom. Snake venoms are secreting materials of lethal snakes are store in venomous glands. Venoms are composite combinations of various protein, peptides, enzymes, toxins and non proteinaceous secretions. Snake venom possesses immense valuable mixtures of proteins and enzymes. Venoms have potential to combat with the cancerous cells and produce positive effect. Besides the toxicological effects of venoms, several proteins of snake venom e.g. disintegrins, phospholipases A2, metalloproteinases, and L-amino acid oxidases and peptides e.g. bradykinin potentiators, natriuretic, and analgesic peptides have shown potential as pharmaceutical agents, including areas of diagnosis and cancer treatment. In this review we have discussed recent remarkable research that has involved the dynamic snake venoms compounds, having anticancer bustle especially in case of colorectal cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacological Aspects of Vipera xantina palestinae Venom

Science.gov (United States)

Momic, Tatjana; Arlinghaus, Franziska T.; Arien-Zakay, Hadar; Katzhendler, Jeoshua; Eble, Johannes A.; Marcinkiewicz, Cezary; Lazarovici, Philip

2011-01-01

In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation. PMID:22174978

Hymenoptera venom review focusing on Apis mellifera

Directory of Open Access Journals (Sweden)

P. R. de Lima

2003-01-01

Full Text Available Hymenoptera venoms are complex mixtures containing simple organic molecules, proteins, peptides, and other bioactive elements. Several of these components have been isolated and characterized, and their primary structures determined by biochemical techniques. These compounds are responsible for many toxic or allergic reactions in different organisms, such as local pain, inflammation, itching, irritation, and moderate or severe allergic reactions. The most extensively characterized Hymenoptera venoms are bee venoms, mainly from the Apis genus and also from social wasps and ant species. However, there is little information about other Hymenoptera groups. The Apis venom presents high molecular weight molecules - enzymes with a molecular weight higher than 10.0 kDa - and peptides. The best studied enzymes are phospholipase A2, responsible for cleaving the membrane phospholipids, hyaluronidase, which degrades the matrix component hyaluronic acid into non-viscous segments and acid phosphatase acting on organic phosphates. The main peptide compounds of bee venom are lytic peptide melittin, apamin (neurotoxic, and mastocyte degranulating peptide (MCD.

Bee Venom Phospholipase A2: Yesterday's Enemy Becomes Today's Friend.

Science.gov (United States)

Lee, Gihyun; Bae, Hyunsu

2016-02-22

Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson's disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes.

Snake population venomics and antivenomics of Bothrops atrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management

OpenAIRE

Calvete, Juan J.; Sanz, Libia; Pérez, Alicia; Borges, Adolfo; Vargas, Alba M.; Lomonte, Bruno; Angulo, Yamileth; Gutiérrez, José María; Chalkidis, Hipócrates M.; Mourão, Rosa H.V.; Furtado, María de Fátima; Moura Da Silva, Ana M.

2011-01-01

We describe two geographically differentiated venom phenotypes across the wide distribution range of Bothrops atrox, from the Colombian Magdalena Medio Valley through Puerto Ayacucho and El Paují, in the Venezuelan States of Amazonas and Orinoquia, respectively, and São Bento in the Brazilian State of Maranhão. Colombian and Venezuelan venoms show an ontogenetic toxin profile phenotype whereas Brazilian venoms exhibit paedomorphic phenotypes. Venoms from each of the 16 localities sampled cont...

Antigenic Cross-Reactivity Anti-Birtoxin Antibody against Androctonus crassicauda Venom

Directory of Open Access Journals (Sweden)

SuhandanAdigüzel Van-Zoelen

2015-10-01

Full Text Available Background: Antivenom is still widely used in the treatment of envenomation as there are no vaccines or other effective agents available against animal venoms. Recently, neurotoxins named birtoxin family have been described from Parabuthus transvaalicus and Androctonus crassicauda. The aim of the present study was to test the antibirtoxinantibodies for their ability to neutralize the lethal effects of A. crassicauda scorpion venom.Methods: SDS-PAGE and Western blotting used the presence of components from A. crassicauda and P.transvaalicus scorpion venoms and to determine the degree of cross-reactivity. The Minimum Lethal Dose (MLD of venom was assessed by subcutaneously (sc injections in mice.Results: The MLD of the A. crassicauda venom was 35 μg/ 20g mouse by sc injection route. Western blotting showed the presence of components from A. crassicauda and P. transvaalicus scorpion venoms strongly cross react with the A. crassicauda antivenom. However, Western blotting of the A. crassicauda scorpion venom using the Refik Saydam Public Health Agency (RSPHA generated antibody showed that not all the venom components cross reacted with the anti-birtoxin antibody. The antibodies only cross reacted with components falling under the 19 kDa protein size of A. crassicauda venom.Conclusion: The bioassays and Western blotting of A. crassicauda venom with the anti-birtoxin antibodies produced against a synthetic peptide showed that these antibodies cross reacted but did not neutralize the venom of A. crassicauda.

Development of Brigade Staff Tasks for the COBRAS II Brigade Staff Exercise

National Research Council Canada - National Science Library

Deter, Daniel

1998-01-01

... and development of simulation-based training for the conventional mounted brigade staff. The work was performed under a project called Combined Arms Operations at Brigade Level, Realistically Achieved Through Simulation (COBRAS).

Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom.

Science.gov (United States)

Junqueira-de-Azevedo, Inácio L M; Bastos, Carolina Mancini Val; Ho, Paulo Lee; Luna, Milene Schmidt; Yamanouye, Norma; Casewell, Nicholas R

2015-03-01

Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Science.gov (United States)

Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M.; Metz, Martin; Guzzetta, Andrew; Åbrink, Magnus; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

2011-01-01

Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell–derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell–deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function. PMID:21926462

Moving pieces in a venomic puzzle

DEFF Research Database (Denmark)

Verano-Braga, Thiago; Dutra, Alexandre A A; León, Ileana R

2013-01-01

Besides being a public health problem, scorpion venoms have a potential biotechnological application since they contain peptides that may be used as drug leads and/or to reveal novel pharmacological targets. A comprehensive Tityus serrulatus venom proteome study with emphasis on the phosphoproteo...

Comparison of the effect of Crotalus simus and Crotalus durissus ruruima venoms on the equine antibody response towards Bothrops asper venom: implications for the production of polyspecific snake antivenoms.

Science.gov (United States)

Dos-Santos, Maria Cristina; Arroyo, Cynthia; Solano, Sergio; Herrera, María; Villalta, Mauren; Segura, Alvaro; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo

2011-02-01

Antivenoms are preparations of immunoglobulins purified from the plasma of animals immunized with snake venoms. Depending on the number of venoms used during the immunization, antivenoms can be monospecific (if venom from a single species is used) or polyspecific (if venoms from several species are used). In turn, polyspecific antivenoms can be prepared by purifying antibodies from the plasma of animals immunized with a mixture of venoms, or by mixing antibodies purified from the plasma of animals immunized separately with single venom. The suitability of these strategies to produce polyspecific antibothropic-crotalic antivenoms was assessed using as models the venoms of Bothrops asper, Crotalus simus and Crotalus durissus ruruima. It was demonstrated that, when used as co-immunogen, C. simus and C. durissus ruruima venoms exert a deleterious effect on the antibody response towards different components of B. asper venom and in the neutralization of hemorrhagic and coagulant effect of this venom when compared with a monospecific B. asper antivenom. Polyspecific antivenoms produced by purifying immunoglobulins from the plasma of animals immunized with venom mixtures showed higher antibody titers and neutralizing capacity than those produced by mixing antibodies purified from the plasma of animals immunized separately with single venom. Thus, despite the deleterious effect of Crotalus sp venoms on the immune response against B. asper venom, the use of venom mixtures is more effective than the immunization with separate venoms for the preparation of polyspecific bothropic-crotalic antivenoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Intraspecific Variation of Centruroides Edwardsii Venom from Two Regions of Colombia

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Sebastián Estrada-Gómez

2014-07-01

Full Text Available We report the first description studies, partial characterization, and intraspecific difference of Centruroides edwardsii, Gervais 1843, venom. C. edwardsii from two Colombian regions (Antioquia and Tolima were evaluated. Both venoms showed hemolytic activity, possibly dependent of enzymatic active phospholipases, and neither coagulant nor proteolytic activities were observed. Venom electrophoretic profile showed significant differences between C. edwardsii venom from both regions. A high concentration of proteins with molecular masses between 31 kDa and 97.4 kDa, and an important concentration close or below 14.4 kDa were detected. RP-HPLC retention times between 38.2 min and 42.1 min, showed bands close to 14.4 kDa, which may correspond to phospholipases. RP-HPLC venom profile showed a well conserved region in both venoms between 7 and 17 min, after this, significant differences were detected. From Tolima region venom, 50 well-defined peaks were detected, while in the Antioquia region venom, 55 well-defined peaks were detected. Larvicidal activity was only detected in the C. edwardsii venom from Antioquia. No antimicrobial activity was observed using complete venom or RP-HPLC collected fractions of both venoms. Lethally activity (carried out on female albino swiss mice was detected at doses over 19.2 mg/kg of crude venom. Toxic effects included distress, excitability, eye irritation and secretions, hyperventilation, ataxia, paralysis, and salivation.

Cobra-IE Evaluation by Simulation of the NUPEC BWR Full-Size Fine-Mesh Bundle Test (BFBT)

International Nuclear Information System (INIS)

Burns, C. J.; Aumiler, D.L.

2006-01-01

The COBRA-IE computer code is a thermal-hydraulic subchannel analysis program capable of simulating phenomena present in both PWRs and BWRs. As part of ongoing COBRA-IE assessment efforts, the code has been evaluated against experimental data from the NUPEC BWR Full-Size Fine-Mesh Bundle Tests (BFBT). The BFBT experiments utilized an 8 x 8 rod bundle to simulate BWR operating conditions and power profiles, providing an excellent database for investigation of the capabilities of the code. Benchmarks performed included steady-state and transient void distribution, single-phase and two-phase pressure drop, and steady-state and transient critical power measurements. COBRA-IE effectively captured the trends seen in the experimental data with acceptable prediction error. Future sensitivity studies are planned to investigate the effects of enabling and/or modifying optional code models dealing with void drift, turbulent mixing, rewetting, and CHF

Proteomic Characterization of the Venom of Five Bombus (Thoracobombus) Species

OpenAIRE

Barkan, Nezahat Pınar; Bayazit, Mustafa Bilal; Ozel Demiralp, Duygu

2017-01-01

Venomous animals use venom, a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees (Bombus sp.) is largely unknown. The Thoracobombus subgenus of Bombus sp. is a diverse subgenus represented by 14 members across Turkey. In this study, we sought out to proteomically characterize the venom of five Thoracobombus species by u...

Harvesting Venom Toxins from Assassin Bugs and Other Heteropteran Insects.

Science.gov (United States)

Walker, Andrew Allan; Rosenthal, Max; Undheim, Eivind E A; King, Glenn F

2018-04-21

Heteropteran insects such as assassin bugs (Reduviidae) and giant water bugs (Belostomatidae) descended from a common predaceous and venomous ancestor, and the majority of extant heteropterans retain this trophic strategy. Some heteropterans have transitioned to feeding on vertebrate blood (such as the kissing bugs, Triatominae; and bed bugs, Cimicidae) while others have reverted to feeding on plants (most Pentatomomorpha). However, with the exception of saliva used by kissing bugs to facilitate blood-feeding, little is known about heteropteran venoms compared to the venoms of spiders, scorpions and snakes. One obstacle to the characterization of heteropteran venom toxins is the structure and function of the venom/labial glands, which are both morphologically complex and perform multiple biological roles (defense, prey capture, and extra-oral digestion). In this article, we describe three methods we have successfully used to collect heteropteran venoms. First, we present electrostimulation as a convenient way to collect venom that is often lethal when injected into prey animals, and which obviates contamination by glandular tissue. Second, we show that gentle harassment of animals is sufficient to produce venom extrusion from the proboscis and/or venom spitting in some groups of heteropterans. Third, we describe methods to harvest venom toxins by dissection of anaesthetized animals to obtain the venom glands. This method is complementary to other methods, as it may allow harvesting of toxins from taxa in which electrostimulation and harassment are ineffective. These protocols will enable researchers to harvest toxins from heteropteran insects for structure-function characterization and possible applications in medicine and agriculture.

Analysis of the intersexual variation in Thalassophryne maculosa fish venoms.

Science.gov (United States)

Lopes-Ferreira, Mônica; Sosa-Rosales, Ines; Bruni, Fernanda M; Ramos, Anderson D; Vieira Portaro, Fernanda Calheta; Conceição, Katia; Lima, Carla

2016-06-01

Gender related variation in the molecular composition of venoms and secretions have been described for some animal species, and there are some evidences that the difference in the toxin (s) profile among males and females may be related to different physiopathological effects caused by the envenomation by either gender. In order to investigate whether this same phenomenon occurs to the toadfish Thalassophryne maculosa, we have compared some biological and biochemical properties of female and male venoms. Twenty females and males were collected in deep waters of the La Restinga lagoon (Venezuela) and, after protein concentration assessed, the induction of toxic activities in mice and the biochemical properties were analyzed. Protein content is higher in males than in females, which may be associated to a higher size and weight of the male body. In vivo studies showed that mice injected with male venoms presented higher nociception when compared to those injected with female venoms, and both venoms induced migration of macrophages into the paw of mice. On the other hand, mice injected with female venoms had more paw edema and extravasation of Evans blue in peritoneal cavity than mice injected with male venoms. We observed that the female venoms had more capacity for necrosis induction when compared with male venoms. The female samples present a higher proteolytic activity then the male venom when gelatin, casein and FRETs were used as substrates. Evaluation of the venoms of females and males by SDS-PAGE and chromatographic profile showed that, at least three components (present in two peaks) are only present in males. Although the severity of the lesion, characterized by necrosis development, is related with the poisoning by female specimens, the presence of exclusive toxins in the male venoms could be associated with the largest capacity of nociception induction by this sample. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proteomic Characterization of the Venom of Five Bombus (Thoracobombus) Species.

Science.gov (United States)

Barkan, Nezahat Pınar; Bayazit, Mustafa Bilal; Ozel Demiralp, Duygu

2017-11-11

Venomous animals use venom, a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees ( Bombus sp.) is largely unknown. The Thoracobombus subgenus of Bombus sp. is a diverse subgenus represented by 14 members across Turkey. In this study, we sought out to proteomically characterize the venom of five Thoracobombus species by using bottom-up proteomic techniques. We have obtained two-dimensional polyacrylamide gel (2D-PAGE) images of each species' venom sample. We have subsequently identified the protein spots by using matrix assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS). We have identified 47 proteins for Bombus humilis , 32 for B. pascuorum , 60 for B. ruderarius , 39 for B. sylvarum , and 35 for B. zonatus . Moreover, we illustrated that intensities of 2DE protein spots corresponding to putative venom toxins vary in a species-specific manner. Our analyses provide the primary proteomic characterization of five bumble bee species' venom composition.

Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest.

Science.gov (United States)

Gonçalves-Machado, Larissa; Pla, Davinia; Sanz, Libia; Jorge, Roberta Jeane B; Leitão-De-Araújo, Moema; Alves, Maria Lúcia M; Alvares, Diego Janisch; De Miranda, Joari; Nowatzki, Jenifer; de Morais-Zani, Karen; Fernandes, Wilson; Tanaka-Azevedo, Anita Mitico; Fernández, Julián; Zingali, Russolina B; Gutiérrez, José María; Corrêa-Netto, Carlos; Calvete, Juan J

2016-03-01

Bothrops jararaca is a slender and semi-arboreal medically relevant pit viper species endemic to tropical and subtropical forests in southern Brazil, Paraguay, and northern Argentina (Misiones). Within its geographic range, it is often abundant and is an important cause of snakebite. Although no subspecies are currently recognized, geographic analyses have revealed the existence of two well-supported B. jararaca clades that diverged during the Pliocene ~3.8Mya and currently display a southeastern (SE) and a southern (S) Atlantic rainforest (Mata Atlântica) distribution. The spectrum, geographic variability, and ontogenetic changes of the venom proteomes of snakes from these two B. jararaca phylogroups were investigated applying a combined venom gland transcriptomic and venomic analysis. Comparisons of the venom proteomes and transcriptomes of B. jararaca from the SE and S geographic regions revealed notable interpopulational variability that may be due to the different levels of population-specific transcriptional regulation, including, in the case of the southern population, a marked ontogenetic venom compositional change involving the upregulation of the myotoxic PLA2 homolog, bothropstoxin-I. This population-specific marker can be used to estimate the proportion of venom from the southern population present in the B. jararaca venom pool used for the Brazilian soro antibotrópico (SAB) antivenom production. On the other hand, the southeastern population-specific D49-PLA2 molecules, BinTX-I and BinTX-II, lend support to the notion that the mainland ancestor of Bothrops insularis was originated within the same population that gave rise to the current SE B. jararaca phylogroup, and that this insular species endemic to Queimada Grande Island (Brazil) expresses a pedomorphic venom phenotype. Mirroring their compositional divergence, the two geographic B. jararaca venom pools showed distinct bioactivity profiles. However, the SAB antivenom manufactured in Vital Brazil

Peptidomic and transcriptomic profiling of four distinct spider venoms.

Directory of Open Access Journals (Sweden)

Vera Oldrati

Full Text Available Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae, Poecilotheria formosa (Theraphosidae, Viridasius fasciatus (Viridasiidae and Latrodectus mactans (Theridiidae. This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins, revealed the presence of 14

Anti-arthritic effects of microneedling with bee venom gel

OpenAIRE

Mengdi Zhao; Jie Bai; Yang Lu; Shouying Du; Kexin Shang; Pengyue Li; Liu Yang; Boyu Dong; Ning Tan

2016-01-01

Objective: To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel. Methods: In this study, the sodium urate and LPS were used on rats and mice to construct the model. Bee venom gel–microneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors. Results: Compared with the model group, the bee venom gel–microneedle combination group can r...

Analysis of Brazilian snake venoms by neutron activation analysis

International Nuclear Information System (INIS)

Saiki, M.; Vasconcellos, M.B.A.; Rogero, J.R.; Cruz, M.C.G.

1991-01-01

Instrumental neutron activation analysis (INAA) has been applied to multielemental determinations of Brazilian snake venoms from the species: Bothrops jararacussu, Crotalus durissus terrificus and Bothrops jararaca. Concentrations of Br, Ca, Cl, Cs, K, Mg, Na, Rb, Sb, Se and Zn have been determined in lyophilized venoms by using short and long irradiations in the IEA-RI nuclear reactor under a thermal neutron flux of 10 11 to 10 13 n · cm -2 · s -1 . The reference materials NIST Bovine Liver 1577 and IUPAC Bowen's Kale were also analyzed simultaneously with the venoms to evaluate the accuracy and the reproducibility of the method. The concentrations of the elements found in snake venoms from different species were compared. The Crotalus durissus terrificus venoms presented high concentration of Se but low concentrations of Zn when these results are compared with those obtained from genera Bothrops venoms. (author) 9 refs.; 2 tabs

Snake population venomics and antivenomics of Bothrops atrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management.

Science.gov (United States)

Calvete, Juan J; Sanz, Libia; Pérez, Alicia; Borges, Adolfo; Vargas, Alba M; Lomonte, Bruno; Angulo, Yamileth; Gutiérrez, José María; Chalkidis, Hipócrates M; Mourão, Rosa H V; Furtado, M Fatima D; Moura-Da-Silva, Ana M

2011-04-01

We describe two geographically differentiated venom phenotypes across the wide distribution range of Bothrops atrox, from the Colombian Magdalena Medio Valley through Puerto Ayacucho and El Paují, in the Venezuelan States of Amazonas and Orinoquia, respectively, and São Bento in the Brazilian State of Maranhão. Colombian and Venezuelan venoms show an ontogenetic toxin profile phenotype whereas Brazilian venoms exhibit paedomorphic phenotypes. Venoms from each of the 16 localities sampled contain both population-specific toxins and proteins shared by neighboring B. atrox populations. Mapping the molecular similarity between conspecific populations onto a physical map of B. atrox range provides clues for tracing dispersal routes that account for the current biogeographic distribution of the species. The proteomic pattern is consistent with a model of southeast and southwest dispersal and allopatric fragmentation northern of the Amazon Basin, and trans-Amazonian expansion through the Andean Corridor and across the Amazon river between Monte Alegre and Santarém. An antivenomic approach applied to assess the efficacy towards B. atrox venoms of two antivenoms raised in Costa Rica and Brazil using Bothrops venoms different than B. atrox in the immunization mixtures showed that both antivenoms immunodepleted very efficiently the major toxins (PIII-SVMPs, serine proteinases, CRISP, LAO) of paedomorphic venoms from Puerto Ayacucho (Venezuelan Amazonia) through São Bento, but had impaired reactivity towards PLA(2) and P-I SVMP molecules abundantly present in ontogenetic venoms. The degree of immunodepletion achieved suggests that each of these antivenoms may be effective against envenomations by paedomorphic, and some ontogenetic, B. atrox venoms. Copyright © 2010 Elsevier B.V. All rights reserved.

Hormone-like peptides in the venoms of marine cone snails

Science.gov (United States)

Robinson, Samuel D.; Li, Qing; Bandyopadhyay, Pradip K.; Gajewiak, Joanna; Yandell, Mark; Papenfuss, Anthony T.; Purcell, Anthony W.; Norton, Raymond S.; Safavi-Hemami, Helena

2015-01-01

The venoms of cone snails (genus Conus) are remarkably complex, consisting of hundreds of typically short, disulfide-rich peptides termed conotoxins. These peptides have diverse pharmacological targets, with injection of venom eliciting a range of physiological responses, including sedation, paralysis and sensory overload. Most conotoxins target the prey’s nervous system but evidence of venom peptides targeting neuroendocrine processes is emerging. Examples include vasopressin, RFamide neuropeptides and recently also insulin. To investigate the diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we systematically mined the venom gland transcriptomes of several cone snail species and examined secreted venom peptides in dissected and injected venom of the Australian cone snail Conus victoriae. Using this approach we identified several novel hormone/neuropeptide-like toxins, including peptides similar to the bee brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and thyrostimulin, a member of the glycoprotein hormone family, and confirmed the presence of insulin. We confirmed that at least two of these peptides are not only expressed in the venom gland but also form part of the injected venom cocktail, unambiguously demonstrating their role in envenomation. Our findings suggest that hormone/neuropeptide-like toxins are a diverse and integral part of the complex envenomation strategy of Conus. Exploration of this group of venom components offers an exciting new avenue for the discovery of novel pharmacological tools and drug candidates, complementary to conotoxins. PMID:26301480

Hormone-like peptides in the venoms of marine cone snails.

Science.gov (United States)

Robinson, Samuel D; Li, Qing; Bandyopadhyay, Pradip K; Gajewiak, Joanna; Yandell, Mark; Papenfuss, Anthony T; Purcell, Anthony W; Norton, Raymond S; Safavi-Hemami, Helena

2017-04-01

The venoms of cone snails (genus Conus) are remarkably complex, consisting of hundreds of typically short, disulfide-rich peptides termed conotoxins. These peptides have diverse pharmacological targets, with injection of venom eliciting a range of physiological responses, including sedation, paralysis and sensory overload. Most conotoxins target the prey's nervous system but evidence of venom peptides targeting neuroendocrine processes is emerging. Examples include vasopressin, RFamide neuropeptides and recently also insulin. To investigate the diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we systematically mined the venom gland transcriptomes of several cone snail species and examined secreted venom peptides in dissected and injected venom of the Australian cone snail Conus victoriae. Using this approach we identified several novel hormone/neuropeptide-like toxins, including peptides similar to the bee brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and thyrostimulin, a member of the glycoprotein hormone family, and confirmed the presence of insulin. We confirmed that at least two of these peptides are not only expressed in the venom gland but also form part of the injected venom cocktail, unambiguously demonstrating their role in envenomation. Our findings suggest that hormone/neuropeptide-like toxins are a diverse and integral part of the complex envenomation strategy of Conus. Exploration of this group of venom components offers an exciting new avenue for the discovery of novel pharmacological tools and drug candidates, complementary to conotoxins. Copyright © 2015 Elsevier Inc. All rights reserved.

Proteomic identification of gender molecular markers in Bothrops jararaca venom.

Science.gov (United States)

Zelanis, André; Menezes, Milene C; Kitano, Eduardo S; Liberato, Tarcísio; Tashima, Alexandre K; Pinto, Antonio F M; Sherman, Nicholas E; Ho, Paulo L; Fox, Jay W; Serrano, Solange M T

2016-04-29

Variation in the snake venom proteome is a well-documented phenomenon; however, sex-based variation in the venom proteome/peptidome is poorly understood. Bothrops jararaca shows significant sexual size dimorphism and here we report a comparative proteomic/peptidomic analysis of venoms from male and female specimens and correlate it with the evaluation of important venom features. We demonstrate that adult male and female venoms have distinct profiles of proteolytic activity upon fibrinogen and gelatin. These differences were clearly reflected in their different profiles of SDS-PAGE, two-dimensional electrophoresis and glycosylated proteins. Identification of differential protein bands and spots between male or female venoms revealed gender-specific molecular markers. However, the proteome comparison by in-solution trypsin digestion and label-free quantification analysis showed that the overall profiles of male and female venoms are similar at the polypeptide chain level but show striking variation regarding their attached carbohydrate moieties. The analysis of the peptidomes of male and female venoms revealed different contents of peptides, while the bradykinin potentiating peptides (BPPs) showed rather similar profiles. Furthermore we confirmed the ubiquitous presence of four BPPs that lack the C-terminal Q-I-P-P sequence only in the female venom as gender molecular markers. As a result of these studies we demonstrate that the sexual size dimorphism is associated with differences in the venom proteome/peptidome in B. jararaca species. Moreover, gender-based variations contributed by different glycosylation levels in toxins impact venom complexity. Bothrops jararaca is primarily a nocturnal and generalist snake species, however, it exhibits a notable ontogenetic shift in diet and in venom proteome upon neonate to adult transition. As is common in the Bothrops genus, B. jararaca shows significant sexual dimorphism in snout-vent length and weight, with females being

Differing patterns of P-selectin expression in lung injury

DEFF Research Database (Denmark)

Bless, N M; Tojo, S J; Kawarai, H

1998-01-01

Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P......-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of 125I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression......-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor alpha. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl...

CoBra - a global tool for braking system development; CoBra - ein Tool fuer den globalen Einsatz in der Bremssystementwicklung

Energy Technology Data Exchange (ETDEWEB)

Sailer, U. [Robert Bosch GmbH, Stuttgart (Germany)

1999-07-01

When Robert Bosch GmbH took over the braking system activities of Allied Signal in 1996, they became able to develop complete braking systems for passenger cars. Braking systes for the different markets are now produced in three sites in Germany, France and the USA. Braking system development with its interfaces to component development and to car producers is a new development challenge, and the department K1 (ABS and braking systems) is cooperating with internal and external partners in developing a globally standardized program for design, simulation and analysis of passenger car braking systems. This contribution presents parts of the development project CoBra (Computation of Braking Systems). [German] Mit dem Kauf der Bremsenaktivitaeten der Firma Allied Signal im Jahre 1996 ist die Robert Bosch GmbH in der Lage, komplette Pkw-Bremssysteme zu entwickeln. Nunmehr werden an drei Entwicklungsstandorten in Deutschland, Frankreich und den USA Bremssysteme fuer die verschiedenen Maerkte entwickelt. Die Bremssystementwicklung, insbesondere die damit verbundenen Schnittstellen zu der Komponentenentwicklung und zum Automobilhersteller, stellt technisch und vom Entwicklungsprozess aus gesehen eine neue Herausforderung dar. Um ihr zu begegnen, wird im Geschaeftsbereich K1 (ABS and Braking Systems) derzeit in Zusammenarbeit mit internen und externen Partnern ein global einheitliches Programm zur Auslegung, Simulation und Analyse von Pkw-Bremssystemen entwickelt. Dieser Beitrag stellt Teile des Entwicklungsprojekts CoBra (Computation of Braking Systems) vor. (orig.)

Mechanisms of bee venom-induced acute renal failure.

Science.gov (United States)

Grisotto, Luciana S D; Mendes, Glória E; Castro, Isac; Baptista, Maria A S F; Alves, Venancio A; Yu, Luis; Burdmann, Emmanuel A

2006-07-01

The spread of Africanized bees in the American continent has increased the number of severe envenomation after swarm attacks. Acute renal failure (ARF) is one of the major hazards in surviving patients. To assess the mechanisms of bee venom-induced ARF, rats were evaluated before, up to 70 min and 24h after 0.5mg/kg of venom injection. Control rats received saline. Bee venom caused an early and significant reduction in glomerular filtration rate (GFR, inulin clearance, 0.84+/-0.05 to 0.40+/-0.08 ml/min/100g, pbee venom-induced ARF that may occur even without hemolysis or hypotension.

Effects of Animal Venoms and Toxins on Hallmarks of Cancer

Science.gov (United States)

Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

2016-01-01

Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

The Comparison of Effectiveness between Bee Venom and Sweet Bee Venom Therapy on Low back pain with Radiating pain

OpenAIRE

Lee Tae-ho; Hwang Hee-sang; Chang So-young; Cha Jung-ho; Jung Ki-hoon; Lee Eun-young; Roh Jeongdu

2007-01-01

Objective : The aim of this study is to investigate if Sweet Bee Venom therapy has the equal effect in comparison with Bee Venom Therapy on Low back pain with Radiation pain. Methods : Clinical studies were done 24 patients who were treated low back pain with radiation pain to Dept. of Acupuncture & Moxibusition, of Oriental Medicine Se-Myung University from April 1, 2007 to September 30, 2007. Subjects were randomly divided into two groups ; Bee Venom treated group(Group A, n=10), Sweet B...

Proteomic Characterization of the Venom of Five Bombus (Thoracobombus Species

Directory of Open Access Journals (Sweden)

Nezahat Pınar Barkan

2017-11-01

Full Text Available Venomous animals use venom, a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees (Bombus sp. is largely unknown. The Thoracobombus subgenus of Bombus sp. is a diverse subgenus represented by 14 members across Turkey. In this study, we sought out to proteomically characterize the venom of five Thoracobombus species by using bottom-up proteomic techniques. We have obtained two-dimensional polyacrylamide gel (2D-PAGE images of each species’ venom sample. We have subsequently identified the protein spots by using matrix assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS. We have identified 47 proteins for Bombus humilis, 32 for B. pascuorum, 60 for B. ruderarius, 39 for B. sylvarum, and 35 for B. zonatus. Moreover, we illustrated that intensities of 2DE protein spots corresponding to putative venom toxins vary in a species-specific manner. Our analyses provide the primary proteomic characterization of five bumble bee species’ venom composition.

Individual variability in the venom proteome of juvenile Bothrops jararaca specimens.

Science.gov (United States)

Dias, Gabriela S; Kitano, Eduardo S; Pagotto, Ana H; Sant'anna, Sávio S; Rocha, Marisa M T; Zelanis, André; Serrano, Solange M T

2013-10-04

Snake venom proteomes/peptidomes are highly complex and subject to ontogenetic changes. Individual variation in the venom proteome of juvenile snakes is poorly known. We report the proteomic analysis of venoms from 21 juvenile specimens of Bothrops jararaca of different geographical origins and correlate it with the evaluation of important venom features. Individual venoms showed similar caseinolytic activities; however, their amidolytic activities were significantly different. Rather intriguingly, plasma coagulant activity showed remarkable variability among the venoms but not the prothrombin-activating activity. LC-MS analysis showed significant differences between venoms; however, an interesting finding was the ubiquitous presence of the tripeptide ZKW, an endogenous inhibitor of metalloproteinases. Electrophoretic profiles of proteins submitted to reduction showed significant variability in total proteins, glycoproteins, and in the subproteomes of proteinases. Moreover, identification of differential bands revealed variation in most B. jararaca toxin classes. Profiles of venoms analyzed under nonreducing conditions showed less individual variability and identification of proteins in a conserved band revealed the presence of metalloproteinases and l-amino acid oxidase as common components of these venoms. Taken together, our findings suggest that individual venom proteome variability in B. jararaca exists from a very early animal age and is not a result of ontogenetic and diet changes.

What killed Karl Patterson Schmidt? Combined venom gland transcriptomic, venomic and antivenomic analysis of the South African green tree snake (the boomslang), Dispholidus typus.

Science.gov (United States)

Pla, Davinia; Sanz, Libia; Whiteley, Gareth; Wagstaff, Simon C; Harrison, Robert A; Casewell, Nicholas R; Calvete, Juan J

2017-04-01

Non-front-fanged colubroid snakes comprise about two-thirds of extant ophidian species. The medical significance of the majority of these snakes is unknown, but at least five species have caused life-threatening or fatal human envenomings. However, the venoms of only a small number of species have been explored. A combined venomic and venom gland transcriptomic approach was employed to characterise of venom of Dispholidus typus (boomslang), the snake that caused the tragic death of Professor Karl Patterson Schmidt. The ability of CroFab™ antivenom to immunocapture boomslang venom proteins was investigated using antivenomics. Transcriptomic-assisted proteomic analysis identified venom proteins belonging to seven protein families: three-finger toxin (3FTx); phospholipase A 2 (PLA 2 ); cysteine-rich secretory proteins (CRISP); snake venom (SV) serine proteinase (SP); C-type lectin-like (CTL); SV metalloproteinases (SVMPs); and disintegrin-like/cysteine-rich (DC) proteolytic fragments. CroFab™ antivenom efficiently immunodepleted some boomslang SVMPs. The present work is the first to address the overall proteomic profile of D. typus venom. This study allowed us to correlate the toxin composition with the toxic activities of the venom. The antivenomic analysis suggested that the antivenom available at the time of the unfortunate accident could have exhibited at least some immunoreactivity against the boomslang SVMPs responsible for the disseminated intravascular coagulation syndrome that caused K.P. Schmidt's fatal outcome. This study may stimulate further research on other non-front-fanged colubroid snake venoms capable of causing life-threatening envenomings to humans, which in turn should contribute to prevent fatal human accidents, such as that unfortunately suffered by K.P. Schmidt. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

A Study on Major Components of Bee Venom Using Electrophoresis

Directory of Open Access Journals (Sweden)

Lee, Jin-Seon

2000-12-01

Full Text Available This study was designed to study on major components of various Bee Venom(Bee Venom by electrical stimulation in Korea; K-BV I, Bee Venom by Microwave stimulation in Korea; K -BV II, 0.5rng/ml, Fu Yu Pharmaceutical Factory, China; C-BV, 1mg /ml, Monmouth Pain Institute, Inc., U.S.A.; A-BV using Electrophoresis. The results were summarized as follows: 1. In 1:4000 Bee Venom solution rate, the band was not displayed distinctly usmg Electrophoresis. But in 1: 1000, the band showed clearly. 2. The results of Electrophoresis at solution rate 1:1000, K-BV I and K-BVII showed similar band. 3. The molecular weight of Phospholipase A2 was known as 19,000 but its band was seen at 17,000 in Electrophoresis. 4. Protein concentration of Bee Venom by Lowry method was different at solution rate 1:4000 ; C-BV was 250μg/ml, K-BV I was 190μg/ml, K-BV Ⅱ was 160μg/ml and C-BV was 45μg/ml. 5. Electrophoresis method was unuseful for analysis of Bee Venom when solution rate is above 1:4000 but Protein concentration of Bee Venom by Lowry method was possible. These data from the study can be applied to establish the standard measurement of Bee Venom and prevent pure bee venom from mixing of another components. I think it is desirable to study more about safety of Bee Venom as time goes by.

Brown Spider (Loxosceles genus Venom Toxins: Tools for Biological Purposes

Directory of Open Access Journals (Sweden)

Andrea Senff-Ribeiro

2011-03-01

Full Text Available Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus venom is enriched in low molecular mass proteins (5–40 kDa. Although their venom is produced in minute volumes (a few microliters, and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins.

Hemolytic potency and phospholipase activity of some bee and wasp venoms.

Science.gov (United States)

Watala, C; Kowalczyk, J K

1990-01-01

1. The action of crude venoms of four aculeate species: Apis mellifera, Vespa crabro, Vespula germanica and Vespula vulgaris on human erythrocytes was investigated in order to determine the lytic and phospholipase activity of different aculeate venoms and their ability to induce red blood cell hemolysis. 2. Bee venom was the only extract to completely lyse red blood cells at the concentration of 2-3 micrograms/ml. 3. Phospholipase activity in all of the examined vespid venoms was similar and the highest value was recorded in V. germanica. 4. Vespid venoms exhibited phospholipase B activity, which is lacking in honeybee venom. 5. In all membrane phospholipids but lecithin, lysophospholipase activity of vespid venoms was 2-6 times lower than the relevant phospholipase activity. 6. The incubation of red blood cells with purified bee venom phospholipase A2 was not accompanied by lysis and, when supplemented with purified melittin, the increase of red blood cell lysis was approximately 30%.

Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

Science.gov (United States)

Metz, Martin; Piliponsky, Adrian M.; Chen, Ching-Cheng; Lammel, Verena; Åbrink, Magnus; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

2006-07-01

Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.

Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy

Directory of Open Access Journals (Sweden)

Naruo Yoshida

2015-07-01

Conclusions: The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan.

Characterization of the gila monster (Heloderma suspectum suspectum) venom proteome.

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Sanggaard, Kristian W; Dyrlund, Thomas F; Thomsen, Line R; Nielsen, Tania A; Brøndum, Lars; Wang, Tobias; Thøgersen, Ida B; Enghild, Jan J

2015-03-18

The archetypical venomous lizard species are the helodermatids, the gila monsters (Heloderma suspectum) and the beaded lizards (Heloderma horridum). In the present study, the gila monster venom proteome was characterized using 2D-gel electrophoresis and tandem mass spectrometry-based de novo peptide sequencing followed by protein identification based on sequence homology. A total of 39 different proteins were identified out of the 58 selected spots that represent the major constituents of venom. Of these proteins, 19 have not previously been identified in helodermatid venom. The data showed that helodermatid venom is complex and that this complexity is caused by genetic isoforms and post-translational modifications including proteolytic processing. In addition, the venom proteome analysis revealed that the major constituents of the gila monster venom are kallikrein-like serine proteinases (EC 3.4.21) and phospholipase A2 (type III) enzymes (EC 3.1.1.4). A neuroendocrine convertase 1 homolog that most likely converts the proforms of the previously identified bioactive exendins into the mature and active forms was identified suggesting that these peptide toxins are secreted as proforms that are activated by proteolytic cleavage following secretion as opposed to being activated intracellularly. The presented global protein identification-analysis provides the first overview of the helodermatid venom composition. The helodermatid lizards are the classical venomous lizards, and the pharmacological potential of the venom from these species has been known for years; best illustrated by the identification of exendin-4, which is now used in the treatment of type 2 diabetes. Despite the potential, no global analyses of the protein components in the venom exist. A hindrance is the lack of a genome sequence because it prevents protein identification using a conventional approach where MS data are searched against predicted protein sequences based on the genome sequence

Some Neuropharmacological Effects of the Crude Venom Extract of ...

African Journals Online (AJOL)

This study reports some neuropharmacological effects of the crude venom extract of Conus musicus (family Conidae) in mice using various experimental models. The crude venom was found to significantly increase tail flick reaction time in mice. The effects of the venom on the central nervous system were studied by ...

Chem I Supplement: Bee Sting: The Chemistry of an Insect Venom.

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O'Connor, Rod; Peck, Larry

1980-01-01

Considers various aspects of bee stings including the physical mechanism of the venom apparatus in the bee, categorization of physiological responses of nonprotected individuals to bee sting, chemical composition of bee venom and the mechanisms of venom action, and areas of interest in the synthesis of bee venom. (CS)

Proteomic comparisons of venoms of long-term captive and recently wild-caught Eastern brown snakes (Pseudonaja textilis) indicate venom does not change due to captivity.

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McCleary, Ryan J R; Sridharan, Sindhuja; Dunstan, Nathan L; Mirtschin, Peter J; Kini, R Manjunatha

2016-07-20

Snake venom is a highly variable phenotypic character, and its variation and rapid evolution are important because of human health implications. Because much snake antivenom is produced from captive animals, understanding the effects of captivity on venom composition is important. Here, we have evaluated toxin profiles from six long-term (LT) captive and six recently wild-caught (RC) eastern brown snakes, Pseudonaja textilis, utilizing gel electrophoresis, HPLC-MS, and shotgun proteomics. We identified proteins belonging to the three-finger toxins, group C prothrombin activators, Kunitz-type serine protease inhibitors, and phospholipases A2, among others. Although crude venom HPLC analysis showed LT snakes to be higher in some small molecular weight toxins, presence/absence patterns showed no correlation with time in captivity. Shotgun proteomics indicated the presence of similar toxin families among individuals but with variation in protein species. Although no venom sample contained all the phospholipase A2 subunits that form the textilotoxin, all did contain both prothrombin activator subunits. This study indicates that captivity has limited effects on venom composition, that venom variation is high, and that venom composition may be correlated to geographic distribution. Through proteomic comparisons, we show that protein variation within LT and RC groups of snakes (Pseudonaja textilis) is high, thereby resulting in no discernible differences in venom composition between groups. We utilize complementary techniques to characterize the venom proteomes of 12 individual snakes from our study area, and indicate that individuals captured close to one another have more similar venom gel electrophoresis patterns than those captured at more distant locations. These data are important for understanding natural variation in and potential effects of captivity on venom composition. Copyright © 2016 Elsevier B.V. All rights reserved.

Utility of laboratory testing for the diagnosis of Hymenoptera venom allergy.

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Vachová, Martina; Panzner, Petr; Malkusová, Ivana; Hanzlíková, Jana; Vlas, Tomáš

2016-05-01

A diagnosis of Hymenoptera venom allergy is based on clinical history and the results of skin tests and/or laboratory methods. To analyze the utility of available laboratory tests in diagnosing Hymenoptera venom allergy. Ninety-five patients with Hymenoptera venom allergy with a history of bee (35) or wasp (60) anaphylactic sting reaction and positive skin test with bee or wasp venom were included in this analysis. Specific immunoglobulin E (to bee venom extract, wasp venom extract, available recombinant molecules, and a basophil activation test with venom extracts were assessed in all the patients. Test sensitivity and specificity were calculated by using standard threshold values; then, receiver operating characteristic curve analysis was performed to compute optimal threshold values. Also, statistical analysis of the utility of different combinations of laboratory tests was performed. The optimal threshold values were revealed to be the following: 1.0 kIU/L for bee venom extract (sensitivity, 97.14%; specificity, 100%), 0.35 kIU/L for rApi m 1 (sensitivity, 68.57%; specificity, 100%), 1.22 kIU/L for wasp venom extract (sensitivity, 88.33%; specificity, 95.45%), 0.7 kIU/L for rVes v 5 (sensitivity, 86.67%; specificity, 95.45%), 1.0 kIU/L for rVes v 1 (sensitivity, 56.67%; specificity, 95.45%), 6.5% for basophil activation test with bee venom extract (sensitivity, 80%; specificity, 95.45%), and 4.5% for basophil activation test with wasp venom extract (sensitivity, 91.53%; specificity, 95.45%). The best test combinations were found to be the following: bee venom extract plus rApi m 1 (sensitivity, 97.14%; specificity, 95.45%) in bee and either wasp venom extract plus rVes v 5, or rVes v 5 plus rVes v 1 (both sensitivity, 98.33%; specificity, 95.45%) in patients with wasp venom allergy. Our analysis confirmed that currently used laboratory tests represent effective tools in diagnosing Hymenoptera venom allergy. Moreover, our probabilistic approach offered another

Pain-Causing Venom Peptides: Insights into Sensory Neuron Pharmacology

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Sina Jami

2017-12-01

Full Text Available Venoms are produced by a wide variety of species including spiders, scorpions, reptiles, cnidarians, and fish for the purpose of harming or incapacitating predators or prey. While some venoms are of relatively simple composition, many contain hundreds to thousands of individual components with distinct pharmacological activity. Pain-inducing or “algesic” venom compounds have proven invaluable to our understanding of how physiological nociceptive neural networks operate. In this review, we present an overview of some of the diverse nociceptive pathways that can be modulated by specific venom components to evoke pain.

Venom-derived peptides inhibiting Kir channels: Past, present, and future.

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Doupnik, Craig A

2017-12-01

Inwardly rectifying K + (Kir) channels play a significant role in vertebrate and invertebrate biology by regulating the movement of K + ions involved in membrane transport and excitability. Yet unlike other ion channels including their ancestral K + -selective homologs, there are very few venom toxins known to target and inhibit Kir channels with the potency and selectivity found for the Ca 2+ -activated and voltage-gated K + channel families. It is unclear whether this is simply due to a lack of discovery, or instead a consequence of the evolutionary processes that drive the development of venom components towards their targets based on a collective efficacy to 1) elicit pain for defensive purposes, 2) promote paralysis for prey capture, or 3) facilitate delivery of venom components into the circulation. The past two decades of venom screening has yielded three venom peptides with inhibitory activity towards mammalian Kir channels, including the discovery of tertiapin, a high-affinity pore blocker from the venom of the European honey bee Apis mellifera. Venomics and structure-based computational approaches represent exciting new frontiers for venom peptide development, where re-engineering peptide 'scaffolds' such as tertiapin may aid in the quest to expand the palette of potent and selective Kir channel blockers for future research and potentially new therapeutics. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Embriotoxic effects of maternal exposure to Tityus serrulatus scorpion venom

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A. A. S. Barão

2008-01-01

Full Text Available Tityus serrulatus is the most venomous scorpion in Brazil; however, it is not known whether its venom causes any harm to the offspring whose mothers have received it. This study investigates whether the venom of T. serrulatus may lead to deleterious effects in the offspring, when once administered to pregnant rats at a dose that causes moderate envenomation (3mg/kg. The venom effects were studied on the 5th and on the 10th gestation day (GD5 and GD10. The maternal reproductive parameters of the group that received the venom on GD5 showed no alteration. The group that received the venom on GD10 presented an increase in post-implantation losses. In this group, an increase in the liver weight was also observed and one-third of the fetuses presented incomplete ossification of skull bones. None of the groups that received the venom had any visceral malformation or delay in the fetal development of their offspring. The histopathological analysis revealed not only placentas and lungs but also hearts, livers and kidneys in perfect state. Even having caused little effect on the dams, the venom may act in a more incisive way on the offspring, whether by stress generation or by a direct action.

[Influence of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom].

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Abiev, G A; Babaev, E I; Topchieva, Sh A; Chumburidze, T B; Nemsitsveridze, N G

2009-11-01

The aim of the article was to study the effect of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom. It was found that mice intoxicated with snake venom, with moderate to high exposure to electromagnetic radiation and mice intoxicated with venom, which had not been exposed to the radiation showed the same symptoms of intoxication and death. At the same time, the longevity of mice intoxicated with venom exposed to electromagnetic radiation was higher. The longevity of mice in control group was 25+/-5 min. The longevity of mice intoxicated with exposed to electromagnetic radiation snake venom was from 29 to 60 min. The research showed that the longevity of mice intoxicated with snake venom rose with the level of electromagnetic radiation intensity the snake was exposed to. Accordingly, snake venom, with exposure to high intensity electromagnetic radiation is less toxic.

Comparison of the venom immunogenicity of various species of yellow jackets (genus Vespula).

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Wicher, K; Reisman, R E; Wypych, J; Elliott, W; Steger, R; Mathews, R S; Arbesman, C E

1980-09-01

Venoms from various yellow jacket species were examined by two-dimensional thin-layer chromatography (TDTLC), double-diffusion gel precipitation (DDGP) using rabbit antisera, and the radioallergosorbent test (RAST). Comparison of representative venoms by the TDTLC showed that the venoms of V. vulgaris and V. maculifrons have a larger number of Ninhydrin (triketohydrindene hydrate)-positive substances than the venom of V. squamosa. The results of the DDGP confirmed the differences; venoms of V. vulgaris, V. maculifrons, V. flavopilosa, and V. germanica have one or more major components with immunogenic identity. The venom of V. squamosa has a species-specific major component and some minor components immunologically identical to the other venoms examined. Sera from 21 patients with a history of anaphylaxis following yellow jacket stings were examined by the RAST. Using the venoms of V. maculifrons, V. vulgaris, V. flavopilosa, and V. germanica as coupling antigens, most sera reacted similarly. The sera did not react with V. squamosa. These results suggest that the major component in venom obtained from the four yellow jacket species has immunogenic identity. Venom of V. squamosa differs from the remaining venoms. As a practical corollary, with the exception of venom from V. squamosa, common sensitivity appears to exist among the yellow jacket venoms examined.

Neutralization of Apis mellifera bee venom activities by suramin.

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El-Kik, Camila Z; Fernandes, Fabrício F A; Tomaz, Marcelo Amorim; Gaban, Glauco A; Fonseca, Tatiane F; Calil-Elias, Sabrina; Oliveira, Suellen D S; Silva, Claudia L M; Martinez, Ana Maria Blanco; Melo, Paulo A

2013-06-01

In this work we evaluated the ability of suramin, a polysulfonated naphthylurea derivative, to antagonize the cytotoxic and enzymatic effects of the crude venom of Apis mellifera. Suramin was efficient to decrease the lethality in a dose-dependent way. The hemoconcentration caused by lethal dose injection of bee venom was abolished by suramin (30 μg/g). The edematogenic activity of the venom (0.3 μg/g) was antagonized by suramin (10 μg/g) in all treatment protocols. The changes in the vascular permeability caused by A. mellifera (1 μg/g) venom were inhibited by suramin (30 μg/g) in the pre- and posttreatment as well as when the venom was preincubated with suramin. In addition, suramin also inhibited cultured endothelial cell lesion, as well as in vitro myotoxicity, evaluated in mouse extensor digitorum longus muscle, which was inhibited by suramin (10 and 25 μM), decreasing the rate of CK release, showing that suramin protected the sarcolemma against damage induced by components of bee venom (2.5 μg/mL). Moreover, suramin inhibited the in vivo myotoxicity induced by i.m. injection of A. mellifera venom in mice (0.5 μg/g). The analysis of the area under the plasma CK vs. time curve showed that preincubation, pre- and posttreatment with suramin (30 μg/g) inhibited bee venom myotoxic activity in mice by about 89%, 45% and 40%, respectively. Suramin markedly inhibited the PLA2 activity in a concentration-dependent way (1-30 μM). Being suramin a polyanion molecule, the effects observed may be due to the interaction of its charges with the polycation components present in A. mellifera bee venom. Copyright © 2013 Elsevier Ltd. All rights reserved.

Study of gas-puff Z-pinches on COBRA

Energy Technology Data Exchange (ETDEWEB)

Qi, N.; Rosenberg, E. W.; Gourdain, P. A.; Grouchy, P. W. L. de; Kusse, B. R.; Hammer, D. A.; Bell, K. S.; Shelkovenko, T. A.; Potter, W. M.; Atoyan, L.; Cahill, A. D.; Evans, M.; Greenly, J. B.; Hoyt, C. L.; Pikuz, S. A.; Schrafel, P. C. [Laboratory of Plasma Studies, Cornell University, Ithaca, New York 14853 (United States); Kroupp, E.; Fisher, A.; Maron, Y. [Weizmann Institute of Science, Rehovot 76100 (Israel)

2014-11-15

Gas-puff Z-pinch experiments were conducted on the 1 MA, 200 ns pulse duration Cornell Beam Research Accelerator (COBRA) pulsed power generator in order to achieve an understanding of the dynamics and instability development in the imploding and stagnating plasma. The triple-nozzle gas-puff valve, pre-ionizer, and load hardware are described. Specific diagnostics for the gas-puff experiments, including a Planar Laser Induced Fluorescence system for measuring the radial neutral density profiles along with a Laser Shearing Interferometer and Laser Wavefront Analyzer for electron density measurements, are also described. The results of a series of experiments using two annular argon (Ar) and/or neon (Ne) gas shells (puff-on-puff) with or without an on- (or near-) axis wire are presented. For all of these experiments, plenum pressures were adjusted to hold the radial mass density profile as similar as possible. Initial implosion stability studies were performed using various combinations of the heavier (Ar) and lighter (Ne) gasses. Implosions with Ne in the outer shell and Ar in the inner were more stable than the opposite arrangement. Current waveforms can be adjusted on COBRA and it was found that the particular shape of the 200 ns current pulse affected on the duration and diameter of the stagnated pinched column and the x-ray yield.

Diversity of Snakes in Rajegwesi Tourism Area, Meru Betiri National Park

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Aji Dharma Raharjo

2015-02-01

Full Text Available Rajegwesi tourism area is one of the significant tourism areas in Meru Betiri National Park, East Java, Indonesia. The area rich in term of biodiversity which are potential for developed as natural tourism attraction.  The aim of this study is to identify snakes species diversity and its distribution in Rajegwesi tourism area. Field survey was done in Rajegwesi area, namely swamps forest, residential area, rice fields, agriculture area (babatan, resort area, and Plengkang cliff. This study found some snakes, encompasses Colubridae (10 species, Elapidae (four species, and Phytonidae (one species. There are Burmese Python (Python reticulatus, Red-necked Keelback (Rhabdophis subminiatus, Painted Bronzeback Snake (Dendrelaphis Pictus, Black Copper Rat Snake (Coelognathus flavolineatus, Radiated Rat Snake (C. radiatus, Striped Keelback (Xenochrophis vittatus, Checkered Keelback (X. piscator, Spotted Ground Snake (Gongyosoma balioderius, Gold-ringed Cat Snake (Boiga dendrophila, Common Wolf Snake (Lycodon capucinus, Banded Wolf snake (L. subcinctus, Cobra (Naja sputatrix, King Cobra (Ophiophagus hannah, Malayan Krait (Bungarus candidus, and Banded Krait (B. fasciatus was found. These snake habitats distributes at 21 coordinate points. Keywords: conservation, ecotourism, snakes.

COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

Energy Technology Data Exchange (ETDEWEB)

Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

2012-05-08

Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to the enormous complexity and dynamic nature of their chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions of monomers pertinent to secondary organic aerosol (SOA) formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next one. The simulation generated thousands of molecular structures in the mass range of 120-500 Da, and correctly predicted ~70% of the individual SOA constituents observed by high-resolution mass spectrometry (HR-MS). Selected predicted structures were confirmed with tandem mass spectrometry. Esterification and hemiacetal formation reactions were shown to play the most significant role in oligomer formation, whereas aldol condensation was shown to be insignificant. COBRA is not limited to atmospheric aerosol chemistry, but is broadly applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods.

Lipase and phospholipase activities of Hymenoptera venoms ...

African Journals Online (AJOL)

native gel), Polistes flavis venom has four major protein bands, one of which has lipase activity; with sodium dodecyl sulfate (SDS-PAGE), the venom had eighteen bands with molecular weights ranging from a maximum of 94 kD and a minimum of ...

Identification of snake venom allergens by two-dimensional electrophoresis followed by immunoblotting.

Science.gov (United States)

Hu, Yujing; Yang, Liming; Yang, Haiwei; He, Shaoheng; Wei, Ji-Fu

2017-01-01

This allergic reaction to snake venom was described to occur in patients after recurrent exposure through bites in amateur and professional snake handlers, which might be underestimated and contribute to fatal snakebites in victim, independently from the toxicity of the venom itself. Few allergens were identified from snake venoms by normal SDS-PAGE, which cannot separate the snake venom completely. In the present study, we identified nine potential allergens by two-dimensional (2D) electrophoresis followed by immunoblotting (named as allergenomics) in Protobothrops mucrosquamatus venom. By multidimensional liquid chromatography-ion trap mass spectrometry (MDLC-ESI-LTQ-MS/MS) analysis, six allergens showed sequence similarity to snake venom serine proteinases. Other allergens showed sequence similarity to snake venom metalloproteinase. These allergic reactions to snake venom allergens might contribute to fatal snakebites in victim, independently. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Insect venom allergies : Update 2016 for otorhinolaryngologists].

Science.gov (United States)

Klimek, L; Dippold, N; Sperl, A

2016-12-01

Due to the increasing incidence of hymenoptera venom allergies and the potentially life-threatening reactions, it is important for otolaryngologists working in allergology to have an understanding of modern diagnostic and treatment standards for this allergic disease. Molecular diagnosis with recombinant single allergens from bee and wasp venom components improves the diagnostics of insect venom allergies, particularly in patients with double-positive extract-based test results. Detection of specific sensitizations to bee or wasp venom enables double sensitizations to be better distinguished from cross-reactivity. Based on patient history and test results, the patient is initially advised on avoidance strategies and prescribed an emergency medication kit. Then, the indication for allergen-specific immunotherapy (AIT) is evaluated. The dose-increase phase can be performed using conventional, cluster, rush, or ultra-rush schedules, whereby rapid desensitization (rush AIT) performed in the clinic seems to be particularly effective as initial treatment.

Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of IgE antibodies to species-specific major allergens Api m1 and Ves v5.

Science.gov (United States)

Müller, U R; Johansen, N; Petersen, A B; Fromberg-Nielsen, J; Haeberli, G

2009-04-01

In patients with hymenoptera venom allergy diagnostic tests are often positive with honey bee and Vespula venom causing problems in selection of venoms for immunotherapy. 100 patients each with allergic reactions to Vespula or honey bee stings and positive i.e. skin tests to the respective venom, were analysed for serum IgE to bee venom, Vespula venom and crossreacting carbohydrate determinants (CCDs) by UNICAP (CAP) and ADVIA Centaur (ADVIA). IgE-antibodies to species specific recombinant major allergens (SSMA) Api m1 for bee venom and Ves v5 for Vespula venom, were determined by ADVIA. 30 history and skin test negative patients served as controls. By CAP sensitivity was 1.0 for bee and 0.91 for Vespula venom, by ADVIA 0.99 for bee and 0.91 for Vespula venom. None of the controls were positive with either test. Double positivity was observed in 59% of allergic patients by CAP, in 32% by ADVIA. slgE to Api m1 was detected in 97% of bee and 17% of Vespula venom allergic patients, slgE to Ves v5 in 87% of Vespula and 17% of bee venom allergic patients. slgE to CCDs were present in 37% of all allergic patients and in 56% of those with double positivity and were more frequent in bee than in Vespula venom allergic patients. Double positivity of IgE to bee and Vespula venom is often caused by crossreactions, especially to CCDs. IgE to both Api m1 and Ves v5 indicates true double sensitization and immunotherapy with both venoms.

Development in High-Density Cobra Fiber Positioners for the Subaru Telescope's Prime Focus Spectrometer

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Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Mic D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger S.

2012-01-01

The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed "Cobra", will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual "SCARA robot" mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5 micrometers of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

Intraspecies variation in the venom of the rattlesnake Crotalus simus from Mexico: different expression of crotoxin results in highly variable toxicity in the venoms of three subspecies.

Science.gov (United States)

Castro, Edgar Neri; Lomonte, Bruno; del Carmen Gutiérrez, María; Alagón, Alejandro; Gutiérrez, José María

2013-07-11

The composition and toxicological profile of the venom of the rattlesnake Crotalus simus in Mexico was analyzed at the subspecies and individual levels. Venoms of the subspecies C. s. simus, C. s. culminatus and C. s. tzabcan greatly differ in the expression of the heterodimeric neurotoxin complex 'crotoxin', with highest concentrations in C. s. simus, followed by C. s. tzabcan, whereas the venom of C. s. culminatus is almost devoid of this neurotoxic PLA2. This explains the large variation in lethality (highest in C. s. simus, which also exerts higher myotoxicity). Coagulant activity on plasma and fibrinogen occurs with the venoms of C. s. simus and C. s. tzabcan, being absent in C. s. culminatus which, in turn, presents higher crotamine-like activity. Proteomic analysis closely correlates with toxicological profiles, since the venom of C. s. simus has high amounts of crotoxin and of serine proteinases, whereas the venom of C. s. culminatus presents higher amounts of metalloproteinases and crotamine. This complex pattern of intraspecies venom variation provides valuable information for the diagnosis and clinical management of envenoming by this species in Mexico, as well as for the preparation of venom pools for the production and quality control of antivenoms. This study describes the variation in venom composition and activities of the three subspecies of Crotalus simus from Mexico. Results demonstrate that there is a notorious difference in these venoms, particularly regarding the content of the potent neurotoxic phospholipase A2 complex 'crotoxin'. In addition, other differences were observed regarding myotoxic and coagulant activities, and expression of the myotoxin 'crotamine'. These findings have implications in, at least, three levels: (a) the adaptive role of variations in venom composition; (b) the possible differences in the clinical manifestations of envenomings by these subspecies in Mexico; and (c) the design of venom mixtures for the preparation of

Addiction to Snake Venom.

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Das, Saibal; Barnwal, Preeti; Maiti, Tanay; Ramasamy, Anand; Mondal, Somnath; Babu, Dinesh

2017-07-03

The nature of addiction depends on various factors. The tendency to have already used several addictive substances and to seek high sensation experiences as a result of specific personality traits may lead to extreme and peculiar forms of addictions. Even belonging to specific social and cultural background may lead to such forms of addiction such as intentional snake bite and willful envenomation. In this article, we have discussed the peculiarities and practical insight of such addiction to snake venom. The possible molecular mechanism behind such venom-mediated reinforcement has also been highlighted. Finally, we have stressed upon the treatment and de-addiction measures.

Bee Venom Pharmacopuncture Responses According to Sasang Constitution and Gender

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Kim Chaeweon

2013-12-01

Full Text Available Objectives: The current study was performed to compare the bee venom pharmacopuncture skin test reactions among groups with different sexes and Sasang constitutions. Methods: Between July 2012 and June 2013, all 76 patients who underwent bee venom pharmacopuncture skin tests and Sasang constitution diagnoses at Oriental Medicine Hospital of Sangji University were included in this study. The skin test was performed on the patient’s forearm intracutaneously with 0.05 ml of sweet bee venom (SBV on their first visit. If the patients showed a positive response, the test was discontinued. On the other hand, if the patient showed a negative response, the test was performed on the opposite forearm intracutaneously with 0.05 ml of bee venom pharmacopuncture 25% on the next day or the next visit. Three groups were made to compare the differences in the bee venom pharmacopuncture skin tests according to sexual difference and Sasang constitution: group A showed a positive response to SBV, group B showed a positive response to bee venom pharmacopuncture 25%, and group C showed a negative response on all bee venom pharmacopuncture skin tests. Fisher’s exact test was performed to evaluate the differences statistically. Results: The results of the bee venom pharmacopuncture skin tests showed no significant differences according to Sasang constitution (P = 0.300 or sexual difference (P = 0.163. Conclusion: No significant differences on the results of bee venom pharmacopuncture skin tests were observed according to two factors, Sasang constitution and the sexual difference.

Anti-arthritic effects of microneedling with bee venom gel

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Mengdi Zhao

2016-10-01

Conclusions: Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction. Choose the 750 μm microneedle with 10N force on skin about 3 minutes, bee venom can play the optimal role, and the anti-inflammatory effect is obvious. Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.

A Study on the Stability of Diluted Bee Venom Solution

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Mi-Suk Kang

2003-06-01

Full Text Available Objective : The purpose of this study was to investigate the stability of bee venom according to the keeping method and period. Method : The author observed microbial contamination of bee venom in nutrient agar, broth, YPD agar and YPD media and antibacterial activity for S. aureus, E. coli manufactured 12, 6 and 3 months ago as the two type of room temperature and 4℃ cold storage. Result : 1. 1:3,000 and 1:4,000 diluted bee venom solution did not show microbial contamination both room temperature and cold storage within twelve months. 2. There was antibacterial activity of diluted bee venom for S. aureus in cold storage within twelve months and there was no antibacterial activity of diluted bee venom for S. aureus in twelve months, room temperature storage. 3. We could not observe the zone of inhibition around paper disc of all for E.coli. in 1:3,000, 1:30,000 and 1:3,000,000 diluted bee venom solution, respectively. According to results, we expect that diluted bee venom solution is stable both cold and room temperature storage within twelve months.

Factors underlying the natural resistance of animals against snake venoms

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H. Moussatché

1989-01-01

Full Text Available The existence of mammals and reptilia with a natural resistance to snake venoms is known since a long time. This fact has been subjected to the study by several research workers. Our experiments showed us that in the marsupial Didelphis marsupialis, a mammal highly resistant to the venom of Bothrops jararaca, and other Bothrops venoms, has a genetically origin protein, a alpha-1, acid glycoprotein, now highly purified, with protective action in mice against the jararaca snake venom.

Functional Morphology of Venom Apparatus of Euscorpius mingrelicus(Scorpiones: Euscorpiidae)

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YİĞİT, Nazife; BAYRAM, Abdullah; DANIŞMAN, Tarık

2007-01-01

The objective of the present study is to describe the functional morphology of venom apparatus of Euscorpius mingrelicus (Kessler, 1874) by using light microscope and scanning electron microscope (SEM). The venom apparatus, situates in the last segment of metasoma (telson), is composed of a pair of venom glands and sting. Telson is covered by cuticular exoskeleton as well as all body, and there are cuticular setae and pits on it as serve sensory organ. The general organization of the venom ap...

Molecular barcoding, DNA from snake venom, and toxinological research: Considerations and concerns.

Science.gov (United States)

Powell, Randy L; Reyes, Steven R; Lannutti, Dominic I

2006-12-15

The problem of species identification in toxinological research and solutions such as molecular barcoding and DNA extraction from venom samples are addressed. Molecular barcoding is controversial with both perceived advantages and inherent problems. A method of species identification utilizing mitochondrial DNA from venom has been identified. This method could result in deemphasizing the importance of obtaining detailed information on the venom source prior to analysis. Additional concerns include; a cost prohibitive factor, intraspecific venom variation, and venom processing issues. As researchers demand more stringent records and verification, venom suppliers may be prompted to implement improved methods and controls.

Irradiation of the Crude Venom of Bothrops jararacussu to Obtain Toxoid

International Nuclear Information System (INIS)

Ferreira, Camila G.; Avalloni, Tania M.; Oshima-Franco, Yoko; Oliveira, Sara de J; Oliveira, Jose M. Jr. de; Cogo, Jose C.

2011-01-01

The aim of this work was to reduce the toxicity of Bothrops jararacussu venom using gamma-rays of low-energy coming from a source of Americium-241 (E = 59.6 keV and 3.7x10 9 Bq of activity) in order to obtain a toxoid. The radiation dose that each sample received was controlled by exposure time of the venom to the radiation beam. Mouse nerve phrenic-diaphragm preparation was used for testing the loss of venom toxicity, since the venom causes an irreversible neuromuscular blockade. In this condition, the several samples of irradiated venom, when assayed in neuromuscular preparation showed that with a dose of 0.051 Gy the paralysis caused by the irradiated venom was of 91%, at 0.360 Gy was of 79%, at 1.662 Gy was of 50% and at 2.448 Gy was of 42%. Therefore, it can be concluded that the irradiation model was able to induce a progressive loss of the venom toxicity.

Irradiation of the Crude Venom of Bothrops jararacussu to Obtain Toxoid

Science.gov (United States)

Ferreira, Camila G.; Avalloni, Tânia M.; Oshima-Franco, Yoko; de J. Oliveira, Sara; de Oliveira, José M.; Cogo, José C.

2011-08-01

The aim of this work was to reduce the toxicity of Bothrops jararacussu venom using gamma-rays of low-energy coming from a source of Americium-241 (E = 59.6 keV and 3.7×109 Bq of activity) in order to obtain a toxoid. The radiation dose that each sample received was controlled by exposure time of the venom to the radiation beam. Mouse nerve phrenic-diaphragm preparation was used for testing the loss of venom toxicity, since the venom causes an irreversible neuromuscular blockade. In this condition, the several samples of irradiated venom, when assayed in neuromuscular preparation showed that with a dose of 0.051 Gy the paralysis caused by the irradiated venom was of 91%, at 0.360 Gy was of 79%, at 1.662 Gy was of 50% and at 2.448 Gy was of 42%. Therefore, it can be concluded that the irradiation model was able to induce a progressive loss of the venom toxicity.

Snake venoms: A brief treatise on etymology, origins of terminology, and definitions.

Science.gov (United States)

Weinstein, Scott A

2015-09-01

The ancient perceptions of "venomous" and "poisonous snakes", as well as the Indo-European (IE) etymological origins of the term "venom" specifically associated with snakes are considered. Although several ancient cultures perceived snakes as symbols of fecundity and renewal, concurrent beliefs also associated venomous snakes with undesirable human characteristics or as portending non-propitious events. The respective IE roots of the terms "venom" and "poison", "wen" and "poi" refer to desire or the act of ingesting liquids. The origin of the term, "venom", is associated with polytheistic cults that emphasized attainment of desires sometimes assisted by "love potions", a term later interpolated with the word, "poison". Specific interpretation of the term, venom, has varied since its first probable use in the mid-Thirteenth Century. The definition of snake venom has long been contended, and interpretations have often reflected emphasis on the pharmacological or experimental toxicity of medically relevant snake venoms with less regard for the basic biological bases of these venoms, as well as those from snakes with no known medical significance. Several definitions of "snake venom" and their defining criteria are reviewed, and critical consideration is given to traditional criteria that might facilitate the future establishment of a biologically accurate definition. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

[Effects of venom from Sclerodermus sichuanensis Xiao on pupa of Tenebrio molitor].

Science.gov (United States)

Zhuo, Zhi-Hang; Yang, Wei; Qin, Huan; Yang, Chun-Ping; Yang, Hua; Xu, Dan-Ping

2013-11-01

To explore the regulatory mechanisms of parasitism of Sclerodermus sichuanensis on Tenebrio molitor, the methods of natural parasitism and venom injection were adopted to investigate the effects of the venom from S. sichuanensis on the pupa of T. molitor in the parasitic process. Under venom injection, the paralytic degree of the pupa had a positive correlation with the concentration of injected venom, and the number of recovered pupa had a negative correlation with the injected venom concentration. The T. molitor pupa was in slight and reversible paralysis when injected with 0.01 VRE (venom reservoir equivalent) of venom, and in non-reversible and complete paralysis when 0.2 VRE was injected. The pupa died massively and appeared a wide range of melanization when injected with soil bacterial suspension alone, but the melanization delayed and the mortality declined significantly when the mixed liquor of bacterium and venom was injected. The bacteriostasis of the venom on Staphylococcus aureus was significantly stronger than that on Escherichia coli. Within a definite range of temperature, the paralytic activity decreased significantly with increasing temperature, the bacteriostasis on S. aureus increased significantly, while that on E. coli was opposite. This study showed that the venom from S. sichuanensis had the effects of paralysis, bacteriostasis, inhibiting exuviations, and delaying melanization.

Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

Science.gov (United States)

Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

2016-12-14

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

[Therapy control of specific hymenoptera venom allergy].

Science.gov (United States)

Aust, W; Wichmann, G; Dietz, A

2010-12-01

In Germany anaphylactic reactions after insect stings are mostly caused by honey bee (Apis mellifera) and wasp (Vespula vulgaris, Vespula germanica). In the majority of cases venom immunotherapy is a successful therapy and protects patients from recurrent systemic anaphylactic reaction. In some patients persistent severe reactions after insect sting can even occur in spite of venom therapy, as a sign of therapy failure. It is important to identify these patients, who do not benefit from venom immunotherapy, in an early stage of therapy. In this case dose rate of venom immunotherapy must be adjusted for a successful therapy outcome. Up to now skin prick tests, specific IgE-antibodies and in vitro diagnostics are not suitable for detecting therapy failure. Patients with treatment failure can be diagnosed by insect sting test and almost all of them will become fully protected by increasing the maintenance dose. © Georg Thieme Verlag KG Stuttgart · New York.

Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

Science.gov (United States)

Thakur, Rupamoni; Mukherjee, Ashis K

2017-06-01

Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits

Science.gov (United States)

Walker, Andrew A.; Weirauch, Christiane; Fry, Bryan G.; King, Glenn F.

2016-01-01

The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools. PMID:26907342

Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits.

Science.gov (United States)

Walker, Andrew A; Weirauch, Christiane; Fry, Bryan G; King, Glenn F

2016-02-12

The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools.

Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits

Directory of Open Access Journals (Sweden)

Andrew A. Walker

2016-02-01

Full Text Available The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools.

The Study on the Snake by TOXICON

Directory of Open Access Journals (Sweden)

Sung-wook Kim

2003-06-01

Full Text Available The study was carried out to investigate the researches of Snake which was published papers in the TOXICON(1990-2.000, one of the most famous Journal of toxicology. And the results were as follows: 1. The number related with Snake is 195papers. 2. There were great papers related wih Cobra, and next is Tigris, Viper, etc. 3. There were great papers related wih protein in the composition of snake venom. 4. There were great papers related wih neurotoxin in the research of poisonous character. 5. There were great papers related wih Viper according to the anticoagulation. 6. Eight papers were published to study the immune response of snake venom. 7. The papers of molecular study of snake venom were seven. 8. The papers of anti-snake venom study were three.

Effect of gamma irradiation on toxicity and immunogenicity of Androctonus australis hector venom

International Nuclear Information System (INIS)

Abib, L.; Laraba-Djebari, F.

2003-01-01

An investigation was made of the radiosensitivity of the toxic and immunological properties of Androctonus australis hector venom. This venom was irradiated with two doses of gamma rays (1 and 2 kGy) from a 60 Co source. The results showed that venom toxicity was abolished for the two radiation doses (1 and 2 kGy) with, respectively, 10 and 25 times its initial LD50 value. However, irradiated venoms were immunogenic, and the antibodies elicited by them were able to recognize the native venom by enzyme-linked immunosorbent assay. Antisera raised against these toxoids (1 and 2 kGy) had a higher neutralizing capacity and immunoreactivity against all components of native venom than did the antiserum produced against the native venom. The antiserum of rabbits immunized with 2-kGy-irradiated venom was more efficient than 1-kGy-irradiated toxoid antiserum. Indeed, in vivo protection assays showed that the mice immunized with 2-kGy-irradiated venom resisted lethal doses (i.p.) of A. australis hector venom. (author)

Study on Bee venom and Pain

Directory of Open Access Journals (Sweden)

Hyoung-Seok Yun

2000-07-01

Full Text Available In order to study Bee venom and Pain, We searched Journals and Internet. The results were as follows: 1. The domestic papers were total 13. 4 papers were published at The journal of korean acupuncture & moxibustion society, 3 papers were published at The journal of korean oriental medical society, Each The journal of KyoungHee University Oriental Medicine and The journal of korean sports oriental medical society published 1 papers and Unpublished desertations were 3. The clinical studies were 4 and the experimental studies were 9. 2. The domestic clinical studies reported that Bee venom Herbal Acupuncture therapy was effective on HIVD, Subacute arthritis of Knee Joint and Sequale of sprain. In the domestic experimental studies, 5 were related to analgesic effect of Bee vnom and 4 were related to mechanism of analgesia. 3. The journals searched by PubMed were total 18. 5 papers were published at Pain, Each 2 papers were published at Neurosci Lett. and Br J Pharmacol, and Each Eur J Pain, J Rheumatol, Brain Res, Neuroscience, Nature and Toxicon et al published 1 paper. 4. In the journals searched by PubMed, Only the experimental studies were existed. 8 papers used Bee Venom as pain induction substance and 1 paper was related to analgesic effects of Bee venom. 5. 15 webpage were searched by internet related to Bee Venom and pain. 11 were the introduction related to arthritis, 1 was the advertisement, 1 was the patient's experience, 1 was the case report on RA, 1 was review article.

SNAKE VENOM INSTABILITY • Department of Physiology, Medical ...

African Journals Online (AJOL)

preferable to desiccated samples for use in snake venom research (Bjork ... experimental results suggest that dried venom samples may be influenced by different ..... true for the commercial samples, as these are collectively pooled before ...

Differential Properties of Venom Peptides and Proteins in Solitary vs. Social Hunting Wasps

Science.gov (United States)

Lee, Si Hyeock; Baek, Ji Hyeong; Yoon, Kyungjae Andrew

2016-01-01

The primary functions of venoms from solitary and social wasps are different. Whereas most solitary wasps sting their prey to paralyze and preserve it, without killing, as the provisions for their progeny, social wasps usually sting to defend their colonies from vertebrate predators. Such distinctive venom properties of solitary and social wasps suggest that the main venom components are likely to be different depending on the wasps’ sociality. The present paper reviews venom components and properties of the Aculeata hunting wasps, with a particular emphasis on the comparative aspects of venom compositions and properties between solitary and social wasps. Common components in both solitary and social wasp venoms include hyaluronidase, phospholipase A2, metalloendopeptidase, etc. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, some neurotoxic peptides (e.g., pompilidotoxin and dendrotoxin-like peptide) and proteins (e.g., insulin-like peptide binding protein) appear to be specific to solitary wasp venom. In contrast, several proteins, such as venom allergen 5 protein, venom acid phosphatase, and various phospholipases, appear to be relatively more specific to social wasp venom. Finally, putative functions of main venom components and their application are also discussed. PMID:26805885

Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients

NARCIS (Netherlands)

Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K.; Wijmenga, Cisca; Jassem, Ewa; Oude Elberink, Joanne N. G.

Background: Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of

A study on the numerical instability of COBRA-series subchannel analysis codes at low-pressure and low-flow conditions

International Nuclear Information System (INIS)

Yoo, Y. J.; Hwnag, T. H.; Kim, K. K.; Ji, S. K.

2001-01-01

The numerical instability at low-pressure and low-flow conditions has been confirmed to be the common problem of the existing COBRA-series subchannel analysis codes. In addition, the range of operating conditions at which the analyses by the codes are impossible has been evaluated. To evaluate the MATRA's inapplicable range of operating conditions of the SMART core that is to be operated at the low flow condition, i.e. about 30% of the flow of the existing commercial pressurized water reactors at the steady-state condition, the analyses of various operating conditions were performed by using several representative COBRA-series subchannel analysis codes including MATRA. TORC of CE, COBRA3CP of Siemens/KWU, COBRA4I of PNL, and MATRA of KAERI were chosen as the subchannel analysis codes to be evaluated. The various operating conditions used in the CHF tests carried out at the Winfrith Establishment of UKAEA were chosen as the conditions to be analyzed. As the result, the numerical instabilities at low-pressure and low-flow conditions occurred in the analyses by all of the codes. It was revealed that the MATRA code, which numerically more stable thatn the other codes, was not able to analyze the conditions of the pressure not more than 100 bar and the mass velocity not more than 300 kg/sec-m 2 . Hereafter it is required to find out the exact reason for the numerical instability of the existing COBRA-series subchannel analysis codes at low-pressure and low-flow conditions and to devise the new method to get over that numerical problem

Antioxidant activity and irritation property of venoms from Apis species.

Science.gov (United States)

Somwongin, Suvimol; Chantawannakul, Panuwan; Chaiyana, Wantida

2018-04-01

Pharmacological effects of bee venom has been reported, however, it has been restricted to the bee venom collected from European honey bee (Apis mellifera). The aim of the present study was to compare the antioxidant activities and irritation properties of venoms collected from four different Apis species in Thailand, which includes Apis cerena (Asian cavity nesting honeybee), Apis florea (dwarf honeybee), Apis dorsata (giant honeybee), and A. mellifera. Melittin content of each bee venom extracts was investigated by using high-performance liquid chromatography. Ferric reducing antioxidant power, 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), and 1, 1-diphenyl-2-picrylhydrazyl assay were used to determine the antioxidant activity, whereas, hen's egg test chorioallantoic membrane assay was used to determine the irritation property of each bee venom extracts. Melittin was the major constituent in all bee venom extracts. The melittin content in A. dorsata, A. mellifera, A. florea, and A. cerena were 95.8 ± 3.2%, 76.5 ± 1.9%, 66.3 ± 8.6%, and 56.8 ± 1.8%, respectively. Bee venom extract from A. dorsata possessed the highest antioxidant activity with the inhibition of 41.1 ± 2.2% against DPPH, Trolox equivalent antioxidant capacity of 10.21 ± 0.74 mM Trolox/mg and equivalent concentration (EC 1 ) of 0.35 ± 0.02 mM FeSO 4 /mg. Bee venom extract from A. mellifera exhibited the highest irritation, followed by A. cerena, A. dorsata, and A. florea, respectively. Melittin was the compound responsible for the irritation property of bee venom extracts since it could induce severe irritation (irritation score was 13.7 ± 0.5, at the concentration of 2 mg/ml). The extract from A. dorsata which possessed the highest antioxidant activity showed no irritation up to the concentration of 0.1 mg/ml. Therefore, bee venom extract from A. dorsata at the concentration not more than 0.1 mg/ml would be suggested for using

A study of bacterial contamination of rattlesnake venom

Directory of Open Access Journals (Sweden)

E. Garcia-Lima

1987-03-01

Full Text Available The authors studied the bacterial contamination of rattlesnake venom isolated from snakes in captivity and wild snakes caught recently. The captive snakes showed a relatively high incidence of bacterial contamination of their venom.

Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

Science.gov (United States)

Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

2014-01-01

The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms.

Science.gov (United States)

Dos Santos-Pinto, José Roberto Aparecido; Perez-Riverol, Amilcar; Lasa, Alexis Musacchio; Palma, Mario Sergio

2018-06-15

Among venomous animals, Hymenoptera have been suggested as a rich source of natural toxins. Due to their broad ecological diversity, venom from Hymenoptera insects (bees, wasps and ants) have evolved differentially thus widening the types and biological functions of their components. To date, insect toxinology analysis have scarcely uncovered the complex composition of bee, wasp and ant venoms which include low molecular weight compounds, highly abundant peptides and proteins, including several allergens. In Hymenoptera, these complex mixtures of toxins represent a potent arsenal of biological weapons that are used for self-defense, to repel intruders and to capture prey. Consequently, Hymenoptera venom components have a broad range of pharmacological targets and have been extensively studied, as promising sources of new drugs and biopesticides. In addition, the identification and molecular characterization of Hymenoptera venom allergens have allowed for the rational design of component-resolved diagnosis of allergy, finally improving the outcome of venom immunotherapy (VIT). Until recently, a limited number of Hymenoptera venoms had been unveiled due to the technical limitations of the approaches used to date. Nevertheless, the application of novel techniques with high dynamic range has significantly increased the number of identified peptidic and proteinaceous toxins. Considering this, the present review summarizes the current knowledge about the most representative Hymenoptera venom peptides and proteins which are under study for a better understanding of the insect-caused envenoming process and the development of new drugs and biopesticides. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

Science.gov (United States)

Lee, Gihyun; Bae, Hyunsu

2016-01-01

Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson’s disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes. PMID:26907347

Embryotoxicity following repetitive maternal exposure to scorpion venom

Directory of Open Access Journals (Sweden)

BN Hmed

2012-01-01

Full Text Available Although it is a frequent accident in a few countries, scorpion envenomation during pregnancy remains scarcely studied. In the present study, the effects of repetitive maternal exposure to Buthus occitanus tunetanus venom are investigated and its possible embryotoxic consequences on rats. Primigravid rats received a daily intraperitoneal dose of 1 mL/kg of saline solution or 300 µg/kg of crude scorpion venom, from the 7th to the 13th day of gestation. On the 21st day, the animals were deeply anesthetized using diethyl-ether. Then, blood was collected for chemical parameter analysis. Following euthanasia, morphometric measurements were carried out. The results showed a significant increase in maternal heart and lung absolute weights following venom treatment. However, the mean placental weight per rat was significantly diminished. Furthermore, blood urea concentration was higher in exposed rats (6.97 ± 0.62 mmol/L than in those receiving saline solution (4.94 ± 0.90 mmol/L. Many organs of venom-treated rat fetuses (brain, liver, kidney and spleen were smaller than those of controls. On the contrary, fetal lungs were significantly heavier in fetuses exposed to venom (3.2 ± 0.4 g than in the others (3.0 ± 0.2 g. Subcutaneous blood clots, microphthalmia and total body and tail shortening were also observed in venom-treated fetuses. It is concluded that scorpion envenomation during pregnancy potentially causes intrauterine fetal alterations and growth impairment.

Structures and Functions of Snake Venom Metalloproteinases (SVMP) from Protobothrops venom Collected in Japan.

Science.gov (United States)

Oyama, Etsuko; Takahashi, Hidenobu

2017-08-04

Snake venom metalloproteinases (SVMP) are widely distributed among the venoms of Crotalinae and Viperidae, and are organized into three classes (P-I, P-II and P-III) according to their size and domain structure. P-I SVMP are the smallest SVMP, as they only have a metalloproteinase (M) domain. P-II SVMP contain a disintegrin-like (D) domain, which is connected by a short spacer region to the carboxyl terminus of the M domain. P-III SVMP contain a cysteine-rich (C) domain, which is attached to the carboxyl terminus of the D domain. Some SVMP exhibit hemorrhagic activity, whereas others do not. In addition, SVMP display fibrinolytic/fibrinogenolytic (FL) activity, and the physiological functions of SVMP are controlled by their structures. Furthermore, these proteinases also demonstrate fibrinogenolytic and proteolytic activity against synthetic substrates for matrix metalloproteinases and ADAM (a disintegrin and metalloproteinase). This article describes the structures and FL, hemorrhagic, and platelet aggregation-inhibiting activity of SVMP derived from Protobothrops snake venom that was collected in Japan.

Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development

DEFF Research Database (Denmark)

Laustsen, Andreas Hougaard; Lomonte, Bruno; Lohse, Brian

2015-01-01

The venom proteome of the black mamba, Dendroaspis polylepis, from Eastern Africa, was, for the first time, characterized. Forty- different proteins and one nucleoside were identified or assigned to protein families. The most abundant proteins were Kunitz-type proteinase inhibitors, which include...... the unique mamba venom components ‘dendrotoxins’, and α-neurotoxins and other representatives of the three-finger toxin family. In addition, the venom contains lower percentages of proteins from other families, including metalloproteinase, hyaluronidase, prokineticin, nerve growth factor, vascular...... to toxicity by influencing the toxin biodistribution. ELISA immunoprofiling and preclinical assessment of neutralization showed that polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of D. polylepis venom, albeit showing different potencies. Antivenoms had...

Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms.

Science.gov (United States)

Casewell, Nicholas R; Wagstaff, Simon C; Wüster, Wolfgang; Cook, Darren A N; Bolton, Fiona M S; King, Sarah I; Pla, Davinia; Sanz, Libia; Calvete, Juan J; Harrison, Robert A

2014-06-24

Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite.

Component Analysis of Bee Venom from lune to September

Directory of Open Access Journals (Sweden)

Ki Rok Kwon

2007-06-01

Full Text Available Objectives : The aim of this study was to observe variation of Bee Venom content from the collection period. Methods : Content analysis of Bee Venom was rendered using HPLC method by standard melittin Results : Analyzing melittin content using HPLC, 478.97mg/g at june , 493.89mg/g at july, 468.18mg/g at August and 482.15mg/g was containing in Bee Venom at september. So the change of melittin contents was no significance from June to September. Conclusion : Above these results, we concluded carefully that collecting time was not important factor for the quality control of Bee Venom, restricted the period from June to September.

Characterization of the gila monster (Heloderma suspectum suspectum) venom proteome

DEFF Research Database (Denmark)

Sanggaard, Kristian Wejse; Dyrlund, Thomas Franck; Thomsen, Line Rold

2015-01-01

of venom. Of these proteins, 19 have not previously been identified in helodermatid venom. The data showed that helodermatid venom is complex and that this complexity is caused by genetic isoforms and post-translational modifications including proteolytic processing. In addition, the venom proteome...... analysis revealed that the major constituents of the gila monster venom are kallikrein-like serine proteinases (EC 3.4.21) and phospholipase A2 (type III) enzymes (EC 3.1.1.4). A neuroendocrine convertase 1 homolog that most likely converts the proforms of the previously identified bioactive exendins...... into the mature and active forms was identified suggesting that these peptide toxins are secreted as proforms that are activated by proteolytic cleavage following secretion as opposed to being activated intracellularly. The presented global protein identification-analysis provides the first overview...

Ampulexins: A New Family of Peptides in Venom of the Emerald Jewel Wasp, Ampulex compressa.

Science.gov (United States)

Moore, Eugene L; Arvidson, Ryan; Banks, Christopher; Urenda, Jean Paul; Duong, Elizabeth; Mohammed, Haroun; Adams, Michael E

2018-03-27

The parasitoid wasp Ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach Periplaneta americana, inducing a 7 to 10 day lethargy termed hypokinesia. Hypokinesia presents as a significant reduction in both escape response and spontaneous walking. We examined aminergic and peptidergic components of milked venom with HPLC and MALDI-TOF mass spectrometry. HPLC coupled with electrochemical detection confirmed the presence of dopamine in milked venom, while mass spectrometry revealed that the venom gland and venom sac have distinct peptide profiles, with milked venom predominantly composed of venom sac peptides. We isolated and characterized novel α-helical, amphipathic venom sac peptides that constitute a new family of venom toxins termed ampulexins. Injection of the most abundant venom peptide, ampulexin 1, into the subesophageal ganglion of cockroaches resulted in a short-term increase in escape threshold. Neither milked venom nor venom peptides interfered with growth of Escherichia coli or Bacillus thuringiensis on agar plates, and exposure to ampulexins or milked venom did not induce cell death in Chinese hamster ovary cells (CHO-K1) or Hi5 cells ( Trichoplusia ni).

Introducing COBRAs: a holistic exploration of motivations for brand-related social media use

NARCIS (Netherlands)

Muntinga, D.G.; Moorman, M.; Smit, E.G.

2009-01-01

Propelled by highly interactive technologies, internet users are increasingly becoming active consumers, contributors and producers of content on brands. Consumer’s Online Brand-Related Activities ("COBRAs") have significant consequences for firms and brands. To effectively respond to and steer

Comparison of Treatment Effects and Allergic responses to stiff neck between Sweet Bee Venom and Bee Venom Pharmacopuncture (A pilot study, Double blind, Randomized Controlled Clinical Trail

Directory of Open Access Journals (Sweden)

Kyoung-hee Lee

2008-12-01

Full Text Available Objective : The purpose of this study is to investigate the difference of treatment effects and allergic responses to stiff neck between Bee Venom Pharmacopuncture and Sweet Bee Venom Pharmacopuncture. Methods : Forty one patients who felt stiff neck were randomly divided into two groups, a Bee Venom Pharmacopuncture group(group Ⅰ and a Sweet Bee Venom Pharmacopuncture group(group Ⅱ. Evaluations of the treatment effects were made before and after a treatment using Visual Analog Scale(VAS, Neck Disability Index(NDI, Clinical Evaluation Grade(CEG. The comparison of allergic responses was measured with VAS. The obtained data were analyzed and compared with SPSS. Results : The group Ⅰ and group Ⅱ showed significant improvement(p<0.05 according to the VAS, NDI, CEG. And the differences between the two groups were insignificant according to VAS, NDI, CEG. But allergic responses such as localized edema, localized itching were significantly lower in group Ⅱ than group Ⅰ. Conclusions : It seems that there are no big different treatment effects between the two groups. Sweet Bee Venom Pharmacopuncture appears to be more effective measurement against allergic reactions than the Bee Venom Pharmacopuncture. Further studies are needed for the comparison of Bee Venom Pharmacopuncture and Sweet Bee Venom Pharmacopuncture.

Mycobacterium chelonae infections associated with bee venom acupuncture.

Science.gov (United States)

Cho, Sun Young; Peck, Kyong Ran; Kim, Jungok; Ha, Young Eun; Kang, Cheol-In; Chung, Doo Ryeon; Lee, Nam Yong; Song, Jae-Hoon

2014-03-01

We report 3 cases of Mycobacterium chelonae infections after bee venom acupuncture. All were treated with antibiotics and surgery. Mycobacterium chelonae infections should be included in the differential diagnosis of chronic skin and soft tissue infections following bee venom acupuncture.

Immunological assessment of mice hyperimmunized with native and Cobalt-60-irradiated Bothrops venoms

International Nuclear Information System (INIS)

Ferreira Junior, R.S.; Meira, D.A.; Martinez, J.C.

2005-01-01

ELISA was used to evaluate, accompany, and compare the humoral immune response of Swiss mice during hyperimmunization with native and Cobalt-60-irradiated ( 60 Co) venoms of Bothrops jararaca, Bothrops jararacussu and Bothrops moojeni. Potency and neutralization were evaluated by in vitro challenges. After hyperimmunization, immunity was observed by in vivo challenge, and the side effects were assessed. The animals immunization with one LD50 of each venom occurred on days 1, 15, 21, 30, and 45, when blood samples were collected; challenges happened on the 60th day. Results showed that ELISA was efficient in evaluating, accompanying and comparing mouse immune response during hyperimmunization. Serum titers produced with natural venom were similar to those produced with irradiated venom. Immunogenic capacity was maintained after 60 Co-irradiation. The sera produced with native venom showed neutralizing potency and capacity similar to those of the sera produced with irradiated venom. All antibodies were able to neutralize five LD50 from these venoms. Clinical alterations were minimum during hyperimmunization with irradiated venom, however, necrosis and death occurred in animals inoculated with native venom. (author)

Expermental Studies of quantitative evaluation using HPLC and safety of Sweet Bee Venom

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Ki Rok Kwon

2007-06-01

Full Text Available Objectives : This study was conducted to carry out quantitative evaluation and safety of Sweet Bee Venom. Methods : Content analysis was done using HPLC, measurement of LD50 was conducted intravenous, subcutaneous, and intra-muscular injection to the ICR mice. Results : 1. According to HPLC analysis, removal of the enzymes containing phospholipase A2 was successfully rendered on Sweet Bee Venom. And analyzing melittin content, Sweet Bee Venom contained 12% more melittin than Bee Venom. 2. LD50 of ICR mice with Sweet Bee Venom was more than 20mg/kg in subcutaneous injection and intravenous injection, between 15mg/kg and 20mg/kg in muscular injection. 3. LD50 of ICR mice with Bee Venom was between 6 and 9mg/kg in subcutaneous injection and intravenous injection, and more than 9mg/kg in muscular injection. Conclusion : Above results indicate that Sweet Bee Venom was more safe than Bee Venom and the process of removing enzymes was well rendered in Sweet Bee Venom.

Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

OpenAIRE

Gihyun Lee; Hyunsu Bae

2016-01-01

Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases inc...

The protective effect of bee venom on fibrosis causing inflammatory diseases.

Science.gov (United States)

Lee, Woo-Ram; Pak, Sok Cheon; Park, Kwan-Kyu

2015-11-16

Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient's skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. Studies have proven the effectiveness of bee venom in treating pathological conditions such as arthritis, pain and cancerous tumors. However, there has not been sufficient review to fully elucidate the cellular mechanisms of the anti-inflammatory effects of bee venom and its components. In this respect, the present study reviews current understanding of the mechanisms of the anti-inflammatory properties of bee venom and its components in the treatment of liver fibrosis, atherosclerosis and skin disease.

Classifying snakebite in South Africa: Validating a scoring system

African Journals Online (AJOL)

There are some 38 venomous snake species in South Africa (SA), of which approximately half are dangerous to humans.[1] Snake species and density vary across the regions of SA.[2] Prevalent species include the Mozambique spitting cobra (Naja mossambica) and puff adder. (Bitis arietans), an elapid and viperid ...

First extensive characterization of the venom gland from an egg parasitoid

NARCIS (Netherlands)

Cusumano, Antonino; Duvic, Bernard; Jouan, Véronique; Ravallec, Marc; Legeai, Fabrice; Peri, Ezio; Colazza, Stefano; Volkoff, Anne Nathalie

2018-01-01

The venom gland is a ubiquitous organ in Hymenoptera. In insect parasitoids, the venom gland has been shown to have multiple functions including regulation of host immune response, host paralysis, host castration and developmental alteration. However, the role played by the venom gland has been

Bee venom treatment for refractory postherpetic neuralgia: a case report.

Science.gov (United States)

Lee, Seung Min; Lim, Jinwoong; Lee, Jae-Dong; Choi, Do-Young; Lee, Sanghoon

2014-03-01

Bee venom has been reported to have antinociceptive and anti-inflammatory effects in experimental studies. However, questions still remain regarding the clinical use of bee venom. This report describes the successful outcome of bee venom treatment for refractory postherpetic neuralgia. A 72-year-old Korean man had severe pain and hypersensitivity in the region where he had developed a herpes zoster rash 2 years earlier. He was treated with antivirals, painkillers, steroids, and analgesic patches, all to no effect. The patient visited the East-West Pain Clinic, Kyung Hee University Medical Center, to receive collaborative treatment. After being evaluated for bee venom compatibility, he was treated with bee venom injections. A 1:30,000 diluted solution of bee venom was injected subcutaneously along the margins of the rash once per week for 4 weeks. Pain levels were evaluated before every treatment, and by his fifth visit, his pain had decreased from 8 to 2 on a 10-point numerical rating scale. He experienced no adverse effects, and this improvement was maintained at the 3-month, 6-month, and 1-year phone follow-up evaluations. Bee venom treatment demonstrates the potential to become an effective treatment for postherpetic neuralgia. Further large-sample clinical trials should be conducted to evaluate the overall safety and efficacy of this treatment.

Biological and Proteolytic Variation in the Venom of Crotalus scutulatus scutulatus from Mexico

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Miguel Borja

2018-01-01

Full Text Available Rattlesnake venoms may be classified according to the presence/absence and relative abundance of the neurotoxic phospholipases A 2 s (PLA 2 s, such as Mojave toxin, and snake venom metalloproteinases (SVMPs. In Mexico, studies to determine venom variation in Mojave Rattlesnakes (Crotalus scutulatus scutulatus are limited and little is known about the biological and proteolytic activities in this species. Tissue (34 and venom (29 samples were obtained from C. s. scutulatus from different locations within their distribution in Mexico. Mojave toxin detection was carried out at the genomic (by PCR and protein (by ELISA levels for all tissue and venom samples. Biological activity was tested on representative venoms by measuring LD 50 and hemorrhagic activity. To determine the approximate amount of SVMPs, 15 venoms were separated by RP-HPLC and variation in protein profile and proteolytic activity was evaluated by SDS-PAGE (n = 28 and Hide Powder Azure proteolytic analysis (n = 27. Three types of venom were identified in Mexico which is comparable to the intraspecific venom diversity observed in the Sonoran Desert of Arizona, USA: Venom Type A (∼Type II, with Mojave toxin, highly toxic, lacking hemorrhagic activity, and with scarce proteolytic activity; Type B (∼Type I, without Mojave toxin, less toxic than Type A, highly hemorrhagic and proteolytic; and Type A + B, containing Mojave toxin, as toxic as venom Type A, variable in hemorrhagic activity and with intermediate proteolytic activity. We also detected a positive correlation between SVMP abundance and hemorrhagic and proteolytic activities. Although more sampling is necessary, our results suggest that venoms containing Mojave toxin and venom lacking this toxin are distributed in the northwest and southeast portions of the distribution in Mexico, respectively, while an intergradation in the middle of both zones is present.

The dielectric properties of neutron irradiated snake venom and its pathological impact

International Nuclear Information System (INIS)

Hanafy, M.S.; Rahmy, N.A.; Abd El-Khalek, M.M.

1999-01-01

The changes in the dielectric properties of a saline solution of Cerastes cerastes snake venom after irradiation with low-level doses of fast neutrons from a Cf-252 source, were investigated. The pathological changes in the internal organs such as liver, kidney spleen, lung and heart of the rats injected with unirradiated and irradiated venom were also studied. The changes in the molecular structure of a diluted saline solution of snake venom were measured through dielectric relaxation studies in the frequency range 0.1-10 MHz at 4±0.5 deg C. The absorption spectra of the venom solution were measured in the wavelength range 200 to 600 nm. The results indicated remarkable changes in the molecular radii, shape, relaxation time and dielectric increment of the venom molecules as a result of irradiation. Also, the intensities of the absorption bands of the venom solution decreased as a result of the irradiation process. Furthermore, the pathological examination results indicated that the toxicity of the irradiated venom decreased as compared with that of unirradiated venom, hence increasing the chance of repair of the affected organs. (author)

Venom toxicity and composition in three Pseudomyrmex ant species having different nesting modes.

Science.gov (United States)

Touchard, Axel; Labrière, Nicolas; Roux, Olivier; Petitclerc, Frédéric; Orivel, Jérôme; Escoubas, Pierre; Koh, Jennifer M S; Nicholson, Graham M; Dejean, Alain

2014-09-01

We aimed to determine whether the nesting habits of ants have influenced their venom toxicity and composition. We focused on the genus Pseudomyrmex (Pseudomyrmecinae) comprising terrestrial and arboreal species, and, among the latter, plant-ants that are obligate inhabitants of myrmecophytes (i.e., plants sheltering ants in hollow structures). Contrary to our hypothesis, the venom of the ground-dwelling species, Pseudomyrmex termitarius, was as efficacious in paralyzing prey as the venoms of the arboreal and the plant-ant species, Pseudomyrmex penetrator and Pseudomyrmex gracilis. The lethal potency of P. termitarius venom was equipotent with that of P. gracilis whereas the venom of P. penetrator was less potent. The MALDI-TOF MS analysis of each HPLC fraction of the venoms showed that P. termitarius venom is composed of 87 linear peptides, while both P. gracilis and P. penetrator venoms (23 and 26 peptides, respectively) possess peptides with disulfide bonds. Furthermore, P. penetrator venom contains three hetero- and homodimeric peptides consisting of two short peptidic chains linked together by two interchain disulfide bonds. The large number of peptides in P. termitarius venom is likely related to the large diversity of potential prey plus the antibacterial peptides required for nesting in the ground. Whereas predation involves only the prey and predator, P. penetrator venom has evolved in an environment where trees, defoliating insects, browsing mammals and ants live in equilibrium, likely explaining the diversity of the peptide structures. Copyright © 2014 Elsevier Ltd. All rights reserved.

Snake Venom: From Deadly Toxins to Life-saving Therapeutics.

Science.gov (United States)

Waheed, Humera; Moin, Syed F; Choudhary, M I

2017-01-01

Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated. Researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements. Since the development of captopril, the first drug that was derived from bradykininpotentiating peptide of Bothrops jararaca, to the disintegrins that have potent activity against certain types of cancers, snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous development of new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents. In this review, we have focused on different snake venom proteins / peptides derived drugs that are in clinical use or in developmental stages till to date. Also, some commonly used snake venom derived diagnostic tools along with the recent updates in this exciting field are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bee venom suppresses methamphetamine-induced conditioned place preference in mice.

Science.gov (United States)

Kwon, Young Bae; Li, Jing; Kook, Ji Ae; Kim, Tae Wan; Jeong, Young Chan; Son, Ji Seon; Lee, Hyejung; Kim, Kee Won; Lee, Jang Hern

2010-02-01

Although acupuncture is most commonly used for its analgesic effect, it has also been used to treat various drug addictions including cocaine and morphine in humans. This study was designed to investigate the effect of bee venom injection on methamphetamine-induced addictive behaviors including conditioned place preference and hyperlocomotion in mice. Methamphetamine (1 mg/kg) was subcutaneously treated on days 1, 3 and 5 and the acquisition of addictive behaviors was assessed on day 7. After confirming extinction of addictive behaviors on day 17, addictive behaviors reinstated by priming dose of methamphetamine (0.1 mg/kg) was evaluated on day 18. Bee venom (20 microl of 1 mg/ml in saline) was injected to the acupuncture point ST36 on days 1, 3 and 5. Repeated bee venom injections completely blocked development of methamphetamine-induced acquisition and subsequent reinstatement. Single bee venom acupuncture 30 minutes before acquisition and reinstatement test completely inhibited methamphetamine-induced acquisition and reinstatement. Repeated bee venom acupunctures from day 8 to day 12 after methamphetamine-induced acquisition partially but significantly suppressed reinstatement. These findings suggest that bee venom acupuncture has a preventive and therapeutic effect on methamphetamine-induced addiction.

Cross-reactivity and phospholipase A2 neutralization of anti-irradiated Bothrops jararaca venom antibodies

International Nuclear Information System (INIS)

Spencer, P.J.; Nascimento, N. do; Paula, R.A. de; Cardi, B.A.; Rogero, J.R.

1995-01-01

The detoxified Bothrops jararaca venom, immunized rabbits with the toxoid obtained and investigated cross-reactivity of the antibodies obtained against autologous and heterelogous venoms was presented. It was also investigated the ability of the IgGs, purified by affinity chromatography, from those sera to neutralize phospholipase. A 2 , an ubiquous enzyme in animal venoms. Results indicate that venom irradiation leads to an attenuation of toxicity of 84%. Cross-reactivity was investigated by ELISA and Western blot and all venoms were reactive to the antibodies. On what refers to phospholipase A 2 activity neutralization, the antibodies neutralized autologous venoms efficiently and, curiously, other venoms from the same genus were not neutralized, while Lachesis muta venom, a remote related specier, was neutralized by this serum. These data suggest that irradiation preserve important epitopes for induction of neutralizing antibodies and that these epitopes are not shared by all venoms assayed. (author). 8 refs, 2 figs, 3 tabs

Therapeutic potential of snake venom in cancer therapy: current perspectives

Science.gov (United States)

Vyas, Vivek Kumar; Brahmbhatt, Keyur; Bhatt, Hardik; Parmar, Utsav

2013-01-01

Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity. PMID:23593597

Circus Venomous: an interactive tool for toxinology education.

Science.gov (United States)

Vohra, Rais; Spano, Susanne

2013-07-01

Clinical education about envenomations and their treatment may convey clinical and zoological details inadequately or flatly. In recent years, the widespread availability of models and videos of venomous species have created unique opportunities for toxinology education. We share our experiences using a new toolkit for educating a diverse array of clinicians, students, and wilderness medicine enthusiasts. We examined the cost, number of participants, and satisfaction data since the initiation of a portable workshop featuring high-fidelity exhibits of venomous species. Termed the "Circus Venomous," this educational toolkit consists of several boxes of props, such as plastic models, photos, and preserved specimens of injurious species. The workshop consists of three phases: 1.) participants view all exhibits and answer clinical questions regarding venomous injuries; 2.) short video clips from television, internet, and cinema are viewed together, and myths about envenomation injuries are debunked; 3.) debriefing session and wrap-up. We have utilized the Circus Venomous to teach medical students, residents, practicing community clinicians, nurses, PAs, national and regional parkmedics, and wilderness enthusiasts. The major cost (about $800) was spent on the purchase of highly durable, lifelike models and well preserved real reptile and arachnid specimens. When formal feedback was solicited, the participants expressed high levels of satisfaction, scoring an average of 4.3, 4.4, and 4.3 out of 5 points in the respective areas of content, presentation, and practical value of the activity. Since we have used this exhibit with approximately 250 participants over 2 years, we estimate the materials cost per participant is approximately $3. The Circus Venomous is a novel, interactive, flexible, and cost-effective teaching tool about envenomation emergencies. We hope that this concept will encourage other clinical educators toward further innovation. Future directions for our

21 CFR 864.8950 - Russell viper venom reagent.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Russell viper venom reagent. 864.8950 Section 864.8950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8950 Russell viper venom...

PENSAMIENTOS COMPARTIDOS. ALDO VAN EYCK, EL GRUPO COBRA Y EL ARTE / Shared thoughts. Aldo van Eyck, the COBRA group, and art

Directory of Open Access Journals (Sweden)

Esther Mayoral Campa

2014-11-01

Full Text Available RESUMEN El periodo inmediatamente posterior a la II Guerra Mundial es uno de los episodios más interesantes desde el punto de vista cultural del siglo XX, un momento vivido por muchos de los intelectuales europeos coetáneos a esta época como un punto de inflexión, una oportunidad para repensar el mundo, para comenzar de nuevo tras el cataclismo bélico. En ese contexto comienza su andadura como arquitecto Aldo van Eyck, así como su colaboración con el breve, pero intenso, movimiento Cobra, grupo esencial para comprender el panorama cultural europeo de posguerra y una de las últimas vanguardias del siglo XX. Este artículo explora la vinculación del arquitecto holandés Aldo van Eyck con el mundo del arte. Una relación poliédrica, parte esencial de su discurso, que engloba su formación cultural, sus relaciones de amistad, su pensamiento crítico y su obra. En esa correlación entre la arquitectura y las artes será determinante la vinculación del arquitecto con Cobra, con el que compartirá una mirada común sobre la realidad, una relación compleja con líneas de investigación comunes, escritos, exposiciones y trabajos compartidos. A todo ello se suma la aportación fundamental que supone un trasvase de valores constantes entre la arquitectura y el mundo del arte, que caracterizó la relación entre el arquitecto y los miembros del grupo.

The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms.

Science.gov (United States)

Fry, Bryan G; Roelants, Kim; Champagne, Donald E; Scheib, Holger; Tyndall, Joel D A; King, Glenn F; Nevalainen, Timo J; Norman, Janette A; Lewis, Richard J; Norton, Raymond S; Renjifo, Camila; de la Vega, Ricardo C Rodríguez

2009-01-01

Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have included AVIT/colipase/prokineticin, CAP, chitinase, cystatin, defensins, hyaluronidase, Kunitz, lectin, lipocalin, natriuretic peptide, peptidase S1, phospholipase A(2), sphingomyelinase D, and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of invertebrates (e.g., fleas, leeches, kissing bugs, mosquitoes, and ticks) and vertebrates (e.g., vampire bats). Here, we discuss a number of overarching structural, functional, and evolutionary generalities of the protein families from which these toxins have been frequently recruited and propose a revised and expanded working definition for venom. Given the large number of striking similarities between the protein compositions of conventional venoms and hematophagous secretions, we argue that the latter should also fall under the same definition.

Allergen immunotherapy for insect venom allergy

DEFF Research Database (Denmark)

Dhami, S; Zaman, H; Varga, E-M

2016-01-01

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety...... of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were...

Biochemical and immunological alterations of 60 Co irradiated Bothrops jararacussu venom

International Nuclear Information System (INIS)

Spencer, Patrick J.

1995-01-01

Proteins irradiation leads to structural alterations resulting in activity and function loss. This process has been useful to detoxify animal venoms and toxins, resulting in low toxicity products which increased immunogenicity. The Bothrops jararacussu venom behaves as a weak immunogen and its lethal activity in not neutralized by either autologous, heterologous or bothropic polyvalent antisera. This venom is markedly myotoxic and and the commercial bothropic antiserum does not neutralize this activity, because of this low immunogenicity of the myotoxins. This present work was done in order to evaluate the possibility of irradiating Bothrops jararacussu, intending to increase the immunogenicity of the myotoxic components, leading to productions of myotoxins neutralizing antibodies. Bothrops jararacussu venom samples were irradiated with 500, 1000 and 2000 Gy of 60 Co gamma rays. A 2.3 folds decrease of toxicity was observed for the 1000 Gy irradiated samples while the 2000 Gy irradiated sample was at least 3.7 folds attenuated. On the other hand, the 500 Gy did not promote any detoxification. Electrophoresis and HPLC data indicate that the irradiation lead to the formation of high molecular weight products (aggregates). The proteolytic and phospholipasic activities decreased in a dose dependent manner, the phospholipases being more resistant than the proteases. Both the animals (rabbit) immunized with either native or 2000 Gy irradiated venom produced native venom binding antibodies, a slightly higher titer being obtained in the serum of the rabbit immunized with the irradiated samples. Western blot data indicate that the anti-irradiated venom Ig Gs recognised a greater amount of either autologous or heterologous venom bands, both sera behaving as genus specific. The anti-native serum did not neutralize the myotoxic activity of native venom, while the anti-irradiated one was able to neutralize this activity. (author)

Proteomic analysis of venom variability and ontogeny across the arboreal palm-pitvipers (genus Bothriechis).

Science.gov (United States)

Pla, Davinia; Sanz, Libia; Sasa, Mahmood; Acevedo, Manuel E; Dwyer, Quetzal; Durban, Jordi; Pérez, Alicia; Rodriguez, Yania; Lomonte, Bruno; Calvete, Juan J

2017-01-30

Bothriechis is a genus of eleven currently recognized slender and arboreal venomous snakes, commonly called palm-pitvipers that range from southern Mexico to northern South America. Despite dietary studies suggesting that palm-pitvipers are generalists with an ontogenetic shift toward endothermic prey, venom proteomic analyses have revealed remarkable divergence between the venoms of the Costa Rican species, B. lateralis, B. schlegelii, B. supraciliaris, and B. nigroviridis. To achieve a more complete picture of the venomic landscape across Bothriechis, the venom proteomes of biodiversity of the northern Middle American highland palm-pitvipers, B. thalassinus, B. aurifer, and B. bicolor from Guatemala, B. marchi from Honduras, and neonate Costa Rican B. lateralis and B. schlegelii, were investigated. B. thalassinus and B. aurifer venoms are comprised by similar toxin arsenals dominated by SVMPs (33-39% of the venom proteome), CTLs (11-16%), BPP-like molecules (10-13%), and CRISPs (5-10%), and are characterized by the absence of PLA 2 proteins. Conversely, the predominant (35%) components of B. bicolor are D49-PLA 2 molecules. The venom proteome of B. marchi is similar to B. aurifer and B. thalassinus in that it is rich in SVMPs and BPPs, but also contains appreciable amounts (14.3%) of PLA 2 s. The major toxin family found in the venoms of both neonate B. lateralis and B. schlegelii, is serine proteinase (SVSP), comprising about 20% of their toxin arsenals. The venom of neonate B. schlegelii is the only palm-pitviper venom where relative high amounts of Kunitz-type (6.3%) and γPLA 2 (5.2%) inhibitors have been identified. Despite notable differences between their proteomes, neonate venoms are more similar to each other than to adults of their respective species. However, the ontogenetic changes taking place in the venom of B. lateralis strongly differ from those that occur in the venom of B. schlegelii. Thus, the ontogenetic change in B. lateralis produces a SVMP

A Study on the Effects of Bee Venom Aqua-Acupuncture on Writhing Reflex

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Jeong Sun-Hee

2000-07-01

Full Text Available Introduction:In spite of the use of Bee Venom aqua-acupuncture in the clinics, the scientific evaluation on effects is not enough. Bee Venom aqua-acupuncture is used according to the stimulation of acupuncture point and the chemical effects of Bee Venom. The aims of this study is to investigate the analgegic effects of the Bee Venom aqua-acupuncture, through the change of writhing reflex Materials and Methods:Pain animal model was used acetic acid method. The changes of writhing reflex of the mice which were derived pain by injecting acetic acid into the abdomen, after stimulating Bee Venom aqua-acupuncture on Chungwan(CV12 and non acupuncture point on the backside were measured. Results:1. It showed that the writhing reflex were appeared on the groups which injected acetic acid only, and saline-acetic acid group(sample I, but not on the group bee venom-saline group(sample II. 2. The change of writhing reflex by Chungwan(CV12 Bee Venom aqua-acupuncture showed significant decrease in the order of Chungwan(CV12 Bee Venom aqua-acupuncture group III(2.5×10-3g/kg, II(2.5×10-4g/kg, and I(2.5×10-5g/kg, compared with control group. There were significant decrease of number of writhing reflex in 5～10, 10～15 and 15～20 minutes intervals of Chung wan(CV12 Bee Venom aqua-acupuncture group I, and in 0～5, 5～10, 10～15 and 15～20 minutes intervals of II and III, compared with control group. 3. The change of writhing reflex by non acupuncture point Bee Venom aqua-acupuncture showed significant decrease in the 0～5 and 5～10 minutes intervals and the total number of writhing reflex in 2.5×10-4g/kg group, compared with control group 4. The effects of writhing reflex of Chungwan(CV12 Bee Venom aqua-acupuncture group showed significant decrease, compared with non acupuncture point Bee Venom aqua-acupuncture group. Conclusion:This study shows that the Bee Venom aqua-acupuncture on Chungwan(CV12 decreases the numbers of writhing reflex. As the

Results of a search for neutrinoless double-beta decay using the COBRA demonstrator

Energy Technology Data Exchange (ETDEWEB)

Quante, Thomas; Goessling, Claus; Kroeninger, Kevin [TU Dortmund, Exp. Physik IV, Dortmund (Germany)

2016-07-01

COBRA is an experiment aiming to search for neutrinoless double-beta-decay (0νββ-decay) using CdZnTe semiconductor detectors. The main focus is on {sup 116}Cd, with a Q-value of 2813.5 keV well above the highest dominant naturally occurring gamma lines. By measuring the half-life of the 0νββ-decay, it is possible to clarify the nature of the neutrino as either Dirac or Majorana particle and furthermore to determine its effective Majorana mass. The COBRA collaboration operates a demonstrator to search for these decays at the Laboratori Nazionali del Gran Sasso in Italy. The exposure of 234.7 kg d considered in this analysis was collected between September 2011 and February 2015. The analysis focuses on the decay of the nuclides {sup 114}Cd, {sup 128}Te, {sup 70}Zn, {sup 130}Te and {sup 116}Cd. A Bayesian analysis is performed to estimate the signal strength of 0νββ-decay.