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Sample records for ophiophagus hannah venom

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

    PubMed

    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.

  2. Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah).

    PubMed

    Tan, Choo Hock; Tan, Kae Yi; Fung, Shin Yee; Tan, Nget Hong

    2015-09-10

    The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS. Transcriptomic results reveal high redundancy of toxin transcripts (3357.36 FPKM/transcript) despite small cluster numbers, implying gene duplication and diversification within restricted protein families. Among the 23 toxin families identified, three-finger toxins (3FTxs) and snake-venom metalloproteases (SVMPs) have the most diverse isoforms. These 2 toxin families are also the most abundantly transcribed, followed in descending order by phospholipases A2 (PLA2s), cysteine-rich secretory proteins (CRISPs), Kunitz-type inhibitors (KUNs), and L-amino acid oxidases (LAAOs). Seventeen toxin families exhibited low mRNA expression, including hyaluronidase, DPP-IV and 5'-nucleotidase that were not previously reported in the venom-gland transcriptome of a Balinese O. hannah. On the other hand, the MOh proteome includes 3FTxs, the most abundantly expressed proteins in the venom (43 % toxin sbundance). Within this toxin family, there are 6 long-chain, 5 short-chain and 2 non-conventional 3FTx. Neurotoxins comprise the major 3FTxs in the MOh venom, consistent with rapid neuromuscular paralysis reported in systemic envenoming. The presence of toxic enzymes such as LAAOs, SVMPs and PLA2 would explain tissue inflammation and necrotising destruction in local envenoming. Dissimilarities in the subtypes and sequences between the neurotoxins of MOh and Naja kaouthia (monocled cobra) are in agreement with the poor cross-neutralization activity of N. kaouthia antivenom used against MOh venom. Besides, the presence of cobra venom factor, nerve growth factors

  3. Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom.

    PubMed

    Salama, R; Sattayasai, J; Gande, A K; Sattayasai, N; Davis, M; Lattmann, E

    2012-02-01

    The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.

  4. Antiproliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase.

    PubMed

    Li Lee, Mui; Chung, Ivy; Yee Fung, Shin; Kanthimathi, M S; Hong Tan, Nget

    2014-04-01

    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF-7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50 value of 0.04±0.00 and 0.05±0.00 μg/mL, respectively, after 72-hr treatment. In comparison, its cytotoxicity was about 3-4 times lower when tested against human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC50 value of 0.18±0.03 and 0.63±0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7-amino-actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO-treated tumour cells than in their non-tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase-3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  5. Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches.

    PubMed

    Petras, Daniel; Heiss, Paul; Süssmuth, Roderich D; Calvete, Juan J

    2015-06-05

    We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world's longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom's components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research.

  6. Cross-reactivity and neutralization of Indian King cobra (Ophiophagus hannah) venom by polyvalent and monovalent antivenoms.

    PubMed

    Gowtham, Yashonandana J; Mahadeswaraswamy, Y H; Girish, K S; K, Kemparaju

    2014-07-01

    The venom of the largest venomous snake, the king cobra (Ophiophagus hannah), is still out of league for the production of therapeutic polyvalent antivenom nor it is characterized immunologically in the Indian subcontinent. In the present study, the king cobra venom is comparatively studied for the cross-reactivity/reactivity and toxicity neutralization by the locally available equine therapeutic polyvalent BSV and VB antivenoms, and monovalent antivenom (OH-IgG) prepared in rabbit. None of the two therapeutic antivenoms procured from two different firms showed any signs of cross-reactivity in terms of antigen-antibody precipitin lines in immunodouble diffusion assay; however, a weak and an insignificant cross-reactivity pattern was observed in ELISA and Western blot studies. Further, both BSV and VB antivenoms failed to neutralize proteolytic, hyaluronidase and phospholipase activities as well as toxic properties such as edema, myotoxicity and lethality of the venom. As expected, OH-IgG showed strong reactivity in immunodouble diffusion, ELISA and in Western blot analysis and also neutralized both enzyme activities as well as the toxic properties of the venom. Thus, the study provides insight into the likely measures that are to be taken in cases of accidental king cobra bites for which the Indian subcontinent is still not prepared for. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  11. Antihemorrhagin in the blood serum of king cobra (Ophiophagus hannah): purification and characterization.

    PubMed

    Chanhome, Lawan; Khow, Orawan; Omori-Satoh, Tamotsu; Sitprija, Visith

    2003-06-01

    King cobra (Ophiophagus hannah) serum was found to possess antihemorrhagic activity against king cobra hemorrhagin. The activity was stronger than that in commercial king cobra antivenom. An antihemorrhagin has been purified by ion exchange chromatography, affinity chromatography and gel filtration with a 22-fold purification and an overall yield of 12% of the total antihemorrhagic activity contained in crude serum. The purified antihemorrhagin was homogeneous in disc-PAGE and SDS-PAGE. Its apparent molecular weight determined by SDS-PAGE was 120 kDa. The antihemorrhagin was also active against other hemorrhagic snake venoms obtained in Thailand and Japan such as Calloselasma rhodostoma, Trimeresurus albolabris, Trimeresurus macrops and Trimeresurus flavoviridis (Japanese Habu). It inhibited the proteolytic activity of king cobra venom. It is an acid- and thermolabile protein and does not form precipitin lines against king cobra venom.

  12. King cobra (Ophiophagus hannah) venom L-amino acid oxidase induces apoptosis in PC-3 cells and suppresses PC-3 solid tumor growth in a tumor xenograft mouse model.

    PubMed

    Lee, Mui Li; Fung, Shin Yee; Chung, Ivy; Pailoor, Jayalakshmi; Cheah, Swee Hung; Tan, Nget Hong

    2014-01-01

    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.

  13. Cloning and purification of alpha-neurotoxins from king cobra (Ophiophagus hannah).

    PubMed

    He, Ying-Ying; Lee, Wei-Hui; Zhang, Yun

    2004-09-01

    Thirteen complete and three partial cDNA sequences were cloned from the constructed king cobra (Ophiophagus hannah) venom gland cDNA library. Phylogenetic analysis of nucleotide sequences of king cobra with those from other snake venoms revealed that obtained cDNAs are highly homologous to snake venom alpha-neurotoxins. Alignment of deduced mature peptide sequences of the obtained clones with those of other reported alpha-neurotoxins from the king cobra venom indicates that our obtained 16 clones belong to long-chain neurotoxins (seven), short-chain neurotoxins (seven), weak toxin (one) and variant (one), respectively. Up to now, two out of 16 newly cloned king cobra alpha-neurotoxins have identical amino acid sequences with CM-11 and Oh-6A/6B, which have been characterized from the same venom. Furthermore, five long-chain alpha-neurotoxins and two short-chain alpha-neurotoxins were purified from crude venom and their N-terminal amino acid sequences were determined. The cDNAs encoding the putative precursors of the purified native peptide were also determined based on the N-terminal amino acid sequencing. The purified alpha-neurotoxins showed different lethal activities on mice.

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

    PubMed

    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.

  15. Hematology, morphology, cytochemical staining, and ultrastuctural characteristics of blood cells in king cobras (Ophiophagus hannah).

    PubMed

    Salakij, Chaleow; Salakij, Jarernsak; Apibal, Suntaree; Narkkong, Nual-Anong; Chanhome, Lawan; Rochanapat, Nirachara

    2002-01-01

    King cobras (Ophiophagus hannah) have been captive-bred at Queen Saovabha Memorial Institute since 1996 to supply venom for antivenom production. Hematologic tests would be useful for evaluating the health of the snakes, however, basic hematologic data and morphology have not been described for this species. The purpose of this study was to determine basic hematologic values and evaluate light microscopic, cytochemical, and electron microscopic characteristics of king cobra blood cells. Blood samples from 13 wild-caught and 15 captive-bred king cobras were collected into EDTA from the ventral caudal vein. A CBC was done using standard methods. Significant differences between groups were determined using t-tests. Cytochemical stains (periodic acid-Schiff [PAS], Sudan black B [SBB], alpha-naphthyl acetate esterase [ANAE], acid phosphatase [AcP], and beta-glucuronidase [beta-glu]), and scanning and transmission electron microscopy were done using standard techniques. Eighteen snakes (64.3%) were positive for Hepatozoon infection. Hepatozoon organisms were detected nearly twice as frequently in wild-caught (11/13) as in captive-bred (7/15) snakes. Total WBC, azurophil, and lymphocyte counts were higher and fibrinogen concentration was lower in Hepatozoon-positive snakes. Captive-bred snakes had higher RBC values, lower azurophil, heterophil, and punctate reticulocyte percentages, and higher lymphocyte numbers compared with wild-caught snakes. Lymphocytes were the most commonly observed WBCs, and stained positive with PAS, ANAE, AcP, and beta-glu. Azurophil granules stained positive with SBB, PAS, and ANAE. Heterophils were the largest WBCs; their granules stained with SBB, ANAE, and beta-glu. Basophil granules stained with PAS, SBB, ANAE, and beta-glu. Thrombocytes were strongly positive with PAS. Transmission electron microscopic examination revealed organelles within all WBCs except eosinophils and revealed the gamonts of Hepatozoon sp in RBCs and azurophils. These

  16. Venomous snakebite in Thailand. I: Medically important snakes.

    PubMed

    Chanhome, L; Cox, M J; Wilde, H; Jintakoon, P; Chaiyabutr, N; Sitprija, V

    1998-05-01

    Thailand has an abundance of venomous snakes. Among the neurotoxic family Elapidae, there are three species of the genus Naja (cobras), three of the genus Bungarus (kraits), and the king cobra of the genus Ophiophagus. Other Elapidae snakes in Thailand include sea snakes and Asian coral snakes of the genus Calliophis. They have potent venoms but rarely bite humans. Tissue and hemotoxic snakes are represented by family Viperidae, subfamilies Viperinae and Crotalinae. They remain an occupational hazard for farmers and rubber tappers, causing serious morbidity but only rare deaths, since competent treatment is now widely available throughout Thailand. Purified equine antivenin is manufactured locally for the monocled and Siamese spitting cobras (Naja kaouthia and N. siamensis), king cobra (Ophiophagus hannah), banded krait (Bungarus fasciatus), most green pit vipers (Trimeresurus sp.), Malayan pit viper (Calloselasma rhodostoma), and the Siamese Russell's viper (Daboia russelli siamensis).

  17. Wide distribution of cysteine-rich secretory proteins in snake venoms: isolation and cloning of novel snake venom cysteine-rich secretory proteins.

    PubMed

    Yamazaki, Yasuo; Hyodo, Fumiko; Morita, Takashi

    2003-04-01

    Cysteine-rich secretory proteins (CRISPs) are found in epididymis and granules of mammals, and they are thought to function in sperm maturation and in the immune system. Recently, we isolated and obtained clones for novel snake venom proteins that are classified as CRISP family proteins. To elucidate the distribution of snake venom CRISP family proteins, we evaluated a wide range of venoms for immuno-cross-reactivity. Then we isolated, characterized, and cloned genes for three novel CRISP family proteins (piscivorin, ophanin, and catrin) from the venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus), king cobra (Ophiophagus hannah), and western diamondback rattlesnake (Crotalus atrox). Our results show the wide distribution of snake venom CRISP family proteins among Viperidae and Elapidae from different continents, indicating that CRISP family proteins compose a new group of snake venom proteins.

  18. Phospholipase a properties of several snake venom preparations.

    PubMed

    Nutter, L J; Privett, O S

    1966-07-01

    The hydrolytic properties of the venoms of seven species of snakes,Crotalus adamanteus, Ancistrodon contortrix, Naja naja, Bothrops atrox, Ophiophagus hannah, Crotalus atrox andVipera russeli, were studied with purified lecithins and mixtures of lecithins of known fatty acid and class composition as substrates.The relative rates of hydrolysis of the fatty acids by the above venoms were studied by analysis of the products of the reaction at intervals during the course of the reaction. Of the seven venoms studied, that ofOphiophagus hannah was the only one which did not give some degree of preferential rate of hydrolysis of individual fatty acids.In general, saturated fatty acids were liberated faster than unsaturated fatty acids; differences in the rates of the hydrolysis of individual saturate and unsaturated fatty acids were also observed. Individual classes of lecithin were also hydrolyzed at different rates. For the determination of the distribution of the fatty acids between the alpha- and beta-position of lecithin, the reaction should be carried to completion. If the reaction requires a prolonged time to go to completion, it should be carried out under nitrogen to prevent autoxidation.

  19. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

    PubMed Central

    Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Heimberg, Alysha M.; Jansen, Hans J.; McCleary, Ryan J. R.; Kerkkamp, Harald M. E.; Vos, Rutger A.; Guerreiro, Isabel; Calvete, Juan J.; Wüster, Wolfgang; Woods, Anthony E.; Logan, Jessica M.; Harrison, Robert A.; Castoe, Todd A.; de Koning, A. P. Jason; Pollock, David D.; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B.; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S.; Ribeiro, José M. C.; Arntzen, Jan W.; van den Thillart, Guido E. E. J. M.; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P.; Spaink, Herman P.; Duboule, Denis; McGlinn, Edwina; Kini, R. Manjunatha; Richardson, Michael K.

    2013-01-01

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection. PMID:24297900

  20. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.

    PubMed

    Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Heimberg, Alysha M; Jansen, Hans J; McCleary, Ryan J R; Kerkkamp, Harald M E; Vos, Rutger A; Guerreiro, Isabel; Calvete, Juan J; Wüster, Wolfgang; Woods, Anthony E; Logan, Jessica M; Harrison, Robert A; Castoe, Todd A; de Koning, A P Jason; Pollock, David D; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S; Ribeiro, José M C; Arntzen, Jan W; van den Thillart, Guido E E J M; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P; Spaink, Herman P; Duboule, Denis; McGlinn, Edwina; Kini, R Manjunatha; Richardson, Michael K

    2013-12-17

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection.

  1. Development of a polymerase chain reaction to distinguish monocellate cobra (Naja khouthia) bites from other common Thai snake species, using both venom extracts and bite-site swabs.

    PubMed

    Suntrarachun, S; Pakmanee, N; Tirawatnapong, T; Chanhome, L; Sitprija, V

    2001-07-01

    A PCR technique was used in this study to identify and distinguish monocellate cobra snake bites using snake venoms and swab specimens from snake bite-sites in mice from bites by other common Thai snakes. The sequences of nucleotide primers were selected for the cobrotoxin-encoding gene from the Chinese cobra (Naja atra) since the sequences of monocellate cobra (Naja kaouthia) venom are still unknown. However, the 113-bp fragment of cDNA of the cobrotoxin-encoding gene was detected in the monocellate cobra venom using RT-PCR. This gene was not found in the venoms of Ophiophagus hannah (king cobra), Bungarus fasciatus (banded krait), Daboia russelii siamensis (Siamese Russell's Viper, and Calloselasma rhodostoma (Malayan pit viper). Moreover, direct PCR could detect a 665-bp fragment of the cobrotoxin-encoding gene in the monocellate cobra venom but not the other snake venoms. Likewise, this gene was only observed in swab specimens from cobra snake bite-sites in mice. This is the first report demonstrating the ability of PCR to detect the cobrotoxin-encoding gene from snake venoms and swab specimens. Further studies are required for identification of this and other snakes from the bite-sites on human skin.

  2. Hannah Arendt

    ERIC Educational Resources Information Center

    Stern, Peter; Yarbrough, Jean

    1978-01-01

    Hannah Arendt's gaity, wit, and passion, her testy impatience, her love of debate, her shrewd common sense, her joy in communicating her knowledge, and her brilliance and learning are the qualities that made her such a remarkable and inspiring teacher. Here is an evaluation of her teaching performance by two former students. (Author/RK)

  3. Hannah Miller | NREL

    Science.gov Websites

    Hannah Miller desc Hannah Miller Group Administrative Assistant Hannah.Miller@nrel.gov | 303-275 -3671 Hannah Miller is staff support for the Applied Engineering and Modeling Group in the Integrated Applications Center. Hannah is a former office manager, communications director, and sales consultant for

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  8. Functional proteomic approach to discover geographic variations of king cobra venoms from Southeast Asia and China.

    PubMed

    Chang, Hui-Ching; Tsai, Tein-Shun; Tsai, Inn-Ho

    2013-08-26

    This study deciphers the geographic variations of king cobra (Ophiophagus hannah) venom using functional proteomics. Pooled samples of king cobra venom (abbreviated as Ohv) were obtained from Indonesia, Malaysia, Thailand, and two provinces of China, namely Guangxi and Hainan. Using two animal models to test and compare the lethal effects, we found that the Chinese Ohvs were more fatal to mice, while the Southeast Asian Ohvs were more fatal to lizards (Eutropis multifasciata). Various phospholipases A2 (PLA2s), three-finger toxins (3FTxs) and Kunitz-type inhibitors were purified from these Ohvs and compared. Besides the two Chinese Ohv PLA2s with known sequences, eight novel PLA2s were identified from the five Ohv samples and their antiplatelet activities were compared. While two 3FTxs (namely oh-55 and oh-27) were common in all the Ohvs, different sets of 3FTx markers were present in the Chinese and Southeast Asian Ohvs. All the Ohvs contain the Kunitz inhibitor, OH-TCI, while only the Chinese Ohvs contain the inhibitor variant, Oh11-1. Relative to the Chinese Ohvs which contained more phospholipases, the Southeast Asian Ohvs had higher metalloproteinase, acetylcholine esterase, and alkaline phosphatase activities. Remarkable variations in five king cobra geographic samples reveal fast evolution and dynamic translational regulation of the venom which probably adapted to different prey ecology as testified by the lethal tests on mice and lizards. Our results predict possible variations of the king cobra envenoming to human and the importance of using local antivenin for snakebite treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  10. Molecular barcoding of venomous snakes and species-specific multiplex PCR assay to identify snake groups for which antivenom is available in Thailand.

    PubMed

    Supikamolseni, A; Ngaoburanawit, N; Sumontha, M; Chanhome, L; Suntrarachun, S; Peyachoknagul, S; Srikulnath, K

    2015-10-30

    DNA barcodes of mitochondrial COI and Cytb genes were constructed from 54 specimens of 16 species for species identification. Intra- and interspecific sequence divergence of the COI gene (10 times) was greater than that of the Cytb gene (4 times), which suggests that the former gene may be a better marker than the latter for species delimitation in snakes. The COI barcode cut-off scores differed by more than 3% between most species, and the minimum interspecific divergence was greater than the maximum intraspecific divergence. Clustering analysis indicated that most species fell into monophyletic clades. These results suggest that these species could be reliably differentiated using COI DNA barcodes. Moreover, a novel species-specific multiplex PCR assay was developed to distinguish between Naja spp, Ophiophagus hannah, Trimeresurus spp, Hydrophiinae, Daboia siamensis, Bungarus fasciatus, and Calloselasma rhodostoma. Antivenom for these species is produced and kept by the Thai Red Cross for clinical use. Our novel PCR assay could easily be applied to venom and saliva samples and could be used effectively for the rapid and accurate identification of species during forensic work, conservation study, and medical research.

  11. A new peptide (Ruviprase) purified from the venom of Daboia russelii russelii shows potent anticoagulant activity via non-enzymatic inhibition of thrombin and factor Xa.

    PubMed

    Thakur, Rupamoni; Kumar, Ashok; Bose, Biplab; Panda, Dulal; Saikia, Debashree; Chattopadhyay, Pronobesh; Mukherjee, Ashis K

    2014-10-01

    Compounds showing dual inhibition of thrombin and factor Xa (FXa) are the subject of great interest owing to their broader specificity for effective anticoagulation therapy against cardiovascular disorders. This is the first report on the functional characterization and assessment of therapeutic potential of a 4423.6 Da inhibitory peptide (Ruviprase) purified from Daboia russelii russelii venom. The secondary structure of Ruviprase is composed of α-helices (61.9%) and random coils (38.1%). The partial N-terminal sequence (E(1)-V(2)-X(3)-W(4)-W(5)-W(6)-A(7)-Q(8)-L(9)-S(10)) of Ruviprase demonstrated significant similarity (80.0%) with an internal sequence of apoptosis-stimulating protein reported from the venom of Ophiophagus hannah and Python bivittatus; albeit Ruviprase did not show sequence similarity with existing thrombin/FXa inhibitors, suggesting its uniqueness. Ruviprase demonstrated a potent in vitro anticoagulant property and inhibited both thrombin and FXa following slow binding kinetics. Ruviprase inhibited thrombin by binding to its active site via an uncompetitive mechanism with a Ki value and dissociation constant (KD) of 0.42 μM and 0.46 μM, respectively. Conversely, Ruviprase demonstrated mixed inhibition (Ki = 0.16 μM) of FXa towards its physiological substrate prothrombin. Furthermore, the biological properties of Ruviprase could not be neutralized by commercial polyvalent or monovalent antivenom. Ruviprase at a dose of 2.0 mg/kg was non-toxic and showed potent in vivo anticoagulant activity after 6 h of intraperitoneal treatment in mice. Because of the potent anticoagulant property as well as non-toxic nature of Ruviprase, the possible application of the peptide as an antithrombotic agent for combating thrombosis-associated ailments appears promising. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Acetylcholinesterases from Elapidae snake venoms: biochemical, immunological and enzymatic characterization.

    PubMed

    Frobert, Y; Créminon, C; Cousin, X; Rémy, M H; Chatel, J M; Bon, S; Bon, C; Grassi, J

    1997-05-23

    We analyzed 45 batches of venom from 20 different species belonging to 11 genera from the 3 main families of venomous snakes (Elapidae, Viperidae and Crotalidae). We found high acetylcholinesterase (AChE) activity in all venoms from Elapidae, except in those from the Dendroaspis genus. AChE was particularly abundant in Bungarus venoms which contain up to 8 mg of enzyme per gram of dried venom. We could not detect acetylcholinesterase activity in any batch of venom from Viperidae or Crotalidae. Titration of active sites with an organophosphorous agent (MPT) revealed that the AChE of all venoms have similar turnovers (6000 to 8000 s(-1)) which are clearly higher than those of Torpedo and mammalian enzymes but lower than that of Electrophorus. AChEs from the venom of elapid snakes of the Bungarus, Naja, Ophiophagus and Haemacatus genera were purified by affinity chromatography. SDS-PAGE analysis and sucrose gradient centrifugation demonstrated that AChE is exclusively present as a nonamphiphilic monomer. These enzymes are true AChEs, hydrolyzing acetylthiocholine faster than propionylthiocholine and butyrylthiocholine and exhibiting excess substrate inhibition. Twenty-seven different monoclonal antibodies directed against AChE from Bungarus fasciatus venom were raised in mice. Half of them recognized exclusively the Bungarus enzyme while the others cross-reacted with AChEs from other venoms. Polyspecific mAbs were used to demonstrate that venoms from Dendroaspis, which contain the AChE inhibitor fasciculin but lack AChE activity, were also devoid of immunoreactive AChE protein. AChE inhibitors acting at the active site (edrophonium, tacrine) and at the peripheral site (propidium, fasciculin), as well as bis-quaternary ligands (BW284C51, decamethonium), were tested against the venom AChEs from 11 different species. All enzymes had a very similar pattern of reactivity with regard to the different inhibitors, with the exception of fasciculin. AChEs from Naja and

  13. Lasting Impressions: Hannah Arendt's Educational Legacy

    ERIC Educational Resources Information Center

    Gardiner, Rita A.

    2016-01-01

    Hannah Arendt's work is gaining increasing recognition in educational administration. But less has been written about her as an educator, colleague, and provocateur. Here, I explore the lasting impressions that Arendt had on former students, colleagues, and friends. This exploration is conducted through the lens of Arendtian narrative inquiry. For…

  14. Allergies to Insect Venom

    MedlinePlus

    ... colored clothing. Dark clothing and clothing with flowery designs is more likely to attract insects.  Use unscented ... keep insecticide available. Treatment tips:  Venom immunotherapy (allergy shots to insect venom(s) is highly effective in preventing ...

  15. Venomous snakebites.

    PubMed

    Adukauskienė, Dalia; Varanauskienė, Eglė; Adukauskaitė, Agnė

    2011-01-01

    More than 5 million people are bitten by venomous snakes annually and more than 100,000 of them die. In Europe, one person dies due to envenomation every 3 years. There is only one venomous snake species in Lithuania--the common adder (Vipera berus)--which belongs to the Viperidae family; however, there are some exotic poisonous snakes in the zoos and private collections, such as those belonging to the Elapidae family (cobras, mambas, coral snakes, etc.) and the Crotalidae subfamily of the Viperidae family (pit vipers, such as rattlesnakes). Snake venom can be classified into hemotoxic, neurotoxic, necrotoxic, cardiotoxic, and nephrotoxic according to the different predominant effects depending on the family (i.e., venom of Crotalidae and Viperidae snakes is more hemotoxic and necrotoxic, whereas venom of Elapidae family is mainly neurotoxic). The intoxication degree is estimated according to the appearance of these symptoms: 1) no intoxication ("dry" bite); 2) mild intoxication (local edema and pain); 3) moderate intoxication (pain, edema spreading out of the bite zone, and systemic signs); 4) severe intoxication (shock, severe coagulopathy, and massive edemas). This topic is relevant because people tend to make major mistakes providing first aid (e.g., mouth suction, wound incision, and application of ice or heat). Therefore, this article presents the essential tips on how first aid should be performed properly according to the "Guidelines for the Management of Snake-Bites" by the World Health Organization (2010). Firstly, the victim should be reassured. Rings or other things must be removed preventing constriction of the swelling limb. Airway/breathing must be maintained. The bitten limb should be immobilized and kept below heart level to prevent venom absorption and systemic spread. Usage of pressure bandage is controversial since people usually apply it improperly. Incision, mouth suction, or excision should not be performed; neither a tourniquet nor ice or

  16. Are ticks venomous animals?

    PubMed Central

    2014-01-01

    Introduction As an ecological adaptation venoms have evolved independently in several species of Metazoa. As haematophagous arthropods ticks are mainly considered as ectoparasites due to directly feeding on the skin of animal hosts. Ticks are of major importance since they serve as vectors for several diseases affecting humans and livestock animals. Ticks are rarely considered as venomous animals despite that tick saliva contains several protein families present in venomous taxa and that many Ixodida genera can induce paralysis and other types of toxicoses. Tick saliva was previously proposed as a special kind of venom since tick venom is used for blood feeding that counteracts host defense mechanisms. As a result, the present study provides evidence to reconsider the venomous properties of tick saliva. Results Based on our extensive literature mining and in silico research, we demonstrate that ticks share several similarities with other venomous taxa. Many tick salivary protein families and their previously described functions are homologous to proteins found in scorpion, spider, snake, platypus and bee venoms. This infers that there is a structural and functional convergence between several molecular components in tick saliva and the venoms from other recognized venomous taxa. We also highlight the fact that the immune response against tick saliva and venoms (from recognized venomous taxa) are both dominated by an allergic immunity background. Furthermore, by comparing the major molecular components of human saliva, as an example of a non-venomous animal, with that of ticks we find evidence that ticks resemble more venomous than non-venomous animals. Finally, we introduce our considerations regarding the evolution of venoms in Arachnida. Conclusions Taking into account the composition of tick saliva, the venomous functions that ticks have while interacting with their hosts, and the distinguishable differences between human (non-venomous) and tick salivary

  17. Possibly Preventing Catastrophes: Hannah Arendt on Democracy, Education and Judging

    ERIC Educational Resources Information Center

    Monig, Julia Maria

    2012-01-01

    In this paper, I try to argue why it is worth turning to Hannah Arendt when reflecting on education. I am exploring her political theory in "The Human Condition" which, with the anthropologic category of natality, seems to offer an interesting approach for democratic education. Apparently everyone can participate in politics or even…

  18. Hannah Arendt & Jean Baudrillard: Pedagogy in the Consumer Society

    ERIC Educational Resources Information Center

    Norris, Trevor

    2006-01-01

    This paper considers the place of education within our "consumers' society", beginning with Hannah Arendt's account of the rise of consumerism to a position of political dominance and the resulting eclipse of public life. Connections are then made between Arendt's account of this rise and Jean Baudrillard's account of the postmodern proliferation…

  19. Hannah Arendt and Karl Jaspers: The Time of Friendship

    ERIC Educational Resources Information Center

    Nixon, Jon

    2016-01-01

    This paper provides an introduction to the enduring friendship between Hannah Arendt and Karl Jaspers. It shows how their intellectual development as public educators was sustained by their ongoing dialogue which flourished not in spite of but because of their huge differences of circumstance and personality. This friendship between two renowned…

  20. Hannah Arendt's Fame Rests on the Wrong Foundation

    ERIC Educational Resources Information Center

    Jacoby, Russell

    2006-01-01

    A street is named after her. Back-to-back conferences celebrate her. New books champion her. Hannah Arendt has joined the small world of philosophical heroes. During her life, she received honorary degrees from Princeton, Smith, and other colleges and universities. Denmark awarded her its Sonning Prize for "commendable work that benefits European…

  1. Immunology of Bee Venom.

    PubMed

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

    2018-06-01

    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.

  2. The venom optimization hypothesis revisited.

    PubMed

    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.

  3. Elemental analysis of scorpion venoms.

    PubMed

    Al-Asmari, AbdulRahman K; Kunnathodi, Faisal; Al Saadon, Khalid; Idris, Mohammed M

    2016-01-01

    Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of different mass ranges were detected in the venom at PPB level. Quantitative analysis of the venoms revealed copper to be the most abundant element in Androctonus sp. venom but at lower level in Leiurus quinquestriatus venom; whereas zinc and manganese was found at higher levels in Leiurus sp. venom but at lower level in Androctonus sp. venom. These data and the concentrations of other different elements present in the various venoms are likely to increase our understanding of the mechanisms of venom activity and their pharmacological potentials.

  4. The Vita Activa as Compass: Navigating Uncertainty in Teaching with Hannah Arendt

    ERIC Educational Resources Information Center

    Rogers, Carrie Ann Barnes

    2010-01-01

    This dissertation is an exploration of stories of uncertainty in the lives of elementary teachers and the value that the ideas of Hannah Arendt lend to the discussion around uncertainty. In "The Human Condition" (1958) Hannah Arendt theorizes the life of action, the "vita activa". Arendtian action is inherently uncertain because to be "capable of…

  5. Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

    PubMed Central

    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

  6. Pharmacokinetics of Snake Venom

    PubMed Central

    Sanhajariya, Suchaya; Duffull, Stephen B.

    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, 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. PMID:29414889

  7. Understanding and utilising mammalian venom via a platypus venom transcriptome.

    PubMed

    Whittington, Camilla M; Koh, Jennifer M S; Warren, Wesley C; Papenfuss, Anthony T; Torres, Allan M; Kuchel, Philip W; Belov, Katherine

    2009-03-06

    Only five mammalian species are known to be venomous, and while a large amount of research has been carried out on reptile venom, mammalian venom has been poorly studied to date. Here we describe the status of current research into the venom of the platypus, a semi-aquatic egg-laying Australian mammal, and discuss our approach to platypus venom transcriptomics. We propose that such construction and analysis of mammalian venom transcriptomes from small samples of venom gland, in tandem with proteomics studies, will allow the identification of the full range of mammalian venom components. Functional studies and pharmacological evaluation of the identified toxins will then lay the foundations for the future development of novel biomedical substances. A large range of useful molecules have already been identified in snake venom, and many of these are currently in use in human medicine. It is therefore hoped that this basic research to identify the constituents of platypus venom will eventually yield novel drugs and new targets for painkillers.

  8. Venom therapy in multiple sclerosis.

    PubMed

    Mirshafiey, Abbas

    2007-09-01

    To date many people with multiple sclerosis (MS) seek complementary and alternative medicines (CAM) to treat their symptoms as an adjunct to conventionally used therapies. Among the common CAM therapies, there is a renewed interest in the therapeutic potential of venoms in MS. The efficacy of this therapeutic method remains unclear. However, venom-based therapy using bee, snakes and scorpions venom and/or sea anemones toxin has been recently developed because current investigations have identified the various components and molecular mechanism of the effects of venoms under in vitro and in vivo conditions. The aim of this review is to describe the recent findings regarding the role of venoms and their components in treatment of MS disease and that whether venom therapy could be recommended as a complementary treatment or not.

  9. Mining on scorpion venom biodiversity.

    PubMed

    Rodríguez de la Vega, Ricardo C; Schwartz, Elisabeth F; Possani, Lourival D

    2010-12-15

    Scorpion venoms are complex mixtures of dozens or even hundreds of distinct proteins, many of which are inter-genome active elements. Fifty years after the first scorpion toxin sequences were determined, chromatography-assisted purification followed by automated protein sequencing or gene cloning, on a case-by-case basis, accumulated nearly 250 amino acid sequences of scorpion venom components. A vast majority of the available sequences correspond to proteins adopting a common three-dimensional fold, whose ion channel modulating functions have been firmly established or could be confidently inferred. However, the actual molecular diversity contained in scorpion venoms -as revealed by bioassay-driven purification, some unexpected activities of "canonical" neurotoxins and even serendipitous discoveries- is much larger than those "canonical" toxin types. In the last few years mining into the molecular diversity contained in scorpion has been assisted by high-throughput Mass Spectrometry techniques and large-scale DNA sequencing, collectively accounting for the more than twofold increase in the number of known sequences of scorpion venom components (now reaching 500 unique sequences). This review, from a comparative perspective, deals with recent data obtained by proteomic and transcriptomic studies on scorpion venoms and venom glands. Altogether, these studies reveal a large contribution of non canonical venom components, which would account for more than half of the total protein diversity of any scorpion venom. On top of aiding at the better understanding of scorpion venom biology, whether in the context of venom function or within the venom gland itself, these "novel" venom components certainly are an interesting source of bioactive proteins, whose characterization is worth pursuing. Copyright © 2009 Elsevier Ltd. All rights reserved.

  10. Capturing the worlds of multiple sclerosis: Hannah Laycock's photography.

    PubMed

    Bolaki, Stella

    2017-03-01

    This essay explores UK photographer Hannah Laycock's Awakenings and, to a lesser extent, Perceiving Identity that were created in 2015, following her diagnosis with multiple sclerosis (MS) in 2013. It draws on scholarship by people with chronic illness while situating these two MS projects in the context of Laycock's earlier art and portrait photography dealing with fragility, image and desire, and power relations between subject and observer. The analysis illustrates how her evocative photography captures the lived or subjective experience of an invisible and often misunderstood condition by initially focusing on the tension between transparency and opacity in her work. It further shows how her images counter dominant didactic metaphors such as, 'the body as machine', that perpetuate the dehumanising and objectifying aspects of medical care. Subsequent sections trace the influence that Oliver Sacks has had on Laycock's practice, and reflect on other metaphors and tropes in Awakenings that illuminate the relationship between body and self in MS. The essay concludes by acknowledging the therapeutic power of art and calling upon health professionals to make more use of such artistic work in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Interview: Investigating immunomodulators among the Actinomycetales. Interview by Hannah Wilson.

    PubMed

    Stanford, John L

    2013-05-01

    John L Stanford speaks to Hannah Wilson, Assistant Commissioning Editor John L Stanford is Chief Scientific Officer at BioEos Ltd (Kent, UK). Dr Stanford began his career as a senior lecturer and then reader in microbiology at Middlesex Hospital Medical School (London, UK), then University College London Medical School, where he became Professor in Medical Microbiology and Head of Department in 1997. He retired and became Professor Emeritus in 2004. Dr Stanford's career has been devoted to research into mycobacteria, the diseases that they cause and the practical uses of this research. His special interest in recent years has been the development of bacterial immunotherapeutics for a range of diseases including tuberculosis and cancer. Dr Stanford was one of the founding directors of Stanford Rook Ltd (London) and of BioEos Ltd, where he remains a director. He also played a part in the founding of Immodulon Therapeutics Ltd (London) and of a new company, ActinoPharma Ltd (London), and has published more than 200 peer-reviewed scientific papers.

  12. Interview: interview with P Jeffrey Conn. Interview by Hannah Coaker.

    PubMed

    Conn, P Jeffrey

    2013-09-01

    Dr Conn is the Lee E Limbird Professor of Pharmacology at Vanderbilt University and Director of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD). Dr Conn received a PhD in Pharmacology from Vanderbilt in 1986 and pursued postdoctoral studies at Yale University. He served as a professor of Pharmacology at Emory University from 1988 to 2000, before moving to Merck and Co. (PA, USA) as head of the Department of Neuroscience. Dr Conn moved to Vanderbilt University in 2003 where he is the founding director of the VCNDD, with a primary mission of facilitating translation of recent advances in basic science to novel therapeutics. The VCNDD consists of approximately 100 full-time scientists and has advanced novel molecules from four major programs as development candidates for clinical testing with industry partners. Dr Conn has served in editorial positions with multiple international journals and has served the scientific advisory boards of multiple foundations and companies. He has received numerous awards based on the impact of his basic and translational research. Dr Conn's current research is focused on development of novel treatment strategies for schizophrenia, Parkinson's disease and other serious brain disorders. Interview conducted by Hannah Coaker, Assistant Commissioning Editor.

  13. Hannah Arendt, evil and the eradication of thought.

    PubMed

    Covington, Coline

    2012-10-01

    Evil deeds may be committed intentionally or out of madness, but it is those who follow orders that present us with the most complex moral, philosophical and psychological questions. In writing about the banality of evil, Hannah Arendt argues that "in granting pardon, it is the person and not the crime that is forgiven; in rootless evil there is no person left whom one could ever forgive." Arendt postulates that "being a person" necessarily entails the acts of memory and thought. This paper explores Arendt's ideas on memory and thought and how these processes can become subverted in the service of a higher order. Clinical material illustrates Whitmer's idea of dissociation as an "impairment of subjectivity" as distinct from Freud's view of dissociation as a form of repression. This shift in theoretical perspective sheds new light on our understanding of the totalitarian state of mind, i.e. of the mind of a "nobody", and the conditions within which evil is committed. Copyright © 2012 Institute of Psychoanalysis.

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

    PubMed Central

    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.

    2017-01-01

    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 sea

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

    PubMed

    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

  16. Immune drug discovery from venoms.

    PubMed

    Jimenez, Rocio; Ikonomopoulou, Maria P; Lopez, J Alejandro; Miles, John J

    2018-01-01

    This review catalogues recent advances in knowledge on venoms as standalone therapeutic agents or as blueprints for drug design, with an emphasis on venom-derived compounds that affects the immune system. We discuss venoms and venom-derived compounds that affect total immune cell numbers, immune cell proliferation, immune cell migration, immune cell phenotype and cytokine secretion. Identifying novel compounds that 'tune' the system, up-regulating the immune response during infectious disease and cancer and down-regulating the immune response during autoimmunity, will greatly expand the tool kit of human immunotherapeutics. Targeting these pathways may also open therapeutic options that alleviate symptoms of envenomation. Finally, combining recent advances in venomics with progress in low cost, high-throughput screening platforms will no doubt yield hundreds of prototype immune modulating compounds in the coming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Interview with James Bradner. Interviewed by Hannah Coaker.

    PubMed

    Bradner, James E

    2013-08-01

    James E Bradner is an Assistant Professor in Medicine at Harvard Medical School (MA, USA) as well as a Staff Physician in the Division of Hematologic Malignancies at Dana-Farber Cancer Institute (MA, USA). The present research focus of the Bradner laboratory concerns the discovery and optimization of prototype drugs targeting cancer gene regulation. The clinical objective of the Bradner group is to deliver novel therapeutics for human clinical investigation in hematologic diseases. Bradner's awards and honors include the Damon Runyon-Rachleff Innovation Award, the Smith Family Award for Excellence in Biomedical Research, the Dunkin' Donuts Rising Star Award and the HMS Distinguished Excellence in Teaching Award. He is a member of the American Society of Clinical Investigation, the American Society of Hematology, the American Chemical Society and the American Association of Cancer Research. His recent research has been published in Nature, Cell, Nature Chemical Biology and the Journal of the American Chemical Society. He has authored more than 20 US Patent applications, licensed to five pharmaceutical companies, and is a scientific founder of Acetylon Pharmaceuticals, SHAPE Pharmaceuticals, Tensha Therapeutics and Syros Pharmaceuticals. Bradner received his AB from Harvard University, his MD from the University of Chicago (IL, USA) and a MMS from Harvard Medical School. He completed his postgraduate training in Internal Medicine at Brigham & Women's Hospital (MA, USA), followed by a fellowship in Medical Oncology and Hematology at Dana-Farber Cancer Institute. Following additional post-doctoral training in Chemistry at Harvard University and the Broad Institute (MA, USA) with Professor Stuart Schreiber, Bradner joined the research faculty of Dana-Farber in 2008. Interview conducted by Hannah Coaker, Assistant Commissioning Editor.

  18. Unusual Stability of Messenger RNA in Snake Venom Reveals Gene Expression Dynamics of Venom Replenishment

    PubMed Central

    Currier, Rachel B.; Calvete, Juan J.; Sanz, Libia; Harrison, Robert A.; Rowley, Paul D.; Wagstaff, Simon C.

    2012-01-01

    Venom is a critical evolutionary innovation enabling venomous snakes to become successful limbless predators; it is therefore vital that venomous snakes possess a highly efficient venom production and delivery system to maintain their predatory arsenal. Here, we exploit the unusual stability of messenger RNA in venom to conduct, for the first time, quantitative PCR to characterise the dynamics of gene expression of newly synthesised venom proteins following venom depletion. Quantitative PCR directly from venom enables real-time dynamic studies of gene expression in the same animals because it circumvents the conventional requirement to sacrifice snakes to extract mRNA from dissected venom glands. Using qPCR and proteomic analysis, we show that gene expression and protein re-synthesis triggered by venom expulsion peaks between days 3–7 of the cycle of venom replenishment, with different protein families expressed in parallel. We demonstrate that venom re-synthesis occurs very rapidly following depletion of venom stores, presumably to ensure venomous snakes retain their ability to efficiently predate and remain defended from predators. The stability of mRNA in venom is biologically fascinating, and could significantly empower venom research by expanding opportunities to produce transcriptomes from historical venom stocks and rare or endangered venomous species, for new therapeutic, diagnostic and evolutionary studies. PMID:22879897

  19. Bioactive Components in Fish Venoms

    PubMed Central

    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

  20. Polymerized soluble venom--human serum albumin

    SciTech Connect

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

    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 againstmore » 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.« less

  1. Hannah Arendt and Norwegian Muslim Children's Schooling: In Pursuit of Democratic Practices

    ERIC Educational Resources Information Center

    Giaever, Katrine; Jones, Liz

    2017-01-01

    The aim of this paper is to consider whether Hannah Arendt's (1996) [Arendt, H. (1958/1998). "Vita Activa. The Human Condition." Chicago: University of Chicago] concept of "public space" is a potentially useful and creative way of thinking about aspects of Muslim children's experiences within the context of education. Following…

  2. Friendship and the Public Stage: Revisiting Hannah Arendt's Resistance to "Political Education"

    ERIC Educational Resources Information Center

    Schutz, Aaron; Sandy, Marie G.

    2015-01-01

    Hannah Arendt's essays about the 1957 crisis over efforts of a group of youth, the "Little Rock Nine," to desegregate a high school in Little Rock, Arkansas, reveal a tension in her vision of the "public." In this article Aaron Schutz and Marie Sandy look closely at the experiences of the youth desegregating the school,…

  3. Beginning and Becoming: Hannah Arendt's Theory of Action and Action Research in Education

    ERIC Educational Resources Information Center

    Rogers, Carrie

    2014-01-01

    This paper demonstrates the importance and implications of Hannah Arendt's theory of action for action research. Using examples from my teaching experience I demonstrate the relevance of her ideas in understanding the purpose and aims of action research in the classroom.

  4. Mastocytosis and insect venom allergy.

    PubMed

    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.

  5. Animal venoms as antimicrobial agents.

    PubMed

    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.

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

    PubMed

    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.

  7. Evolution: Fangtastic Venoms Underpin Parasitic Mimicry.

    PubMed

    Taylor, Martin I

    2017-04-24

    Venomous teeth are rare in fishes, which typically utilise spines for defence. A new study reveals the evolutionary origins of fangs and venom in the Nemophini blennies and shows that, in contrast to snakes and lizards, the fangs pre-date the venom. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  8. A petition to Mr Peel: Gideon Mantell and the trial of Hannah Russell.

    PubMed

    Flanagan, R J; Watson, K D

    2009-07-01

    In the summer of 1826, Hannah Russell was tried for petty treason, viz. the murder of her husband, Benjamin Russell, by poisoning. Their lodger, Daniel Leney, was indicted as her accomplice. The exact circumstances surrounding the death were unclear but Hannah was known to have purchased white arsenic (arsenious oxide). A local surgeon, Thomas Evans, supported at the post-mortem examination by two further surgeons, not only reported severe corrosion of the gastrointestinal tract, but also the recovery of nearly an eighth of an ounce of arsenic from the victim's stomach. Both accused were convicted and sentenced to death. Leney was executed, but Hannah Russell was respited because the trial judge, Sir Robert Graham, had doubts as to a direction he had given to the jury. The surgeon and paleontologist Gideon Mantell took up her case, stressing that death from arsenic could not have taken place as quickly as was alleged and maintaining that the chemical evidence of arsenic poisoning was inconclusive. He gained the support of some eminent chemists and physicians. Subsequently, forensic toxicologists [Sir] Robert Christison and Alfred Swaine Taylor pointed out that Mantell's arguments as to the possible time to death in arsenic poisoning were quite wrong. Moreover, Evans gave details of the analyses he and his colleagues had undertaken to Christison, who pronounced the findings sound, as indeed did Mantell after Evans and his colleagues published details of their investigations in the Sussex Advertiser. Papers in The National Archives show that Hannah was pardoned for the offence for which she was indicted, leaving it open to prefer a lesser charge. That this was never done may have been due to Mantell's campaign, at least in part, but the pardon she did receive was due to the concern of the trial judge as to the implications of the evidence presented at trial.

  9. Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes.

    PubMed

    Brahma, Rajeev Kungur; McCleary, Ryan J R; Kini, R Manjunatha; Doley, Robin

    2015-01-01

    Snake venoms are cocktails of protein toxins that play important roles in capture and digestion of prey. Significant qualitative and quantitative variation in snake venom composition has been observed among and within species. Understanding these variations in protein components is instrumental in interpreting clinical symptoms during human envenomation and in searching for novel venom proteins with potential therapeutic applications. In the last decade, transcriptomic analyses of venom glands have helped in understanding the composition of various snake venoms in great detail. Here we review transcriptomic analysis as a powerful tool for understanding venom profile, variation and evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Scorpion venom complexity fractal analysis. Its relevance for comparing venoms.

    PubMed

    D'Suze, Gina; Sevcik, Carlos

    2010-12-07

    We analyzed the venom elution pattern of 15 scorpions species. Data were scanned at 1 Hz and stored digitally. Approximate fractal dimension (D) [Sevcik (1998)] was calculated for minutes 0-60 of the elutions. D was calculated for either the whole time range, or calculated using a window of 500 points, which was displaced by one time increment recursively, and stored [(t(i),D(i)) sets]. We avoid the term complexity as much as possible since defining complexity is difficult; instead we propose the term contortedness and represent it by the variable Q=D-1. To compare venom contortednesses of different species, a phase plot with their (t(i),Q(i)) sets was constructed and determination coefficient (d(s)) were calculated squaring the Spearman rank correlation coefficient. (t(i),Q(i)) sets of several elutions of the same species were averaged and compared with other species finding that some were amazingly similar (Tityus clathratus vs Tityus caripitensis, d(s) = 0.813). Tityus discrepans was similar to 6 of 8 species of the same genus (d(s) ranging from 0.23 to 0.49), and also similar to Centruroides gracilis and Chactas laevipes (d(s) 0.54 and 0.49, respectively). Serendipitously,T. discrepans was chosen many years ago to produce anti-Tityus antivenom in Venezuela; perhaps the clinical success in neutralizing the venom of the other known Venezuelan Tityus, stems from the mimetism of this venom with the remaining species' venom. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Colubrid Venom Composition: An -Omics Perspective

    PubMed Central

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

    2016-01-01

    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. PMID:27455326

  12. Novel venom gene discovery in the platypus

    PubMed Central

    2010-01-01

    Background To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. Results We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation. Conclusions This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom. PMID:20920228

  13. Novel venom gene discovery in the platypus.

    PubMed

    Whittington, Camilla M; Papenfuss, Anthony T; Locke, Devin P; Mardis, Elaine R; Wilson, Richard K; Abubucker, Sahar; Mitreva, Makedonka; Wong, Emily S W; Hsu, Arthur L; Kuchel, Philip W; Belov, Katherine; Warren, Wesley C

    2010-01-01

    To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation. This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom.

  14. Novel active principles from spider venom.

    PubMed

    Vassilevski, Alexander A; Grishin, Eugene V

    2011-12-01

    Spiders are one of the most intriguing groups of venomous animals. Substances found in their venom vary from simple inorganic compounds to large multi-domain proteins. In this article, we review some of the latest work presenting active principles that add to the known spider toxin universe. Two aspects of novelty are addressed in particular, structural (novel types of molecules in terms of structure) and functional (novel types of biological targets hit by substances from spider venom and novel mechanisms of action).

  15. Pharmacological studies of stonefish (Synanceja trachynis) venom.

    PubMed

    Hopkins, B J; Hodgson, W C; Sutherland, S K

    1994-10-01

    The present study was designed to examine some of the pharmacological properties of venom from the stonefish (Synanceja trachynis), with particular reference to the presence in the venom of pain-producing/enhancing substances. Stonefish venom (1-6 micrograms/ml) produced concentration-dependent contractile responses in guinea-pig isolated ileum. No tachyphylaxis, or reduction in responses with time, was observed to venom (3 micrograms/ml) in ileum. The response to venom (3 micrograms/ml) was not significantly affected by the histamine antagonist mepyramine (0.5 microM), or a preceding anaphylactic response. Mecamylamine, 5HT-desensitization or EXP3174 failed to have any significant effect on responses to venom (3 micrograms/ml). Responses to venom (3 micrograms/ml) were significantly inhibited by the cyclooxygenase inhibitor indomethacin (5 microM), the leukotriene D4 receptor antagonist FLP55712 (1 microM), the thromboxane A2 receptor antagonist GR32191B (1 microM), the muscarinic receptor antagonist atropine (10 nM) and the neurokinin-1 receptor antagonist CP96345 (0.1 microM). Venom (6 micrograms/ml) produced contractile responses in the rat isolated vas deferens which were abolished by the alpha 1-adrenoceptor antagonist prazosin (0.3 microM) and significantly potentiated by the neuronal uptake inhibitor DMI (1 microM). However, noradrenergic transmitter depletion with reserpine (5 mg/kg, i.p.) did not significantly inhibit responses to venom (6 micrograms/ml). Histamine fluorometric and phospholipase A2 assays failed to detect significant quantities of either substance in the venom. These results suggest that stonefish venom may cause the release of acetylcholine, substance P, and cyclooxygenase products, or contain components which act at these receptors. The venom also appears to contain a component which is a substrate for neuronal uptake and has a direct action at alpha 1-adrenoceptors.

  16. The Biochemical Toxin Arsenal from Ant Venoms

    PubMed Central

    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

  17. Reflective thinking and medical students: some thoughtful distillations regarding John Dewey and Hannah Arendt

    PubMed Central

    Papadimos, Thomas J

    2009-01-01

    Reflective thought (critical thinking) is essential to the medical student who hopes to become an effective physician. John Dewey, one of America's foremost educators in the early twentieth century, revolutionized critical thinking and its role in education. In the mid twentieth century Hannah Arendt provided profound insights into the problem of diminishing human agency and political freedom. Taken together, Dewey's insight regarding reflective thought, and Arendt's view of action, speech, and power in the public realm, provide mentors and teachers of medical students guidance in the training of thought and the need for its effective projection at the patient's bedside and in the community. PMID:19368737

  18. Paleobotany of Livingston Island: The first report of a Cretaceous fossil flora from Hannah Point

    USGS Publications Warehouse

    Leppe, M.; Michea, W.; Muñoz, C.; Palma-Heldt, S.; Fernandoy, F.

    2007-01-01

    This is the first report of a fossil flora from Hannah Point, Livingston Island, South Shetland Islands, Antarctica. The fossiliferous content of an outcrop, located between two igneous rock units of Cretaceous age are mainly composed of leaf imprints and some fossil trunks. The leaf assemblage consists of 18 taxa of Pteridophyta, Pinophyta and one angiosperm. The plant assemblage can be compared to other Early Cretaceous floras from the South Shetland Islands, but several taxa have an evidently Late Cretaceous affinity. A Coniacian-Santonian age is the most probable age for the outcrops, supported by previous K/Ar isotopic studies of the basalts over and underlying the fossiliferous sequence

  19. Reflective thinking and medical students: some thoughtful distillations regarding John Dewey and Hannah Arendt.

    PubMed

    Papadimos, Thomas J

    2009-04-16

    Reflective thought (critical thinking) is essential to the medical student who hopes to become an effective physician. John Dewey, one of America's foremost educators in the early twentieth century, revolutionized critical thinking and its role in education. In the mid twentieth century Hannah Arendt provided profound insights into the problem of diminishing human agency and political freedom. Taken together, Dewey's insight regarding reflective thought, and Arendt's view of action, speech, and power in the public realm, provide mentors and teachers of medical students guidance in the training of thought and the need for its effective projection at the patient's bedside and in the community.

  20. Snake venomics and venom gland transcriptomic analysis of Brazilian coral snakes, Micrurus altirostris and M. corallinus.

    PubMed

    Corrêa-Netto, Carlos; Junqueira-de-Azevedo, Inácio de L M; Silva, Débora A; Ho, Paulo L; Leitão-de-Araújo, Moema; Alves, Maria Lúcia M; Sanz, Libia; Foguel, Débora; Zingali, Russolina Benedeta; Calvete, Juan J

    2011-08-24

    The venom proteomes of Micrurus altirostris and M. corallinus were analyzed by combining snake venomics and venom gland transcriptomic surveys. In both coral snake species, 3FTx and PLA(2) were the most abundant and diversified toxin families. 33 different 3FTxs and 13 PLA(2) proteins, accounting respectively for 79.5% and 13.7% of the total proteins, were identified in the venom of M. altirostris. The venom of M. corallinus comprised 10 3FTx (81.7% of the venom proteome) and 4 (11.9%) PLA(2) molecules. Transcriptomic data provided the full-length amino acid sequences of 18 (M. altirostris) and 10 (M. corallinus) 3FTxs, and 3 (M. altirostris) and 1 (M. corallinus) novel PLA(2) sequences. In addition, venom from each species contained single members of minor toxin families: 3 common (PIII-SVMP, C-type lectin-like, L-amino acid oxidase) and 4 species-specific (CRISP, Kunitz-type inhibitor, lysosomal acid lipase in M. altirostris; serine proteinase in M. corallinus) toxin classes. The finding of a lipase (LIPA) in the venom proteome and in the venom gland transcriptome of M. altirostris supports the view of a recruitment event predating the divergence of Elapidae and Viperidae more than 60 Mya. The toxin profile of both M. altirostris and M. corallinus venoms points to 3FTxs and PLA(2) molecules as the major players of the envenoming process. In M. altirostris venom, all major, and most minor, 3FTxs display highest similarity to type I α-neurotoxins, suggesting that these postsynaptically acting toxins may play the predominant role in the neurotoxic effect leading to peripheral paralysis, respiratory arrest, and death. M. corallinus venom posesses both, type I α-neurotoxins and a high-abundance (26% of the venom proteome) protein of subfamily XIX of 3FTxs, exhibiting similarity to bucandin from Malayan krait, Bungarus candidus, venom, which enhances acetylcholine release presynaptically. This finding may explain the presynaptic neurotoxicity of M. corallinus venom

  1. Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China.

    PubMed

    Xu, Ning; Zhao, Hong-Yan; Yin, Yin; Shen, Shan-Shan; Shan, Lin-Lin; Chen, Chuan-Xi; Zhang, Yan-Xia; Gao, Jian-Fang; Ji, Xiang

    2017-04-21

    We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A 2 (PLA 2 ), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA 2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome. Furthermore, N. kaouthia venom expressed strong lethality (i.p. LD 50 : 0.79μg/g) and myotoxicity (CK: 5939U/l) in mice, and showed notable activity in PLA 2 but weak activity in SVMP, l-amino acid oxidase or 5' nucleotidase. Antivenomic assessment revealed that several venom components (nearly 17.5% of total venom) from N. kaouthia could not be thoroughly immunocaptured by commercial Naja atra antivenom. ELISA analysis revealed that there was no difference in the cross-reaction between N. kaouthia and N. atra venoms against the N. atra antivenom. The use of commercial N. atra antivenom in treatment of snakebites caused by N. kaouthia is reasonable, but design of novel antivenom with the attention on enhancing the immune response of non-immunocaptured components should be encouraged. The venomics, antivenomics and venom-gland transcriptome of the monocoled cobra (Naja kaouthia) from China have been elucidated. Quantitative and qualitative differences are evident when venom proteomic and venom-gland transcriptomic profiles are compared. Two protein families (3-FTx and PLA 2 ) are found to be the predominated components in N. kaouthia venom, and considered as the major players in functional role of venom. Other protein families with relatively low abundance appear to be minor in the functional significance. Antivenomics and ELISA evaluation reveal that the N. kaouthia venom can be effectively immunorecognized by commercial N. atra

  2. Myonecrosis Induced by Rattlesnake Venom

    PubMed Central

    Stringer, John M.; Kainer, Robert A.; Tu, Anthony T.

    1972-01-01

    The myonecrotic effect of rattlesnake (Crotalus viridis viridis) venom on mouse skeletal muscle was studied. The biceps femoris muscle was examined with the electron microscope after one-fourth the LD50 of the crude venom was injected into the gracilis and semimembranosus muscles. Focal areas of myonecrosis were abundant. Injured fibers contained dilated sarcoplasmic reticulum, disoriented, coagulated myofilamentous components and condensed, rounded and enlarged mitochondria. The external lamina and sarcolemma remained intact in many fibers. Hemorrhage was apparent in the endomysial connective tissue, and hemolysis was discernible. In areas where the erythrocytes were tightly packed between the muscle fibers, there was disruption of the external lamina and sarcolemma. Degeneration of the fibers in these areas was pronounced. These findings correlate well with the breakdown of muscle fibers by various methods described in the literature. Myonecrosis induced by snake venom may serve as a useful model for studying muscle necrosis because of its rapid onset and relative ease of induction. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14 PMID:5045877

  3. "The Human Condition" as social ontology: Hannah Arendt on society, action and knowledge.

    PubMed

    Walsh, Philip

    2011-01-01

    Hannah Arendt is widely regarded as a political theorist who sought to rescue politics from "society," and political theory from the social sciences. This conventional view has had the effect of distracting attention from many of Arendt's most important insights concerning the constitution of "society" and the significance of the social sciences. In this article, I argue that Hannah Arendt's distinctions between labor, work, and action, as these are discussed in "The Human Condition" and elsewhere, are best understood as a set of claims about the fundamental structures of human societies. Understanding Arendt in this way introduces interesting parallels between Arendt's work and both classical and contemporary sociology. From this I draw a number of conclusions concerning Arendt's conception of "society," and extend these insights into two contemporary debates within contemporary theoretical sociology: the need for a differentiated ontology of the social world, and the changing role that novel forms of knowledge play in contemporary society as major sources of social change and order.

  4. Pharmacological screening technologies for venom peptide discovery.

    PubMed

    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.

  5. Tears of Venom: Hydrodynamics of Reptilian Envenomation

    NASA Astrophysics Data System (ADS)

    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.

  6. Pharmacological Aspects of Vipera xantina palestinae Venom

    PubMed Central

    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

  7. [Bites of venomous snakes in Switzerland].

    PubMed

    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.

  8. Hannah's Feeding Journey: A Multidisciplinary Treatment Approach to Establishing Oral Acceptance for a Toddler with a Complex Medical History

    ERIC Educational Resources Information Center

    Dunn, Dena M.; Galbally, Sandra Lynn; Markowitz, Goldie; Pucci, Kristy N.; Brochi, Ligia; Cohen, Sherri Shubin

    2017-01-01

    This article presents the importance of multidisciplinary, family-centered care, and a developmental bio-psycho-social approach to treating feeding difficulties in a child with a complex medical history. Hannah spent the first 9 months of her life in the hospital and was discharged dependent on nasogastric tube feeding. Her journey to recovery…

  9. The Pursuit of Memory: Examining Art Teaching and Pedagogical Practices through Hannah Arendt's Actor-Spectator Theory

    ERIC Educational Resources Information Center

    Lee, Mun Yee

    2011-01-01

    Memories of our schooling and teaching experiences shape our curriculum and pedagogical decision-making process in art education when we become teachers and teacher educators. In this paper, using Hannah Arendt's Actor-Spectator Theory, I engage in retrospective critical introspection of my practices as an art teacher and curriculum developer in…

  10. And Worldlessness, Alas, Is Always a Kind of Barbarism: Hannah Arendt and the Challenge of Educating in Worldless Times

    ERIC Educational Resources Information Center

    Mackler, Stephanie

    2010-01-01

    Background/Context: In 1958, Hannah Arendt wrote "The Crisis in Education," arguing that schools should not be used for political purposes and should instead introduce children to what she calls "the world." The world, for Arendt, comprises the artifacts, ideas, values, and interactions that connect people together. In that same year, she…

  11. A "More General Crisis": Hannah Arendt, World-Alienation, and the Challenges of Teaching for the World as It Is

    ERIC Educational Resources Information Center

    Levinson, Natasha

    2010-01-01

    Background/Context: This article is part of a special issue on the 50th anniversary of the publication of Hannah Arendt's essay, "The Crisis in Education" and her book The Human Condition. Despite the proliferation of books and articles on Arendt's work since the mid-90s, "The Crisis in Education" does not figure all that much in writing on…

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

    PubMed Central

    Romano, Joseph D.; Tatonetti, Nicholas P.

    2015-01-01

    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. PMID:26601758

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

    PubMed

    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.

  14. Venomics of Remipede Crustaceans Reveals Novel Peptide Diversity and Illuminates the Venom's Biological Role.

    PubMed

    von Reumont, Björn M; Undheim, Eivind A B; Jauss, Robin-Tobias; Jenner, Ronald A

    2017-07-26

    We report the first integrated proteomic and transcriptomic investigation of a crustacean venom. Remipede crustaceans are the venomous sister group of hexapods, and the venom glands of the remipede Xibalbanus tulumensis express a considerably more complex cocktail of proteins and peptides than previously thought. We identified 32 venom protein families, including 13 novel peptide families that we name xibalbins, four of which lack similarities to any known structural class. Our proteomic data confirm the presence in the venom of 19 of the 32 families. The most highly expressed venom components are serine peptidases, chitinase and six of the xibalbins. The xibalbins represent Inhibitory Cystine Knot peptides (ICK), a double ICK peptide, peptides with a putative Cystine-stabilized α-helix/β-sheet motif, a peptide similar to hairpin-like β-sheet forming antimicrobial peptides, two peptides related to different hormone families, and four peptides with unique structural motifs. Remipede venom components represent the full range of evolutionary recruitment frequencies, from families that have been recruited into many animal venoms (serine peptidases, ICKs), to those having a very narrow taxonomic range (double ICKs), to those unique for remipedes. We discuss the most highly expressed venom components to shed light on their possible functional significance in the predatory and defensive use of remipede venom, and to provide testable ideas for any future bioactivity studies.

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

    PubMed

    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

  16. [Venomous and poisonous animals. IV. Envenomations by venomous aquatic vertebrates].

    PubMed

    Bédry, R; De Haro, L

    2007-04-01

    Epidemiological information on marine envenomation is generally less extensive in Europe than in tropical regions where these injuries are more severe and the need for medical advice is more frequent. For these reasons use of regional Poison Control Centers in the area where the injury occurs must be encouraged. The purpose of this review is to describe envenomation by bony fish (lion fish, stone fish, and catfish), cartilaginous fish (stingrays and poisonous sharks), or other venomous aquatic vertebrates (moray-eels and marine snakes). Understanding of these envenomation syndromes is important not only in tropical areas but also in Europe where importation of dangerous species has increased in recent years.

  17. Computational Studies of Snake Venom Toxins

    PubMed Central

    Ojeda, Paola G.; Caballero, Julio; Kaas, Quentin; González, Wendy

    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 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. PMID:29271884

  18. Venom immunotherapy: an updated review.

    PubMed

    Antolín-Amérigo, Darío; Moreno Aguilar, Carmen; Vega, Arantza; Alvarez-Mon, Melchor

    2014-07-01

    Venom immunotherapy (VIT) is the most effective form of specific immunotherapy to date. Hitherto, several relevant queries remain unanswered, namely optimal doses, duration, and means of assessment. Important progress has been lately made in terms of diagnosis by means of component-resolved diagnosis. Moreover, basophil activation test results in patients with negative serum immunoglobulin E (IgE) and skin prick test confer this technique a promising future, although these outcomes shall be considered with caution. This review aims to unravel the important advances made on diagnosis, management, and prognosis and also focuses on several undetermined aspects of VIT.

  19. SNAKE VENOMICS OF Crotalus tigris: THE MINIMALIST TOXIN ARSENAL OF THE DEADLIEST NEARTIC RATTLESNAKE VENOM

    PubMed Central

    CALVETE, Juan J.; PÉREZ, Alicia; LOMONTE, Bruno; SÁNCHEZ, Elda E.; SANZ, Libia

    2012-01-01

    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 PLA2, 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 represents 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 towards neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by paedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, C. horridus, C. oreganus helleri, C. scutulatus scutulatus, and S. 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 American and North American Crotalus. PMID:22181673

  20. Protease inhibitor in scorpion (Mesobuthus eupeus) venom prolongs the biological activities of the crude venom.

    PubMed

    Ma, Hakim; Xiao-Peng, Tang; Yang, Shi-Long; Lu, Qiu-Min; Lai, Ren

    2016-08-01

    It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT-1 selectively inhibited trypsin with a Kivalue of 130 nmol·L(-1). Furthermore, MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  1. The birdlike raptor Sinornithosaurus was venomous

    PubMed Central

    Gong, Enpu; Martin, Larry D.; Burnham, David A.; Falk, Amanda R.

    2009-01-01

    We suggest that some of the most avian dromaeosaurs, such as Sinornithosaurus, were venomous, and propose an ecological model for that taxon based on its unusual dentition and other cranial features including grooved teeth, a possible pocket for venom glands, and a groove leading from that pocket to the exposed bases of the teeth. These features are all analogous to the venomous morphology of lizards. Sinornithosaurus and related dromaeosaurs probably fed on the abundant birds of the Jehol forests during the Early Cretaceous in northeastern China. PMID:20080749

  2. Comments on "cyclical swings" by Professor Hannah Decker: The underappreciated "solid center" of psychiatry.

    PubMed

    Pies, Ronald W

    2016-02-01

    The history of psychiatry is characterized by some deep ideological and conceptual divisions, as adumbrated in Professor Hannah Decker's essay. However, the schism between "biological" and "psychosocial" models of mental illness and its treatment represents extreme positions among some psychiatrists-not the model propounded by academic psychiatry or its affiliated professional organizations. Indeed, the "biopsycho-social model" (BPSM) developed by Dr. George L. Engel has been, and remains, the foundational model for academic psychiatry, notwithstanding malign market forces that have undermined the BPSM's use in clinical practice. The BPSM is integrally related to "centralizing" and integrative trends in American psychiatry that may be traced to Franz Alexander, Karl Jaspers, and Engel himself, among others. This "Alexandrian-Jaspersian-Engelian" tradition is explored in relation to Professor Decker's "cyclical swing" model of psychiatry's history. (c) 2016 APA, all rights reserved).

  3. Socializing the public: invoking Hannah Arendt's critique of modernity to evaluate reproductive technologies.

    PubMed

    Sperling, Daniel

    2012-02-01

    The article examines the writings of one of the most influential political philosophers, Hannah Arendt, and specifically focuses on her views regarding the distinction between the private and the public and the transformation of the public to the social by modernity. Arendt's theory of human activity and critique of modernity are explored to critically evaluate the social contributions and implications of reproductive technologies especially where the use of such technologies is most dominant within Western societies. Focusing on empirical studies on new reproductive technologies in Israel, it is argued, powerfully demonstrates Arendt's theory, and broadens the perspectives through which society should evaluate these new technologies towards a more reflective understanding of its current laws and policies and their affect on women more generally.

  4. Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species.

    PubMed

    D'Suze, Gina; Sandoval, Moisés; Sevcik, Carlos

    2015-12-15

    A characteristic of venom elution patterns, shared with many other complex systems, is that many their features cannot be properly described with statistical or euclidean concepts. The understanding of such systems became possible with Mandelbrot's fractal analysis. Venom elution patterns were produced using the reversed phase high performance liquid chromatography (HPLC) with 1 mg of venom. One reason for the lack of quantitative analyses of the sources of venom variability is parametrizing the venom chromatograms' complexity. We quantize this complexity by means of an algorithm which estimates the contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and to measure inter- and intra-specific venom variability. We studied variations in venom complexity derived from gender, seasonal and environmental factors, duration of captivity in the laboratory, technique used to milk venom. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Extreme diversity of scorpion venom peptides and proteins revealed by transcriptomic analysis: implication for proteome evolution of scorpion venom arsenal.

    PubMed

    Ma, Yibao; He, Yawen; Zhao, Ruiming; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2012-02-16

    Venom is an important genetic development crucial to the survival of scorpions for over 400 million years. We studied the evolution of the scorpion venom arsenal by means of comparative transcriptome analysis of venom glands and phylogenetic analysis of shared types of venom peptides and proteins between buthids and euscorpiids. Fifteen types of venom peptides and proteins were sequenced during the venom gland transcriptome analyses of two Buthidae species (Lychas mucronatus and Isometrus maculatus) and one Euscorpiidae species (Scorpiops margerisonae). Great diversity has been observed in translated amino acid sequences of these transcripts for venom peptides and proteins. Seven types of venom peptides and proteins were shared between buthids and euscorpiids. Molecular phylogenetic analysis revealed that at least five of the seven common types of venom peptides and proteins were likely recruited into the scorpion venom proteome before the lineage split between Buthidae and Euscorpiidae with their corresponding genes undergoing individual or multiple gene duplication events. These are α-KTxs, βKSPNs (β-KTxs and scorpines), anionic peptides, La1-like peptides, and SPSVs (serine proteases from scorpion venom). Multiple types of venom peptides and proteins were demonstrated to be continuously recruited into the venom proteome during the evolution process of individual scorpion lineages. Our results provide an insight into the recruitment pattern of the scorpion venom arsenal for the first time. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  7. [Insect venom allergies : Update 2016 for otorhinolaryngologists].

    PubMed

    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.

  8. Snake oil and venoms for medical research

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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

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

    PubMed

    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

  11. Troubling practices of control: re-visiting Hannah Arendt's ideas of human action as praxis of the unpredictable.

    PubMed

    Kohlen, Helen

    2015-07-01

    In this article, Hannah Arendt's concept of action will be used to problematize current transformations of the health care sector and examine some responses by ethicists in light of those transformations. The sphere of human interaction that should typify health care work is identified as an action of unpredictable praxis in contrast to controllable procedures and techniques which increasingly take place in the health care sector. © 2015 John Wiley & Sons Ltd.

  12. Unraveling snake venom complexity with 'omics' approaches: challenges and perspectives.

    PubMed

    Zelanis, André; Tashima, Alexandre Keiji

    2014-09-01

    The study of snake venom proteomes (venomics) has been experiencing a burst of reports, however the comprehensive knowledge of the dynamic range of proteins present within a single venom, the set of post-translational modifications (PTMs) as well as the lack of a comprehensive database related to venom proteins are among the main challenges in venomics research. The phenotypic plasticity in snake venom proteomes together with their inherent toxin proteoform diversity, points out to the use of integrative analysis in order to better understand their actual complexity. In this regard, such a systems venomics task should encompass the integration of data from transcriptomic and proteomic studies (specially the venom gland proteome), the identification of biological PTMs, and the estimation of artifactual proteomes and peptidomes generated by sample handling procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Tityus serrulatus venom--A lethal cocktail.

    PubMed

    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.

  14. Venom proteomic and venomous glands transcriptomic analysis of the Egyptian scorpion Scorpio maurus palmatus (Arachnida: Scorpionidae).

    PubMed

    Abdel-Rahman, Mohamed A; Quintero-Hernandez, Veronica; Possani, Lourival D

    2013-11-01

    Proteomic analysis of the scorpion venom Scorpio maurus palmatus was performed using reverse-phase HPLC separation followed by mass spectrometry determination. Sixty five components were identified with molecular masses varying from 413 to 14,009 Da. The high percentage of peptides (41.5%) was from 3 to 5 KDa which may represent linear antimicrobial peptides and KScTxs. Also, 155 expressed sequence tags (ESTs) were analyzed through construction the cDNA library prepared from a pair of venomous gland. About 77% of the ESTs correspond to toxin-like peptides and proteins with definite open reading frames. The cDNA sequencing results also show the presence of sequences whose putative products have sequence similarity with antimicrobial peptides (24%), insecticidal toxins, β-NaScTxs, κ-KScTxs, α-KScTxs, calcines and La1-like peptides. Also, we have obtained 23 atypical types of venom molecules not recorded in other scorpion species. Moreover, 9% of the total ESTs revealed significant similarities with proteins involved in the cellular processes of these scorpion venomous glands. This is the first set of molecular masses and transcripts described from this species, in which various venom molecules have been identified. They belong to either known or unassigned types of scorpion venom peptides and proteins, and provide valuable information for evolutionary analysis and venomics. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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.

    2017-01-01

    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 previously, appear to

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

    PubMed Central

    Modahl, Cassandra M.; Mackessy, Stephen P.

    2016-01-01

    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

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

    PubMed

    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.

  19. Fibrin(ogen)olytic activity of bumblebee venom serine protease

    SciTech Connect

    Qiu Yuling; Joint Laboratory between Dong-A University and Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Shenyang; Choo, Young Moo

    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)olyticmore » 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.« less

  20. Tracing Monotreme Venom Evolution in the Genomics Era

    PubMed Central

    Whittington, Camilla M.; Belov, Katherine

    2014-01-01

    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. PMID:24699339

  1. Tracing monotreme venom evolution in the genomics era.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27077884

  5. Phylogenomic reclassification of the world's most venomous spiders (Mygalomorphae, Atracinae), with implications for venom evolution.

    PubMed

    Hedin, Marshal; Derkarabetian, Shahan; Ramírez, Martín J; Vink, Cor; Bond, Jason E

    2018-01-26

    Here we show that the most venomous spiders in the world are phylogenetically misplaced. Australian atracine spiders (family Hexathelidae), including the notorious Sydney funnel-web spider Atrax robustus, produce venom peptides that can kill people. Intriguingly, eastern Australian mouse spiders (family Actinopodidae) are also medically dangerous, possessing venom peptides strikingly similar to Atrax hexatoxins. Based on the standing morphology-based classification, mouse spiders are hypothesized distant relatives of atracines, having diverged over 200 million years ago. Using sequence-capture phylogenomics, we instead show convincingly that hexathelids are non-monophyletic, and that atracines are sister to actinopodids. Three new mygalomorph lineages are elevated to the family level, and a revised circumscription of Hexathelidae is presented. Re-writing this phylogenetic story has major implications for how we study venom evolution in these spiders, and potentially genuine consequences for antivenom development and bite treatment research. More generally, our research provides a textbook example of the applied importance of modern phylogenomic research.

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

    PubMed

    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

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

    PubMed

    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.

  8. Outcome survey of insect venom allergic patients with venom immunotherapy in a rural population.

    PubMed

    Roesch, Alexander; Boerzsoenyi, Julia; Babilas, Philipp; Landthaler, Michael; Szeimies, Rolf-Markus

    2008-04-01

    Hymenoptera venom anaphylaxis is a frightening event that affects physical and psychical functioning. Retrospective survey of 182 Hymenoptera venom allergic patients living in a rural area using a questionnaire targeting on patients' satisfaction during therapy, fear of anaphylactic recurrences and changes in lifestyle before and after venom immunotherapy (VIT). Additionally, patients' self-assessment of quality of life, daily outdoor time and re-sting rate were recorded. 146 patients returned the questionnaire (58.9% male, 41.1% female, 25.3% honey bee allergic, 67.8% wasp allergic, 41.1% re-sting rate, mean follow-up time 6.5 years). Measurement of the parameters fear, satisfaction and changes in lifestyle revealed a significant improvement after VIT. This correlated with the patients'self-assessment of quality of life,when 89.7% declared an improvement after VIT. Although the improvement was higher in patients with re-stings, also patients without re-stings clearly benefited from VIT. Interestingly, females were significantly more affected by Hymenoptera venom allergy than males,whereas both genders showed a similar improvement after VIT. Patients with Hymenoptera venom sting allergy significantly benefit from VIT in regard to both biological and psychological outcome. VIT should still be provided to all Hymenoptera venom allergic patients as standard of care.

  9. Applications of Venom Proteins as Potential Anticancer agents.

    PubMed

    Ejaz, Samina; Hashmi, Fatima Bashir; Malik, Waqas Nazir; Ashraf, Muhammad; Nasim, Faiz Ul-Hassan; Iqbal, Muhammad

    2018-06-13

    Venoms, the secretions of venomous animals, are conventionally thought to be the source of toxic substances though the views about venoms in the recent era have been changed. Venoms are the proven source of many biologically and pharmacologically important useful molecules. Bioactive components present in different venoms are mainly proteins and peptides either enzymatic or non-enzymatic which have tremendous therapeutic potential and are being used for the treatment of variety of diseases including cancer. Many venoms proteins and peptides have been reported as potential anticancer agents. Venom proteins kill cancer cells through a variety of mechanisms which induce apoptosis and ultimately lead to cell death. Therefore, the understanding regarding sources and classification of venoms, biological role of venomous proteins, their anticancer potential and mechanisms to suppress/kill cancer cells needs to be addressed. The present review is an attempt to highlight the reported work and develop strategies to answer the key questions regarding the use of venomous proteins as therapeutic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed

    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.

  11. Early evolution of the venom system in lizards and snakes.

    PubMed

    Fry, Bryan G; Vidal, Nicolas; Norman, Janette A; Vonk, Freek J; Scheib, Holger; Ramjan, S F Ryan; Kuruppu, Sanjaya; Fung, Kim; Hedges, S Blair; Richardson, Michael K; Hodgson, Wayne C; Ignjatovic, Vera; Summerhayes, Robyn; Kochva, Elazar

    2006-02-02

    Among extant reptiles only two lineages are known to have evolved venom delivery systems, the advanced snakes and helodermatid lizards (Gila Monster and Beaded Lizard). Evolution of the venom system is thought to underlie the impressive radiation of the advanced snakes (2,500 of 3,000 snake species). In contrast, the lizard venom system is thought to be restricted to just two species and to have evolved independently from the snake venom system. Here we report the presence of venom toxins in two additional lizard lineages (Monitor Lizards and Iguania) and show that all lineages possessing toxin-secreting oral glands form a clade, demonstrating a single early origin of the venom system in lizards and snakes. Construction of gland complementary-DNA libraries and phylogenetic analysis of transcripts revealed that nine toxin types are shared between lizards and snakes. Toxinological analyses of venom components from the Lace Monitor Varanus varius showed potent effects on blood pressure and clotting ability, bioactivities associated with a rapid loss of consciousness and extensive bleeding in prey. The iguanian lizard Pogona barbata retains characteristics of the ancestral venom system, namely serial, lobular non-compound venom-secreting glands on both the upper and lower jaws, whereas the advanced snakes and anguimorph lizards (including Monitor Lizards, Gila Monster and Beaded Lizard) have more derived venom systems characterized by the loss of the mandibular (lower) or maxillary (upper) glands. Demonstration that the snakes, iguanians and anguimorphs form a single clade provides overwhelming support for a single, early origin of the venom system in lizards and snakes. These results provide new insights into the evolution of the venom system in squamate reptiles and open new avenues for biomedical research and drug design using hitherto unexplored venom proteins.

  12. Proteomics and Deep Sequencing Comparison of Seasonally Active Venom Glands in the Platypus Reveals Novel Venom Peptides and Distinct Expression Profiles*

    PubMed Central

    Wong, Emily S. W.; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M.; Temple-Smith, Peter; Renfree, Marilyn B.; Whittington, Camilla M.; King, Glenn F.; Warren, Wesley C.; Papenfuss, Anthony T.; Belov, Katherine

    2012-01-01

    The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution. PMID:22899769

  13. Proteomics and deep sequencing comparison of seasonally active venom glands in the platypus reveals novel venom peptides and distinct expression profiles.

    PubMed

    Wong, Emily S W; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M; Temple-Smith, Peter; Renfree, Marilyn B; Whittington, Camilla M; King, Glenn F; Warren, Wesley C; Papenfuss, Anthony T; Belov, Katherine

    2012-11-01

    The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.

  14. Hyaluronidase and hyaluronan in insect venom allergy.

    PubMed

    King, Te Piao; Wittkowski, Knut M

    2011-01-01

    Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. HA oligomers (8- to 50-mer; 3-20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300-2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p < 0.05), respectively, for the polymer. Hyaluronidase by its action on HA in skin can function indirectly as adjuvant to promote IgE and IgG1 response in mice. Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people. Copyright © 2011 S. Karger AG, Basel.

  15. Mediterranean Jellyfish Venoms: A Review on Scyphomedusae

    PubMed Central

    Mariottini, Gian Luigi; Pane, Luigi

    2010-01-01

    The production of natural toxins is an interesting aspect, which characterizes the physiology and the ecology of a number of marine species that use them for defence/offence purposes. Cnidarians are of particular concern from this point of view; their venoms are contained in specialized structures–the nematocysts–which, after mechanical or chemical stimulation, inject the venom in the prey or in the attacker. Cnidarian stinging is a serious health problem for humans in the zones where extremely venomous jellyfish or anemones are common, such as in temperate and tropical oceanic waters and particularly along several Pacific coasts, and severe cases of envenomation, including also lethal cases mainly induced by cubomedusae, were reported. On the contrary, in the Mediterranean region the problem of jellyfish stings is quite modest, even though they can have anyhow an impact on public health and be of importance from the ecological and economic point of view owing to the implications on ecosystems and on some human activities such as tourism, bathing and fishing. This paper reviews the knowledge about the various aspects related to the occurrence and the stinging of the Mediterranean scyphozoan jellyfish as well as the activity of their venoms. PMID:20479971

  16. INVESTIGATIONS ON THE ANTIGENICITY OF SNAKE VENOMS

    DTIC Science & Technology

    The chemical composition of viperotoxin, the neurotoxic protein isolated from the venom of Vipera palestinae has been determined. Viperotoxin is...carboxy-terminal position of the viperotoxin chain. Vipera palestinae hemorrhagin has been purified and isolated. Further tests have established that...active sites, or selective blocking of a part of one active center having two distinct biological activities. Purified neurotoxin of V. palestinae

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

    PubMed

    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 (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published 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

  18. Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland

    PubMed Central

    2013-01-01

    Background Honeybee venom is a complicated defensive toxin that has a wide range of pharmacologically active compounds. Some of these compounds are useful for human therapeutics. There are two major forms of honeybee venom used in pharmacological applications: manually (or reservoir disrupting) extracted glandular venom (GV), and venom extracted through the use of electrical stimulation (ESV). A proteome comparison of these two venom forms and an understanding of the phosphorylation status of ESV, are still very limited. Here, the proteomes of GV and ESV were compared using both gel-based and gel-free proteomics approaches and the phosphoproteome of ESV was determined through the use of TiO2 enrichment. Results Of the 43 proteins identified in GV, < 40% were venom toxins, and > 60% of the proteins were non-toxic proteins resulting from contamination by gland tissue damage during extraction and bee death. Of the 17 proteins identified in ESV, 14 proteins (>80%) were venom toxic proteins and most of them were found in higher abundance than in GV. Moreover, two novel proteins (dehydrogenase/reductase SDR family member 11-like and histone H2B.3-like) and three novel phosphorylation sites (icarapin (S43), phospholipase A-2 (T145), and apamin (T23)) were identified. Conclusions Our data demonstrate that venom extracted manually is different from venom extracted using ESV, and these differences may be important in their use as pharmacological agents. ESV may be more efficient than GV as a potential pharmacological source because of its higher venom protein content, production efficiency, and without the need to kill honeybee. The three newly identified phosphorylated venom proteins in ESV may elicit a different immune response through the specific recognition of antigenic determinants. The two novel venom proteins extend our proteome coverage of honeybee venom. PMID:24199871

  19. Bee venom therapy: Potential mechanisms and therapeutic applications.

    PubMed

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

    2018-06-15

    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.

  20. Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

    PubMed

    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.

  1. Comparison between two methods of scorpion venom milking in Morocco

    PubMed Central

    2013-01-01

    Background The present study compared two methods used successfully in a large-scale program for the collection of scorpion venoms, namely the milking of adult scorpions via manual and electrical stimulation. Results Our immunobiochemical characterizations clearly demonstrate that regularly applied electrical stimulation obtains scorpion venom more easily and, most importantly, in greater quantity. Qualitatively, the electrically collected venom showed lack of hemolymph contaminants such as hemocyanin. In contrast, manual obtainment of venom subjects scorpions to maximal trauma, leading to hemocyanin secretion. Our study highlighted the importance of reducing scorpion trauma during venom milking. Conclusions In conclusion, to produce high quality antivenom with specific antibodies, it is necessary to collect venom by the gentler electrical stimulation method. PMID:23849043

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

    PubMed

    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

  3. Analysis of the intersexual variation in Thalassophryne maculosa fish venoms.

    PubMed

    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.

  4. Studies on Bee Venom and Its Medical Uses

    NASA Astrophysics Data System (ADS)

    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.

  5. Animal venom studies: Current benefits and future developments

    PubMed Central

    Utkin, Yuri N

    2015-01-01

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and

  6. Cross-neutralisation of Australian brown snake, taipan and death adder venoms by monovalent antibodies.

    PubMed

    Isbister, Geoffrey K; O'Leary, Margaret A; Hagan, Jessica; Nichols, Kearney; Jacoby, Tammy; Davern, Kathleen; Hodgson, Wayne C; Schneider, Jennifer J

    2010-01-08

    An understanding of the cross-neutralisation of snake venoms by antibodies is important for snake antivenom development. We investigated the cross-neutralisation of brown snake (Pseudonaja textilis) venom, taipan (Oxyuranus scutellatus) venom and death adder (Acanthophis antarcticus) with commercial antivenoms and monovalent anti-snake IgG, using enzyme immunoassays, in vitro clotting and neurotoxicity assays. Each commercial antivenom bound all three venoms, and neutralised clotting activity of brown snake and taipan venoms and neurotoxicity of death adder venom. The 'in-house' monovalent anti-snake venom IgG raised against procoagulant brown snake and taipan venoms, did not neutralise the neurotoxic effects of death adder venom. However, they did cross-neutralise the procoagulant effects of both procoagulant venoms. This supports the idea of developing antivenoms against groups of snake toxins rather than individual snake venoms.

  7. Bee Venom Pharmacopuncture Responses According to Sasang Constitution and Gender

    PubMed Central

    Kim, Chaeweon; Lee, Kwangho

    2013-01-01

    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. PMID:25780682

  8. Snake Venom As An Effective Tool Against Colorectal Cancer.

    PubMed

    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.

  9. Venom Proteins from Parasitoid Wasps and Their Biological Functions

    PubMed Central

    Moreau, Sébastien J. M.; Asgari, Sassan

    2015-01-01

    Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies. PMID:26131769

  10. [Venom as a cure--some notes on ancient medicine].

    PubMed

    Teichfischer, Philipp

    2015-01-01

    Very little is known today about the linguistics and facts relating to venoms in the ancient world. The article concerns itself initially with the terminology: How were venoms conceptualized and what position did they occupy among medicines and other poisons? Additionally ancient knowledge of the constitution and location of the venoms will be examined. Furthermore, it shall be outlined how it was perceived that the poisons actually took effect. The results of our investigations indicate that it was unlikely that venoms were used for medicinal purposes in ancient times.

  11. Inactivation of complement by Loxosceles reclusa spider venom.

    PubMed

    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.

  12. Treating autoimmune disorders with venom-derived peptides.

    PubMed

    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.

  13. Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals

    PubMed Central

    Mourão, Caroline B.F.; Schwartz, Elisabeth F.

    2013-01-01

    The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared. PMID:23771044

  14. For the Love of Our Children: Hannah Arendt, the Limits of Freedom and the Role of Education in a Culture of Violence

    ERIC Educational Resources Information Center

    Gordon, Mordechai

    2015-01-01

    This essay critically examines the underlying assumptions about freedom and democracy at the basis of those like the NRA who argue that the United States does not have a gun problem and that the second amendment protects citizens' rights to own any gun they wish. Inspired by Hannah Arendt's political philosophy, the author first discusses three…

  15. Participation in Education as an Invitation to Become towards the World: Hannah Arendt on the Authority, Thoughtfulness and Imagination of the Educator

    ERIC Educational Resources Information Center

    Veck, Wayne

    2013-01-01

    This article draws on Hannah Arendt's analysis of authority in education, along with her insights into the workings of the imagination and the thinking process, to argue that participation in education should be conceived as an invitation to become towards the world. The potential of this invitation, the article argues, is located in the…

  16. Skin Test Reactivity to Hymenoptera Venom after Venom Immunotherapy Correlates Inversely with the IgG/IgE Ratio.

    PubMed

    Saulite, Ieva; Hoetzenecker, Wolfram; Guenova, Emmanuella; Schmid-Grendelmeier, Peter; Glatz, Martin

    2017-01-01

    Skin test reactivity to hymenoptera venom and venom-specific IgE are important for diagnosing venom allergy and deciding on the appropriate allergen for venom immunotherapy (VIT). Longitudinal data on skin test reactivity during VIT and their correlation with venom-specific immunoglobulin (Ig)E and IgG are scarce. We retrospectively analyzed shifts in skin test reactivity and serum levels of venom-specific IgE and IgG in patients allergic to hymenoptera venom before the initiation of VIT with ultrarush therapy and after ≥3 years of VIT. Fifty-four patients received ultrarush desensitization and subsequent VIT with wasp venom, 26 with honeybee venom, and 8 with both wasp and honeybee venom. Hymenoptera-specific skin test reactivity decreased during VIT in most patients, and became negative in 8% of the wasp-allergic patients and in 25% of the honeybee-allergic patients. Serum levels of venom-specific IgE positively correlated to skin test reactivity before VIT, but did not change significantly during VIT. IgG serum levels and the IgG/IgE ratio increased during VIT in most patients. A high IgG/IgE ratio correlated with low skin test reactivity after ≥3 years of VIT. The correlation between a high venom-specific IgG/IgE ratio and low skin test reactivity after VIT may be interesting for future investigations that assess its role as a potential marker for VIT efficacy. © 2017 S. Karger AG, Basel.

  17. Proteomic analysis of the venom from the scorpion Mesobuthus martensii.

    PubMed

    Xu, Xiaobo; Duan, Zhigui; Di, Zhiyong; He, Yawen; Li, Jianglin; Li, Zhongjie; Xie, Chunliang; Zeng, Xiongzhi; Cao, Zhijian; Wu, Yingliang; Liang, Songping; Li, Wenxin

    2014-06-25

    The scorpion Mesobuthus martensii is the most populous species in eastern Asian countries, and several toxic components have been identified from their venoms. Nevertheless, a complete proteomic profile of the venom of M. martensii is still not available. In this study, the venom of M. martensii was analyzed by comprehensive proteomic approaches. 153 fractions were isolated from the M. martensii venom by 2-DE, SDS-PAGE and RP-HPLC. The ESI-Q-TOF MS results of all fractions were used to search the scorpion genomic and transcriptomic databases. Totally, 227 non-redundant protein sequences were unambiguously identified, composed of 134 previously known and 93 previously unknown proteins. Among 134 previously known proteins, 115 proteins were firstly confirmed from the M. martensii crude venom and 19 toxins were confirmed once again, involving 43 typical toxins, 7 atypical toxins, 12 venom enzymes and 72 cell associated proteins. In typical toxins, 7 novel-toxin sequences were identified, including 3 Na(+)-channel toxins, 3K(+)-channel toxins and 1 no-annotation toxin. These results increased 230% (115/50) venom components compared with previous studies from the M. martensii venom, especially 50% (24/48) typical toxins. Additionally, a mass fingerprint obtained by MALDI-TOF MS indicated that the scorpion venom contained more than 200 different molecular mass components. This work firstly gave a systematic investigation of the M. martensii venom by combined proteomics strategy coupled with genomics and transcriptomics. A large number of protein components were unambiguously identified from the venom of M. martensii, most of which were confirmed for the first time. We also contributed 7 novel-toxin sequences and 93 protein sequences previously unknown to be part of the venom, for which we assigned potential biological functions. Besides, we obtained a mass fingerprint of the M. martensii venom. Together, our study not only provides the most comprehensive catalog of the

  18. Biphasic rattlesnake venom-induced thrombocytopenia.

    PubMed

    Offerman, Steven R; Barry, J David; Schneir, Aaron; Clark, Richard F

    2003-04-01

    Thrombocytopenia is a common occurrence in moderate to severe crotaline envenomation. The exact mechanism by which rattlesnake venom leads to thrombocytopenia is unclear, but aggressive treatment with crotaline-specific antivenom often leads to resolution of this disorder. Crotalinae Polyvalent Immune Fab (CroFab(TM), Protherics Inc., Nashville, TN) (crotaline Fab) is now available for the treatment of symptomatic rattlesnake envenomation. Although recurrence of thrombocytopenia has been reported in patients after envenomation treated with crotaline Fab, cases refractory to this therapy have not been described. We report a case of severe crotaline envenomation that appears to have exhibited two separate episodes of thrombocytopenia, only one of which responded to antivenom. The second, later phase was refractory to both crotaline Fab as well as traditional Antivenin (Crotalinae) Polyvalent (Wyeth-Ayerst Pharmaceuticals, Philadelphia, PA) (ACP). By reviewing the literature regarding venom-induced thrombocytopenia, we attempt to explain this "biphasic" phenomenon and the inability of crotaline Fab to reverse this toxic effect.

  19. Important biological activities induced by Thalassophryne maculosa fish venom.

    PubMed

    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.

  20. Functional and structural diversification of the Anguimorpha lizard venom system.

    PubMed

    Fry, Bryan G; Winter, Kelly; Norman, Janette A; Roelants, Kim; Nabuurs, Rob J A; van Osch, Matthias J P; Teeuwisse, Wouter M; van der Weerd, Louise; McNaughtan, Judith E; Kwok, Hang Fai; Scheib, Holger; Greisman, Laura; Kochva, Elazar; Miller, Laurence J; Gao, Fan; Karas, John; Scanlon, Denis; Lin, Feng; Kuruppu, Sanjaya; Shaw, Chris; Wong, Lily; Hodgson, Wayne C

    2010-11-01

    Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained

  1. Harvesting Venom Toxins from Assassin Bugs and Other Heteropteran Insects.

    PubMed

    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.

  2. Whole Transcriptome of the Venom Gland from Urodacus yaschenkoi Scorpion

    PubMed Central

    Juárez-González, Víctor Rivelino; Possani, Lourival D.

    2015-01-01

    Australian scorpion venoms have been poorly studied, probably because they do not pose an evident threat to humans. In addition, the continent has other medically important venomous animals capable of causing serious health problems. Urodacus yaschenkoi belongs to the most widely distributed family of Australian scorpions (Urodacidae) and it is found all over the continent, making it a useful model system for studying venom composition and evolution. This communication reports the whole set of mRNA transcripts produced by the venom gland. U. yaschenkoi venom is as complex as its overseas counterparts. These transcripts certainly code for several components similar to known scorpion venom components, such as: alpha-KTxs, beta-KTxs, calcins, protease inhibitors, antimicrobial peptides, sodium-channel toxins, toxin-like peptides, allergens, La1-like, hyaluronidases, ribosomal proteins, proteasome components and proteins related to cellular processes. A comparison with the venom gland transcriptome of Centruroides noxius (Buthidae) showed that these two scorpions have similar components related to biological processes, although important differences occur among the venom toxins. In contrast, a comparison with sequences reported for Urodacus manicatus revealed that these two Urodacidae species possess the same subfamily of scorpion toxins. A comparison with sequences of an U. yaschenkoi cDNA library previously reported by our group showed that both techniques are reliable for the description of the venom components, but the whole transcriptome generated with Next Generation Sequencing platform provides sequences of all transcripts expressed. Several of which were identified in the proteome, but many more transcripts were identified including uncommon transcripts. The information reported here constitutes a reference for non-Buthidae scorpion venoms, providing a comprehensive view of genes that are involved in venom production. Further, this work identifies new putative

  3. Whole Transcriptome of the Venom Gland from Urodacus yaschenkoi Scorpion.

    PubMed

    Luna-Ramírez, Karen; Quintero-Hernández, Verónica; Juárez-González, Víctor Rivelino; Possani, Lourival D

    2015-01-01

    Australian scorpion venoms have been poorly studied, probably because they do not pose an evident threat to humans. In addition, the continent has other medically important venomous animals capable of causing serious health problems. Urodacus yaschenkoi belongs to the most widely distributed family of Australian scorpions (Urodacidae) and it is found all over the continent, making it a useful model system for studying venom composition and evolution. This communication reports the whole set of mRNA transcripts produced by the venom gland. U. yaschenkoi venom is as complex as its overseas counterparts. These transcripts certainly code for several components similar to known scorpion venom components, such as: alpha-KTxs, beta-KTxs, calcins, protease inhibitors, antimicrobial peptides, sodium-channel toxins, toxin-like peptides, allergens, La1-like, hyaluronidases, ribosomal proteins, proteasome components and proteins related to cellular processes. A comparison with the venom gland transcriptome of Centruroides noxius (Buthidae) showed that these two scorpions have similar components related to biological processes, although important differences occur among the venom toxins. In contrast, a comparison with sequences reported for Urodacus manicatus revealed that these two Urodacidae species possess the same subfamily of scorpion toxins. A comparison with sequences of an U. yaschenkoi cDNA library previously reported by our group showed that both techniques are reliable for the description of the venom components, but the whole transcriptome generated with Next Generation Sequencing platform provides sequences of all transcripts expressed. Several of which were identified in the proteome, but many more transcripts were identified including uncommon transcripts. The information reported here constitutes a reference for non-Buthidae scorpion venoms, providing a comprehensive view of genes that are involved in venom production. Further, this work identifies new putative

  4. Deciphering the main venom components of the ectoparasitic ant-like bethylid wasp, Scleroderma guani.

    PubMed

    Zhu, Jia-Ying

    2016-04-01

    Similar to venom found in most venomous animals, parasitoid venoms contain a complex cocktail of proteins with potential agrichemical and pharmaceutical use. Even though parasitoids are one of the largest group of venomous animals, little is known about their venom composition. Recent few studies revealed high variated venom composition existing not only in different species but also between closely related strains, impling that increasing information on the venom proteins from more greater diversity of species of different taxa is key to comprehensively uncover the complete picture of parasitoid venom. Here, we explored the major protein components of the venom of ectoparasitic ant-like bethylid wasp, Scleroderma guani by an integrative transcriptomic-proteomic approach. Illumina deep sequencing of venom apparatus cDNA produced 49,873 transcripts. By mapping the peptide spectral data derived from venom reservoir against these transcripts, mass spectrometry analysis revealed ten main venom proteins, including serine proteinase, metalloprotease, dipeptidyl peptidase IV, esterase, antithrombin-III, acid phosphatase, neural/ectodermal development factor IMP-L2 like protein, venom allergen 3, and unknown protein. Interestingly, one serine proteinase was firstly identified with rarely high molecular weight about 200 kDa in parasitoid venom. The occurrence of abundant acid phosphatase, antithrombin-III and venom allergen 3 demonstrated that S. guani venom composition is similar to that of social wasp venoms. All identified venom genes showed abundantly biased expression in venom apparatus, indicating their virulent functions involved in parasitization. This study shed light on the more better understanding of parasitoid venom evolution across species and will facilitate the further elucidation of function and toxicity of these venom proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    ERIC Educational Resources Information Center

    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)

  6. Molecular diversity of Chaerilidae venom peptides reveals the dynamic evolution of scorpion venom components from Buthidae to non-Buthidae.

    PubMed

    He, Yawen; Zhao, Ruiming; Di, Zhiyong; Li, Zhongjie; Xu, Xiaobo; Hong, Wei; Wu, Yingliang; Zhao, Huabin; Li, Wenxin; Cao, Zhijian

    2013-08-26

    The scorpion family Chaerilidae is phylogenetically differentiated from Buthidae. Their venom components are not known, and the evolution of the venom components is not well understood. Here, we performed a transcriptome analysis of the venom glands from two scorpion species, Chaerilus tricostatus and Chaerilus tryznai. Fourteen types of venom peptides were discovered from two species, 10 of which were shared by both C. tricostatus and C. tryznai. Notably, the venom components of Chaerilidae were also found to contain four toxin types (NaTx, β-KTx, Scamp and bpp-like peptides), previously considered to be specific to Buthidae. Moreover, cytolytic peptides were the most abundant toxin type in C. tricostatus, C. tryznai and the family Euscorpiidae. Furthermore, 39 and 35 novel atypical venom molecules were identified from C. tricostatus and C. tryznai, respectively. Finally, the evolutionary analysis showed that the NaTx, β-KTx, and bpp-like toxin types were recruited into the venom before the lineage split between Buthidae and non-Buthidae families. This study provides an integrated understanding of the venom components of the scorpion family Chaerilidae. The family Chaerilidae has a specific venom arsenal that is intermediate between Buthidae and non-Buthidae, which suggests the dynamic evolution of scorpion venom components from Buthidae to non-Buthidae species. This work gave a first overview of the venom components of Chaerilidae scorpions, and discovered large numbers of new toxin molecules, which significantly enriches the molecular diversity of scorpion venom peptides/proteins components. Based on phylogenetic analysis we speculated that the NaTx, β-KTx and bpp-like toxin type genes were recruited into venom before the lineage split between Buthidae and non-Buthidae. By Comparing the toxin types and abundance of the Buthidae, Chaerilidae and non-Buthidae families, we found that the family Chaerilidae has a specific venom arsenal that is intermediate

  7. Evolution of Venomous Cartilaginous and Ray-Finned Fishes.

    PubMed

    Smith, W Leo; Stern, Jennifer H; Girard, Matthew G; Davis, Matthew P

    2016-11-01

    Venom and its associated delivery systems have evolved in numerous animal groups ranging from jellyfishes to spiders, lizards, shrews, and the male platypus. Building off new data and previously published anatomical and molecular studies, we explore the evolution of and variation within venomous fishes. We show the results of the first multi-locus, ordinal-level phylogenetic analysis of cartilaginous (Chondrichthyes) and ray-finned (Actinopterygii) fishes that hypothesizes 18 independent evolutions of this specialization. Ancestral-states reconstruction indicates that among the 2386-2962 extant venomous fishes, envenomed structures have evolved four times in cartilaginous fishes, once in eels (Anguilliformes), once in catfishes (Siluriformes), and 12 times in spiny-rayed fishes (Acanthomorpha). From our anatomical studies and phylogenetic reconstruction, we show that dorsal spines are the most common envenomed structures (∼95% of venomous fish species and 15 independent evolutions). In addition to envenomed spines, fishes have also evolved venomous fangs (2% of venomous fish species, two independent evolutions), cleithral spines (2% of venomous fish species, one independent evolution), and opercular or subopercular spines (1% of venomous fish species, three independent evolutions). © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  8. Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms.

    PubMed

    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.

  9. Analysis of scorpion venom composition by Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Martínez-Zérega, Brenda E.; González-Solís, José L.

    2015-01-01

    In this work we study the venom of two Centruroides scorpion species using Raman spectroscopy. The spectra analysis allows to determine the venoms chemical composition and to establish the main differences and similarities among the species. It is also shown that the use of Principal Component Analysis may help to tell apart between the scorpion species.

  10. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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...

  11. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2010 CFR

    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...

  12. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

  13. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  14. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

  15. [Accidents with venomous and poisonous animals in Central Europe].

    PubMed

    Bodio, Mauro; Junghanss, Thomas

    2009-05-01

    Central Europe is largely safe from accidents with venomous and poisonous animals. The regions where European vipers are regularly found are shrinking. Today accidents with jellyfish and stings of venomous fish afflicted during leisure activities at the sea side play the dominant role. Life threatening accidents in Europe are mainly due to exotic snakes held in captivity. A system useful in daily medical practice is explained to classify and stage accidents due to poisonous and venomous animals. The important poisonous and venomous animals of Central Europe and the specific therapeutics, the antivenoms, are covered. The antivenom depot "Antivenin-CH" of the Swiss Toxicology Information Centre in Zurich and the MRITox in Munich with the antivenom registry Munich AntiVenom INdex (MAVIN) are presented.

  16. Dynamics of venom composition across a complex life cycle

    PubMed Central

    Macrander, Jason; Fridrich, Arie; Modepalli, Vengamanaidu; Reitzel, Adam M; Sunagar, Kartik

    2018-01-01

    Little is known about venom in young developmental stages of animals. The appearance of toxins and stinging cells during early embryonic stages in the sea anemone Nematostella vectensis suggests that venom is already expressed in eggs and larvae of this species. Here, we harness transcriptomic, biochemical and transgenic tools to study venom production dynamics in Nematostella. We find that venom composition and arsenal of toxin-producing cells change dramatically between developmental stages of this species. These findings can be explained by the vastly different interspecific interactions of each life stage, as individuals develop from a miniature non-feeding mobile planula to a larger sessile polyp that predates on other animals and interact differently with predators. Indeed, behavioral assays involving prey, predators and Nematostella are consistent with this hypothesis. Further, the results of this work suggest a much wider and dynamic venom landscape than initially appreciated in animals with a complex life cycle. PMID:29424690

  17. Banal no more: an essay on the film Hannah Arendt, with special reference to Eichmann and the Nazi killing groups.

    PubMed

    Roth, Bennett

    2015-04-01

    This movie review and essay about the recent film Hannah Arendt by director Margarethe von Trotta seeks to examine Arendt's controversial term "banality of evil" as well as the nature of Arendt's misperception of Adolph Eichmann as thoughtless, and to situate Eichmann's personality within recent understandings of totalitarian group behavior and organizational killers. What emerges is that Arendt was unable to understand Eichmann's ruthless indifference to others as well as his attraction to being a Nazi and to organized mass killing. This paper examines Mann's (2005) formulation of different levels of functional attraction to totalitarian perpetrators, in which a racial morality is imposed and restrictions to eliminist violence are removed. Under such group conditions, violent "sleeper" needs emerge and are rationalized by political beliefs. In conclusion, the term "banality of evil" has little explanative value, while violent mass murder continues to this day as a totalitarian solution.

  18. Variability of Venom-Neutralizing Properties of Serum from Snakes of the Colubrid Genus Lampropeltis

    DTIC Science & Technology

    1992-01-01

    venoms of C. atrx , S. m. bar- potentials for C s. scauhatus (type B) venom bouri, or A. c. mokasen showed persistent (Table 2). inflammation and/or edema...SMITH propeltis with these toxins would cause vascu- thality. Other workers have proposed antibody lotoxic effects. Klauber (1956) reported immu...tested, those injected with venom alone. This suggests Harvey (1960) described inhibition of C. atrx that elapid venom myolytic phospholipases Al venom

  19. CD30 serum levels and response to hymenoptera venom immunotherapy.

    PubMed

    Foschi, F G; Emiliani, F; Savini, S; Quercia, O; Stefanini, G F

    2008-01-01

    The glycoprotein CD30 is expressed and released by T lymphocytes that secrete type 2 helper cytokines of (T(H)2). These molecules play a role in the pathogenesis of allergic diseases. Venom immunotherapy has proven to be very effective in hymenoptera venom allergy through a shift in cytokine production from T(H)2-type cytokines to T(H)1-type cytokines. To evaluate the relationship between the soluble form of CD30 (sCD30) and venom immunotherapy in patients with hymenoptera venom allergy. sCD30 levels were assayed by enzyme-linked immunosorbent assay in the sera of 61 healthy controls and 14 patients with hymenoptera venom allergy who had undergone immunotherapy before treatment and 1,3, and 12 months after treatment started. Nine patients were allergic to Apis venom, 4 to Vespula venom, and 1 to Polistes venom. CD30 serum levels (median, interquartile range) were significantly higher in venom-allergic patients before treatment (33.6 U/mL; 14.8-61.6) than in controls (9.7 U/mL, 1.9-21.3) (P < .000). These levels decreased progressively during treatment in all patients except 2 (P < .000). At the third month of therapy, the levels reached statistical significance in comparison with baseline. This study shows that sCD30 levels are significantly higher in patients with hymenoptera venom allergy and indirectly confirms a preferential T(H)2-type cytokine production in these patients. sCD30 expression decreases during immunotherapy, thus confirming the immunomodulatory role of this treatment in promoting a shift to T(H)1-type cytokines.

  20. Virocidal activity of Egyptian scorpion venoms against hepatitis C virus.

    PubMed

    El-Bitar, Alaa M H; Sarhan, Moustafa M H; Aoki, Chie; Takahara, Yusuke; Komoto, Mari; Deng, Lin; Moustafa, Mohsen A; Hotta, Hak

    2015-03-24

    Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

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

    PubMed Central

    Chaim, Olga Meiri; Trevisan-Silva, Dilza; Chaves-Moreira, Daniele; Wille, Ana Carolina M.; Ferrer, Valéria Pereira; Matsubara, Fernando Hitomi; Mangili, Oldemir Carlos; da Silveira, Rafael Bertoni; Gremski, Luiza Helena; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Veiga, Silvio Sanches

    2011-01-01

    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. PMID:22069711

  2. The genesis of an exceptionally lethal venom in the timber rattlesnake (Crotalus horridus) revealed through comparative venom-gland transcriptomics

    PubMed Central

    2013-01-01

    Background Snake venoms generally show sequence and quantitative variation within and between species, but some rattlesnakes have undergone exceptionally rapid, dramatic shifts in the composition, lethality, and pharmacological effects of their venoms. Such shifts have occurred within species, most notably in Mojave (Crotalus scutulatus), South American (C. durissus), and timber (C. horridus) rattlesnakes, resulting in some populations with extremely potent, neurotoxic venoms without the hemorrhagic effects typical of rattlesnake bites. Results To better understand the evolutionary changes that resulted in the potent venom of a population of C. horridus from northern Florida, we sequenced the venom-gland transcriptome of an animal from this population for comparison with the previously described transcriptome of the eastern diamondback rattlesnake (C. adamanteus), a congener with a more typical rattlesnake venom. Relative to the toxin transcription of C. adamanteus, which consisted primarily of snake-venom metalloproteinases, C-type lectins, snake-venom serine proteinases, and myotoxin-A, the toxin transcription of C. horridus was far simpler in composition and consisted almost entirely of snake-venom serine proteinases, phospholipases A2, and bradykinin-potentiating and C-type natriuretic peptides. Crotalus horridus lacked significant expression of the hemorrhagic snake-venom metalloproteinases and C-type lectins. Evolution of shared toxin families involved differential expansion and loss of toxin clades within each species and pronounced differences in the highly expressed toxin paralogs. Toxin genes showed significantly higher rates of nonsynonymous substitution than nontoxin genes. The expression patterns of nontoxin genes were conserved between species, despite the vast differences in toxin expression. Conclusions Our results represent the first complete, sequence-based comparison between the venoms of closely related snake species and reveal in unprecedented

  3. The First Venomous Crustacean Revealed by Transcriptomics and Functional Morphology: Remipede Venom Glands Express a Unique Toxin Cocktail Dominated by Enzymes and a Neurotoxin

    PubMed Central

    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. PMID:24132120

  4. Mass fingerprinting of the venom and transcriptome of venom gland of scorpion Centruroides tecomanus.

    PubMed

    Valdez-Velázquez, Laura L; Quintero-Hernández, Verónica; Romero-Gutiérrez, Maria Teresa; Coronas, Fredy I V; Possani, Lourival D

    2013-01-01

    Centruroides tecomanus is a Mexican scorpion endemic of the State of Colima, that causes human fatalities. This communication describes a proteome analysis obtained from milked venom and a transcriptome analysis from a cDNA library constructed from two pairs of venom glands of this scorpion. High perfomance liquid chromatography separation of soluble venom produced 80 fractions, from which at least 104 individual components were identified by mass spectrometry analysis, showing to contain molecular masses from 259 to 44,392 Da. Most of these components are within the expected molecular masses for Na(+)- and K(+)-channel specific toxic peptides, supporting the clinical findings of intoxication, when humans are stung by this scorpion. From the cDNA library 162 clones were randomly chosen, from which 130 sequences of good quality were identified and were clustered in 28 contigs containing, each, two or more expressed sequence tags (EST) and 49 singlets with only one EST. Deduced amino acid sequence analysis from 53% of the total ESTs showed that 81% (24 sequences) are similar to known toxic peptides that affect Na(+)-channel activity, and 19% (7 unique sequences) are similar to K(+)-channel especific toxins. Out of the 31 sequences, at least 8 peptides were confirmed by direct Edman degradation, using components isolated directly from the venom. The remaining 19%, 4%, 4%, 15% and 5% of the ESTs correspond respectively to proteins involved in cellular processes, antimicrobial peptides, venom components, proteins without defined function and sequences without similarity in databases. Among the cloned genes are those similar to metalloproteinases.

  5. Effects of Animal Venoms and Toxins on Hallmarks of Cancer

    PubMed Central

    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

  6. Role of the inflammasome in defense against venoms

    PubMed Central

    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

  7. Micrurus snake venoms activate human complement system and generate anaphylatoxins.

    PubMed

    Tanaka, Gabriela D; Pidde-Queiroz, Giselle; de Fátima D Furtado, Maria; van den Berg, Carmen; Tambourgi, Denise V

    2012-01-16

    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. 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. 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.

  8. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    PubMed Central

    2012-01-01

    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. PMID:22248157

  9. Ancient Venom Systems: A Review on Cnidaria Toxins.

    PubMed

    Jouiaei, Mahdokht; Yanagihara, Angel A; Madio, Bruno; Nevalainen, Timo J; Alewood, Paul F; Fry, Bryan G

    2015-06-18

    Cnidarians are the oldest extant lineage of venomous animals. Despite their simple anatomy, they are capable of subduing or repelling prey and predator species that are far more complex and recently evolved. Utilizing specialized penetrating nematocysts, cnidarians inject the nematocyst content or "venom" that initiates toxic and immunological reactions in the envenomated organism. These venoms contain enzymes, potent pore forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion channel specific activities. In addition, certain cnidarian venoms contain or induce the release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and caissarone accelerating the pathogenic effects of other venom enzymes and porins. The cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation of humans may result in death, in some cases within a few minutes to an hour after sting. The complexity of venom components represents a unique therapeutic challenge and probably reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.

  10. Secreted Phospholipases A₂ from Animal Venoms in Pain and Analgesia.

    PubMed

    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.

  11. 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.

    PubMed

    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.

  12. Detection and Identification of Vipera Russelli Venom

    DTIC Science & Technology

    1990-01-01

    1257. (Unclassified). 26. Rael, E.D., Salo, R.J., and Zepeda , H. (1986). Monocvlonal antibodies to Majave toxin and use for isolation of cross-reacting...moccasin venom labelled with iodine 131. Nature (Lond.) 184: 1244-1245. 48. Labez, D ., Gubensek, F., Maretic, Z., (1968). Studies on labelled animal...UNCLASSIFIED SM 1291 3600" 2800 , I- Z 2400- D 0 U o 2000 Li o 1600- .-J 1200wu 800 400 25 5 10 20 40 80 HORSE ANTI-V. russelli ANTIBODY (pg mL1 Figure 1

  13. Neutralization of Apis mellifera bee venom activities by suramin.

    PubMed

    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.

  14. [Relationships between venomous function and innate immune function].

    PubMed

    Goyffon, Max; Saul, Frederick; Faure, Grazyna

    2015-01-01

    Venomous function is investigated in relation to innate immune function in two cases selected from scorpion venom and serpent venom. In the first case, structural analysis of scorpion toxins and defensins reveals a close interrelation between both functions (toxic and innate immune system function). In the second case, structural and functional studies of natural inhibitors of toxic snake venom phospholipases A2 reveal homology with components of the innate immune system, leading to a similar conclusion. Although there is a clear functional distinction between neurotoxins, which act by targeting membrane ion channels, and the circulating defensins which protect the organism from pathogens, the scorpion short toxins and defensins share a common protein folding scaffold with a conserved cysteine-stabilized alpha-beta motif of three disulfide bridges linking a short alpha helix and an antiparallel beta sheet. Genomic analysis suggests that these proteins share a common ancestor (long venom toxins were separated from an early gene family which gave rise to separate short toxin and defensin families). Furthermore, a scorpion toxin has been experimentally synthetized from an insect defensin, and an antibacterial scorpion peptide, androctonin (whose structure is similar to that of a cone snail venom toxin), was shown to have a similar high affinity for the postsynaptic acetylcholine receptor of Torpedo sp. Natural inhibitors of phospholipase A2 found in the blood of snakes are associated with the resistance of venomous snakes to their own highly neurotoxic venom proteins. Three classes of phospholipases A2 inhibitors (PLI-α, PLI-β, PLI-γ) have been identified. These inhibitors display diverse structural motifs related to innate immune proteins including carbohydrate recognition domains (CRD), leucine rich repeat domains (found in Toll-like receptors) and three finger domains, which clearly differentiate them from components of the adaptive immune system. Thus, in

  15. Cross reactivity between European hornet and yellow jacket venoms.

    PubMed

    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 (<75%). In 6 subjects the CAP-inhibition provided inconclusive results and their sera were analysed by immunoblotting. The SDS-PAGE identified hyaluronidase, phospholipase A1 and antigen 5 as the main proteins of the venoms. In 5 sera the levels of IgE against antigen 5 of Vespa crabro were higher than IgE against 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.

  16. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

    PubMed

    Sturm, G J; Varga, E-M; Roberts, G; Mosbech, H; Bilò, M B; Akdis, C A; Antolín-Amérigo, D; Cichocka-Jarosz, E; Gawlik, R; Jakob, T; Kosnik, M; Lange, J; Mingomataj, E; Mitsias, D I; Ollert, M; Oude Elberink, J N G; Pfaar, O; Pitsios, C; Pravettoni, V; Ruëff, F; Sin, B A; Agache, I; Angier, E; Arasi, S; Calderón, M A; Fernandez-Rivas, M; Halken, S; Jutel, M; Lau, S; Pajno, G B; van Ree, R; Ryan, D; Spranger, O; van Wijk, R G; Dhami, S; Zaman, H; Sheikh, A; Muraro, A

    2018-04-01

    Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H 1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  17. Evolution and diversification of the Toxicofera reptile venom system.

    PubMed

    Fry, Bryan G; Vidal, Nicolas; van der Weerd, Louise; Kochva, Elazar; Renjifo, Camila

    2009-03-06

    The diversification of the reptile venom system has been an area of major research but of great controversy. In this review we examine the historical and modern-day efforts of all aspects of the venom system including dentition, glands and secreted toxins and highlight areas of future research opportunities. We use multidisciplinary techniques, including magnetic resonance imaging of venom glands through to molecular phylogenetic reconstruction of toxin evolutionary history, to illustrate the diversity within this integrated weapons system and map the timing of toxin recruitment events over the toxicoferan organismal evolutionary tree.

  18. Antioxidant activity and irritation property of venoms from Apis species.

    PubMed

    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

  19. Speedy milking of fresh venom from aculeate hymenopterans.

    PubMed

    Fox, Eduardo G P; Xu, Meng; Wang, Lei; Chen, Li; Lu, Yong-Yue

    2018-05-01

    A straightforward method for extracting aculeate arthropod venoms by centrifugation is described, based on adapting a glass insert containing a piece of metal mesh or glass wool into a centrifuge tube. Venom apparatuses are centrifuged for 30 s intervals at ≈2000-6000 g, with samples being dislodged between cycles. Venom from fire ants, honeybees, and a social wasp were extracted within minutes. The method is suited for small-scale bioassays and allows for faithful descriptions of unmodified toxin cocktails. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Venomics of Bungarus caeruleus (Indian krait): Comparable venom profiles, variable immunoreactivities among specimens from Sri Lanka, India and Pakistan.

    PubMed

    Oh, Angeline Mei Feng; Tan, Choo Hock; Ariaranee, Gnanathasan Christeine; Quraishi, Naeem; Tan, Nget Hong

    2017-07-05

    The Indian krait (Bungarus caeruleus) is one of the "Big Four" venomous snakes widely distributed in South Asia. The present venomic study reveals that its venom (Sri Lankan origin) is predominated by phospholipases A 2 (64.5% of total proteins), in which at least 4.6% are presynaptically-acting β-bungarotoxin A-chains. Three-finger toxins (19.0%) are the second most abundant, comprising 15.6% κ-neurotoxins, the potent postsynaptically-acting long neurotoxins. Comparative chromatography showed that venom samples from Sri Lanka, India and Pakistan did not exhibit significant variation. These venoms exhibited high immunoreactivity toward VINS Indian Polyvalent Antivenom (VPAV). The Pakistani krait venom, however, had a relatively lower degree of binding, consistent with its moderate neutralization by VPAV (potency=0.3mg venom neutralized per ml antivenom) while the Sri Lankan and Indian venoms were more effectively neutralized (potency of 0.44 mg/ml and 0.48 mg/ml, respectively). Importantly, VPAV was able to neutralize the Sri Lankan and Indian venoms to a comparable extent, supporting its use in Sri Lanka especially in the current situation where Sri Lanka-specific antivenom is unavailable against this species. The findings also indicate that the Pakistani B. caeruleus venom is immunologically less comparable and should be incorporated in the production of a pan-regional, polyspecific antivenom. The Indian krait or blue krait, Bungarus caeruleus, is a highly venomous snake that contributes to the snakebite envenoming problem in South Asia. This is a less aggressive snake species but its accidental bite can cause rapid and severe neurotoxicity, in which the patient may succumb to paralysis, respiratory failure and death within a short frame of time. The proteomic analysis of its venom (sourced from Sri Lanka) unveils its content that well correlates to its envenoming pathophysiology, driven primarily by the abundant presynaptic and postsynaptic neurotoxins (

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

    PubMed

    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.

  2. Spider-Venom Peptides as Bioinsecticides

    PubMed Central

    Windley, Monique J.; Herzig, Volker; Dziemborowicz, Sławomir A.; Hardy, Margaret C.; King, Glenn F.; Nicholson, Graham M.

    2012-01-01

    Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world’s annual crop production and transmit many pathogens. Presently, arthropod pests of agricultural and health significance are controlled predominantly through the use of chemical insecticides. Unfortunately, the widespread use of these agrochemicals has resulted in genetic selection pressure that has led to the development of insecticide-resistant arthropods, as well as concerns over human health and the environment. Bioinsecticides represent a new generation of insecticides that utilise organisms or their derivatives (e.g., transgenic plants, recombinant baculoviruses, toxin-fusion proteins and peptidomimetics) and show promise as environmentally-friendly alternatives to conventional agrochemicals. Spider-venom peptides are now being investigated as potential sources of bioinsecticides. With an estimated 100,000 species, spiders are one of the most successful arthropod predators. Their venom has proven to be a rich source of hyperstable insecticidal mini-proteins that cause insect paralysis or lethality through the modulation of ion channels, receptors and enzymes. Many newly characterized insecticidal spider toxins target novel sites in insects. Here we review the structure and pharmacology of these toxins and discuss the potential of this vast peptide library for the discovery of novel bioinsecticides. PMID:22741062

  3. Biochemical and pharmacological characterization of Trimersurus malabaricus snake venom.

    PubMed

    Gowda, Raghavendra; Rajaiah, Rajesh; Angaswamy, Nataraj; Krishna, Sharath; Bannikuppe Sannanayak, Vishwanath

    2018-07-01

    Trimeresurus malabaricus is a venomous pit viper species endemic to southwestern part of India. In earlier reports, we have shown that envenomation by T. malabaricus venom leading to strong local tissue damage but the mechanism of action is not clearly revealed. Local tissue damage affected by T. malabaricus venom is of great importance since the poison has serious systemic effects including death in the case of multiple attacks. The present study details the major manifestations of T. malabaricus venom and the induction of local tissue damage, which suggests that most toxins are present in the form of hydrolytic enzymes. Hydrolytic activity of the enzymes was measured and the data indicated that protease and phospholipase A 2 activity was high which is responsible for local tissue damage. Furthermore, the role of hydrolytic enzymes in the induction of pathological events such as hemorrhage, edema, myotoxicity, and blood coagulation examination were assessed through animal models. © 2018 Wiley Periodicals, Inc.

  4. Proteome analysis of snake venom toxins: pharmacological insights.

    PubMed

    Georgieva, Dessislava; Arni, Raghuvir K; Betzel, Christian

    2008-12-01

    Snake venoms are an extremely rich source of pharmacologically active proteins with a considerable clinical and medical potential. To date, this potential has not been fully explored, mainly because of our incomplete knowledge of the venom proteome and the pharmacological properties of its components, in particular those devoid of enzymatic activity. This review summarizes the latest achievements in the determination of snake venom proteome, based primarily on the development of new strategies and techniques. Detailed knowledge of the venom toxin composition and biological properties of the protein constituents should provide the scaffold for the design of new more effective drugs for the treatment of the hemostatic system and heart disorders, inflammation, cancer and consequences of snake bites, as well as new tools for clinical diagnostic and assays of hemostatic parameters.

  5. Snake Venom Components and Their Cross Reactivity: A Short Review

    DTIC Science & Technology

    1988-10-01

    RESEARCH ESTABLISHMENT SUFFIELD, RALSTON, ALBERTA WARNING ’The vae ofhis infort on is pw tt .jm to recognition of proprietar and patent riqht’. Canada" D ...cross- reactivity with other proteins, such as those in the venom from C. basiliscus, C. durissus dutrissus, C. d . terrificus, C. horridus horrichus, and...48 534-569, 1968. 33. Lind, P. and Eaker, D . Amino acid sequence of a lethal myotoxic phospholipase A2 from the venom of the common sea snake (Eh

  6. Mechanisms of bee venom-induced acute renal failure.

    PubMed

    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, p<0.0001) and renal blood flow (RBF, laser Doppler flowmetry), which was more severe in the cortical (-72%) than in the medullary area (-48%), without systemic blood pressure decrease. Creatine phosphokinase, lactic dehydrogenase (LDH) and serum glutamic oxaloacetic transaminase increased significantly, pointing to rhabdomyolysis, whereas serum glutamic pyruvic transaminase and hematocrit remained stable. Twenty-four hours after venom, RBF recovered but GFR remained significantly impaired. Renal histology showed acute tubular injury and a massive tubular deposition of myoglobin. Venom was added to isolated rat proximal tubules (PT) suspension subjected to normoxia and hypoxia/reoxygenation (H/R) for direct nephrotoxicity evaluation. After 60 min of incubation, 0.1, 2 and 10 microg of venom induced significant increases in LDH release: 47%, 64% and 86%, respectively, vs. 21% in control PT while 2 microg of venom enhanced H/R injury (85% vs. 55%, p<0.01). These results indicate that vasoconstriction, direct nephrotoxicity and rhabdomyolysis are important mechanisms in the installation of bee venom-induced ARF that may occur even without hemolysis or hypotension.

  7. Immune and clinical response to honeybee venom in beekeepers.

    PubMed

    Matysiak, Jan; Matysiak, Joanna; Bręborowicz, Anna; Kycler, Zdzisława; Dereziński, Paweł; Kokot, Zenon J

    2016-01-01

    The aim of the study was to assess immune response to honeybee venom in relation to the degree of exposure, time after a sting and clinical symptoms. Fifty-four volunteers were divided into 2 groups: beekeepers and a control group. The serum levels of total IgE (tIgE), bee venom-specific IgE (venom sIgE), phospholipase A2-specific IgE (phospholipase A2 sIgE), tryptase and venom-specific IgG4 (venom sIgG4) were determined. In beekeepers, diagnostic tests were performed within 3 hours following a sting and were repeated after a minimum of 6 weeks from the last sting. In individuals from the control group, the tests were performed only once, without a sting. The tests showed significant differences in venom sIgE (beekeepers' median = 0.34 kUA/l, control group median = 0.29 kUA/l), baseline serum tryptase (beekeepers' median = 4.25 µg/l, control group median = 2.74 µg/l) and sIgG4 (beekeepers' median = 21.2 mgA/l, control group median = 0.14 mgA/l), confirming higher levels of the tested substances in the beekeepers than in the control group. A significant positive correlation was observed between phospholipase A2 sIgE concentration and severity of clinical symptoms after a sting in the group of beekeepers. It was also demonstrated that the clinical symptoms after a sting became less severe with increasing age of the beekeepers. The differences in the immune response to a bee sting between the beekeepers and individuals not exposed to bees were probably due to the high exposure of the beekeepers to honeybee venom allergens. This may suggest a different approach to the bee venom allergy diagnostic tests in this occupational group.

  8. The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus.

    PubMed

    Kazemi-Lomedasht, Fatemeh; Khalaj, Vahid; Bagheri, Kamran Pooshang; Behdani, Mahdi; Shahbazzadeh, Delavar

    2017-01-01

    Hemiscorpius lepturus scorpion is one of the most venomous members of the Hemiscorpiidae family. H. lepturus is distributed in Iran, Iraq and Yemen. The prevalence and severity of scorpionism is high and health services are not able to control it. Scorpionism in Iran especially in the southern regions (Khuzestan, Sistan and Baluchestan, Hormozgan, Ilam) is one of the main health challenges. Due to the medical and health importance of scorpionism, the focus of various studies has been on the identification of H. lepturus venom components. Nevertheless, until now, only a few percent of H. lepturus venom components have been identified and there is no complete information about the venom components of H. lepturus. The current study reports transcriptome analysis of the venom gland of H. lepturus scorpion. Illumina Next Generation Sequencing results identified venom components of H. lepturus. When compared with other scorpion's venom, the venom of H. lepturus consists of mixtures of peptides, proteins and enzymes such as; phospholipases, metalloproteases, hyaluronidases, potassium channel toxins, calcium channel toxins, antimicrobial peptides (AMPs), venom proteins, venom toxins, allergens, La1-like peptides, proteases and scorpine-like peptides. Comparison of identified components of H. lepturus venom was carried out with venom components of reported scorpions and various identities and similarities between them were observed. With transcriptome analysis of H. lepturus venom unique sequences, coding venom components were investigated. Moreover, our study confirmed transcript expression of previously reported peptides; Hemitoxin, Hemicalcin and Hemilipin. The gene sequences of venom components were investigated employing transcriptome analysis of venom gland of H. lepturus. In summary, new bioactive molecules identified in this study, provide basis for venomics studies of scorpions of Hemiscorpiidae family and promises development of novel biotherapeutics

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

    PubMed Central

    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

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

    PubMed

    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

  11. Small Packages, Big Returns: Uncovering the Venom Diversity of Small Invertebrate Conoidean Snails.

    PubMed

    Gorson, J; Holford, M

    2016-11-01

    Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for both predation and defense, and therefore under strong selection pressures. The need for conoidean venom peptides to be potent and specific to their molecular targets has made them important tools for investigating cellular physiology and bioactive compounds that are beneficial to improving human health. A convincing case for the potential of Conoidean venom is made with the first commercially available conoidean venom peptide drug Ziconotide (Prialt®), an analgesic derived from Conus magus venom that is used to treat chronic pain in HIV and cancer patients. Investigation of conoidean venom using -omics technology provides significant insights into predator-driven diversification in biodiversity and identifies novel compounds for manipulating cellular communication, especially as it pertains to disease and disorders. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.

  12. Ampulexins: A New Family of Peptides in Venom of the Emerald Jewel Wasp, Ampulex compressa.

    PubMed

    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).

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

    PubMed Central

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

    2016-01-01

    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. PMID:27338473

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

    PubMed

    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.

  15. Snake Venom: From Deadly Toxins to Life-saving Therapeutics.

    PubMed

    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.

  16. Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom.

    PubMed

    Lazcano-Pérez, Fernando; Zavala-Moreno, Ariana; Rufino-González, Yadira; Ponce-Macotela, Martha; García-Arredondo, Alejandro; Cuevas-Cruz, Miguel; Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Arreguín-Lozano, Barbarín; Arreguín-Espinosa, Roberto

    2018-01-01

    Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis . The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA 2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. P. caribaeorum venom produced hemolytic and PLA 2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

  17. Animal Venom Peptides: Potential for New Antimicrobial Agents.

    PubMed

    Primon-Barros, Muriel; José Macedo, Alexandre

    2017-01-01

    Microbial infections affect people worldwide, causing diseases with significant impact on public health, indicating the need for research and development of new antimicrobial agents. Animal venoms represent a vast and largely unexploited source of biologically active molecules with attractive candidates for the development of novel therapeutics. Venoms consist of complex mixtures of molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs, they have been studied as promising new antimicrobial drugs. Amongst the remarkable sources of AMPs with known antimicrobial activities are ants, bees, centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial tests against bacteria, protozoans, fungi and viruses using 170 different peptides isolated directly from crude venoms or cDNA libraries of venom glands are listed and discussed in this review, as well as hemolytic ativity. The potential of venoms as source of new compounds, including AMPs, is extensively discussed. Currently, there are six FDA-approved drugs and many others are undergoing preclinical and clinical trials. The search for antimicrobial "weapons" makes the AMPs from venoms promising candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Systemic and local reactions of bee venom immunotherapy in Iran.

    PubMed

    Bemanian, Mohammad Hassan; Farhoudi, Abolhassan; Pourpak, Zahra; Gharagozlou, Mohammad; Movahedi, Masoud; Nabavi, Mohammad; Mozafari, Habibeh; Mohammadzadeh, Iraj; Chavoshzadeh, Zahra; Shirkhoda, Zahra

    2007-12-01

    Severe allergic reactions during specific immunotherapy may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during specific immunotherapy in patients with allergy towards hymenoptera venom in the Iranian population. A prospective study was performed using the clinical reports of 27 patients with anaphylaxis to bee venom (Apis melifera, Geupes vespula and Geupes Polites). Ten patients treated with Cluster protocol during 2002 and 2006 After diagnosis of hymenoptera sting allergy according to history and intradermal tests, the patient were treated with Cluster protocol immunotherapy. The protocol lasted 6 weeks with an increase in the concentration of venom from 0.01 microg/ml to 100 microg/ml. None of the patient received premedication. All patients with hymenoptera venom allergy received 120 injections. Anaphylactic reactions were classified according to the Mueller-classification. The frequencies of systemic reactions during Cluster protocol were 8.33% and 5% for yellow jacket and honey bee venom respectively. No patient experienced severe systemic reaction. Cluster protocol for hymenoptera immunotherapy is a reliable method for the treatment of anaphylactic reactions to bee venom. It is safe with low cost and do not need hospitalization.

  19. Venom Proteome of the Box Jellyfish Chironex fleckeri

    PubMed Central

    Brinkman, Diane L.; Aziz, Ammar; Loukas, Alex; Potriquet, Jeremy; Seymour, Jamie; Mulvenna, Jason

    2012-01-01

    The nematocyst is a complex intracellular structure unique to Cnidaria. When triggered to discharge, the nematocyst explosively releases a long spiny, tubule that delivers an often highly venomous mixture of components. The box jellyfish, Chironex fleckeri, produces exceptionally potent and rapid-acting venom and its stings to humans cause severe localized and systemic effects that are potentially life-threatening. In an effort to identify toxins that could be responsible for the serious health effects caused by C. fleckeri and related species, we used a proteomic approach to profile the protein components of C. fleckeri venom. Collectively, 61 proteins were identified, including toxins and proteins important for nematocyte development and nematocyst formation (nematogenesis). The most abundant toxins identified were isoforms of a taxonomically restricted family of potent cnidarian proteins. These toxins are associated with cytolytic, nociceptive, inflammatory, dermonecrotic and lethal properties and expansion of this important protein family goes some way to explaining the destructive and potentially fatal effects of C. fleckeri venom. Venom proteins and their post-translational modifications (PTMs) were further characterized using toxin-specific antibodies and phosphoprotein/glycoprotein-specific stains. Results indicated that glycosylation is a common PTM of the toxin family while a lack of cross-reactivity by toxin-specific antibodies infers there is significant divergence in structure and possibly function among family members. This study provides insight into the depth and diversity of protein toxins produced by harmful box jellyfish and represents the first description of a cubozoan jellyfish venom proteome. PMID:23236347

  20. Ancient Venom Systems: A Review on Cnidaria Toxins

    PubMed Central

    Jouiaei, Mahdokht; Yanagihara, Angel A.; Madio, Bruno; Nevalainen, Timo J.; Alewood, Paul F.; Fry, Bryan G.

    2015-01-01

    Cnidarians are the oldest extant lineage of venomous animals. Despite their simple anatomy, they are capable of subduing or repelling prey and predator species that are far more complex and recently evolved. Utilizing specialized penetrating nematocysts, cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological reactions in the envenomated organism. These venoms contain enzymes, potent pore forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion channel specific activities. In addition, certain cnidarian venoms contain or induce the release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and caissarone accelerating the pathogenic effects of other venom enzymes and porins. The cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation of humans may result in death, in some cases within a few minutes to an hour after sting. The complexity of venom components represents a unique therapeutic challenge and probably reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are invaluable as a therapeutic target for sting treatment or as lead compounds for drug design. PMID:26094698

  1. Venom-Related Transcripts from Bothrops jararaca Tissues Provide Novel Molecular Insights into the Production and Evolution of Snake Venom

    PubMed Central

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

    2015-01-01

    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. PMID:25502939

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

    PubMed

    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.

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

    PubMed Central

    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

  4. Venomics of the Australian eastern brown snake (Pseudonaja textilis): Detection of new venom proteins and splicing variants.

    PubMed

    Viala, Vincent Louis; Hildebrand, Diana; Trusch, Maria; Fucase, Tamara Mieco; Sciani, Juliana Mozer; Pimenta, Daniel Carvalho; Arni, Raghuvir K; Schlüter, Hartmut; Betzel, Christian; Mirtschin, Peter; Dunstan, Nathan; Spencer, Patrick Jack

    2015-12-01

    The eastern brown snake is the predominant cause of snakebites in mainland Australia. Its venom induces defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia. Cardiovascular collapse has been described as an early cause of death in patients, but, so far, the mechanisms involved have not been fully identified. In the present work, we analysed the venome of Pseudonaja textilis by combining high throughput proteomics and transcriptomics, aiming to further characterize the components of this venom. The combination of these techniques in the analysis and identification of toxins, venom proteins and putative toxins allowed the sequence description and the identification of the following: prothrombinase coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and "acidic PLA2", three-finger toxins (3FTx) and the Kunitz-type protease inhibitor textilinin, venom metalloproteinase, C-type lectins, cysteine rich secretory proteins, calreticulin, dipeptidase 2, as well as evidences of Heloderma lizard peptides. Deep data-mining analysis revealed the secretion of a new transcript variant of venom coagulation factor 5a and the existence of a splicing variant of PLA2 modifying the UTR and signal peptide from a same mature protein. The transcriptome revealed the diversity of transcripts and mutations, and also indicates that splicing variants can be an important source of toxin variation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Parasitism and venom of ectoparasitoid Scleroderma guani impairs host cellular immunity.

    PubMed

    Li, Li-Fang; Xu, Zhi-Wen; Liu, Nai-Yong; Wu, Guo-Xing; Ren, Xue-Min; Zhu, Jia-Ying

    2018-06-01

    Venom is a prominently maternal virulent factor utilized by parasitoids to overcome hosts immune defense. With respect to roles of this toxic mixture involved in manipulating hosts immunity, great interest has been mostly restricted to Ichneumonoidea parasitoids associated with polydnavirus (PDV), of which venom is usually considered as a helper component to enhance the role of PDV, and limited Chalcidoidea species. In contrast, little information is available in other parasitoids, especially ectoparasitic species not carrying PDV. The ectoparasitoid Scleroderma guani injects venom into its host, Tenebrio molitor, implying its venom was involved in suppression of hosts immune response for successful parasitism. Thus, we investigated the effects of parasitism and venom of this parasitoid on counteracting the cellular immunity of its host by examining changes of hemocyte counts, and hemocyte spreading and encapsulation ability. Total hemocyte counts were elevated in parasitized and venom-injected pupae. The spreading behavior of both granulocytes and plasmatocytes was impaired by parasitization and venom. High concentration of venom led to more severely increased hemocyte counts and suppression of hemocyte spreading. The ability of hemocyte encapsulation was inhibited by venom in vitro. In addition to immediate effects observed, venom showed persistent interference in hosts cellular immunity. These results indicate that venom alone from S. guani plays a pivotal role in blocking hosts cellular immune response, serving as a regulator that guarantees the successful development of its progenies. The findings provide a foundation for further investigation of the underlying mechanisms in immune inhibitory action of S. guani venom. © 2018 Wiley Periodicals, Inc.

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

    PubMed Central

    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

  7. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

    PubMed Central

    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.

    2014-01-01

    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. PMID:24927555

  8. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms.

    PubMed

    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.

  9. Changes in predator exposure, but not in diet, induce phenotypic plasticity in scorpion venom.

    PubMed

    Gangur, Alex N; Smout, Michael; Liddell, Michael J; Seymour, Jamie E; Wilson, David; Northfield, Tobin D

    2017-09-27

    Animals embedded between trophic levels must simultaneously balance pressures to deter predators and acquire resources. Venomous animals may use venom toxins to mediate both pressures, and thus changes in this balance may alter the composition of venoms. Basic theory suggests that greater exposure to a predator should induce a larger proportion of defensive venom components relative to offensive venom components, while increases in arms races with prey will elicit the reverse. Alternatively, reducing the need for venom expenditure for food acquisition, for example because of an increase in scavenging, may reduce the production of offensive venom components. Here, we investigated changes in scorpion venom composition using a mesocosm experiment where we manipulated scorpions' exposure to a surrogate vertebrate predator and live and dead prey. After six weeks, scorpions exposed to surrogate predators exhibited significantly different venom chemistry compared with naive scorpions. This change included a relative increase in some compounds toxic to vertebrate cells and a relative decrease in some compounds effective against their invertebrate prey. Our findings provide, to our knowledge, the first evidence for adaptive plasticity in venom composition. These changes in venom composition may increase the stability of food webs involving venomous animals. © 2017 The Author(s).

  10. Hematological parameters on the effect of the jellyfish venom Cassiopea andromeda in animal models.

    PubMed

    Nabipour, Iraj; Mohebbi, Gholamhossein; Vatanpour, Hossein; Vazirizadeh, Amir

    2017-04-01

    For the first time, we previously recorded an enormous population of the Cassiopea andromeda jellyfish that had increased dramatically from Bushehr coasts of Iran. The sub-acute toxicity of the jellyfish venom in rat organs was correspondingly carried out. The data presented in this paper relate to the in vivo and in vitro hematological effects of this venomous species of jellyfish venom.

  11. Intraspecific Variation of Centruroides Edwardsii Venom from Two Regions of Colombia

    PubMed Central

    Estrada-Gómez, Sebastián; Cupitra, Nelson Ivan; Arango, Walter Murillo; Vargas Muñoz, Leidy Johana

    2014-01-01

    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. PMID:25025710

  12. Circus Venomous: an interactive tool for toxinology education.

    PubMed

    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

  13. 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.

    PubMed

    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

  14. Honeybee Venom Proteome Profile of Queens and Winter Bees as Determined by a Mass Spectrometric Approach

    PubMed Central

    Danneels, Ellen L.; Van Vaerenbergh, Matthias; Debyser, Griet; Devreese, Bart; de Graaf, Dirk C.

    2015-01-01

    Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings. PMID:26529016

  15. A Review and Database of Snake Venom Proteomes

    PubMed Central

    Tasoulis, Theo

    2017-01-01

    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. PMID:28927001

  16. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms.

    PubMed

    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.

  17. Sex-related clinical aspects in insect venom anaphylaxis.

    PubMed

    Nittner-Marszalska, Marita; Liebhart, Jerzy; Dor-Wojnarowska, Anna

    2015-06-01

    Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects' venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable. © The Author(s) 2015.

  18. Systemic reactions during maintenance immunotherapy with honey bee venom.

    PubMed

    Bousquet, J; Ménardo, J L; Velasquez, G; Michel, F B

    1988-07-01

    Immunotherapy with hymenoptera venoms is safe and effective in most patients but treatment failures have been reported. Five patients experienced systemic symptoms of anaphylaxis when they were in maintenance immunotherapy with honey bee venom. In one case, the patient presented a severe life-threatening reaction when stung by a honey bee. Three others had the development of new clinical sensitivity suggesting a re-sensitization. This occurred in the fifth patient after a severe viral infection. By means of a rush protocol and monthly doses of 200 to 400 micrograms of honey bee venom, the patients were subsequently protected efficiently. In most cases these reactions might have been predicted since patients experienced large local reactions prior to the systemic reactions when allergens were injected. Further, in four cases there was an increased skin test reactivity or raised serum honey bee venom IgE levels or both. In all patients, the levels of serum honey bee venom IgG was under 200 U/mL (IgG Pharmacia RAST).

  19. Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

    PubMed Central

    Anusha, Sebastian; Hemshekhar, Mahadevappa; Chandra Nayaka, Siddaiah; Kemparaju, Kempaiah; Basappa; Girish, Kesturu S.; Rangappa, Kanchugarakoppal S.

    2014-01-01

    The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management. PMID:25184206

  20. Exon Shuffling and Origin of Scorpion Venom Biodiversity

    PubMed Central

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-01-01

    Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences. PMID:28035955

  1. Exon Shuffling and Origin of Scorpion Venom Biodiversity.

    PubMed

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-12-26

    Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences.

  2. Venomous snakebites in the United States: management review and update.

    PubMed

    Juckett, Gregory; Hancox, John G

    2002-04-01

    Venomous snakebites, although uncommon, are a potentially deadly emergency in the United States. Rattlesnakes cause most snakebites and related fatalities. Venomous snakes in the United States can be classified as having hemotoxic or neurotoxic venom. Patients with venomous snakebites present with signs and symptoms ranging from fang marks, with or without local pain and swelling, to life-threatening coagulopathy, renal failure, and shock. First-aid techniques such as arterial tourniquets, application of ice, and wound incisions are ineffective and can be harmful; however, suction with a venom extractor within the first five minutes after the bite may be useful. Conservative measures, such as immobilization and lymphatic constriction bands, are now advocated until emergency care can be administered. Patients with snakebites should undergo a comprehensive work-up to look for possible hematologic, neurologic, renal, and cardiovascular abnormalities. Equine-derived antivenin is considered the standard of care; however, a promising new treatment is sheep-derived antigen binding fragment ovine (CroFab), which is much less allergenic. Although there is no universal grading system for snakebites, a I through IV grading scale is clinically useful as a guide to antivenin administration. Surgical intervention with fasciotomy is now reserved for rare cases. Snakebite prevention should be taught to patients.

  3. Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis) root extracts.

    PubMed

    Alam, M I; Gomes, A

    2003-05-01

    The methanolic root extracts of Vitex negundo Linn. and Emblica officinalis Gaertn. were explored for the first time for antisnake venom activity. The plant (V. negundo and E. officinalis) extracts significantly antagonized the Vipera russellii and Naja kaouthia venom induced lethal activity both in in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory activity was significantly neutralized by both plant extracts. No precipitating bands were observed between the plant extract and snake venom. The above observations confirmed that the plant extracts possess potent snake venom neutralizing capacity and need further investigation.

  4. Resistance of cervical adenocarcinoma cells (HeLa) to venom from the scorpion Centruroides limpidus limpidus

    PubMed Central

    2013-01-01

    Background The venom of Centruroides limpidus limpidus (Cll) is a mixture of pharmacologically active principles. The most important of these are toxic proteins that interact both selectively and specifically with different cellular targets such as ion channels. Recently, anticancer properties of the venom from other scorpion species have been described. Studies in vitro have shown that scorpion venom induces cell death, inhibits proliferation and triggers the apoptotic pathway in different cancer cell lines. Herein, after treating human cervical adenocarcinoma (HeLa) cells with Cll crude venom, their cytotoxic activity and apoptosis induction were assessed. Results Cll crude venom induced cell death in normal macrophages in a dose-dependent manner. However, through viability assays, HeLa cells showed high survival rates after exposure to Cll venom. Also, Cll venom did not induce apoptosis after performing ethidium bromide/acridine orange assays, nor was there any evidence of chromatin condensation or DNA fragmentation. Conclusions Crude Cll venom exposure was not detrimental to HeLa cell cultures. This may be partially attributable to the absence of specific HeLa cell membrane targets for molecules present in the venom of Centruroides limpidus limpidus. Although these results might discourage additional studies exploring the potential of Cll venom to treat human papilloma cervical cancer, further research is required to explore positive effects of crude Cll venom on other cancer cell lines. PMID:24004568

  5. Intraspecific variation in the venom of the vermivorous cone snail Conus vexillum.

    PubMed

    Abdel-Rahman, Mohamed A; Abdel-Nabi, Ismail M; El-Naggar, Mohamed S; Abbas, Osama A; Strong, Peter N

    2011-11-01

    A combination of proteomic and biochemical assays was used to examine variations in the venom of Conus vexillum taken from two locations (Hurgada and Sharm El-Shaikh) in the Red Sea, Egypt. Using MALDI/TOF-MS, a remarkable degree of intra-species variation between venom samples from both locations was identified. To evaluate variability in the cytotoxic effects of Conus venom, mice were injected with the same dose from each location. The oxidative stress biomarkers [malondialdehyde (MDA), protein carbonyl content (PCC)], antioxidants [glutathione (GSH), superoxide dismutase (SOD), catalase (CAT)], total antioxidant capacity (TAC) and nitric oxide (NO), were measured 3, 6, 9 and 12h post venom injection. The venoms induced a significant increase in the levels of PCC, MDA, NO, GSH and CAT. The venoms significantly inhibited the activity of SOD and reduced the TAC. Toxicological data showed that the venom obtained from Hurgada was more potent than that obtained from Sharm El-Shaikh. It can be concluded that: (1) the venom of the same Conus species from different regions is highly diversified (2) the venoms from different locations reflect clear differences in venom potency and (3) the cytotoxic effects of C. vexillum venom can be attributed to its ability to induce oxidative stress. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

    PubMed Central

    Ferraz, Miriéle Cristina; de Oliveira, Jhones Luiz; de Oliveira Junior, Joel Reis; Cogo, José Carlos; dos Santos, Márcio Galdino; Franco, Luiz Madaleno; Puebla, Pilar; Ferraz, Helena Onishi; Ferraz, Humberto Gomes; da Rocha, Marisa Maria Teixeira; Hyslop, Stephen

    2015-01-01

    We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite. PMID:26633987

  7. Enzymatic and Pro-Inflammatory Activities of Bothrops lanceolatus Venom: Relevance for Envenomation

    PubMed Central

    Delafontaine, Marie; Villas-Boas, Isadora Maria; Mathieu, Laurence; Josset, Patrice; Blomet, Joël

    2017-01-01

    Bothrops lanceolatus, commonly named ‘Fer-de-Lance’, is an endemic snake of the French Caribbean Island of Martinique. Envenomations by B. lanceolatus present clinical aspects characterized by systemic thrombotic syndrome and important local inflammation, involving edema and pain but limited hemorrhage. To investigate mechanisms of venom-induced inflammation, B. lanceolatus venom was characterized, its cross-reactivity with bothropic antivenom explored, its cytotoxicity on human keratinocytes and vascular cells, and the production of cytokines and chemokines were analyzed. We used electrophoretic separation, zymography, colorimetric or fluorimetric enzymatic assays, and immunochemical assays. Therapeutic South American bothropic antivenom cross-reacted with B. lanceolatus venom and completely or partially abolished its PLA2, hyaluronidase, and proteolytic activities, as well as its cytotoxicity for keratinocytes. The substrate specificity of B. lanceolatus venom proteases was emphasized. B. lanceolatus venom cytotoxicity was compared to the B. jararaca venom. Both venoms were highly cytotoxic for keratinocytes (HaCaT), whereas B. lanceolatus venom showed particularly low toxicity for endothelial cells (EAhy926). Patterns of cytokine and chemokine production by cells exposed to the venoms were highly pro-inflammatory. Thus, the results presented here show that B. lanceolatus venom toxins share important antigenic similarities with South American Bothrops species toxins, although their proteases have acquired particular substrate specificity. Moreover, the venom displays important cytotoxic and pro-inflammatory action on human cell types such as keratinocytes and endothelial cells, which are important players in the local and systemic compartments affected by the envenomation. PMID:28783135

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

    PubMed

    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.

  9. Analysis of Protein Composition and Bioactivity of Neoponera villosa Venom (Hymenoptera: Formicidae).

    PubMed

    Pessoa, Wallace Felipe Blohem; Silva, Ludimilla Carvalho Cerqueira; de Oliveira Dias, Leila; Delabie, Jacques Hubert Charles; Costa, Helena; Romano, Carla Cristina

    2016-04-21

    Ants cause a series of accidents involving humans. Such accidents generate different reactions in the body, ranging from a mild irritation at the bite site to anaphylactic shock, and these reactions depend on the mechanism of action of the venom. The study of animal venom is a science known as venomics. Through venomics, the composition of the venom of several ant species has already been characterized and their biological activities described. Thus, the aim of this study was to evaluate the protein composition and biological activities (hemolytic and immunostimulatory) of the venom of Neoponera villosa (N. villosa), an ant widely distributed in South America. The protein composition was evaluated by proteomic techniques, such as two-dimensional electrophoresis. To assess the biological activity, hemolysis assay was carried out and cytokines were quantified after exposure of macrophages to the venom. The venom of N. villosa has a profile composed of 145 proteins, including structural and metabolic components (e.g., tubulin and ATPase), allergenic and immunomodulatory proteins (arginine kinase and heat shock proteins (HSPs)), protective proteins of venom (superoxide dismutase (SOD) and catalase) and tissue degradation proteins (hyaluronidase and phospholipase A2). The venom was able to induce hemolysis in human erythrocytes and also induced release of both pro-inflammatory cytokines, as the anti-inflammatory cytokine release by murine macrophages. These results allow better understanding of the composition and complexity of N. villosa venom in the human body, as well as the possible mechanisms of action after the bite.

  10. Analysis of Protein Composition and Bioactivity of Neoponera villosa Venom (Hymenoptera: Formicidae)

    PubMed Central

    Pessoa, Wallace Felipe Blohem; Silva, Ludimilla Carvalho Cerqueira; de Oliveira Dias, Leila; Delabie, Jacques Hubert Charles; Costa, Helena; Romano, Carla Cristina

    2016-01-01

    Ants cause a series of accidents involving humans. Such accidents generate different reactions in the body, ranging from a mild irritation at the bite site to anaphylactic shock, and these reactions depend on the mechanism of action of the venom. The study of animal venom is a science known as venomics. Through venomics, the composition of the venom of several ant species has already been characterized and their biological activities described. Thus, the aim of this study was to evaluate the protein composition and biological activities (hemolytic and immunostimulatory) of the venom of Neoponera villosa (N. villosa), an ant widely distributed in South America. The protein composition was evaluated by proteomic techniques, such as two-dimensional electrophoresis. To assess the biological activity, hemolysis assay was carried out and cytokines were quantified after exposure of macrophages to the venom. The venom of N. villosa has a profile composed of 145 proteins, including structural and metabolic components (e.g., tubulin and ATPase), allergenic and immunomodulatory proteins (arginine kinase and heat shock proteins (HSPs)), protective proteins of venom (superoxide dismutase (SOD) and catalase) and tissue degradation proteins (hyaluronidase and phospholipase A2). The venom was able to induce hemolysis in human erythrocytes and also induced release of both pro-inflammatory cytokines, as the anti-inflammatory cytokine release by murine macrophages. These results allow better understanding of the composition and complexity of N. villosa venom in the human body, as well as the possible mechanisms of action after the bite. PMID:27110765

  11. Anti-cobra venom activity of plant Andrographis paniculata and its comparison with polyvalent anti-snake venom

    PubMed Central

    Premendran, S. Jhon; Salwe, Kartik J.; Pathak, Swanand; Brahmane, Ranjana; Manimekalai, K.

    2011-01-01

    Background: To investigate the anti-cobra venom effect of alcoholic extract of Andrographis paniculata. Materials and Methods: After calculating the LD99 of snake venom, the venom-neutralizing ability of plant extract at the dose 1 g/kg and 2 g/kg was determined using in vitro and in vivo methods. The alleviation in the mean survival time of the animals were used to infer the antivenom property of the drug after challenging with LD99 of snake venom. Results: The ethanolic extract of plant A. paniculata significantly increases mean survival time and the protection fold, but could not protect animals from death when used alone. The higher dose, i.e., 2 g/kg was found better than that of the lower. ASV was found more effective than the plant extract. When ASV was given along with plant extract, it potentiates its effect. Conclusion: The observation demonstrates the anti-cobra venom activity of ethanolic extract of A. paniculata which is comparable with ASV. PMID:22346236

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

    PubMed

    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.

  13. Cabinet of Curiosities: Venom Systems and Their Ecological Function in Mammals, with a Focus on Primates

    PubMed Central

    Rode-Margono, Johanna E.; Nekaris, K. Anne-Isola

    2015-01-01

    Venom delivery systems (VDS) are common in the animal kingdom, but rare amongst mammals. New definitions of venom allow us to reconsider its diversity amongst mammals by reviewing the VDS of Chiroptera, Eulipotyphla, Monotremata, and Primates. All orders use modified anterior dentition as the venom delivery apparatus, except Monotremata, which possesses a crural system. The venom gland in most taxa is a modified submaxillary salivary gland. In Primates, the saliva is activated when combined with brachial gland exudate. In Monotremata, the crural spur contains the venom duct. Venom functions include feeding, intraspecific competition, anti-predator defense and parasite defense. Including mammals in discussion of venom evolution could prove vital in our understanding protein functioning in mammals and provide a new avenue for biomedical and therapeutic applications and drug discovery. PMID:26193318

  14. Spider leg autotomy induced by prey venom injection: An adaptive response to “pain”?*

    PubMed Central

    Eisner, Thomas; Camazine, Scott

    1983-01-01

    Field observations showed orb-weaving spiders (Argiope spp.) to undergo leg autotomy if they are stung in a leg by venomous insect prey (Phymata fasciata). The response occurs within seconds, before the venom can take lethal action by spread to the body of the spiders. Autotomy is induced also by honeybee venom and wasp venom, as well as by several venom components (serotonin, histamine, phospholipase A2, melittin) known to be responsible for the pain characteristically elicited by venom injection in humans. The sensing mechanism by which spiders detect injected harmful chemicals such as venoms therefore may be fundamentally similar to the one in humans that is coupled with the perception of pain. Images PMID:16593325

  15. Cabinet of Curiosities: Venom Systems and Their Ecological Function in Mammals, with a Focus on Primates.

    PubMed

    Rode-Margono, Johanna E; Nekaris, K Anne-Isola

    2015-07-17

    Venom delivery systems (VDS) are common in the animal kingdom, but rare amongst mammals. New definitions of venom allow us to reconsider its diversity amongst mammals by reviewing the VDS of Chiroptera, Eulipotyphla, Monotremata, and Primates. All orders use modified anterior dentition as the venom delivery apparatus, except Monotremata, which possesses a crural system. The venom gland in most taxa is a modified submaxillary salivary gland. In Primates, the saliva is activated when combined with brachial gland exudate. In Monotremata, the crural spur contains the venom duct. Venom functions include feeding, intraspecific competition, anti-predator defense and parasite defense. Including mammals in discussion of venom evolution could prove vital in our understanding protein functioning in mammals and provide a new avenue for biomedical and therapeutic applications and drug discovery.

  16. The venom gland transcriptome of the Desert Massasauga Rattlesnake (Sistrurus catenatus edwardsii): towards an understanding of venom composition among advanced snakes (Superfamily Colubroidea)

    PubMed Central

    Pahari, Susanta; Mackessy, Stephen P; Kini, R Manjunatha

    2007-01-01

    Background Snake venoms are complex mixtures of pharmacologically active proteins and peptides which belong to a small number of superfamilies. Global cataloguing of the venom transcriptome facilitates the identification of new families of toxins as well as helps in understanding the evolution of venom proteomes. Results We have constructed a cDNA library of the venom gland of a threatened rattlesnake (a pitviper), Sistrurus catenatus edwardsii (Desert Massasauga), and sequenced 576 ESTs. Our results demonstrate a high abundance of serine proteinase and metalloproteinase transcripts, indicating that the disruption of hemostasis is a principle mechanism of action of the venom. In addition to the transcripts encoding common venom proteins, we detected two varieties of low abundance unique transcripts in the library; these encode for three-finger toxins and a novel toxin possibly generated from the fusion of two genes. We also observed polyadenylated ribosomal RNAs in the venom gland library, an interesting preliminary obsevation of this unusual phenomenon in a reptilian system. Conclusion The three-finger toxins are characteristic of most elapid venoms but are rare in viperid venoms. We detected several ESTs encoding this group of toxins in this study. We also observed the presence of a transcript encoding a fused protein of two well-characterized toxins (Kunitz/BPTI and Waprins), and this is the first report of this kind of fusion in a snake toxin transcriptome. We propose that these new venom proteins may have ancillary functions for envenomation. The presence of a fused toxin indicates that in addition to gene duplication and accelerated evolution, exon shuffling or transcriptional splicing may also contribute to generating the diversity of toxins and toxin isoforms observed among snake venoms. The detection of low abundance toxins, as observed in this and other studies, indicates a greater compositional similarity of venoms (though potency will differ) among

  17. Venomous snakebites in an urban area: what are the possibilities?

    PubMed

    Jasper, E H; Miller, M; Neuburger, K J; Widder, P C; Snyder, J W; Lopez, B L

    2000-01-01

    To estimate the number of different species of venomous snakes privately kept in a large urban area. An anonymous survey of potential snake owners in the Philadelphia urban and suburban area. The survey was mailed to members of the Philadelphia Herpetological Society. In addition, the survey was published in 2 herpetological newsletters and online in the Herpetology Network. One hundred sixty responses were obtained during a 6-month period. Ownership of 74 different varieties of venomous snakes was reported. Antivenin was not locally available for 13 of these species. A wide variety of venomous captive snakes can be found in the private sector. The potential for having to treat an envenomation requires the emergency physician to maintain an education of snakebite management options, including the various antivenin options available in their geographical location.

  18. Effects of Mucuna pruriens protease inhibitors on Echis carinatus venom.

    PubMed

    Hope-Onyekwere, Nnadozie Stanley; Ogueli, Godwin Ifeanyi; Cortelazzo, Alessio; Cerutti, Helena; Cito, Annarita; Aguiyi, John C; Guerranti, Roberto

    2012-12-01

    The medicinal plant Mucuna pruriens, with reputed anti-snake venom properties has been reported to contain a kunitz-type trypsin inhibitor. This study was undertaken to further evaluate the protease inhibitory potential of gpMuc, a multiform glycoprotein, and other protein fractions from M. pruriens seeds against trypsin, chymotrypsin, Echis carinatus snake venom, ecarin and thrombin. The results showed that gpMuc inhibited both trypsin and chymotrypsin activities and was thermally stable, maintaining its trypsin inhibitory activity at temperatures of up to 50°C. Its structural conformation was also maintained at pH ranges of 4-7. Immunoreactivity study confirms that it contains protease-recognizing epitope on one of its isoforms. The whole protein extract of M. pruriens seeds inhibited prothrombin activation by ecarin and whole E. carinatus venom, and also thrombin-like activity using chromogenic assay. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Mastocytosis and insect venom allergy: diagnosis, safety and efficacy of venom immunotherapy.

    PubMed

    Niedoszytko, M; de Monchy, J; van Doormaal, J J; Jassem, E; Oude Elberink, J N G

    2009-09-01

    The most important causative factor for anaphylaxis in mastocytosis are insect stings. The purpose of this review is to analyse the available data concerning prevalence, diagnosis, safety and effectiveness of venom immunotherapy (VIT) in mastocytosis patients. If data were unclear, authors were contacted personally for further information. Quality of evidence (A: high, B: moderate, C: low and D: very low) and strength of recommendation (strong 1 and weak 2) concerning VIT in mastocytosis patients are assessed according to the Grading of Recommendations Assessment, Development and Evaluation and are marked in square brackets. Results of VIT were described in 117 patients to date. The mean rate of side-effects during treatment in studies published so far is 23.9% (7.6% requiring adrenaline) with an overall protection rate of 72%. Based on the review we conclude that (1) mastocytosis patients have a high risk of severe sting reactions in particular to yellow jacket, (2) VIT could be suggested [2] in mastocytosis, (3) probably should be done life long [2], (4) VIT in mastocytosis is accompanied by a higher frequency of side-effects, so (5) special precautions should be taken into account notably during the built up phase of the therapy [2], (6) VIT is able to reduce systemic reactions, but to a lesser extent compared to the general insect venom allergic population [2], so (7) patients should be warned that the efficacy of VIT might be less than optimal and they should continue carrying two adrenaline auto injectors [2].

  20. Safety and efficacy of venom immunotherapy: a real life study

    PubMed Central

    Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr

    2017-01-01

    Introduction Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. Aim To analyze the safety and efficacy of VIT in a real life setting. Material and methods One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Results Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p < 0.0001). Early and late side effects were more common during the maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients, 17.8%), were more frequent in patients allergic to bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received (r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001) and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom allergy. Conclusions Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom. PMID:28507496

  1. Safety and efficacy of venom immunotherapy: a real life study.

    PubMed

    Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr; Kupczyk, Maciej

    2017-04-01

    Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. To analyze the safety and efficacy of VIT in a real life setting. One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p < 0.0001). Early and late side effects were more common during the maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients, 17.8%), were more frequent in patients allergic to bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received ( r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001) and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom allergy. Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom.

  2. Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study

    PubMed Central

    Savi, Eleonora; Incorvaia, Cristoforo; Boni, Elisa; Mauro, Marina; Peveri, Silvia; Pravettoni, Valerio; Quercia, Oliviero; Reccardini, Federico; Montagni, Marcello; Pessina, Laura

    2017-01-01

    Background Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal. Methods We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP). Results The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom. Conclusion The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom. PMID:28686638

  3. Sex Differences in Defensive Behavior and Venom of The Striped Bark Scorpion Centruroides vittatus (Scorpiones: Buthidae).

    PubMed

    Miller, D W; Jones, A D; Goldston, J S; Rowe, M P; Rowe, A H

    2016-11-01

    Studies of venom variability have advanced from describing the mechanisms of action and relative potency of medically important toxins to understanding the ecological and evolutionary causes of the variability itself. While most studies have focused on differences in venoms among taxa, populations, or age-classes, there may be intersexual effects as well. Striped bark scorpions (Centruroides vittatus) provide a good model for examining sex differences in venom composition and efficacy, as this species exhibits dramatic sexual dimorphism in both size and defensive behavior; when threatened by an enemy, larger, slower females stand and fight while smaller, fleeter males prefer to run. We here add evidence suggesting that male and female C. vittatus indeed have different defensive propensities; when threatened via an electrical stimulus, females were more likely to sting than were males. We reasoned that intersexual differences in defensive phenotypes would select for venoms with different functions in the two sexes; female venoms should be effective at predator deterrence, whereas male venoms, less utilized defensively, might be better suited to capturing prey or courting females. This rationale led to our predictions that females would inject more venom and/or possess more painful venom than males. We were wrong. While females do inject more venom than males in a defensive sting, females are also larger; when adjusted for body size, male and female C. vittatus commit equal masses of venom in a sting to a potential enemy. Additionally, house mice (Mus musculus) find an injection of male venom more irritating than an equal amount of female venom, likely because male venom contains more of the toxins that induce pain. Taken together, our results suggest that identifying the ultimate causes of venom variability will, as we move beyond adaptive storytelling, be hard-won. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and

  4. Arizona bark scorpion venom resistance in the pallid bat, Antrozous pallidus

    PubMed Central

    Hopp, Bradley H.; Arvidson, Ryan S.; Adams, Michael E.; Razak, Khaleel A.

    2017-01-01

    The pallid bat (Antrozous pallidus), a gleaning bat found in the western United States and Mexico, hunts a wide variety of ground-dwelling prey, including scorpions. Anecdotal evidence suggests that the pallid bat is resistant to scorpion venom, but no systematic study has been performed. Here we show with behavioral measures and direct injection of venom that the pallid bat is resistant to venom of the Arizona bark scorpion, Centruroides sculpturatus. Our results show that the pallid bat is stung multiple times during a hunt without any noticeable effect on behavior. In addition, direct injection of venom at mouse LD50 concentrations (1.5 mg/kg) has no effect on bat behavior. At the highest concentration tested (10 mg/kg), three out of four bats showed no effects. One of the four bats showed a transient effect suggesting that additional studies are required to identify potential regional variation in venom tolerance. Scorpion venom is a cocktail of toxins, some of which activate voltage-gated sodium ion channels, causing intense pain. Dorsal root ganglia (DRG) contain nociceptive neurons and are principal targets of scorpion venom toxins. To understand if mutations in specific ion channels contribute to venom resistance, a pallid bat DRG transcriptome was generated. As sodium channels are a major target of scorpion venom, we identified amino acid substitutions present in the pallid bat that may lead to venom resistance. Some of these substitutions are similar to corresponding amino acids in sodium channel isoforms responsible for reduced venom binding activity. The substitution found previously in the grasshopper mouse providing venom resistance to the bark scorpion is not present in the pallid bat, indicating a potentially novel mechanism for venom resistance in the bat that remains to be identified. Taken together, these results indicate that the pallid bat is resistant to venom of the bark scorpion and altered sodium ion channel function may partly underlie

  5. Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study.

    PubMed

    Savi, Eleonora; Incorvaia, Cristoforo; Boni, Elisa; Mauro, Marina; Peveri, Silvia; Pravettoni, Valerio; Quercia, Oliviero; Reccardini, Federico; Montagni, Marcello; Pessina, Laura; Ridolo, Erminia

    2017-01-01

    Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal. We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP). The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom. The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

  6. Arizona bark scorpion venom resistance in the pallid bat, Antrozous pallidus.

    PubMed

    Hopp, Bradley H; Arvidson, Ryan S; Adams, Michael E; Razak, Khaleel A

    2017-01-01

    The pallid bat (Antrozous pallidus), a gleaning bat found in the western United States and Mexico, hunts a wide variety of ground-dwelling prey, including scorpions. Anecdotal evidence suggests that the pallid bat is resistant to scorpion venom, but no systematic study has been performed. Here we show with behavioral measures and direct injection of venom that the pallid bat is resistant to venom of the Arizona bark scorpion, Centruroides sculpturatus. Our results show that the pallid bat is stung multiple times during a hunt without any noticeable effect on behavior. In addition, direct injection of venom at mouse LD50 concentrations (1.5 mg/kg) has no effect on bat behavior. At the highest concentration tested (10 mg/kg), three out of four bats showed no effects. One of the four bats showed a transient effect suggesting that additional studies are required to identify potential regional variation in venom tolerance. Scorpion venom is a cocktail of toxins, some of which activate voltage-gated sodium ion channels, causing intense pain. Dorsal root ganglia (DRG) contain nociceptive neurons and are principal targets of scorpion venom toxins. To understand if mutations in specific ion channels contribute to venom resistance, a pallid bat DRG transcriptome was generated. As sodium channels are a major target of scorpion venom, we identified amino acid substitutions present in the pallid bat that may lead to venom resistance. Some of these substitutions are similar to corresponding amino acids in sodium channel isoforms responsible for reduced venom binding activity. The substitution found previously in the grasshopper mouse providing venom resistance to the bark scorpion is not present in the pallid bat, indicating a potentially novel mechanism for venom resistance in the bat that remains to be identified. Taken together, these results indicate that the pallid bat is resistant to venom of the bark scorpion and altered sodium ion channel function may partly underlie

  7. Venomous snake bites, scorpions, and spiders.

    PubMed

    Kularatne, S A M; Senanayake, Nimal

    2014-01-01

    Neurologic dysfunction due to natural neurotoxins is an important, but neglected, public health hazard in many parts of the world, particularly in the tropics. These toxins are produced by or found among a variety of live forms that include venomous snakes, arthropods such as scorpions, spiders, centipedes, stinging insects (Hymenoptera), ticks, certain poisonous fish, shellfish, crabs, cone shells, skin secretions of dart-poison frogs, and bacterial poisons such as botulinum toxin. These toxins commonly act on neuromuscular transmission at the neuromuscular junction where acetylcholine is the neurotransmitter, but in certain situations the toxins interfere with neurotransmitters such as GABA, noradrenaline, adrenaline, dopamine, and γ-aminobutyrate. Of the toxins, α-toxins and κ-toxins (e.g., Chinese krait, Bungarus multicinctus) act on the postsynaptic membrane, blocking the receptors, whilst β-toxin (e.g., common krait, B. caeruleus) acts on the presynaptic membrane, causing impairment of acetylcholine release. Conversely, dendrotoxins of the African mamba enhance acetylcholine release. The toxins of scorpions and spiders commonly interfere with voltage-gated ion channels. Clinically, the cardinal manifestation is muscle paralysis. In severe cases respiratory paralysis could be fatal. Effective antivenoms are the mainstay of treatment of envenoming, but their lack of availability is the major concern in the regions of the globe where they are desperately needed. Interestingly, some toxins have proved to be valuable pharmaceutical agents, while some others are widely exploited to study neuromuscular physiology and pathology. © 2014 Elsevier B.V. All rights reserved.

  8. Comparative study of the venoms from three species of bees: effects on heart activity and blood.

    PubMed

    Hussein, A A; Nabil, Z I; Zalat, S M; Rakha, M K

    2001-11-01

    Crude venoms from three highly evolved aculeate species: Apis mellifera (highly social bees), Bombus morrisoni (eusocial bees), and Anthophora pauperata (solitary bees), were used for conducting this study to compare the effects of honey bee, bumble bee, and solitary bee venom on toad cardiac muscle activity. In addition, these venoms were tested on rat whole blood in order to determine their ability to induce red blood cell haemolysis. The main toxic effects on isolated toad heart were monitored by ECG after perfusion with different concentrations of each bee venom, and are represented as a decrease in the heart rate (HR) accompanied by an elongation in the P-R interval. A gradual and progressive increase in R-wave amplitude was also noted. Several electrocardiographic changes were noted 5-30 min after envenomation with any of the bee venoms. The mechanism of action of the three bee venoms was determined by direct application of atropine, nicotine, or verapamil to the isolated toad hearts. Comparison of the three venoms revealed that Anthophora pauperata venom is the most effective venom in inducing bradycardia, and it has the strongest negative dromotropic effect. Apis mellifera venom demonstrates the most positive inotropic effect of the three venoms. The effects of bee venom on the blood indices of erythrocyte osmotic fragility (EOF) and plasma albumin levels were studied after incubation of rat blood with each venom. It was noticed that RBCs decreased while Hb content, HCT, MCV, MCH, and MCHC increased, although this change did fluctuate and was not significant. A nonsignificant decrease in EOF was noted after 60 min with any of the venoms used. Incubation of rat whole blood with 1 microg/ml of any of the bee venom solutions revealed a highly significant decrease in plasma albumin levels. It can be concluded that venoms from the three species of bees we tested have negative chronotropic and dromotropic effects on isolated toad heart, with Anthophora pauperata

  9. Preliminary Fractionation of Tiger Rattlesnake (Crotalus tigris) Venom

    DTIC Science & Technology

    1990-01-31

    J., ZEPEDA , 11. and SCtIWARTZMAN, R. J. (1988) Gyroxin, a toxin from the venom of Crot( _ d !1rissus j!2.rificius, is a thrombin-like enzyme. Toxicon...had low protease activity, lacked hemolytic activity and had an i.p. D 5 0 , of 0.070 mg/kg for mice. Lethal fractions obtained by anion and cation...L.. d . Lerrfic and C ihi IU±L WEINSTEIN et al. (1985) reported the presence of a toxin antigenically related to mojave toxin in £, ligris venom. The

  10. Key Issues in Hymenoptera Venom Allergy: An Update.

    PubMed

    Alfaya Arias, T; Soriano Gómis, V; Soto Mera, T; Vega Castro, A; Vega Gutiérrez, J M; Alonso Llamazares, A; Antolín Amérigo, D; Carballada Gonzalez, F J; Dominguez Noche, C; Gutierrez Fernandez, D; Marques Amat, L; Martinez Arcediano, A; Martinez San Ireneo, M; Moreno Ancillo, A; Puente Crespo, Y; Ruiz Leon, B; Sánchez Morillas, L

    In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

  11. Bioactive Mimetics of Conotoxins and other Venom Peptides

    PubMed Central

    Duggan, Peter J.; Tuck, Kellie L.

    2015-01-01

    Ziconotide (Prialt®), a synthetic version of the peptide ω-conotoxin MVIIA found in the venom of a fish-hunting marine cone snail Conus magnus, is one of very few drugs effective in the treatment of intractable chronic pain. However, its intrathecal mode of delivery and narrow therapeutic window cause complications for patients. This review will summarize progress in the development of small molecule, non-peptidic mimics of Conotoxins and a small number of other venom peptides. This will include a description of how some of the initially designed mimics have been modified to improve their drug-like properties. PMID:26501323

  12. Venom gland transcriptomic and venom proteomic analyses of the scorpion Megacormus gertschi Díaz-Najera, 1966 (Scorpiones: Euscorpiidae: Megacorminae).

    PubMed

    Santibáñez-López, Carlos E; Cid-Uribe, Jimena I; Zamudio, Fernando Z; Batista, Cesar V F; Ortiz, Ernesto; Possani, Lourival D

    2017-07-01

    The soluble venom from the Mexican scorpion Megacormus gertschi of the family Euscorpiidae was obtained and its biological effects were tested in several animal models. This venom is not toxic to mice at doses of 100 μg per 20 g of mouse weight, while being lethal to arthropods (insects and crustaceans), at doses of 20 μg (for crickets) and 100 μg (for shrimps) per animal. Samples of the venom were separated by high performance liquid chromatography and circa 80 distinct chromatographic fractions were obtained from which 67 components have had their molecular weights determined by mass spectrometry analysis. The N-terminal amino acid sequence of seven protein/peptides were obtained by Edman degradation and are reported. Among the high molecular weight components there are enzymes with experimentally-confirmed phospholipase activity. A pair of telsons from this scorpion species was dissected, from which total RNA was extracted and used for cDNA library construction. Massive sequencing by the Illumina protocol, followed by de novo assembly, resulted in a total of 110,528 transcripts. From those, we were able to annotate 182, which putatively code for peptides/proteins with sequence similarity to previously-reported venom components available from different protein databases. Transcripts seemingly coding for enzymes showed the richest diversity, with 52 sequences putatively coding for proteases, 20 for phospholipases, 8 for lipases and 5 for hyaluronidases. The number of different transcripts potentially coding for peptides with sequence similarity to those that affect ion channels was 19, for putative antimicrobial peptides 19, and for protease inhibitor-like peptides, 18. Transcripts seemingly coding for other venom components were identified and described. The LC/MS analysis of a trypsin-digested venom aliquot resulted in 23 matches with the translated transcriptome database, which validates the transcriptome. The proteomic and transcriptomic analyses

  13. Jellyfish venomics and venom gland transcriptomics analysis of Stomolophus meleagris to reveal the toxins associated with sting.

    PubMed

    Li, Rongfeng; Yu, Huahua; Xue, Wei; Yue, Yang; Liu, Song; Xing, Ronge; Li, Pengcheng

    2014-06-25

    Jellyfish Stomolophus meleagris is a very dangerous animal because of its strong toxicity. However, the composition of the venom is still unclear. Both proteomics and transcriptomics approaches were applied in present study to investigate the major components and their possible relationships to the sting. The proteomics of the venom from S. meleagris was conducted by tryptic digestion of the crude venom followed by RP-HPLC separation and MS/MS analysis of the tryptic peptides. The venom gland transcriptome was analyzed using a high-throughput Illumina sequencing platform HiSeq 2000 with de novo assembly. A total of 218 toxins were identified including C-type lectin, phospholipase A₂ (PLA₂), potassium channel inhibitor, protease inhibitor, metalloprotease, hemolysin and other toxins, most of which should be responsible for the sting. Among them, serine protease inhibitor, PLA₂, potassium channel inhibitor and metalloprotease are predominant, representing 28.44%, 21.56%, 16.06% and 15.14% of the identified venom proteins, respectively. Overall, our combined proteomics and transcriptomics approach provides a systematic overview of the toxins in the venom of jellyfish S. meleagris and it will be significant to understand the mechanism of the sting. Jellyfish Stomolophus meleagris is a very dangerous animal because of its strong toxicity. It often bloomed in the coast of China in recent years and caused thousands of people stung and even deaths every year. However, the components which caused sting are still unknown yet. In addition, no study about the venomics of jellyfish S. meleagris has been reported. In the present study, both proteomics and transcriptomics approaches were applied to investigate the major components related to the sting. The result showed that major component included C-type lectin, phospholipase A₂, potassium channel inhibitor, protease inhibitor, metalloprotease, hemolysin and other toxins, which should be responsible for the effect of

  14. Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

    PubMed Central

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

    2015-01-01

    Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

  15. Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms.

    PubMed

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

    2015-10-01

    Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell's viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic type 2 (Th2) immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Unveiling the elusive and exotic: Venomics of the Malayan blue coral snake (Calliophis bivirgata flaviceps).

    PubMed

    Tan, Choo Hock; Fung, Shin Yee; Yap, Michelle Khai Khun; Leong, Poh Kuan; Liew, Jia Lee; Tan, Nget Hong

    2016-01-30

    The venom proteome of the Malayan blue coral snake, Calliophis bivirgata flaviceps from west Malaysia was investigated by 1D-SDS-PAGE and shotgun-LCMS/MS. A total of 23 proteins belonging to 11 protein families were detected from the venom proteome. For the toxin proteins, the venom consists mainly of phospholipase A2 (41.1%), cytotoxin (22.6%), SVMPs (18.7%) and vespryns (14.6%). However, in contrast to the venoms of New World coral snakes and most elapids, there was no post-synaptic α-neurotoxin detected. The proteome also revealed a relatively high level of phosphodiesterase (1.3%), which may be associated with the reported high level of adenosine in the venom. Also detected were 5'-nucleotidase (0.3%), hyaluronidase (0.1%) and cysteine-type endopeptide inhibitor (0.6%). Enzymatic studies confirmed the presence of phospholipase A2, phosphodiesterase, 5'-nucleotidase and acetylcholinesterase activities but not l-amino acid oxidase activity. The venom exhibited moderate cytotoxic activity against CRL-2648 fibroblast cell lines (IC50=62.14±0.87 μg/mL) and myotoxicity in mice, presumably due to the action of its cytotoxin or its synergistic action with phospholipase A2. Interestingly, the venom lethality could be cross-neutralized by a neurotoxic bivalent antivenom from Taiwan. Together, the findings provide insights into the composition and functions of the venom of this exotic oriental elapid snake. While venoms of the New World coral snake have been extensively studied, literature pertaining to the Old World or Asiatic coral snake venoms remains lacking. This could be partly due to the inaccessibility to the venom of this rare species and infrequent cases of envenomation reported. This study identified and profiled the venom proteome of the Malayan blue coral snake (C. b. flaviceps) through SDS-PAGE and a high-resolution nano-LCMS/MS method, detailing the types and abundance of proteins found in the venom. The biological and toxic activities of the venom were

  17. Comparative Studies of the Venom of a New Taipan Species, Oxyuranus temporalis, with Other Members of Its Genus

    PubMed Central

    Barber, Carmel M.; Madaras, Frank; Turnbull, Richard K.; Morley, Terry; Dunstan, Nathan; Allen, Luke; Kuchel, Tim; Mirtschin, Peter; Hodgson, Wayne C.

    2014-01-01

    Taipans are highly venomous Australo-Papuan elapids. A new species of taipan, the Western Desert Taipan (Oxyuranus temporalis), has been discovered with two specimens housed in captivity at the Adelaide Zoo. This study is the first investigation of O. temporalis venom and seeks to characterise and compare the neurotoxicity, lethality and biochemical properties of O. temporalis venom with other taipan venoms. Analysis of O. temporalis venom using size-exclusion and reverse-phase HPLC indicated a markedly simplified “profile” compared to other taipan venoms. SDS-PAGE and agarose gel electrophoresis analysis also indicated a relatively simple composition. Murine LD50 studies showed that O. temporalis venom is less lethal than O. microlepidotus venom. Venoms were tested in vitro, using the chick biventer cervicis nerve-muscle preparation. Based on t90 values, O. temporalis venom is highly neurotoxic abolishing indirect twitches far more rapidly than other taipan venoms. O. temporalis venom also abolished responses to exogenous acetylcholine and carbachol, indicating the presence of postsynaptic neurotoxins. Prior administration of CSL Taipan antivenom (CSL Limited) neutralised the inhibitory effects of all taipan venoms. The results of this study suggest that the venom of the O. temporalis is highly neurotoxic in vitro and may contain procoagulant toxins, making this snake potentially dangerous to humans. PMID:24992081

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

    PubMed Central

    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

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

    PubMed Central

    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

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

    PubMed

    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.

  1. Differences in venom toxicity and antigenicity between females and males Tityus nororientalis (Buthidae) scorpions

    PubMed Central

    De Sousa, Leonardo; Borges, Adolfo; Vásquez-Suárez, Aleikar; Op den Camp, Huub JM; Chadee-Burgos, Rosa I; Romero-Bellorín, Mirna; Espinoza, Jorge; De Sousa-Insana, Leonardo; Pino-García, Oscar

    2010-01-01

    Venom from male and female specimens of the medically important Venezuelan scorpion Tityus nororientalis have been compared. Males showed a significantly higher venom yield (2.39mg/individual) compared to female scorpions (0.98mg/individual). Female venom was significantly more toxic than that of males, with a median lethal dose (LD50) in C57BL/6 mice of 9.46 μg venom protein/gm body weight [95% confidence interval (8.91-9.94)] whereas LD50 for males was 13.36(12.58-14.03) μg/gm. Mass spectral analyses by MALDI-TOF revealed differences in venom composition between males and females. From a clinical standpoint, the time course of toxicity course indicated a tendency, in the case of the female venom, to elicit the earlier occurrence of severe signs such as sialorrhea, dyspnea (bradypnea/apnea) and exophthalmus particularly in the late toxicity phase. Female venom was significantly less efficient than male venom to inhibit the binding of anti-T. discrepans antibodies to immobilized T. discrepans venom in ELISA assays, suggesting sex-related differences in the bioactive surfaces of T. nororientalis toxins. These results indicate that males and females of T. nororientalis produce venoms with different composition and activity which may have epidemiological implications. PMID:21544184

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

    PubMed

    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.

  3. VENOM VARIATION IN HEMOSTASIS OF THE SOUTHERN PACIFIC RATTLESNAKE (Crotalus oreganus helleri): ISOLATION OF HELLERASE

    PubMed Central

    Salazar, Ana Maria; Guerrero, Belsy; Cantu, Bruno; Cantu, Esteban; Rodríguez-Acosta, Alexis; Pérez, John C.; Galán, Jacob A.; Tao, Andy; Sánchez, Elda E.

    2009-01-01

    Envenomations by the Southern Pacific Rattlesnake (Crotalus oreganus helleri) are the most common snakebite accidents in southern California. Intraspecies venom variation may lead to unresponsiveness of antivenom therapy. Even in a known species, venom toxins are recognized as diverse in conformity with interpopulational, seasonal, ontogenetic and individual factors. Five venoms of individual C. o. helleri located in Riverside and San Bernardino counties of southern California were studied for their variation in their hemostasis activity. The results demonstrated that Riverside 2 and San Bernardino 1 venoms presented the highest lethal activity without hemorrhagic activity. In contrast, San Bernardino 2 and 3 venoms had the highest hemorrhagic and fibrinolytic activities with low lethal and coagulant activities. Riverside 1, Riverside 2 and San Bernardino 1 venoms presented a significant thrombin-like activity. San Bernardino 2 and 3 venoms presented an insignificant thrombin-like activity. In relation to the fibrinolytic activity, San Bernardino 3 venom was the most active on fibrin plates, which was in turn neutralized by metal chelating inhibitors. These results demonstrate the differences amongst C. o helleri venoms from close localities. A metalloproteinase, hellerase, was purified by anionic and cationic exchange chromatography from San Bernardino 3 venom. Hellerase exhibited the ability to break fibrin clots in vitro, which can be of biomedically importance in the treatment of heart attacks and strokes. PMID:18804187

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

    PubMed

    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.

  5. Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

    PubMed Central

    Jansa, Sharon A.; Voss, Robert S.

    2011-01-01

    The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae) and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role. PMID:21731638

  6. Venomics of Remipede Crustaceans Reveals Novel Peptide Diversity and Illuminates the Venom’s Biological Role

    PubMed Central

    von Reumont, Björn M.; Undheim, Eivind A. B.; Jauss, Robin-Tobias; Jenner, Ronald A.

    2017-01-01

    We report the first integrated proteomic and transcriptomic investigation of a crustacean venom. Remipede crustaceans are the venomous sister group of hexapods, and the venom glands of the remipede Xibalbanus tulumensis express a considerably more complex cocktail of proteins and peptides than previously thought. We identified 32 venom protein families, including 13 novel peptide families that we name xibalbins, four of which lack similarities to any known structural class. Our proteomic data confirm the presence in the venom of 19 of the 32 families. The most highly expressed venom components are serine peptidases, chitinase and six of the xibalbins. The xibalbins represent Inhibitory Cystine Knot peptides (ICK), a double ICK peptide, peptides with a putative Cystine-stabilized α-helix/β-sheet motif, a peptide similar to hairpin-like β-sheet forming antimicrobial peptides, two peptides related to different hormone families, and four peptides with unique structural motifs. Remipede venom components represent the full range of evolutionary recruitment frequencies, from families that have been recruited into many animal venoms (serine peptidases, ICKs), to those having a very narrow taxonomic range (double ICKs), to those unique for remipedes. We discuss the most highly expressed venom components to shed light on their possible functional significance in the predatory and defensive use of remipede venom, and to provide testable ideas for any future bioactivity studies. PMID:28933727

  7. Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins

    PubMed Central

    Hargreaves, Adam D.; Swain, Martin T.; Hegarty, Matthew J.; Logan, Darren W.; Mulley, John F.

    2014-01-01

    Snake venom has been hypothesized to have originated and diversified through a process that involves duplication of genes encoding body proteins with subsequent recruitment of the copy to the venom gland, where natural selection acts to develop or increase toxicity. However, gene duplication is known to be a rare event in vertebrate genomes, and the recruitment of duplicated genes to a novel expression domain (neofunctionalization) is an even rarer process that requires the evolution of novel combinations of transcription factor binding sites in upstream regulatory regions. Therefore, although this hypothesis concerning the evolution of snake venom is very unlikely and should be regarded with caution, it is nonetheless often assumed to be established fact, hindering research into the true origins of snake venom toxins. To critically evaluate this hypothesis, we have generated transcriptomic data for body tissues and salivary and venom glands from five species of venomous and nonvenomous reptiles. Our comparative transcriptomic analysis of these data reveals that snake venom does not evolve through the hypothesized process of duplication and recruitment of genes encoding body proteins. Indeed, our results show that many proposed venom toxins are in fact expressed in a wide variety of body tissues, including the salivary gland of nonvenomous reptiles and that these genes have therefore been restricted to the venom gland following duplication, not recruited. Thus, snake venom evolves through the duplication and subfunctionalization of genes encoding existing salivary proteins. These results highlight the danger of the elegant and intuitive “just-so story” in evolutionary biology. PMID:25079342

  8. Mechanism of action of honey bee (Apis mellifera L.) venom on different types of muscles.

    PubMed

    Nabil, Z I; Hussein, A A; Zalat, S M; Rakha, M Kh

    1998-03-01

    1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as well as cardiac muscles were studied in this investigation. 2. Perfusion of gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom solution has weakened the mechanical contraction of the muscle without recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom application sustained normal contraction of gastrocnemius muscle. 3. The electrical activity of duodenum rabbits was recorded before and after the application of 1 microgram/ml venom solution. The venom has depressed the amplitude of the muscle contraction after 15 min pretreatment with atropine nearly abolished the depressor effect of the venom on smooth muscle. 4. In concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate of isolated perfused toad heart. This bradycardia was accompanied by elongation in the P-R interval. A gradual and progressive increase in the R-wave amplitude reflected a positive inotropism of the venom. Application of 5 micrograms/ml verapamil, a calcium channels blocking agent, abolished the noticed effect of the venom. 5. Marked electrocardiographic changes were produced within minutes of the venom application on the isolated perfused hearts, like marked injury current (elevation or depression of the S-T segment), atrioventricular conduction disturbances and sinus arrhythmias. Atropine and nicotine could decrease the toxic effect of the venom on the myocardium. 6. Results of the present work lead to the suggestion that bee venom is mediated through the peripheral cholinergic neurotransmitter system. General neurotoxicity of an inhibitory nature involving the autonomic as well as neuromuscular system are established as a result of the venom, meanwhile a direct effect on the myocardium membrane stabilization has been suggested.

  9. Biological and Proteolytic Variation in the Venom of Crotalus scutulatus scutulatus from Mexico.

    PubMed

    Borja, Miguel; Neri-Castro, Edgar; Castañeda-Gaytán, Gamaliel; Strickland, Jason L; Parkinson, Christopher L; Castañeda-Gaytán, Juan; Ponce-López, Roberto; Lomonte, Bruno; Olvera-Rodríguez, Alejandro; Alagón, Alejandro; Pérez-Morales, Rebeca

    2018-01-08

    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.

  10. Biological and Proteolytic Variation in the Venom of Crotalus scutulatus scutulatus from Mexico

    PubMed Central

    Castañeda-Gaytán, Gamaliel; Castañeda-Gaytán, Juan; Ponce-López, Roberto; Olvera-Rodríguez, Alejandro; Alagón, Alejandro; Pérez-Morales, Rebeca

    2018-01-01

    Rattlesnake venoms may be classified according to the presence/absence and relative abundance of the neurotoxic phospholipases A2s (PLA2s), 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 LD50 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. PMID:29316683

  11. [Cross reactions between Hymenoptera venoms from different families, genera and species].

    PubMed

    Hemmer, W

    2014-09-01

    Simultaneous reactivity with the venoms of different Hymenoptera is commonly seen in patients allergic to insect venoms. Strong, though individually variable, cross-reactivity occurs between the venoms of different Vespinae species (Vespula, Dolichovespula, Vespa). In Middle Europe, anaphylaxis after European hornet stings is nearly always due to cross-reactivity with Vespula venom. The identification of the primary venom in patients testing positive for Vespula and Polistes (paper wasps) is particularly important in Mediterranean areas. Component-resolved diagnosis with the marker allergens Ves v 5 and Pol d 5 may directly identify the causative venom in the majority of patients. There is substantial cross-reactivity between honeybee and bumblebee venom, sometimes causing allergic symptoms in patients allergic to honeybee venom after accidental bumblebee stings. However, subjects strongly exposed to bumblebees may show bumblebee-specific sensitization and require immunotherapy with bumblebee venom. More than half of all venom-allergic patients show double-positive test results to honeybee and vespid venoms. This may be due to true double sensitization or due to cross-reactivity between homologous allergens present in both venoms and sharing around 50 % sequence identity, i.e. hyaluronidases (Api m 2/Ves v 2), dipeptidyl peptidases (Api m 5/Ves v 3), and vitellogenins (Api m 12/Ves v 6). The clinical relevance of these cross-reactions is unknown. In up to 50 % the double-positivity is caused by clinically irrelevant IgE antibodies against CCDs. Many (though not all) patients with true double sensitization may be identified by means of the species-specific marker allergens Api m 1 and Ves v 1/5. Some Vespula venom-allergic patients may clinically cross-react to fire ant stings (Solenopsis), but otherwise allergen relationships with other ant species are not well studied.

  12. Molecular Diversity and Gene Evolution of the Venom Arsenal of Terebridae Predatory Marine Snails

    PubMed Central

    Gorson, Juliette; Ramrattan, Girish; Verdes, Aida; Wright, Elizabeth M.; Kantor, Yuri; Rajaram Srinivasan, Ramakrishnan; Musunuri, Raj; Packer, Daniel; Albano, Gabriel; Qiu, Wei-Gang; Holford, Mandë

    2015-01-01

    Venom peptides from predatory organisms are a resource for investigating evolutionary processes such as adaptive radiation or diversification, and exemplify promising targets for biomedical drug development. Terebridae are an understudied lineage of conoidean snails, which also includes cone snails and turrids. Characterization of cone snail venom peptides, conotoxins, has revealed a cocktail of bioactive compounds used to investigate physiological cellular function, predator-prey interactions, and to develop novel therapeutics. However, venom diversity of other conoidean snails remains poorly understood. The present research applies a venomics approach to characterize novel terebrid venom peptides, teretoxins, from the venom gland transcriptomes of Triplostephanus anilis and Terebra subulata. Next-generation sequencing and de novo assembly identified 139 putative teretoxins that were analyzed for the presence of canonical peptide features as identified in conotoxins. To meet the challenges of de novo assembly, multiple approaches for cross validation of findings were performed to achieve reliable assemblies of venom duct transcriptomes and to obtain a robust portrait of Terebridae venom. Phylogenetic methodology was used to identify 14 teretoxin gene superfamilies for the first time, 13 of which are unique to the Terebridae. Additionally, basic local algorithm search tool homology-based searches to venom-related genes and posttranslational modification enzymes identified a convergence of certain venom proteins, such as actinoporin, commonly found in venoms. This research provides novel insights into venom evolution and recruitment in Conoidean predatory marine snails and identifies a plethora of terebrid venom peptides that can be used to investigate fundamental questions pertaining to gene evolution. PMID:26025559

  13. Cobra venom cytotoxins; apoptotic or necrotic agents?

    PubMed

    Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

    2015-12-15

    Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Purification of NAD glycohydrolase from Agkistrodon acutus venom.

    PubMed

    Wu, Shuang Ding; Liu, Yanli; Xu, Xiaolong; Zhu, Zhengang

    2002-07-01

    NAD glycohydrolase (NADase) from Agkistrodon acutus venom was purified to electrophoretic homogeneity by a fast, reproducible 3-step procedure including Q Sepharose Fast Flow, Superdex 75, and Mono S column chromatography. This new procedure gave a 15.6-fold purification with a recovery yield of 7.9% and a specific activity of 12.8 units/mg.

  15. Deaths From Bites and Stings of Venomous Animals

    PubMed Central

    Ennik, Franklin

    1980-01-01

    Data abstracted from 34 death certificates indicate that the three venomous animal groups most often responsible for human deaths in California from 1960 through 1976 were Hymenoptera (bees, wasps, ants and the like) (56 percent), snakes (35 percent) and spiders (6 percent). An average incidence of 2.0 deaths per year occurred during these 17 years, or an average death rate of 0.01 per 100,000 population per year. Nearly three times more males than females died of venomous animal bites and stings. Half of the deaths from venomous snake bites occurred in children younger than 5 years of age. Susceptible persons 40 years or older appeared to be particularly vulnerable to hymenopterous insect stings and often quickly died of anaphylaxis. Fatal encounters with venomous animals occurred more often around the home than at places of employment or during recreational activities. Deaths resulting from spider bites are rare in California but many bites are reported. Medical practitioners are urged to seek professional assistance in identifying offending animals causing human discomfort and to use these animals' scientific names on death certificates and in journal articles. ImagesIGN. PMID:7467305

  16. Snake venoms from Angola: Intra-specific variations and immunogenicity.

    PubMed

    Oliveira, Paula Regina Simões de; França, Felipe Silva de; Villas Boas, Isadora Maria; Rocha, Marisa Maria Teixeira da; Sant'Anna, Sávio Stefanini; Bastos, Maria de Lourdes; Tambourgi, Denise V

    2018-06-15

    Snakebite is a public health problem in many countries of world. These accidents are considered a Neglected Tropical Disease and are responsible for a high morbidity and mortality index in the South and Southeast Asia and Sub-Saharan Africa. Angolan snake venoms are poorly investigated and no specific antivenom against them is available in the country. Thus, the aim of this study was to evaluate biochemical and immunogenic properties of male and female venoms from Naja nigricollis, Bitis arietans and Bitis gabonica snakes. These animals were collected during an expedition covering 1350 km of Angola, including the Provinces of Cuanza Sul, Benguela, Huíla and Malanje. Results showed that Angolan snake venoms present distinctive immunogenic properties and large intra-specific variations, associated to the gender and the geographic origin of the animals. Thus, it is possible to suggest that for the preparation of a therapeutic antivenom, intra-species variability should be taken into account, in order to obtain an efficient serum to neutralize the toxic effects of the Angolan snake venoms. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges

    PubMed Central

    Bastos, Viviane A.; Gomes-Neto, Francisco; Perales, Jonas; Neves-Ferreira, Ana Gisele C.; Valente, Richard H.

    2016-01-01

    The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using “gold-standard” methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted. PMID:27571103

  18. Factor V activation and inactivation by venom proteases.

    PubMed

    Rosing, J; Govers-Riemslag, J W; Yukelson, L; Tans, G

    2001-01-01

    Blood coagulation factor V is a single-chain glycoprotein with M(r) = 330,000 which plays an important role in the procoagulant and anticoagulant pathways. Thrombin activates factor V into factor Va, a two-chain molecule which is composed of a heavy (M(r) = 105,000) and a light chain (M(r) = 71,000/74,000). Factor Va accelerates factor Xa-catalysed prothrombin activation more than 1,000-fold and under physiological conditions the cofactor activity of factor Va in prothrombin activation is down-regulated by activated protein C. Factor V can also be activated by a wide variety of snake venoms (e.g. from Vipera species, Naja naja oxiana, Bothrops atrox) and by proteases present in the bristles of a South American caterpillar (Lonomia achelous). Some venoms, notably of Vipera lebetina turanica and Lonomia achelous, contain proteases that are able to inactivate factor V or factor Va. Venom factor V activators are excellent tools in studying the structure-function relationship of factor V(a) and they are also used in diagnostic tests for quantification of plasma factor V levels and for the screening of defects in the protein C pathway. In this review, the structural and functional properties of animal venom factor V activators and inactivators is described. Copyright 2002 S. Karger AG, Basel

  19. Hemolytic venoms from marine cnidarian jellyfish – an overview

    PubMed Central

    Mariottini, Gian Luigi

    2014-01-01

    Cnidarian jellyfish are viewed as an emergent problem in several coastal zones throughout the world. Recurrent outbreaks pose a serious threat to tourists and bathers, as well as to sea-workers, involving health and economical aspects. As a rule, cnidarian stinging as a consequence of nematocyst firing induces merely local symptoms but cardiovascular or neurological complications can also occur. Hemolysis is a frequent effect of cnidarian stinging; this dangerous condition is known to be caused by several venoms and can sometimes be lethal. At present, the bulk of data concerning hemolytic cnidarian venoms comes from the study of benthic species, such as sea anemones and soft corals, but hemolytic factors were found in venoms of several siphonophore, cubozoan and scyphozoan jellyfish, which are mainly involved in the envenomation of bathers and sea-workers. Therefore, the aim of this paper is to review the scientific literature concerning the hemolytic venoms from cnidarian jellyfish taking into consideration their importance in human pathology as well as health implications and possible therapeutic measures. PMID:25386336

  20. Hemolytic venoms from marine cnidarian jellyfish - an overview.

    PubMed

    Mariottini, Gian Luigi

    2014-01-01

    Cnidarian jellyfish are viewed as an emergent problem in several coastal zones throughout the world. Recurrent outbreaks pose a serious threat to tourists and bathers, as well as to sea-workers, involving health and economical aspects. As a rule, cnidarian stinging as a consequence of nematocyst firing induces merely local symptoms but cardiovascular or neurological complications can also occur. Hemolysis is a frequent effect of cnidarian stinging; this dangerous condition is known to be caused by several venoms and can sometimes be lethal. At present, the bulk of data concerning hemolytic cnidarian venoms comes from the study of benthic species, such as sea anemones and soft corals, but hemolytic factors were found in venoms of several siphonophore, cubozoan and scyphozoan jellyfish, which are mainly involved in the envenomation of bathers and sea-workers. Therefore, the aim of this paper is to review the scientific literature concerning the hemolytic venoms from cnidarian jellyfish taking into consideration their importance in human pathology as well as health implications and possible therapeutic measures.

  1. Assessment of the potential toxicological hazard of the Green Parrot Snake (Leptophis ahaetulla marginatus): Characterization of its venom and venom-delivery system.

    PubMed

    Sánchez, Matías N; Teibler, Gladys P; López, Carlos A; Mackessy, Stephen P; Peichoto, María E

    2018-04-27

    Snakes are the major group of venomous vertebrates, and the rear-fanged snakes represent the vast majority of species and occur worldwide; however, relatively few studies have characterized their venoms and evaluated their potential hazards for humans. Herein we explore the protein composition and properties of the venom of the rear-fanged Green Parrot Snake, Leptophis ahaetulla marginatus, the most common snake found in the Iguazu National Park (Argentina), as well as the main features of its venom delivery system. This species has venom reminiscent of elapid venoms, composed mainly of components such as 3FTxs, CRiSPs and AChE, but it shows low toxicity toward mammals (LD 50  > 20 μg/g mouse). The histology of its Duvernoy's venom gland is similar to that of other colubrids, with serous secretory cells arranged in densely packed secretory tubules. The posterior end of its maxilla exhibits 1-3 blade-shaped and slightly recurved fangs but without grooves. This study provides an initial analysis of the biological role of venom in Leptophis, with implications for potential symptoms that might be anticipated from bites by this species. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components.

    PubMed

    Santibáñez-López, Carlos E; Cid-Uribe, Jimena I; Batista, Cesar V F; Ortiz, Ernesto; Possani, Lourival D

    2016-12-09

    Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis . The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated. We annotated 135 transcripts putatively coding for peptides with identity to known venom components available from different protein databases. Fresh venom collected by electrostimulation was analyzed by LC-MS/MS allowing the identification of 26 distinct components with sequences matching counterparts from the transcriptomic analysis. In addition, the phylogenetic affinities of the found putative calcins, scorpines, La1-like peptides and potassium channel κ toxins were analyzed. The first three components are often reported as ubiquitous in the venom of different families of scorpions. Our results suggest that, at least calcins and scorpines, could be used as molecular markers in phylogenetic studies of scorpion venoms.

  3. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components

    PubMed Central

    Santibáñez-López, Carlos E.; Cid-Uribe, Jimena I.; Batista, Cesar V. F.; Ortiz, Ernesto; Possani, Lourival D.

    2016-01-01

    Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis. The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated. We annotated 135 transcripts putatively coding for peptides with identity to known venom components available from different protein databases. Fresh venom collected by electrostimulation was analyzed by LC-MS/MS allowing the identification of 26 distinct components with sequences matching counterparts from the transcriptomic analysis. In addition, the phylogenetic affinities of the found putative calcins, scorpines, La1-like peptides and potassium channel κ toxins were analyzed. The first three components are often reported as ubiquitous in the venom of different families of scorpions. Our results suggest that, at least calcins and scorpines, could be used as molecular markers in phylogenetic studies of scorpion venoms. PMID:27941686

  4. Rapid Hymenoptera venom immunotherapy: comparative safety of three protocols.

    PubMed

    Birnbaum, J; Charpin, D; Vervloet, D

    1993-03-01

    We compared 284 sting-allergic patients treated with either a 4 day (group 1), 6 hr (group 2) or 210 min (group 3) rapid venom immunotherapy (RVIT) protocol using honey bee (HB) or yellow jacket (YJ) venom at cumulative doses of 527.6 micrograms, 226.6 micrograms and 101.1 micrograms respectively. The 4 day protocol involved four times as many injections as the 210 min protocol and twice as many as the 6 hr protocol. Desensitization was conducted in a hospital providing full emergency resuscitation facilities. In group 1, 1 x 100 micrograms boosters were given on days 7, 10, 15 and 45 and, in groups 2 and 3, 2 x 50 micrograms boosters were given on day 15 and 1 x 100 micrograms on day 45. The patients in the three groups were comparable with regard to clinical characteristics and immunological reactivity determined by skin tests. All patients had large local reactions. Systemic reactions (SR) occurred in 28.2% of patients in group 1, 28.6% in group 2 and 6.9% in group 3. The mean total cumulative venom dose (s.e.m.) for occurrence of SR was 123.75 (+/- 24.2) in group 1, 183.27 (+/- 28.5) in group 2, and 36.43 (+/- 9.3) in group 3. HB led to more systemic reactions than YJ venom. The rate of SR decreased when the cumulative venom dose was reduced during RVIT. The median dose was 137.6 micrograms in group 1, 226.6 micrograms in group 2, and 21.1 micrograms in group 3. No systemic reactions were observed after the booster injections. The results of this study suggest that short RVIT protocols with low cumulative doses carry a lesser risk of SR.

  5. Safety profile of hymenoptera venom immunotherapy (VIT) in monosensitized patients: lack of new sensitization to nontreated insect venom.

    PubMed

    Spoerl, D; Bircher, A J; Scherer, K

    2011-01-01

    Venom immunotherapy (VIT) has proven to be efficacious in reducing the severity of anaphylactic reactions following field stings in patients with Hymenoptera venom allergy. Due to sequence homologies in the allergens used in Hymenoptera vaccines, there is concern that immunotherapy could lead to sensitization to allergens to which patients were not previously sensitized. The relevance of such an undesired phenomenon is unclear. To investigate the incidence of sensitization to Hymenoptera venoms other than those to which the patients were already sensitized and to assess the overall safety profile of VIT in order to compare the risk-benefit ratio in a subpopulation of monosensitized individuals. We performed a retrospective analysis of specific immunoglobulin E (sIgE) levels in patients with no prior detectable sIgE to Hymenoptera venom other than the one for which they received VIT. We assessed the safety profile of VIT using serological and clinical parameters. Of the 56 monosensitized patients who had VIT, 3 (5%) developed sIgE to the other insect with no history of field sting to explain it. This rate was similar to the rate of new sensitization due to field stings during VIT. VIT was well-tolerated and levels of serological markers improved. No patient had a systemic anaphylactic reaction after having been stung by an insect other than the one he/she was desensitized for during follow-up. VIT seems to be safe with respect to clinically significant new sensitizations.

  6. Biological and molecular properties of yellow venom of the Amazonian coral snake Micrurus surinamensis.

    PubMed

    Oliveira, Fabiana da Rocha; Noronha, Maria das Dores Nogueira; Lozano, Jorge Luis Lopez

    2017-01-01

    The coral snake Micrurus surinamensis, which is widely distributed throughout Amazonia, has a neurotoxic venom. It is important to characterize the biological and molecular properties of this venom in order to develop effective antitoxins. Toxins from the venom of M. surinamensis were analyzed by two-dimensional polyacrylamide gel electrophoresis and their neurotoxic effects in vivo were evaluated. Most proteins in the venom had masses < 14kDa, low phospholipase A2 activity, and no proteolytic activity. The toxins inhibited the coagulation cascade. The venom had neurotoxic effects in mice, with a median lethal dose upon intravenous administration of 700 µg/kg. Immunogenic studies revealed abundant cross-reactivity of antielapidic serum with 14kDa toxins and limited cross-reactivity with toxins < 10kDa. These results indicate that antielapidic serum against M. surinamensis venom has weak potency (0.35mg/ml) in mice.

  7. Inactivation of Crotalus atrox venom hemorrhagic activity by direct current exposure using hens' egg assay.

    PubMed

    Calzia, Daniela; Ravera, Silvia; Aluigi, Maria Grazia; Falugi, Carla; Morelli, Alessandro; Panfoli, Isabella

    2011-01-01

    The hemotoxic venoms of Viperidae and Crotalidae are responsible for most of the evenomations in the United States, West Africa, India, South-East Asia, New Guinea, and Latin America. We previously reported that a short exposure of Crotalus atrox venom to direct electric current (dc) from a low-voltage generator, in solution, causes consistent and irreversible inactivation of venom phospholipase A(2) and metalloproteases. Here we report by in vivo assay on chicken embryos at stage 18 of development according to Hamburger and Hamilton that the hemorrhagic activity of C. atrox venom is lost after exposure to dc (from low voltage). Venom was exposed to dc ranging between 0 and 1 mA. dc values above 0.7 mA abolished hemorrhage. Such in vivo data, showing that dc neutralizes C. atrox venom hemorrhagic activity suggest that a deeper knowledge is needed to understand the relationship among dc and biological matter. Copyright © 2011 Wiley Periodicals, Inc.

  8. Spider genomes provide insight into composition and evolution of venom and silk

    PubMed Central

    Sanggaard, Kristian W.; Bechsgaard, Jesper S.; Fang, Xiaodong; Duan, Jinjie; Dyrlund, Thomas F.; Gupta, Vikas; Jiang, Xuanting; Cheng, Ling; Fan, Dingding; Feng, Yue; Han, Lijuan; Huang, Zhiyong; Wu, Zongze; Liao, Li; Settepani, Virginia; Thøgersen, Ida B.; Vanthournout, Bram; Wang, Tobias; Zhu, Yabing; Funch, Peter; Enghild, Jan J.; Schauser, Leif; Andersen, Stig U.; Villesen, Palle; Schierup, Mikkel H; Bilde, Trine; Wang, Jun

    2014-01-01

    Spiders are ecologically important predators with complex venom and extraordinarily tough silk that enables capture of large prey. Here we present the assembled genome of the social velvet spider and a draft assembly of the tarantula genome that represent two major taxonomic groups of spiders. The spider genomes are large with short exons and long introns, reminiscent of mammalian genomes. Phylogenetic analyses place spiders and ticks as sister groups supporting polyphyly of the Acari. Complex sets of venom and silk genes/proteins are identified. We find that venom genes evolved by sequential duplication, and that the toxic effect of venom is most likely activated by proteases present in the venom. The set of silk genes reveals a highly dynamic gene evolution, new types of silk genes and proteins, and a novel use of aciniform silk. These insights create new opportunities for pharmacological applications of venom and biomaterial applications of silk. PMID:24801114

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

    PubMed

    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.

  10. Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.

    PubMed

    Haney, Robert A; Ayoub, Nadia A; Clarke, Thomas H; Hayashi, Cheryl Y; Garb, Jessica E

    2014-06-11

    Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution. We estimated expression of 97,217 L. hesperus transcripts in venom glands relative to silk and cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs), many of which BLAST and GO term analyses indicate may function as toxins or their delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of VSTs had predicted protein domains. Latrotoxins are venom toxins that cause massive neurotransmitter release from vertebrate or invertebrate neurons. We discovered ≥ 20 divergent latrotoxin paralogs expressed in L. hesperus venom glands, significantly increasing this biomedically important family. Mass spectrometry of L. hesperus venom identified 49 proteins from VSTs, 24 of which BLAST to toxins. Phylogenetic analyses showed venom gland specific gene family expansions and shifts in tissue expression. Quantitative expression analyses comparing multiple tissues are necessary to identify venom gland specific transcripts. We present a black widow venom specific exome that uncovers a trove of diverse toxins and associated proteins, suggesting a dynamic evolutionary history. This justifies a reevaluation of the functional activities of black widow venom in light of its emerging complexity.

  11. The beneficial effects of honeybee-venom serum on facial wrinkles in humans

    PubMed Central

    Han, Sang Mi; Hong, In Phyo; Woo, Soon Ok; Chun, Sung Nam; Park, Kwan Kyu; Nicholls, Young Mee; Pak, Sok Cheon

    2015-01-01

    Facial wrinkles are an undesirable outcome caused by extrinsic photodamage and intrinsic aging processes. Currently, no effective strategies are known to prevent facial wrinkles. We assessed the beneficial effects of bee-venom serum on the clinical signs of aging skin. Our results show that bee-venom serum treatment clinically improved facial wrinkles by decreasing total wrinkle area, total wrinkle count, and average wrinkle depth. Therefore, bee-venom serum may be effective for the improvement of skin wrinkles. PMID:26491274

  12. A limited role for gene duplications in the evolution of platypus venom.

    PubMed

    Wong, Emily S W; Papenfuss, Anthony T; Whittington, Camilla M; Warren, Wesley C; Belov, Katherine

    2012-01-01

    Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the "venome" of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.

  13. Role of the Wasp Venom Peptide Mastoparan in the Study of Mechanisms Involved in Cell Death

    DTIC Science & Technology

    1989-08-23

    The vespid venom, unlike the honey bee ( Apis mellifera ) venom, has phospholipase B in addition to phospholipase A2 , proteases, and the peptide...Olson, F.C., D. Munjal, and A.N. Malviya. 1974. structural and respiratory effects of melittin ( apis mellifera ) on rat liver mitochondria. Toxicon...M.D. and A.R. Bridges. 1982. Catechclamines in honey bee ( Apis mellifera ) and various vespid (hymenoptera) venoms. Toxicon 20: 1075-1084. Reinert, M

  14. The Ex vivo Eye Irritation Test (EVEIT) model as a mean of improving venom ophthalmia understanding.

    PubMed

    Delafontaine, Marie; Panfil, Claudia; Spöler, Felix; Kray, Stefan; Burgher, François; Mathieu, Laurence; Blomet, Joël; Schrage, Norbert F; Tambourgi, Denise V

    2018-06-08

    Snakes belonging to the genus Naja (Elapid family), also known as "spitting cobras", can spit venom towards the eyes of the predator as a defensive strategy, causing painful and potentially blinding ocular envenoming. Venom ophthalmia is characterized by pain, hyperemia, blepharitis, blepharospasm and corneal erosions. Elapid venom ophthalmia is not well documented and no specific treatment exists. Furthermore, accidental ejection of venom by non-spitting vipers, as Bothrops, also occurs. The Ex vivo Eye Irritation Test model (EVEIT) has enabled important progress in the knowledge of chemical ocular burns. Considering the lack of experimental animal model, we adapted the EVEIT to study venom ophthalmia mechanisms. Ex vivo rabbit corneas were exposed to venoms from spitting (Naja mossambica, Naja nigricollis) and non-spitting (Naja naja, Bothrops jararaca and Bothrops lanceolatus) snakes, and rinsed or not with water. The corneal thickness and the depth of damage were assessed using high-resolution optical coherence tomography (HR-OCT) imaging and histological analysis. All Naja venoms induced significant corneal edema, collagen structure disorganization and epithelial necrosis. Corneas envenomed by African N. mossambica and N. nigricollis venoms were completely opaque. Opacification was not observed in corneas treated with venoms from non-spitting snakes, such as the Asian cobra, N. naja, and the vipers, B. jararaca and B. lanceolatus. Moreover, Bothrops venoms were able to damage the epithelium and cause collagen structure disorganization, but not edema. Immediate water rinsing improved corneal status, though damage and edema could still be observed. In conclusion, the present study shows that the EVEIT model was successfully adapted to set a new experimental ex vivo animal model of ophthalmia, caused by snake venoms, which will enable to explore new therapies for venom ophthalmia. Copyright © 2018. Published by Elsevier Ltd.

  15. General biochemical and immunological characterization of the venom from the scorpion Tityus trivittatus of Argentina.

    PubMed

    de Roodt, Adolfo R; Coronas, Fredy I V; Lago, Nestor; González, María E; Laskowicz, Rodrigo D; Beltramino, Juan C; Saavedra, Silvina; López, Raúl A; Reati, Gustavo J; Vucharchuk, Miriam G; Bazán, Eduardo; Varni, Liliana; Salomón, Oscar D; Possani, Lourival D

    2010-01-01

    Tityus trivittatus is the Argentinean scorpion reported to cause the majority of human fatalities in the country, however no systematic studies have been conducted with the venom of this species. This communication describes a general biochemical and immunological characterization of the venom obtained from T. trivittatus scorpions collected in the city of Buenos Aires and various provinces of Argentina: Catamarca, Cordoba, Entre Rios, La Rioja, Santa Fe and Santiago del Estero. These are places where human accidents were reported to occur due to this scorpion. For comparative purposes two types of samples were assayed: whole soluble venom obtained by electrical stimulation and supernatant from homogenized venomous glands. Two strains of mice (NIH and CF-1) were used for LD(50) determinations by two distinct routes of administration (intravenously and intraperitoneally). Important variations were found that goes from 0.5 to 12 mg/kg mouse body weight. Samples of soluble venom were always more potent than Telson homogenates. More complex pattern was observed in homogenates compared to soluble venom, as expected. This was supported by gel electrophoretic analysis and high performance liquid chromatographic (HPLC) separations. Additionally, the HPLC profile was enriched in proteins resolved at similar elution times as other known toxins from scorpion venoms studied. Immune enzymatic assays were also conducted comparatively, using four different anti-venoms commercially available for treatment of scorpion stings (Argentinean antidote from INPB, two anti-venoms from Butantan Institute of Brazil and Alacramyn from the Mexican Bioclon Institute). Cross-reactivities were observed and are reported among the various venoms and anti-venoms used. Lung, heart, liver and pancreas pathological modifications were observed on tissues of intoxicated mice. It seems that there are important variations on the venom compositions of the various samples studied and reported here

  16. Differential gene expression profiles in the venom gland/sac of Eumenes pomiformis (Hymenoptera: Eumenidae).

    PubMed

    Baek, Ji Hyeong; Lee, Si Hyeock

    2010-06-01

    To search for novel transcripts encoding biologically active venom components, a subtractive cDNA library specific to the venom gland and sac (gland/sac) of a solitary hunting wasp species, Eumenes pomiformis Fabricius (1781), was constructed by suppression subtractive hybridization. A total of 541 expressed sequence tags (ESTs) were clustered and assembled into 102 contigs (31 multiple sequences and 71 singletons). In total, 37 cDNAs were found in the library via BLASTx searching and manual annotation. Eight contigs (337 ESTs) encoding short venom peptides (10 to 16 amino acids) occupied 62% of the library. The deduced amino acid sequence (78 amino acids) of a novel venom peptide transcript shared sequence similarity with trypsin inhibitors and dendrotoxin-like venom peptides known to be K(+) channel blockers, implying that this novel peptide may play a role in the paralysis of prey. In addition to phospholipase A2 and hyaluronidase, which are known to be the main components of wasp venoms, several transcripts encoding enzymes, including three metallopeptidases and a decarboxylase likely involved in the processing and activation of venomous proteins, peptides, amines, and neurotransmitters, were also isolated from the library. The presence of a transcript encoding a putative insulin/insulin-like peptide binding protein suggests that solitary hunting wasps use their venom to control their prey, leading to larval growth cessation. The abundance of these venom components in the venom gland/sac and in the alimentary canal was confirmed by quantitative real-time PCR. Discovery of venom gland/sac-specific transcripts should promote further studies on biologically active components in the venom of solitary hunting wasps. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Effect of Drugs on the Lethality in Mice of the Venoms and Neurotoxins from Sundry Snakes

    DTIC Science & Technology

    1990-07-10

    nicergoline , primaquine, verapamil, and vesamicol protected mice from the lethality6_)f B. caeruleus venom, B. multicinctus venom, r " and/or’l...the venom or toxin was recorded 24 hr later. Diltia.-em. nicergoline . primaquine, verapamil. and vesamicol protected mice from the lethality of B...hydrochloride were purchased from Sigma Chemical Co., St. Louis, MO, U.S.A. Nicergoline (10-methoxy-1,6-dimethylergoline-8-r-methanol 5

  18. Venom immunotherapy for preventing allergic reactions to insect stings.

    PubMed

    Boyle, Robert J; Elremeli, Mariam; Hockenhull, Juliet; Cherry, Mary Gemma; Bulsara, Max K; Daniels, Michael; Oude Elberink, J N G

    2012-10-17

    Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review. To assess the effects of immunotherapy using extracted insect venom for preventing further allergic reactions to insect stings in people who have had an allergic reaction to a sting. We searched the following databases up to February 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), the Armed Forces Pest Management Board Literature Retrieval System, and OpenGrey. There were no language or publication status restrictions to our searches. We searched trials databases, abstracts from recent European and North American allergy meetings, and the references of identified review articles in order to identify further relevant trials. Randomised controlled trials of venom immunotherapy using standardised venom extract in insect sting allergy. Two authors independently undertook study selection, data extraction, and assessment of risk of bias. We identified adverse events from included controlled trials and from a separate analysis of observational studies identified as part of a National Institute for Health and Clinical Excellence Health Technology Assessment. We identified 6 randomised controlled trials and 1 quasi-randomised controlled trial for inclusion in the review; the total number of participants was 392. The trials had some risk of bias because five of the trials did not blind outcome assessors to treatment allocation. The interventions included ant, bee, and wasp immunotherapy in children or adults with previous systemic or large local reactions to a sting, using sublingual (one trial) or subcutaneous (six trials) VIT. We found that VIT is effective for preventing systemic

  19. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.

    PubMed

    Sousa, Leijiane F; Portes-Junior, José A; Nicolau, Carolina A; Bernardoni, Juliana L; Nishiyama, Milton Y; Amazonas, Diana R; Freitas-de-Sousa, Luciana A; Mourão, Rosa Hv; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

    2017-04-21

    Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA 2 s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA 2 s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not

  20. Dietary breadth is positively correlated with venom complexity in cone snails.

    PubMed

    Phuong, Mark A; Mahardika, Gusti N; Alfaro, Michael E

    2016-05-26

    Although diet is believed to be a major factor underlying the evolution of venom, few comparative studies examine both venom composition and diet across a radiation of venomous species. Cone snails within the family, Conidae, comprise more than 700 species of carnivorous marine snails that capture their prey by using a cocktail of venomous neurotoxins (conotoxins or conopeptides). Venom composition across species has been previously hypothesized to be shaped by (a) prey taxonomic class (i.e., worms, molluscs, or fish) and (b) dietary breadth. We tested these hypotheses under a comparative phylogenetic framework using ecological data from past studies in conjunction with venom duct transcriptomes sequenced from 12 phylogenetically disparate cone snail species, including 10 vermivores (worm-eating), one molluscivore, and one generalist. We discovered 2223 unique conotoxin precursor peptides that encoded 1864 unique mature toxins across all species, >90 % of which are new to this study. In addition, we identified two novel gene superfamilies and 16 novel cysteine frameworks. Each species exhibited unique venom profiles, with venom composition and expression patterns among species dominated by a restricted set of gene superfamilies and mature toxins. In contrast with the dominant paradigm for interpreting Conidae venom evolution, prey taxonomic class did not predict venom composition patterns among species. We also found a significant positive relationship between dietary breadth and measures of conotoxin complexity. The poor performance of prey taxonomic class in predicting venom components suggests that cone snails have either evolved species-specific expression patterns likely as a consequence of the rapid evolution of conotoxin genes, or that traditional means of categorizing prey type (i.e., worms, mollusc, or fish) and conotoxins (i.e., by gene superfamily) do not accurately encapsulate evolutionary dynamics between diet and venom composition. We also show that

  1. Epidemiology, diagnosis, and treatment of Hymenoptera venom allergy in mastocytosis patients.

    PubMed

    Niedoszytko, Marek; Bonadonna, Patrizia; Oude Elberink, Joanne N G; Golden, David B K

    2014-05-01

    Hymenoptera venom allergy is a typical IgE-mediated reaction caused by sensitization to 1 or more allergens of the venom, and accounts for 1.5% to 34% of all cases of anaphylaxis. Patients suffering from mastocytosis are more susceptible to the anaphylactic reactions to an insect sting. This article aims to answer the most important clinical questions raised by the diagnosis and treatment of insect venom allergy in mastocytosis patients. Total avoidance of Hymenoptera is not feasible, and there is no preventive pharmacologic treatment available, although venom immunotherapy reduces the risk of subsequent systemic reactions. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed Central

    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

  3. Extraction and preliminary chemical characterization of the venom of the spider wasp Pepsis decorata (Hymenoptera: Pompilidae).

    PubMed

    Nolasco, Matheus; Biondi, Ilka; Pimenta, Daniel C; Branco, Alexsandro

    2018-04-26

    Arthropod venoms may be considered important sources of bioactive molecules; however, technical difficulties, such as venom extraction and homogeneity may impair the biochemical identification of new molecules. In this context, we have developed a method to maintain wasps in captivity that allows the collection of the venom, without use of chemical, mechanical or electrical stimuli. The crude venom was analyzed by RP-HPLC-ESIQ-ToF and 20 peptides were identified by de novo peptide sequencing, among them Eumenine-Mastoparan and a Ponericin-G2-simile peptide. Copyright © 2018. Published by Elsevier Ltd.

  4. Defensins and the convergent evolution of platypus and reptile venom genes.

    PubMed

    Whittington, Camilla M; Papenfuss, Anthony T; Bansal, Paramjit; Torres, Allan M; Wong, Emily S W; Deakin, Janine E; Graves, Tina; Alsop, Amber; Schatzkamer, Kyriena; Kremitzki, Colin; Ponting, Chris P; Temple-Smith, Peter; Warren, Wesley C; Kuchel, Philip W; Belov, Katherine

    2008-06-01

    When the platypus (Ornithorhynchus anatinus) was first discovered, it was thought to be a taxidermist's hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male platypuses have venomous spurs on each hind leg. The platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of platypus and reptile venom. Here we show that several venom components have evolved separately in the platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules.

  5. Defensins and the convergent evolution of platypus and reptile venom genes

    PubMed Central

    Whittington, Camilla M.; Papenfuss, Anthony T.; Bansal, Paramjit; Torres, Allan M.; Wong, Emily S.W.; Deakin, Janine E.; Graves, Tina; Alsop, Amber; Schatzkamer, Kyriena; Kremitzki, Colin; Ponting, Chris P.; Temple-Smith, Peter; Warren, Wesley C.; Kuchel, Philip W.; Belov, Katherine

    2008-01-01

    When the platypus (Ornithorhynchus anatinus) was first discovered, it was thought to be a taxidermist’s hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male platypuses have venomous spurs on each hind leg. The platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of platypus and reptile venom. Here we show that several venom components have evolved separately in the platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules. PMID:18463304

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

    PubMed

    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

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

    PubMed

    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.

  8. Characterization of Three Venom Peptides from the Spitting Spider Scytodes thoracica

    PubMed Central

    Ariki, Nathanial K.; Muñoz, Lisa E.; Armitage, Elizabeth L.; Goodstein, Francesca R.; George, Kathryn G.; Smith, Vanessa L.; Vetter, Irina; Herzig, Volker; King, Glenn F.; Loening, Nikolaus M.

    2016-01-01

    We present the solution-state NMR structures and preliminary functional characterizations of three venom peptides identified from the spitting spider Scytodes thoracica. Despite little sequence identity to other venom peptides, structural characterization reveals that these peptides contain an inhibitor cystine knot motif common to many venom peptides. These are the first structures for any peptide or protein from spiders of the Scytodidae family. Many venom peptides target neuronal ion channels or receptors. However, we have not been able to determine the target of these Scytodes peptides so we can only state with certainty the channels and receptors that they do not target. PMID:27227898

  9. In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes.

    PubMed

    Hassan, Ehssan Ahmed; Abdel-Rahman, Mohamed Ahmed; Ibrahim, Mohamed Moussa; Soliman, Maha Farid Mohamed

    2016-01-01

    We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC50 doses of venom. The LC50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50%, respectively. LC50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

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

    PubMed

    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 < 0.01) between hornet (R = 0.92) or paper wasp 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

  11. Exosome-like vesicles in Gloydius blomhoffii blomhoffii venom.

    PubMed

    Ogawa, Yuko; Kanai-Azuma, Masami; Akimoto, Yoshihiro; Kawakami, Hayato; Yanoshita, Ryohei

    2008-05-01

    Exosomes are small membrane vesicles (30-100 nm) with an endosome-derived limiting membrane that are secreted by a diverse range of cell types. We provide here the first evidence for the presence of exosome-like vesicles in snake venom. We isolated vesicles from fresh venom from Gloydius blomhoffii blomhoffii by gel-filtration. We found that the vesicles showed a typical exosome-like size and morphology as analyzed by electron microscopy. We observed that the vesicles contained dipeptidyl peptidase IV, aminopeptidase A, ecto-5'-nucleotidase and actin. Vesicle preparations truncated bioactive peptides such as angiotensin II, substance P, cholecystokinin-octapeptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. The role of these vesicles is still unknown, but they may affect blood pressure and glucose homeostasis following envenomation.

  12. [Pietro d'Abano on venoms and poisons].

    PubMed

    Touwaide, Alain

    2008-01-01

    The Treatise on Venoms and Poisons (Liber de venenis) by Pietro d'Abano has been traditionally considered as a collection of superstitions and unscientific data, even though it was also--and paradoxically--deemed interesting for the history of medieval science. The present contribution frames the treatise in the ancient toxicological literature, and suggests textual similarities with classical Greek works, mainly the two treatises On Venoms and On Poisons ascribed to the first-century A.D. author of De materia medica Dioscorides. Since Pietro d'Abano sojourned in Constantinople he might have had access to the Greek texts of these two works and could very well have integrated some of their information in his own treatise.

  13. Scorpion venom peptides with no disulfide bridges: a review.

    PubMed

    Almaaytah, Ammar; Albalas, Qosay

    2014-01-01

    Scorpion venoms are rich sources of biologically active peptides that are classified into disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs). DBPs are the main scorpion venom components responsible for the neurotoxic effects observed during scorpion envenomation as they usually target membrane bound ion channels of excitable and non-excitable cells. Several hundred DBPs have been identified and functionally characterized in the past two decades. The NDBPs represent a novel group of molecules that have gained great interest only recently due to their high diversity both in their primary structures and bioactivities. This review provides an overview of scorpion NDBPs focusing on their therapeutic applications, modes of discovery, mechanisms of NDBPs genetic diversity and structural properties. It also provides a simple classification for NDBPs that could be adopted and applied to other NDBPs identified in future studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Management of venomous snakebite injury to the extremities.

    PubMed

    Anz, Adam W; Schweppe, Mark; Halvorson, Jason; Bushnell, Brandon; Sternberg, Michael; Andrew Koman, L

    2010-12-01

    Pit vipers (subfamily Crotalinae) are responsible for most venomous snakebites in the United States. The mixture of proteins with cytotoxic, proteolytic, and/or neurotoxic enzymes in snake venom varies by species. Treatment in the field consists of safe identification of the species of snake and rapid transport of the patient to the nearest health care facility. Swelling, bruising, and systemic symptoms are seen following snakebite. Most patients respond to elevation of the affected extremity and observation. Some require the administration of antivenin. Crotalidae Polyvalent Immune Fab (Ovine) (CroFab, BTG International, West Conshohocken, PA) antivenin is safe and effective for the management of local and systemic effects of envenomation. Rarely, compartment syndrome may develop in the affected limb because of edema and tissue necrosis. Close monitoring of the extremity via serial physical examination and measurement of compartment pressure is a reliable method of determining whether surgical intervention is required.

  15. A Limited Role for Gene Duplications in the Evolution of Platypus Venom

    PubMed Central

    Wong, Emily S. W.; Papenfuss, Anthony T.; Whittington, Camilla M.; Warren, Wesley C.; Belov, Katherine

    2012-01-01

    Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the “venome” of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation. PMID:21816864

  16. Adrenergic and cholinergic activity contributes to the cardiovascular effects of lionfish (Pterois volitans) venom.

    PubMed

    Church, Jarrod E; Hodgson, Wayne C

    2002-06-01

    The aim of the present study was to further investigate the cardiovascular activity of Pterois volitans crude venom. Venom (0.6-18 microg protein/ml) produced dose- and endothelium-dependent relaxation in porcine coronary arteries that was potentiated by atropine (10nM), but significantly attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NOLA; 0.1mM), by prior exposure of the tissue to stonefish antivenom (SFAV, 3 units/ml, 10 min), or by removal of extracellular Ca(2+). In rat paced left atria, venom (10 microg protein/ml) produced a decrease, followed by an increase, in contractile force. Atropine (0.5 microM) abolished the decrease in force and potentiated the increase. Propranolol (5 microM) did not affect the decrease in force but significantly attenuated the increase. In spontaneously beating right atria, venom (10 microg protein/ml) produced an increase in rate that was significantly attenuated by propranolol (5 microM). Prior incubation with SFAV (0.3 units/microg protein, 10 min) abolished both the inotropic and chronotropic responses to venom. In the anaesthetised rat, venom (100 micro protein/kg, i.v.) produced a pressor response, followed by a sustained depressor response. Atropine (1mg/kg, i.v.) potentiated the pressor response. The further addition of prazosin (50 microg/kg, i.v.) restored the original response to venom. Prior administration of SFAV (100 units/kg, i.v., 10 min) significantly attenuated the in vivo response to venom. It is concluded that P. volitans venom produces its cardiovascular effects primarily by acting on muscarinic cholinergic receptors and adrenoceptors. As SFAV neutralised many of the effects of P. volitans venom, we suggest that the two venoms share a similar component(s). Copright 2002 Elsevier Science Ltd.

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

    PubMed

    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.

  18. Toxicity of scorpion venom in chick embryo and mealworm assay depending on the use of the soluble fraction versus the whole venom.

    PubMed

    van der Valk, Tom; van der Meijden, Arie

    2014-09-01

    The LD50 is an important metric for venom studies and antivenom development. It has been shown that several variables in the protocol influence the LD50 value obtained, such as venom source, extraction and treatment and administration route. These inconsistencies reduce the utility of the results of these test for comparative studies. In scorpion venom LD50 assays, often only the soluble fraction of the venom is used, whereas other studies use the whole venom. We here tested the toxicity of the soluble fraction in isolation, and of the whole venom in two different systems: chick embryos and mealworms Tenebrio molitor. Ten microliters of venom solutions from Hadrurus arizonensis, Leiurus quinquestriatus, Androctonus australis, Grosphus grandidieri and Heterometrus laoticus were applied to five day old chicken embryos at stage 25-27. Our results showed no significant differences between the LD50 based on the whole venom versus that of only the soluble fraction and in the chicken embryo assay in four of the five scorpion species tested. H. laoticus however, showed a significantly lower LD50 value for the whole venom than the soluble fraction. In assays on mealworms however, this pattern was not seen. Nonetheless, caution may be warranted when using LD50 values obtained from only the soluble fraction. The LD50 values of the five species in this study, based on the chicken embryo assay, showed good correlation with values from the literature based on mouse studies. This suggests that the chick embryo assay may be an economic alternative to rodent assays for scorpion LD50 studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Neutralization of venoms from two Southern Pacific Rattlesnakes (Crotalus helleri) with commercial antivenoms and endothermic animal sera.

    PubMed

    Galán, Jacob A; Sánchez, Elda E; Rodríguez-Acosta, Alexis; Pérez, John C

    2004-06-01

    The Southern Pacific Rattlesnake (Crotalus helleri) is found in southwestern California (USA), southward through north Baja California (MX) into the northern part of southern Baja California (MX). In this study, the venoms from two Southern Pacific Rattlesnakes were characterized. The two venoms were different in color, concentration, and enzyme activities. Two commercial antivenoms neutralized both C. helleri venoms differently. Antivipmyn (Fab2H) and CroFab (FabO) neutralized both venoms but had different ED50. Four times more Fab2H antivenom was required to neutralize the C. helleri venom No. 011-084-009 than the venom from the snake No. 010-367-284. The hemorrhagic activity of two C. helleri venoms were neutralized differently by endothermic animal sera having a natural resistance to hemorrhagic activity of snake venoms. Opossums and Mexican ground squirrel sera did not neutralize the hemorrhagic activity of the venom No. 010-367-284. The sera of gray woodrats and hispid cotton rats neutralized all hemorrhagins in both C. helleri venoms. This is the first reported case in which opossum serum has not neutralized hemorrhagic activity of pit viper venom. Differences in the compositions of C. helleri venoms and their ability to be neutralized may help explain why snakebites are a difficult medical problem to treat and why effective polyvalent antivenoms are difficult to produce.

  20. Animal experimentation in snake venom research and in vitro alternatives.

    PubMed

    Sells, Paula G

    2003-08-01

    Current experimental techniques used in snake venom research (with and without the use of animals) are reviewed. The emphasis is on the reduction of the use of animals in the development of antivenoms for the clinical treatment of snakebite. Diagnostic and research techniques for the major pathologies of envenoming are described and those using animals are contrasted with non-sentient methods where possible. In particular, LD50 and ED50 assays using animals (in vivo) and fertilised eggs (in vivo, non-sentient) are compared as well as in vitro procedures (ELISA and haemolytic test) for ED50 estimations. The social context of antivenom production, supply and demand is outlined together with the consequent tension between the benefits derived and the increase in opposition to experiments on animals. Stringent regulations governing the use of animals, limited research funds and public pressure all focus the need for progress towards non-animal, or non-sentient, research methods. Some achievements are noted but success is hampered by lack of detailed knowledge of the many constituents of venom which have to be assessed as a whole rather than individually. The only way to evaluate the net pathological effect of venom is to use a living system, usually a rodent, and similarly, the efficacy of antivenoms is also measured in vivo. The pre-clinical testing of antivenoms in animals is therefore a legal requirement in many countries and is strictly monitored by government authorities. New technologies applied to the characterisation of individual venom proteins should enable novel in vitro assays to be designed thus reducing the number of animals required. In the meantime, the principles of Reduce, Refine and Replace relating to animals in research are increasingly endorsed by those working in the field and the many agencies regulating ethical and research policy.

  1. Venomous spiders, snakes, and scorpions in the United States.

    PubMed

    Holve, Steve

    2009-04-01

    Venomous bites and stings are complex poisonings that have local and systemic effects. Mild envenomations can be treated with supportive care. Severe envenomations can be treated definitively with species-specific antivenom, although the use of these products has potential risk of immediate and a more delayed onset form of hypersensitivity reactions. Consultation with a toxicologist is recommended to help guide therapy. Field treatments such as tourniquets and incision likely cause more harm than benefit and should be avoided.

  2. Activated entomopathogenic nematode infective juveniles release lethal venom proteins

    PubMed Central

    Macchietto, Marissa; Baldwin, James; Mortazavi, Ali

    2017-01-01

    Entomopathogenic nematodes (EPNs) are unique parasites due to their symbiosis with entomopathogenic bacteria and their ability to kill insect hosts quickly after infection. It is widely believed that EPNs rely on their bacterial partners for killing hosts. Here we disproved this theory by demonstrating that the in vitro activated infective juveniles (IJs) of Steinernema carpocapsae (a well-studied EPN species) release venom proteins that are lethal to several insects including Drosophila melanogaster. We confirmed that the in vitro activation is a good approximation of the in vivo process by comparing the transcriptomes of individual in vitro and in vivo activated IJs. We further analyzed the transcriptomes of non-activated and activated IJs and revealed a dramatic shift in gene expression during IJ activation. We also analyzed the venom proteome using mass spectrometry. Among the 472 venom proteins, proteases and protease inhibitors are especially abundant, and toxin-related proteins such as Shk domain-containing proteins and fatty acid- and retinol-binding proteins are also detected, which are potential candidates for suppressing the host immune system. Many of the venom proteins have conserved orthologs in vertebrate-parasitic nematodes and are differentially expressed during IJ activation, suggesting conserved functions in nematode parasitism. In summary, our findings strongly support a new model that S. carpocapsae and likely other Steinernema EPNs have a more active role in contributing to the pathogenicity of the nematode-bacterium complex than simply relying on their symbiotic bacteria. Furthermore, we propose that EPNs are a good model system for investigating vertebrate- and human-parasitic nematodes, especially regarding the function of excretory/secretory products. PMID:28426766

  3. Ipomoea asarifolia neutralizes inflammation induced by Tityus serrulatus scorpion venom.

    PubMed

    Lima, Maira Conceição Jerônimo de Souza; Bitencourt, Mariana Angélica Oliveira; Furtado, Allanny Alves; Oliveira Rocha, Hugo Alexandre; Oliveira, Ruth Medeiros; da Silva-Júnior, Arnóbio Antônio; Tabosa do Egito, Eryvaldo Sócrates; Tambourgi, Denise Vilarinho; Zucolotto, Silvana Maria; Fernandes-Pedrosa, Matheus de Freitas

    2014-05-14

    Envenoming caused by scorpion sting is a serious public health problem. In Brazil, 13,038 accidents caused by venomous animals have been reported. Of this total, 53% of the cases and 14 deaths were caused by scorpions. Furthermore, Tityus serrulatus (Buthidae) is the most dangerous scorpion due to the high toxicity of its venom. The treatment is the common supportive therapy and the serum therapy, but some people do not have access to both therapies and seek healing through the use of medical plants. This study evaluated the ability of the crude extract and fractions from the leaves of Ipomoea asarifolia in neutralizing the main biological effects caused by Tityus serrulatus envenoming in mice. BALB/c mice were pretreated (i.v.) with 100 μλ of aqueous extracts and fractions dichloromethane, ethyl acetate, and n-butanol (CH₂Cl₂, EtOAc, and n-BuOH, respectively) of Ipomoea asarifolia, rutin or saline. Then, the animals received 100 μλ (i.p.) of venom of Tityus serrulatus (0.8 mg/kg). After six hours, the peritoneal lavage was performed with PBS and the number cells were determined using a Neubauer chamber. The supernatants were collected for determination of cytokines, such as IL-6, IL-12, and IL-1β. The aqueous extract, fractions and rutin, at all doses, significantly reduced cell migration, which was endorsed by the reduction of the levels of certain cytokines. This is the first study that demonstrated the potential effect of Ipomoea asarifolia against inflammation caused by Tityus serrulatus venom, suggesting that these extracts and/or their bioactive molecules, especially the flavonoid rutin, have potential use in the therapy of this envenomation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American viperidae venoms in a murine model.

    PubMed

    Richardson, William H; Tanen, David A; Tong, Tri C; Betten, David P; Carstairs, Shaun D; Williams, Saralyn R; Cantrell, Frank L; Clark, Richard F

    2005-06-01

    Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance). A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times. The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P

  5. Effects of Brazilian scorpion venoms on the central nervous system.

    PubMed

    Nencioni, Ana Leonor Abrahão; Neto, Emidio Beraldo; de Freitas, Lucas Alves; Dorce, Valquiria Abrão Coronado

    2018-01-01

    In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus , T. bahiensis , T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus , T. silvestres, T. brazilae , T. confluens , T. costatus , T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis . Little information is available regarding the other Brazilian Tityus species.

  6. Immune thrombocytopenia after bee venom therapy: a case report.

    PubMed

    Abdulsalam, Mohammad Adel; Ebrahim, Bader Esmael; Abdulsalam, Ahmad Jasem

    2016-03-25

    Immune thrombocytopenia (ITP) is a hematological disorder with an isolated decrease in number of circulating platelets. Bee venom therapy (BVT) is a form of alternative medicine. It is still being practiced in the Middle East and other parts of Asia. In BVT, acupuncture points are used to inject diluted bee venom into the body. The pharmacological basis behind BVT is not fully understood. However, it has been used to treat various medical conditions such as arthritis and low back pain. On the other hand there have been a number of reported complications of BVT use such as ITP. We present a case report on ITP after BVT. A 61 year old lady presented with gum bleeding and ecchymosis and found to have isolated thrombocytopenia (platelet count of 9 × 10(9)/L) after receiving four direct bee sting sessions. There was no evidence of any other risk factors of ITP. Bee venom components and toxicity may be associated with thrombocytopenia as a complication. Further research is needed to postulate guidelines and protocol for BVT. In the meantime, monitoring of the practice of BVT should be made, with an emphasis on patient education regarding the safety profile and associated risks compared to the gained benefits.

  7. Scorpions from Mexico: From Species Diversity to Venom Complexity

    PubMed Central

    Santibáñez-López, Carlos E.; Francke, Oscar F.; Ureta, Carolina; Possani, Lourival D.

    2015-01-01

    Scorpions are among the oldest terrestrial arthropods, which are distributed worldwide, except for Antarctica and some Pacific islands. Scorpion envenomation represents a public health problem in several parts of the world. Mexico harbors the highest diversity of scorpions in the world, including some of the world’s medically important scorpion species. The systematics and diversity of Mexican scorpion fauna has not been revised in the past decade; and due to recent and exhaustive collection efforts as part of different ongoing major revisionary systematic projects, our understanding of this diversity has changed compared with previous assessments. Given the presence of several medically important scorpion species, the study of their venom in the country is also important. In the present contribution, the diversity of scorpion species in Mexico is revised and updated based on several new systematic contributions; 281 different species are recorded. Commentaries on recent venomic, ecological and behavioral studies of Mexican scorpions are also provided. A list containing the most important peptides identified from 16 different species is included. A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots showing the current knowledge on scorpion distribution and areas explored in Mexico is also provided. PMID:26712787

  8. Cross-reacting carbohydrate determinants and hymenoptera venom allergy.

    PubMed

    Brehler, Randolf; Grundmann, Sonja; Stöcker, Benedikt

    2013-08-01

    Insect venom allergy is an important cause of anaphylaxis. Venom immunotherapy assume the clear identification of the culprit insect, but this is impeded by Immunoglobulin E (IgE) antibodies to cross reactive carbohydrate determinant (CCD) epitopes of common glycoproteins. Here we give an overview about inducers, importance, and relevance of anti-N-Glycan CCD IgE antibodies. Pollen exposure and insect stings induce anti-CCD IgE antibodies interfering with in-vitro tests for allergy diagnosis due to extensive IgE cross-reactivity. Instead of being biologically active these antibodies are irrelevant for allergic reactions due to hymenoptera stings. The general response of the immune system to the ubiquitous exposure to N-glycan containing glycoproteins is still a matter of debate. CCD specific IgG antibodies in sera of bee keepers suggest tolerance induction due to high-dose exposure. Tolerance induction by pollen and food glycoproteins has not been proved. Hymenoptera stings and pollen exposure induce anti-CCD IgE. In regard to anaphylaxis due to Hymenoptera stings these antibodies are not clinically relevant, but they are important for the specificity of in-vitro tests proving insect venom allergy. The introduction of component based diagnostic IgE testing improves the specificity of in-vitro tests if proteins devoid of CCD epitopes are used.

  9. An insecticidal toxin from Nephila clavata spider venom.

    PubMed

    Jin, Lin; Fang, Mingqian; Chen, Mengrou; Zhou, Chunling; Ombati, Rose; Hakim, Md Abdul; Mo, Guoxiang; Lai, Ren; Yan, Xiuwen; Wang, Yumin; Yang, Shilong

    2017-07-01

    Spiders are the most successful insect predators given that they use their venom containing insecticidal peptides as biochemical weapons for preying. Due to the high specificity and potency of peptidic toxins, discoveries of insecticidal toxins from spider venom have provided an opportunity to obtain natural compounds for agricultural applications without affecting human health. In this study, a novel insecticidal toxin (μ-NPTX-Nc1a) was identified and characterized from the venom of Nephila clavata. Its primary sequence is GCNPDCTGIQCGWPRCPGGQNPVMDKCVSCCPFCPPKSAQG which was determined by automated Edman degradation, cDNA cloning, and MS/MS analysis. BLAST search indicated that Nc1a shows no similarity with known peptides or proteins, indicating that Nc1a belongs to a novel family of insecticidal peptide. Nc1a displayed inhibitory effects on Na V and K V channels in cockroach dorsal unpaired median neurons. The median lethal dose (LD50) of Nc1a on cockroach was 573 ng/g. Herein, a study that identifies a novel insecticidal toxin, which can be a potential candidate and/or template for the development of bioinsecticides, is presented.

  10. Modelling the interactions between animal venom peptides and membrane proteins.

    PubMed

    Hung, Andrew; Kuyucak, Serdar; Schroeder, Christina I; Kaas, Quentin

    2017-12-01

    The active components of animal venoms are mostly peptide toxins, which typically target ion channels and receptors of both the central and peripheral nervous system, interfering with action potential conduction and/or synaptic transmission. The high degree of sequence conservation of their molecular targets makes a range of these toxins active at human receptors. The high selectivity and potency displayed by some of these toxins have prompted their use as pharmacological tools as well as drugs or drug leads. Molecular modelling has played an essential role in increasing our molecular-level understanding of the activity and specificity of animal toxins, as well as engineering them for biotechnological and pharmaceutical applications. This review focuses on the biological insights gained from computational and experimental studies of animal venom toxins interacting with membranes and ion channels. A host of recent X-ray crystallography and electron-microscopy structures of the toxin targets has contributed to a dramatic increase in the accuracy of the molecular models of toxin binding modes greatly advancing this exciting field of study. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Scorpions from Mexico: From Species Diversity to Venom Complexity.

    PubMed

    Santibáñez-López, Carlos E; Francke, Oscar F; Ureta, Carolina; Possani, Lourival D

    2015-12-24

    Scorpions are among the oldest terrestrial arthropods, which are distributed worldwide, except for Antarctica and some Pacific islands. Scorpion envenomation represents a public health problem in several parts of the world. Mexico harbors the highest diversity of scorpions in the world, including some of the world's medically important scorpion species. The systematics and diversity of Mexican scorpion fauna has not been revised in the past decade; and due to recent and exhaustive collection efforts as part of different ongoing major revisionary systematic projects, our understanding of this diversity has changed compared with previous assessments. Given the presence of several medically important scorpion species, the study of their venom in the country is also important. In the present contribution, the diversity of scorpion species in Mexico is revised and updated based on several new systematic contributions; 281 different species are recorded. Commentaries on recent venomic, ecological and behavioral studies of Mexican scorpions are also provided. A list containing the most important peptides identified from 16 different species is included. A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots showing the current knowledge on scorpion distribution and areas explored in Mexico is also provided.

  12. A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom.

    PubMed

    Kong, Yi; Shao, Yu; Chen, Hao; Ming, Xin; Wang, Jin-Bin; Li, Zhi-Yu; Wei, Ji-Fu

    2013-01-01

    Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipes mutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC 50 value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.

  13. A Deeper Examination of Thorellius atrox Scorpion Venom Components with Omic Techonologies.

    PubMed

    Romero-Gutierrez, Teresa; Peguero-Sanchez, Esteban; Cevallos, Miguel A; Batista, Cesar V F; Ortiz, Ernesto; Possani, Lourival D

    2017-12-12

    This communication reports a further examination of venom gland transcripts and venom composition of the Mexican scorpion Thorellius atrox using RNA-seq and tandem mass spectrometry. The RNA-seq, which was performed with the Illumina protocol, yielded more than 20,000 assembled transcripts. Following a database search and annotation strategy, 160 transcripts were identified, potentially coding for venom components. A novel sequence was identified that potentially codes for a peptide with similarity to spider ω-agatoxins, which act on voltage-gated calcium channels, not known before to exist in scorpion venoms. Analogous transcripts were found in other scorpion species. They could represent members of a new scorpion toxin family, here named omegascorpins. The mass fingerprint by LC-MS identified 135 individual venom components, five of which matched with the theoretical masses of putative peptides translated from the transcriptome. The LC-MS/MS de novo sequencing allowed to reconstruct and identify 42 proteins encoded by assembled transcripts, thus validating the transcriptome analysis. Earlier studies conducted with this scorpion venom permitted the identification of only twenty putative venom components. The present work performed with more powerful and modern omic technologies demonstrates the capacity of accomplishing a deeper characterization of scorpion venom components and the identification of novel molecules with potential applications in biomedicine and the study of ion channel physiology.

  14. Prey specificity, comparative lethality and compositional differences of coral snake venoms.

    PubMed

    Jorge da Silva, N; Aird, S D

    2001-03-01

    Toxicities of crude venoms from 49 coral snake (Micrurus sp.) populations, representing 15 nominal taxa, were examined in both laboratory mice and in native prey animals and compared with data gathered from two non-micrurine elapids and a crotalid, which served as outgroups. These venoms were further compared on the basis of 23 enzymatic activities. Both toxicities and enzymatic activities were analyzed with respect to natural prey preferences, as determined from stomach content analyses and literature reports. Venoms of nearly all Micrurus for which prey preferences are known, are more toxic to natural prey than to non-prey species. Except for amphisbaenians, prey are more susceptible to venoms of Micrurus that feed upon them, than to venoms of those that eat other organisms. All venoms were more toxic i.v.>i.p.>i.m. Route-specific differences in toxicity are generally greatest for preferred prey species. Cluster analyses of venom enzymatic activities resulted in five clusters, with the fish-eating M. surinamensis more distant from other Micrurus than even the crotalid, Bothrops moojeni. Ophiophagous and amphisbaenian-eating Micrurus formed two close subclusters, one allied to the outgroup species Naja naja and the other to the fossorial, ophiophagous Bungarus multicinctus. Prey preference is shown to be the most important determinant of venom composition in Micrurus.

  15. Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics.

    PubMed

    Zainal Abidin, Syafiq Asnawi; Rajadurai, Pathmanathan; Chowdhury, Md Ezharul Hoque; Ahmad Rusmili, Muhamad Rusdi; Othman, Iekhsan; Naidu, Rakesh

    2016-10-18

    Tropidolaemus wagleri and Cryptelytrops purpureomaculatus are venomous pit viper species commonly found in Malaysia. Tandem mass spectrometry analysis of the crude venoms has detected different proteins in T. wagleri and C. purpureomaculatus . They were classified into 13 venom protein families consisting of enzymatic and nonenzymatic proteins. Enzymatic families detected in T. wagleri and C. purpureomaculatus venom were snake venom metalloproteinase, phospholipase A₂, ʟ-amino acid oxidase, serine proteases, 5'-nucleotidase, phosphodiesterase, and phospholipase B. In addition, glutaminyl cyclotransferase was detected in C. purpureomaculatus . C-type lectin-like proteins were common nonenzymatic components in both species. Waglerin was present and unique to T. wagleri -it was not in C. purpureomaculatus venom. In contrast, cysteine-rich secretory protein, bradykinin-potentiating peptide, and C-type natriuretic peptide were present in C. purpureomaculatus venom. Composition of the venom proteome of T. wagleri and C. purpureomaculatus provides useful information to guide production of effective antivenom and identification of proteins with potential therapeutic applications.

  16. Western Immunoblot Analysis of Twenty-One Snake Venoms from Three Snake Families

    DTIC Science & Technology

    1989-05-01

    with proteins in Crotalus basciliscus, C. durissus durissus, C. d . terrificus, C. horridis horridis, and C. viridis concolor venoms. Arumae et al, (2...fractions of Prairie Rattle- snake (Crotalus viridis viridis) venom", Toxicon, 25 (1987) pp. 1329 - 1342. 19. Rael, E.D., Salo, R.J. and Zepeda , H

  17. Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics

    PubMed Central

    Zainal Abidin, Syafiq Asnawi; Rajadurai, Pathmanathan; Chowdhury, Md Ezharul Hoque; Ahmad Rusmili, Muhamad Rusdi; Othman, Iekhsan; Naidu, Rakesh

    2016-01-01

    Tropidolaemus wagleri and Cryptelytrops purpureomaculatus are venomous pit viper species commonly found in Malaysia. Tandem mass spectrometry analysis of the crude venoms has detected different proteins in T. wagleri and C. purpureomaculatus. They were classified into 13 venom protein families consisting of enzymatic and nonenzymatic proteins. Enzymatic families detected in T. wagleri and C. purpureomaculatus venom were snake venom metalloproteinase, phospholipase A2, l-amino acid oxidase, serine proteases, 5′-nucleotidase, phosphodiesterase, and phospholipase B. In addition, glutaminyl cyclotransferase was detected in C. purpureomaculatus. C-type lectin-like proteins were common nonenzymatic components in both species. Waglerin was present and unique to T. wagleri—it was not in C. purpureomaculatus venom. In contrast, cysteine-rich secretory protein, bradykinin-potentiating peptide, and C-type natriuretic peptide were present in C. purpureomaculatus venom. Composition of the venom proteome of T. wagleri and C. purpureomaculatus provides useful information to guide production of effective antivenom and identification of proteins with potential therapeutic applications. PMID:27763534

  18. Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms.

    PubMed

    Koludarov, Ivan; Jackson, Timothy Nw; Brouw, Bianca Op den; Dobson, James; Dashevsky, Daniel; Arbuckle, Kevin; Clemente, Christofer J; Stockdale, Edward J; Cochran, Chip; Debono, Jordan; Stephens, Carson; Panagides, Nadya; Li, Bin; Manchadi, Mary-Louise Roy; Violette, Aude; Fourmy, Rudy; Hendrikx, Iwan; Nouwens, Amanda; Clements, Judith; Martelli, Paolo; Kwok, Hang Fai; Fry, Bryan G

    2017-08-06

    While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma , Lanthanotus , and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds.

  19. Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A

    DTIC Science & Technology

    1989-07-15

    PLAz neurotoxins. Experimental Methods: Materials. Vencm from 1 nAjA atra, CTX from Naja n9ja kaouthia venom (Lots 125F-4007), bee venom PLAz ( Apis ... mellifera ), melittin, B-bungarotoxin, Tris base, Hepes (4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid), Mes (4- morpholineethanesulfonic acid), bovine

  20. Protocol to obtain targeted transcript sequence data from snake venom samples collected in the Colombian field.

    PubMed

    Fonseca, Alejandra; Renjifo-Ibáñez, Camila; Renjifo, Juan Manuel; Cabrera, Rodrigo

    2018-03-21

    Snake venoms are a mixture of different molecules that can be used in the design of drugs for various diseases. The study of these venoms has relied on strategies that use complete venom extracted from animals in captivity or from venom glands that require the sacrifice of the animals. Colombia, a country with political and geographical conflicts has difficult access to certain regions. A strategy that can prevent the sacrifice of animals and could allow the study of samples collected in the field is necessary. We report the use of lyophilized venom from Crotalus durissus cumanensis as a model to test, for the first time, a protocol for the amplification of complete toxins from Colombian venom samples collected in the field. In this protocol, primers were designed from conserved region from Crotalus sp. mRNA and EST regions to maximize the likelihood of coding sequence amplification. We obtained the sequences of Metalloproteinases II, Disintegrins, Disintegrin-Like, Phospholipases A 2, C-type Lectins and Serine proteinases from Crotalus durissus cumanensis and compared them to different Crotalus sp sequences available on databases obtaining concordance between the toxins amplified and those reported. Our strategy allows the use of lyophilized venom to obtain complete toxin sequences from samples collected in the field and the study of poorly characterized venoms in challenging environments. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Protein discovery: combined transcriptomic and proteomic analyses of venom from the endoparasitoid Cotesia chilonis (Hymenoptera: Brachonidae)

    USDA-ARS?s Scientific Manuscript database

    Background: Many species of endoparasitoid wasps provide biological control services in agroecosystems. Although there is a great deal of information on the ecology and physiology of host/parasitoid interactions, relatively little is known on the protein composition of venom and how specific venom p...

  2. Comparative proteomic analysis of two wasps venom, Vespa tropica and Vespa affinis.

    PubMed

    Rungsa, Prapenpuksiri; Incamnoi, Paroonkorn; Sukprasert, Sophida; Uawonggul, Nunthawun; Klaynongsruang, Sompong; Daduang, Jureerut; Patramanon, Rina; Roytrakul, Sittiruk; Daduang, Sakda

    2016-09-01

    Vespid venom is composed of many bioactive compounds. The venom of the banded tiger wasp (Vespa affinis, or VA) and the great banded wasp (Vespa tropica, or VT)-which are locally found in the northeastern part of Thailand and are well known for their life-threatening venom potency-were comparatively studied in terms of potency, composition and biological activity. Clinical studies that included word-of-mouth information shared by traditional healers in local areas noted that the venom of VT is more potent than that of VA. Our previous study showed that the venom of VA is lower in potency (PD50 = 12.5 μg/g body weight) than that of VT (PD50 = 3 μg/g body weight). Analysis with the PAGE technique showed that these two venoms showed similar patterns of active proteins. Most protein spots were basic proteins at an isoelectric point (pI) ranging from 5 to 10, with molecular weights between 27 and 50 kDa. These spots were identified as hyaluronidase, phospholipase, antigen 5, dipeptidyl peptidase and albumin-like protein. The proportion of hyaluronidase was 2.5 times higher in VT than in VA. VT also showed higher hyaluronidase, phospholipase and dipeptidyl peptidase activities, suggesting that these components made VT venom more potent than VA venom. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Bee Venom Promotes Hair Growth in Association with Inhibiting 5α-Reductase Expression.

    PubMed

    Park, Seeun; Erdogan, Sedef; Hwang, Dahyun; Hwang, Seonwook; Han, Eun Hye; Lim, Young-Hee

    2016-06-01

    Alopecia is an important issue that can occur in people of all ages. Recent studies show that bee venom can be used to treat certain diseases including rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we investigated the preventive effect of bee venom on alopecia, which was measured by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors responsible for hair growth were analyzed by quantitative real-time PCR and Western blot analysis using mice skins and human dermal papilla cells (hDPCs). Bee venom promoted hair growth and inhibited transition from the anagen to catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase mice, hair growth was increased dose dependently compared with controls. Bee venom inhibited the expression of SRD5A2, which encodes a type II 5α-reductase that plays a major role in the conversion of testosterone into dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee venom-treated hDPCs dose dependently compared with the control group. In conclusion, bee venom is a potentially potent 5α-reductase inhibitor and hair growth promoter.

  4. A Deeper Examination of Thorellius atrox Scorpion Venom Components with Omic Techonologies

    PubMed Central

    Romero-Gutierrez, Teresa; Batista, Cesar V. F.

    2017-01-01

    This communication reports a further examination of venom gland transcripts and venom composition of the Mexican scorpion Thorellius atrox using RNA-seq and tandem mass spectrometry. The RNA-seq, which was performed with the Illumina protocol, yielded more than 20,000 assembled transcripts. Following a database search and annotation strategy, 160 transcripts were identified, potentially coding for venom components. A novel sequence was identified that potentially codes for a peptide with similarity to spider ω-agatoxins, which act on voltage-gated calcium channels, not known before to exist in scorpion venoms. Analogous transcripts were found in other scorpion species. They could represent members of a new scorpion toxin family, here named omegascorpins. The mass fingerprint by LC-MS identified 135 individual venom components, five of which matched with the theoretical masses of putative peptides translated from the transcriptome. The LC-MS/MS de novo sequencing allowed to reconstruct and identify 42 proteins encoded by assembled transcripts, thus validating the transcriptome analysis. Earlier studies conducted with this scorpion venom permitted the identification of only twenty putative venom components. The present work performed with more powerful and modern omic technologies demonstrates the capacity of accomplishing a deeper characterization of scorpion venom components and the identification of novel molecules with potential applications in biomedicine and the study of ion channel physiology. PMID:29231872

  5. High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

    PubMed

    Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam

    2009-01-01

    Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

  6. Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms

    PubMed Central

    Koludarov, Ivan; Jackson, Timothy NW; op den Brouw, Bianca; Dobson, James; Dashevsky, Daniel; Clemente, Christofer J.; Stockdale, Edward J.; Cochran, Chip; Debono, Jordan; Stephens, Carson; Panagides, Nadya; Li, Bin; Roy Manchadi, Mary-Louise; Violette, Aude; Fourmy, Rudy; Hendrikx, Iwan; Nouwens, Amanda; Clements, Judith; Martelli, Paolo; Kwok, Hang Fai; Fry, Bryan G.

    2017-01-01

    While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds. PMID:28783084

  7. Channel-forming activity in the venom of the cockroach-hunting wasp, Ampulex compressa.

    PubMed

    Gincel, Dan; Haspel, Gal; Libersat, Frederic

    2004-05-01

    The parasitoid solitary wasp Ampulex compressa uses the cockroach Periplaneta americana as a food supply for its larvae. To subdue its prey, the wasp injects a venom cocktail into the brain of the cockroach. We investigated channel activity of A. compressa venom by collecting venom and incorporating it into a planar lipid bilayer. The venom, reconstituted into the bilayer, showed ion channel activity, forming a fast-fluctuating channel with a small conductance of 20+/-0.1pS, with no voltage sensitivity. These channels were not observed when the venom was digested with proteases before application to the bilayer, but were not affected by exposure to protease after their incorporation into the bilayer, indicating that the active venom component is a peptide. The channels were found to be cation selective with similar selectivity for the monovalent cations K(+), Li(+) and Na(+), but showed high selectivity against anions (Cl(-)) and divalent cations (Ca(2+) and Mg(2+)). This study is the first demonstration and biophysical characterization of channel activity in the venom of A. compressa. The possible functional significance of this channel activity is discussed in light of the unusual nature of the effects of this wasp venom on the behavior of its prey.

  8. Tentacle Transcriptome and Venom Proteome of the Pacific Sea Nettle, Chrysaora fuscescens (Cnidaria: Scyphozoa).

    PubMed

    Ponce, Dalia; Brinkman, Diane L; Potriquet, Jeremy; Mulvenna, Jason

    2016-04-05

    Jellyfish venoms are rich sources of toxins designed to capture prey or deter predators, but they can also elicit harmful effects in humans. In this study, an integrated transcriptomic and proteomic approach was used to identify putative toxins and their potential role in the venom of the scyphozoan jellyfish Chrysaora fuscescens. A de novo tentacle transcriptome, containing more than 23,000 contigs, was constructed and used in proteomic analysis of C. fuscescens venom to identify potential toxins. From a total of 163 proteins identified in the venom proteome, 27 were classified as putative toxins and grouped into six protein families: proteinases, venom allergens, C-type lectins, pore-forming toxins, glycoside hydrolases and enzyme inhibitors. Other putative toxins identified in the transcriptome, but not the proteome, included additional proteinases as well as lipases and deoxyribonucleases. Sequence analysis also revealed the presence of ShKT domains in two putative venom proteins from the proteome and an additional 15 from the transcriptome, suggesting potential ion channel blockade or modulatory activities. Comparison of these potential toxins to those from other cnidarians provided insight into their possible roles in C. fuscescens venom and an overview of the diversity of potential toxin families in cnidarian venoms.

  9. Tentacle Transcriptome and Venom Proteome of the Pacific Sea Nettle, Chrysaora fuscescens (Cnidaria: Scyphozoa)

    PubMed Central

    Ponce, Dalia; Brinkman, Diane L.; Potriquet, Jeremy; Mulvenna, Jason

    2016-01-01

    Jellyfish venoms are rich sources of toxins designed to capture prey or deter predators, but they can also elicit harmful effects in humans. In this study, an integrated transcriptomic and proteomic approach was used to identify putative toxins and their potential role in the venom of the scyphozoan jellyfish Chrysaora fuscescens. A de novo tentacle transcriptome, containing more than 23,000 contigs, was constructed and used in proteomic analysis of C. fuscescens venom to identify potential toxins. From a total of 163 proteins identified in the venom proteome, 27 were classified as putative toxins and grouped into six protein families: proteinases, venom allergens, C-type lectins, pore-forming toxins, glycoside hydrolases and enzyme inhibitors. Other putative toxins identified in the transcriptome, but not the proteome, included additional proteinases as well as lipases and deoxyribonucleases. Sequence analysis also revealed the presence of ShKT domains in two putative venom proteins from the proteome and an additional 15 from the transcriptome, suggesting potential ion channel blockade or modulatory activities. Comparison of these potential toxins to those from other cnidarians provided insight into their possible roles in C. fuscescens venom and an overview of the diversity of potential toxin families in cnidarian venoms. PMID:27058558

  10. Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

    PubMed Central

    Nicolau, Carolina Alves; Prorock, Alyson; Bao, Yongde; Neves-Ferreira, Ana Gisele da Costa; Fox, Jay William

    2018-01-01

    Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents. PMID:29415440

  11. Proteomic characterization and comparison of venoms from two elapid snakes (Bungarus multicinctus and Naja atra) from China.

    PubMed

    Shan, Lin-Lin; Gao, Jian-Fang; Zhang, Yan-Xia; Shen, Shan-Shan; He, Ying; Wang, Jin; Ma, Xiao-Mei; Ji, Xiang

    2016-04-14

    Bungarus multicinctus (many-banded krait) and Naja atra (Chinese cobra) are widely distributed and medically important venomous snakes in China; however, their venom proteomic profiles have not been fully compared. Here, we fractionated crude venoms and analyzed them using a combination of proteomic techniques. Three-finger toxins (3-FTx) and phospholipase A2 (PLA2) were most abundant in both species, respectively accounting for 32.6% and 66.4% of total B. multicinctus venom, and 84.3% and 12.2% of total N. atra venom. Venoms from these two species contained one common protein family and six less abundant species-specific protein families. The proteomic profiles of B. multicinctus and N. atra venoms and analysis of toxicological activity in mice suggested that 3-FTx and PLA2 are the major contributors to clinical symptoms caused by envenomation. The venoms differed in enzymatic activity, likely the result of inter-specific variation in the amount of related venom components. Antivenomics assessment revealed that a small number of venom components (3-FTxs and PLA2s in B. multicinctus, and 3-FTxs in N. atra) could not be immunocaptured completely, suggesting that we should pay attention to enhancing the immune response of these components in designing commercial antivenoms for B. multicinctus and N. atra. The proteomic profiles of venoms from two medically important snake species - B. multicinctus and N. atra - have been explored. Quantitative and qualitative differences are evident in both venoms when proteomic profiles and transcriptomic results are compared; this is a reminder that combined approaches are needed to explore the precise composition of snake venom. Two protein families (3-FTx and PLA2) of high abundance in these snake venoms are major players in the biochemical and pharmacological effects of envenomation. Elucidation of the proteomic profiles of these snake venoms is helpful in understanding composition-function relationships and will facilitate the

  12. Viperous fangs: development and evolution of the venom canal.

    PubMed

    Zahradnicek, Oldrich; Horacek, Ivan; Tucker, Abigail S

    2008-01-01

    Fangs are specialised long teeth that contain either a superficial groove (Gila monster, Beaded lizard, some colubrid snakes), along which the venom runs, or an enclosed canal (viperid, elapid and atractaspid), down which the venom flows inside the tooth. The fangs of viperid snakes are the most effective venom-delivery structures among vertebrates and have been the focus of scientific interests for more than 200 years. Despite this interest the questions of how the canal at the centre of the fang forms remains unresolved. Two different hypotheses have been suggested. The mainstream hypothesis claims that the venom-conducting canal develops by the invagination of the epithelial wall of the developing tooth germ. The sides of this invagination make contact and finally fuse to form the enclosed canal. The second hypothesis, known as the "brick chimney", claims the venom-conducting canal develops directly by successive dentine deposition as the tooth develops. The fang is thus built up from the tip to the base, without any folding of the tooth surface. In an attempt to cast further light on this subject the early development of the fangs was followed in a pit viper, Trimeresurus albolabris, using the expression of Sonic hedgehog (Shh). We demonstrate that the canal is indeed formed by an early folding event, resulting from an invagination of epithelial cells into the dental mesenchyme. The epithelial cells proliferate to enlarge the canal and then the cells die by apoptosis, forming an empty tube through which the poison runs. The entrance and discharge orifices at either end of the canal develop by a similar invagination but the initial width of the invagination is very different from that in the middle of the tooth, and is associated with higher proliferation. The two sides of the invaginating epithelium never come into contact, leaving the orifice open. The mechanism by which the orifices form can be likened to that observed in reptiles with an open groove along

  13. Venom and Antivenom of the Redback Spider (Latrodectus hasseltii) in Japan. Part I. Venom Extraction, Preparation, and Laboratory Testing.

    PubMed

    Matsumura, Takayuki; Mashiko, Reona; Sato, Tomomi; Itokawa, Kentaro; Maekawa, Yoshihide; Ogawa, Kohei; Isawa, Haruhiko; Yamamoto, Akihiko; Mori, Shigemi; Horita, Akira; Ginnaga, Akihiro; Miyatsu, Yoshinobu; Takahashi, Motohide; Taki, Hisashi; Hifumi, Toru; Sawabe, Kyoko; Ato, Manabu

    2018-03-22

    The redback spider (Latrodectus hasseltii Thorell) reportedly invaded Japan in September 1995. To date, 84 redback spider bite cases have been reported; 7 of these cases employed the antivenom. Antivenom has been imported from Australia in the past, but because of restrictions on exportation it was evident that nearly all of the antivenom present in Japan would expire during 2014. In 2014, a plan was proposed to experimentally manufacture and stockpile a horse antiserum for ourselves, using redback spiders indigenous to Japan. A total of 11,403 female spiders were captured alive: 1,217 from the vicinity of Nishinomiya City, Hyogo prefecture, and 10,186 from Osaka prefecture. Of these, 10,007 females were dissected, and the venom was extracted from the venom glands of individuals and subjected to crude purification to yield 4 lots, of which the majority was α-latrotoxin. Among them, a large amount of single lots with an estimated protein content of 236 mg is subsequently scheduled to be used for immunizing horses. We also determined lethal toxicity of the venom (LD 50 : 9.17 μg per mouse), and established the assay for the determination of an anti-lethal titer of antivenom in mice.

  14. The Protective Effect of Bee Venom on Fibrosis Causing Inflammatory Diseases

    PubMed Central

    Lee, Woo-Ram; Pak, Sok Cheon; Park, Kwan-Kyu

    2015-01-01

    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. PMID:26580653

  15. The protective effect of bee venom on fibrosis causing inflammatory diseases.

    PubMed

    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.

  16. Venomous and Poisonous Australian Animals of Veterinary Importance: A Rich Source of Novel Therapeutics

    PubMed Central

    Allavena, Rachel E.

    2014-01-01

    Envenomation and poisoning by terrestrial animals (both vertebrate and invertebrate) are a significant economic problem and health risk for domestic animals in Australia. Australian snakes are some of the most venomous animals in the world and bees, wasps, ants, paralysis ticks, and cane toads are also present as part of the venomous and poisonous fauna. The diagnosis and treatment of envenomation or poisoning in animals is a challenge and can be a traumatic and expensive process for owners. Despite the potency of Australian venoms, there is potential for novel veterinary therapeutics to be modeled on venom toxins, as has been the case with human pharmaceuticals. A comprehensive overview of envenomation and poisoning signs in livestock and companion animals is provided and related to the potential for venom toxins to act as therapeutics. PMID:25143943

  17. Comparative analysis of methods for concentrating venom from jellyfish Rhopilema esculentum Kishinouye

    NASA Astrophysics Data System (ADS)

    Li, Cuiping; Yu, Huahua; Feng, Jinhua; Chen, Xiaolin; Li, Pengcheng

    2009-02-01

    In this study, several methods were compared for the efficiency to concentrate venom from the tentacles of jellyfish Rhopilema esculentum Kishinouye. The results show that the methods using either freezing-dry or gel absorption to remove water to concentrate venom are not applicable due to the low concentration of the compounds dissolved. Although the recovery efficiency and the total venom obtained using the dialysis dehydration method are high, some proteins can be lost during the concentrating process. Comparing to the lyophilization method, ultrafiltration is a simple way to concentrate the compounds at high percentage but the hemolytic activities of the proteins obtained by ultrafiltration appear to be lower. Our results suggest that overall lyophilization is the best and recommended method to concentrate venom from the tentacles of jellyfish. It shows not only the high recovery efficiency for the venoms but high hemolytic activities as well.

  18. Snake Venomics and Antivenomics of Bothrops diporus, a Medically Important Pitviper in Northeastern Argentina

    PubMed Central

    Gay, Carolina; Sanz, Libia; Calvete, Juan J.; Pla, Davinia

    2015-01-01

    Snake species within genus Bothrops are responsible for more than 80% of the snakebites occurring in South America. The species that cause most envenomings in Argentina, B. diporus, is widely distributed throughout the country, but principally found in the Northeast, the region with the highest rates of snakebites. The venom proteome of this medically relevant snake was unveiled using a venomic approach. It comprises toxins belonging to fourteen protein families, being dominated by PI- and PIII-SVMPs, PLA2 molecules, BPP-like peptides, L-amino acid oxidase and serine proteinases. This toxin profile largely explains the characteristic pathophysiological effects of bothropic snakebites observed in patients envenomed by B. diporus. Antivenomic analysis of the SAB antivenom (Instituto Vital Brazil) against the venom of B. diporus showed that this pentabothropic antivenom efficiently recognized all the venom proteins and exhibited poor affinity towards the small peptide (BPPs and tripeptide inhibitors of PIII-SVMPs) components of the venom. PMID:26712790

  19. Marine snail venoms: use and trends in receptor and channel neuropharmacology.

    PubMed

    Favreau, Philippe; Stöcklin, Reto

    2009-10-01

    Venoms are rich mixtures of mainly peptides and proteins evolved by nature to catch and digest preys or for protection against predators. They represent extensive sources of potent and selective bioactive compounds that can lead to original active ingredients, for use as drugs, as pharmacological tools in research and for the biotechnology industry. Among the most fascinating venomous animals, marine snails offer a unique set of pharmacologically active components, targeting a wide diversity of receptors and ion channels. Recent advances still continue to demonstrate their huge neuropharmacological potential. In the quest for interesting pharmacological profiles, researchers face a vast number of venom components to investigate within time and technological constraints. A brief perspective on marine snail venom's complexity and features is given followed by the different discovery strategies and pharmacological approaches, exemplified with some recent developments. These advances will hopefully help further uncovering new pharmacologically important venom molecules.

  20. The venom of Ampulex compressa--effects on behaviour and synaptic transmission of cockroaches.

    PubMed

    Piek, T; Hue, B; Lind, A; Mantel, P; van Marle, J; Visser, J H

    1989-01-01

    1. The solitary wasp Ampulex compressa stings a cockroach, Periplaneta americana, twice. 2. The first sting into the ventral thorax results in a transient paralysis. During this paralysis the wasp stings the suboesophageal ganglion, which gradually results in a permanent deactivation. 3. The venom gland is a paired and highly branched organ, with a common ductus venatus. The large lumen is lined with a folded cuticula. No venom reservoir is present. 4. Extract of the venom gland induces a slow contraction of the guinea pig ileum. 5. The agonist present in the venom cannot be identified with a known agonist. 6. Venom gland extract blocks synaptic transmission from the cercal nerve to giant neurons in the sixth abdominal ganglion of the cockroach. 7. The block develops gradually, like the gradual appearance of the effects of the sting into the suboesophageal ganglion on the behaviour of the cockroach.

  1. Effect of Ottoman Viper (Montivipera xanthina (Gray, 1849)) Venom on Various Cancer Cells and on Microorganisms.

    PubMed

    Yalcın, Husniye Tansel; Ozen, Mehmet Ozgün; Gocmen, Bayram; Nalbantsoy, Ayse

    2014-01-01

    Cytotoxic and antimicrobial effects of Montivipera xanthina venom against LNCaP, MCF-7, HT-29, Saos-2, Hep3B, Vero cells and antimicrobial activity against selected bacterial and fungal species: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, E. coli O157H7, Enterococcus faecalis 29212, Enterococcus faecium DSM 13590, Staphylococcus epidermidis ATCC 12228, S. typhimirium CCM 5445, Proteus vulgaris ATCC 6957 and Candida albicans ATCC 10239 were studied for evaluating the potential medical benefit of this snake venom. Cytotoxicity of venom was determined using MTT assay. Snake venom cytotoxicity was expressed as the venom dose that killed 50 % of the cells (IC50). The antimicrobial activity of venom was studied by minimal inhibitory concentration (MIC) and disc diffusion assay. MIC was determined using broth dilution method. The estimated IC50 values of venom varied from 3.8 to 12.7 or from 1.9 to 7.2 μg/ml after treatment with crude venom for 24 or 48 h for LNCaP, MCF-7, HT-29 and Saos-2 cells. There was no observable cytotoxic effect on Hep3B and Vero cells. Venom exhibited the most potent activity against C. albicans (MIC, 7.8 μg/ml and minimal fungicidal concentration, 62.5 μg/ml) and S. aureus (MIC, 31.25 μg/ml). This study is the first report showing the potential of M. xanthina venom as an alternative therapeutic approach due to its cytotoxic and antimicrobial effects.

  2. Cross neutralization of coral snake venoms by commercial Australian snake antivenoms.

    PubMed

    Ramos, Henrique Roman; Vassão, Ruth Camargo; de Roodt, Adolfo Rafael; Santos E Silva, Ed Carlos; Mirtschin, Peter; Ho, Paulo Lee; Spencer, Patrick Jack

    2017-01-01

    Although rare, coral snake envenomation is a serious health threat in Brazil, because of the highly neurotoxic venom and the scarcely available antivenom. The major bottleneck for antivenom production is the low availability of venom. Furthermore, the available serum is not effective against all coral snake species found in Brazil. An alternative to circumvent the lack of venom for serum production and the restricted protection of the actually available antivenom would be of great value. We compared the Brazilian coral snake and mono and polyvalent Australian antivenoms in terms of reactivity and protection. The immunoreactivity of venoms from 9 coral snakes species were assayed by ELISA and western blot using the Brazilian Micrurus and the Australian pentavalent as well as monovalent anti-Notechis, Oxyuranus and Pseudechis antivenoms. Neutralization assays were performed in mice, using 3 LD 50 of the venoms, incubated for 30 minutes with 100 μL of antivenom/animal. All the venoms reacted against the autologous and heterologous antivenoms. Nevertheless, the neutralization assays showed that the coral snake antivenom was only effective against M. corallinus, M. frontalis, M. fulvius, M. nigrocinctus and M. pyrrhocryptus venoms. On the other hand, the Australian pentavalent antivenom neutralized all venoms except the one from M. spixii. A combination of anti-Oxyuranus and Pseudechis monovalent sera, extended the protection to M. altirostris and, partially, to M. ibiboboca. By adding Notechis antivenom to this mixture, we obtained full protection against M. ibiboboca and partial neutralization against M. lemniscatus venoms. Our findings confirm the limited effectiveness of the Brazilian coral snake antivenom and indicate that antivenoms made from Australian snakes venoms are an effective alternative for coral snake bites in South America and also in the United States were coral snake antivenom production has been discontinued.

  3. Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

    PubMed

    Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie; Corvol, Jean-Christophe; Schüpbach, Michael

    2016-01-01

    In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. ClinicalTrials.gov NCT

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

    PubMed Central

    2013-01-01

    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. PMID:24074353

  5. The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes.

    PubMed

    Casewell, Nicholas R; Visser, Jeroen C; Baumann, Kate; Dobson, James; Han, Han; Kuruppu, Sanjaya; Morgan, Michael; Romilio, Anthony; Weisbecker, Vera; Mardon, Karine; Ali, Syed A; Debono, Jordan; Koludarov, Ivan; Que, Ivo; Bird, Gregory C; Cooke, Gavan M; Nouwens, Amanda; Hodgson, Wayne C; Wagstaff, Simon C; Cheney, Karen L; Vetter, Irina; van der Weerd, Louise; Richardson, Michael K; Fry, Bryan G

    2017-04-24

    Venom systems have evolved on multiple occasions across the animal kingdom, and they can act as key adaptations to protect animals from predators [1]. Consequently, venomous animals serve as models for a rich source of mimicry types, as non-venomous species benefit from reductions in predation risk by mimicking the coloration, body shape, and/or movement of toxic counterparts [2-5]. The frequent evolution of such deceitful imitations provides notable examples of phenotypic convergence and are often invoked as classic exemplars of evolution by natural selection. Here, we investigate the evolution of fangs, venom, and mimetic relationships in reef fishes from the tribe Nemophini (fangblennies). Comparative morphological analyses reveal that enlarged canine teeth (fangs) originated at the base of the Nemophini radiation and have enabled a micropredatory feeding strategy in non-venomous Plagiotremus spp. Subsequently, the evolution of deep anterior grooves and their coupling to venom secretory tissue provide Meiacanthus spp. with toxic venom that they effectively employ for defense. We find that fangblenny venom contains a number of toxic components that have been independently recruited into other animal venoms, some of which cause toxicity via interactions with opioid receptors, and result in a multifunctional biochemical phenotype that exerts potent hypotensive effects. The evolution of fangblenny venom has seemingly led to phenotypic convergence via the formation of a diverse array of mimetic relationships that provide protective (Batesian mimicry) and predatory (aggressive mimicry) benefits to other fishes [2, 6]. Our results further our understanding of how novel morphological and biochemical adaptations stimulate ecological interactions in the natural world. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Neurotoxicity fingerprinting of venoms using on-line microfluidic AChBP profiling.

    PubMed

    Slagboom, Julien; Otvos, Reka A; Cardoso, Fernanda C; Iyer, Janaki; Visser, Jeroen C; van Doodewaerd, Bjorn R; McCleary, Ryan J R; Niessen, Wilfried M A; Somsen, Govert W; Lewis, Richard J; Kini, R Manjunatha; Smit, August B; Casewell, Nicholas R; Kool, Jeroen

    2018-06-15

    Venoms from snakes are rich sources of highly active proteins with potent affinity towards a variety of enzymes and receptors. Of the many distinct toxicities caused by envenomation, neurotoxicity plays an important role in the paralysis of prey by snakes as well as by venomous sea snails and insects. In order to improve the analytical discovery component of venom toxicity profiling, this paper describes the implementation of microfluidic high-resolution screening (HRS) to obtain neurotoxicity fingerprints from venoms that facilitates identification of the neurotoxic components of envenomation. To demonstrate this workflow, 47 snake venoms were profiled using the acetylcholine binding protein (AChBP) to mimic the target of neurotoxic proteins, in particular nicotinic acetylcholine receptors (nAChRs). In the microfluidic HRS system, nanoliquid chromatographic (nanoLC) separations were on-line connected to both AChBP profiling and parallel mass spectrometry (MS). For virtually all neurotoxic elapid snake venoms tested, we obtained bioactivity fingerprints showing major and minor bioactive zones containing masses consistent with three-finger toxins (3FTxs), whereas, viperid and colubrid venoms showed little or no detectable bioactivity. Our findings demonstrate that venom interactions with AChBP correlate with the severity of neurotoxicity observed following human envenoming by different snake species. We further, as proof of principle, characterized bioactive venom peptides from a viperid (Daboia russelli) and an elapid (Aspidelaps scutatus scutatus) snake by nanoLC-MS/MS, revealing that different toxin classes interact with the AChBP, and that this binding correlates with the inhibition of α7-nAChR in calcium-flux cell-based assays. The on-line post-column binding assay and subsequent toxin characterization methodologies described here provide a new in vitro analytic platform for rapidly investigating neurotoxic snake venom proteins. Copyright © 2018 The Author

  7. Cytotoxicity and hemolytic activity of jellyfish Nemopilema nomurai (Scyphozoa: Rhizostomeae) venom.

    PubMed

    Kang, Changkeun; Munawir, Al; Cha, Mijin; Sohn, Eun-Tae; Lee, Hyunkyoung; Kim, Jong-Shu; Yoon, Won Duk; Lim, Donghyun; Kim, Euikyung

    2009-07-01

    The recent bloom of a giant jellyfish Nemopilema nomurai has caused a danger to sea bathers and fishery damages in the waters of China, Korea, and Japan. The present study investigated the cytotoxic and hemolytic activities of crude venom extract of N. nomurai using a number of in vitro assays. The jellyfish venom showed a much higher cytotoxic activity in H9C2 heart myoblast than in C2C12 skeletal myoblast (LC(50)=2 microg/mL vs. 12 microg/mL, respectively), suggesting its possible in vivo selective toxicity on cardiac tissue. This result is consistent with our previous finding that cardiovascular function is a target of the venom. In order to determine the stability of N. nomurai venom, its cytotoxicity was examined under the various temperature and pH conditions. The activity was relatively well retained at low environmental temperature (or=60 degrees C). In pH stability test, the venom has abruptly lost its activity at low pH environment (pHvenom was examined using the erythrocytes of cat, dog, human, rabbit and rat. Venom concentration-dependent hemolysis could be observed from 10 microg/mL of protein equivalents or higher with variable potencies in different species, among which dog erythrocyte was the most susceptible to the venom (EC(50)=151 microg/mL). SDS-PAGE analysis of N. nomurai venom showed the molecules of 20-40 kDa and 10-15 kDa appeared to be the major protein components of the venom.

  8. Chemical profiling and cytotoxicity assay of bufadienolides in toad venom and toad skin.

    PubMed

    Meng, Qiong; Yau, Lee-Fong; Lu, Jing-Guang; Wu, Zhen-Zhen; Zhang, Bao-Xian; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-07-01

    Toad venom and toad skin have been widely used for treating various cancers in China. Bufadienolides are regarded as the main anticancer components of toad venom, but the difference on composition and anticancer activities of bufadienolides between toad venom and toad skin remains unclear. Fractions enriched with free and conjugated bufadienolides were prepared from toad venom and toad skin. Bufadienolides in each fraction were comprehensively profiled by using a versatile UHPLC-TOF-MS method. Relative contents of major bufadienolides were determined by using three bufogenins and one bufotoxin as marker compounds with validated UHPLC-TOF-MS method. Furthermore, cytotoxicity of the fractions was examined by MTT assay. Two fractions, i.e., bufogenin and bufotoxin fractions (TV-F and TV-C) were isolated from toad venom, and one bufotoxin fraction (TS-C) was isolated from toad skin. Totally 56 bufadienolides in these three fractions were identified, and 29 were quantified or semi-quantified. Bufotoxins were identified in both toad venom and toad skin, whereas bufogenins exist only in toad venom. Bufalin-3-conjugated bufotoxins are major components in toad venom, whereas cinobufotalin and cinobufagin-3-conjugated bufotoxins are main bufotoxins in toad skin. MTT assay revealed potent cytotoxicity of all the fractions in an order of TV-F>TV-C>TS-C. Our study represents the most comprehensive investigation on the chemical profiles of toad venom and toad skin from both qualitative and quantitative aspects. Eight bufotoxins were identified in toad skin responsible for the cytotoxicity for the first time. Our research provides valuable chemical evidence for the appropriate processing method, quality control and rational exploration of toad skin and toad venom for the development of anticancer medicines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Venom-gland transcriptomics and venom proteomics of the black-back scorpion (Hadrurus spadix) reveal detectability challenges and an unexplored realm of animal toxin diversity.

    PubMed

    Rokyta, Darin R; Ward, Micaiah J

    2017-03-15

    The order Scorpiones is one of the most ancient and diverse lineages of venomous animals, having originated approximately 430 million years ago and diversified into 14 extant families. Although partial venom characterizations have been described for numerous scorpion species, we provided the first quantitative transcriptome/proteome comparison for a scorpion species using single-animal approaches. We sequenced the venom-gland transcriptomes of a male and female black-back scorpion (Hadrurus spadix) from the family Caraboctonidae using the Illumina sequencing platform and conducted independent quantitative mass-spectrometry analyses of their venoms. We identified 79 proteomically confirmed venom proteins, an additional 69 transcripts with homology to toxins from other species, and 596 nontoxin proteins expressed at high levels in the venom glands. The venom of H. spadix was rich in antimicrobial peptides, K + -channel toxins, and several classes of peptidases. However, the most diverse and one of the most abundant classes of putative toxins could not be assigned even a tentative functional role on the basis of homology, indicating that this venom contained a wealth of previously unexplored animal toxin diversity. We found good agreement between both transcriptomic and proteomic abundances across individuals, but transcriptomic and proteomic abundandances differed substantially within each individual. Small peptide toxins such as K + -channel toxins and antimicrobial peptides proved challenging to detect proteomically, at least in part due to the significant proteolytic processing involved in their maturation. In addition, we found a significant tendency for our proteomic approach to overestimate the abundances of large putative toxins and underestimate the abundances of smaller toxins. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Anti-proliferative Effects of Androctonus amoreuxi Scorpion and Cerastes cerastes Snake Venoms on Human Prostate Cancer Cells

    PubMed Central

    Akef, Hassan; Kotb, Nahla; Abo-Elmatty, Dina; Salem, Sayed

    2017-01-01

    The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells. PMID:28382285

  11. Isolation and characterization of an immunosuppressive protein from venom of the pupa-specific endoparasitoid Pteromalus puparum.

    PubMed

    Wu, Ma-li; Ye, Gong-yin; Zhu, Jia-ying; Chen, Xue-xin; Hu, Cui

    2008-10-01

    In hymenopteran parasitoids devoid of symbiotic viruses, venom proteins appear to play a major role in host immune suppression and host regulation. Not much is known about the active components of venom proteins in these parasitoids, especially those that have the functions involved in the suppression of host cellular immunity. Here, we report the isolation and characterization of a venom protein Vn.11 with 24.1 kDa in size from Pteromalus puparum, a pupa-specific endoparasitoid of Pieris rapae. The Vn.11 venom protein is isolated with the combination of ammonium sulfate precipitation and anion exchange chromatography, and its purity is verified using SDS-PAGE analysis. Like crude venom, the Vn.11 venom protein significantly inhibits the spreading behavior and encapsulation ability of host hemocytes in vitro. It is suggested that this protein is an actual component of P. puparum crude venom as host cellular-immune suppressive factor.

  12. Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection

    PubMed Central

    Patiño, Arley Camilo; Quintana, Juan Carlos; Gutiérrez, José María; Rucavado, Alexandra; Benjumea, Dora María; Pereañez, Jaime Andrés

    2015-01-01

    Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored. PMID:25941768

  13. Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection.

    PubMed

    Patiño, Arley Camilo; Quintana, Juan Carlos; Gutiérrez, José María; Rucavado, Alexandra; Benjumea, Dora María; Pereañez, Jaime Andrés

    2015-04-30

    Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.

  14. The first report on coagulation and phospholipase A2 activities of Persian Gulf lionfish, Pterois russelli, an Iranian venomous fish.

    PubMed

    Memar, Bahareh; Jamili, Shahla; Shahbazzadeh, Delavar; Bagheri, Kamran Pooshang

    2016-04-01

    Pterois russelli is a venomous fish belonging to scorpionidae family. Regarding to high significance value for tracing potential therapeutic molecules and special agents from venomous marine creatures, the present study was aimed to characterization of the Persian Gulf lionfish venom. Proteolytic, phospholipase, hemolytic, coagulation, edematogenic and dermonecrotic activities were determined for extracted venom. The LD50 of P. russelli venom was determined by intravenous injection in white Balb/c mice. Phospholipase A2 activity was recorded at 20 μg of total venom. Coagulation activity on human plasma was shown by Prothrombin Time (PT) and activated Partial Thromboplastin Time (APTT) assays and coagulation visualized after 7 and 14 s respectively for 60 μg of crude venom. LD50 was calculated as 10.5 mg/kg. SDS-PAGE revealed the presence of major and minor protein bands between 6 and 205 kDa. Different amounts of crude venom ranged from 1.87 to 30 μg showed proteolytic activity on casein. The highest edematic activity was detected at 20 μg. Our findings showed that the edematic activity was dose dependent and persisted for 48 h after injection. The crude venom did not induce dermonecrotic activity on rabbit skin and showed no hemolytic activity on human, mouse and rabbit erythrocytes. This is the first report for phospholipase A2 and coagulation activity in venomous fish and venomous marine animals respectively. Proteolytic activity of P. russelli venom is in accordance with the other genara of scorpionidae family. According to venom activity on intrinsic and extrinsic coagulation pathways, lionfish venom would be contained an interesting pharmaceutical agent. This study is pending to further characterization of phospholipase A2, coagulation, and protease activities and also in vivo activity on animal model of surface and internal bleeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Comparison of the neurotoxic and myotoxic effects of two Moroccan scorpion venoms and their neutralization by experimental polyclonal antivenom.

    PubMed

    Oukkache, Naoual; Ahmad Rusmili, Muhamad Rusdi; Othman, Iekhsan; Ghalim, Noreddine; Chgoury, Fatima; Boussadda, Lofti; Elmdaghri, Naima; Sabatier, Jean-Marc

    2015-03-01

    Scorpion venoms contain complex mixtures of molecules, including peptides. These peptides specifically bind to various targets, in particular ion channels. Toxins modulating Na(+), K(+), Ca(2+) and Cl(-) currents were described from venoms. The Androctonus and Buthus geni of scorpions are widely distributed in Morocco. Their stings can cause pain, inflammation, necrosis, muscle paralysis and death. The myotoxicity is predominantly associated with neurotoxic effects and is a cause of mortality and morbidity. In this study, pharmacological effects of venoms were investigated in vitro on neuromuscular transmission. Effects of Androctonus mauretanicus (Am) and Buthus occitanus (Bo) venoms were investigated using the chick biventer cervicis nerve-muscle preparations. The protective activity of antivenom was also investigated. The antivenom was made from serum of horse that was hyperimmunized with Bo and Androctonus australis hector (Aah) venoms and one venom from Middle East species (Lq). The protective activity of the antivenom was assessed on the neuromuscular system by using stimulated chick nerve-muscle. The results were compared with lethal activity neutralization in mice. Am and Bo venoms contain myotoxins and postsynaptic neurotoxins. In agreement with lethal potencies of these venoms in mice, Am venom displays greater neurotoxicity and myotoxicity. The antivenom prevented lethality caused by Am, Bo and Aah venoms. The antivenom did not prevent toxic effects caused by Am venom whereas it neutralized Bo venom. Am and Bo venoms contain distinct toxins that are responsible for myotoxicity and neurotoxicity. It would be appropriate to add Am venom to produce more efficient antivenom. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Action of Micrurus dumerilii carinicauda coral snake venom on the mammalian neuromuscular junction.

    PubMed

    Serafim, Francine G; Reali, Marielga; Cruz-Höfling, Maria Alice; Fontana, Marcos D

    2002-02-01

    The venoms of coral snakes (mainly Micrurus species) have pre- and/or postsynaptic actions, but only a few of these have been studied in detail. We have investigated the effects of Micrurus dumerilii carinicauda coral snake venom on neurotransmission in rat isolated phrenic nerve-diaphragm muscle and chick biventer cervicis preparations stimulated directly or indirectly. M. d. carinicauda venom (5 or 10 microg/ml) produced neuromuscular blockade in rat (85-90% in 291.8+/-7.3 min and 108.3+/-13.8, respectively; n=5) and avian (95.0+/-2.0 min; 5 microg/ml, n=5) preparations. Neostigmine (5.8 microM) and 3,4-diaminopyridine (230 microM) partially reversed the venom-induced neuromuscular blockade in rat nerve-muscle preparations. In neither preparation did the venom depress the twitch response elicited by direct muscle stimulation. The contractures induced by acetylcholine in chick preparations were inhibited by the venom (95-100%; n=4; p<0.05). In rat preparations, the venom produced a progressive decrease in the amplitude of miniature end-plate potentials (m.e.p.ps control frequency=69.3+/-5.0/min and control amplitude=0.4+/-0.2 mV) until these were abolished. Neostigmine (5.8 microM) and 3,4-diaminopyridine (230 microM) partially antagonized this blockade of m.e.p.ps. The resting membrane potential was not altered with the venom (10 microg/ml). M. d. carinicauda venom produced dose-dependent morphological changes in indirectly stimulated mammal preparations. Twenty-five per cent of muscle fibers were affected by a venom concentration of 5 microg/ml, whilst 60.7% were damaged by 10 microg of venom/ml. In biventer cervicis preparations, the morphological changes were slower in onset and were generally characterized by undulating fibers and, to a lesser extent, by zones of disintegrating myofibrils. A venom concentration of 5 microg/ml damaged 52.2% of the fibers. These findings indicate that M. d. carinicauda venom has neurotoxic and myotoxic effects and that the

  17. Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains*

    PubMed Central

    Brust, Andreas; Sunagar, Kartik; Undheim, Eivind A.B.; Vetter, Irina; Yang, Daryl C.; Casewell, Nicholas R.; Jackson, Timothy N. W.; Koludarov, Ivan; Alewood, Paul F.; Hodgson, Wayne C.; Lewis, Richard J.; King, Glenn F.; Antunes, Agostinho; Hendrikx, Iwan; Fry, Bryan G.

    2013-01-01

    Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteine-rich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands. PMID:23242553

  18. Differential evolution and neofunctionalization of snake venom metalloprotease domains.

    PubMed

    Brust, Andreas; Sunagar, Kartik; Undheim, Eivind A B; Vetter, Irina; Yang, Daryl C; Yang, Dary C; Casewell, Nicholas R; Jackson, Timothy N W; Koludarov, Ivan; Alewood, Paul F; Hodgson, Wayne C; Lewis, Richard J; King, Glenn F; Antunes, Agostinho; Hendrikx, Iwan; Fry, Bryan G

    2013-03-01

    Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteine-rich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands.

  19. Comparative venom gland transcriptomics of Naja kaouthia (monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

    PubMed Central

    Chanhome, Lawan; Tan, Nget Hong

    2017-01-01

    Background The monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes of N. kaouthia from Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology. Methods The transcriptomes were sequenced on the Illumina HiSeq platform, assembled and followed by transcript clustering and annotations for gene expression and function. Pairwise or multiple sequence alignments were conducted on the toxin genes expressed. Substitution rates were studied for the major toxins co-expressed in NK-M and NK-T. Results and discussion The toxin transcripts showed high redundancy (41–82% of the total mRNA expression) and comprised 23 gene families expressed in NK-M and NK-T, respectively (22 gene families were co-expressed). Among the venom genes, three-finger toxins (3FTxs) predominated in the expression, with multiple sequences noted. Comparative analysis and selection study revealed that 3FTxs are genetically conserved between the geographical specimens whilst demonstrating distinct differential expression patterns, implying gene up-regulation for selected principal toxins, or alternatively, enhanced transcript degradation or lack of transcription of certain traits. One of the striking features that elucidates the inter-geographical venom variation is the up-regulation of α-neurotoxins (constitutes ∼80.0% of toxin’s fragments per kilobase of exon model per million mapped reads (FPKM)), particularly the long-chain α-elapitoxin-Nk2a (48.3%) in NK-T but only 1.7% was noted in NK-M. Instead, short neurotoxin isoforms were up-regulated in NK-M (46.4%). Another distinct transcriptional pattern observed is the

  20. Bee Venom and Its Component Apamin as Neuroprotective Agents in a Parkinson Disease Mouse Model

    PubMed Central

    Vulinović, Franca; Grünewald, Anne; Chevarin, Caroline; Klein, Christine; Oertel, Wolfgang H.; Hirsch, Etienne C.; Michel, Patrick P.; Hartmann, Andreas

    2013-01-01

    Bee venom has recently been suggested to possess beneficial effects in the treatment of Parkinson disease (PD). For instance, it has been observed that bilateral acupoint stimulation of lower hind limbs with bee venom was protective in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In particular, a specific component of bee venom, apamin, has previously been shown to have protective effects on dopaminergic neurons in vitro. However, no information regarding a potential protective action of apamin in animal models of PD is available to date. The specific goals of the present study were to (i) establish that the protective effect of bee venom for dopaminergic neurons is not restricted to acupoint stimulation, but can also be observed using a more conventional mode of administration and to (ii) demonstrate that apamin can mimic the protective effects of a bee venom treatment on dopaminergic neurons. Using the chronic mouse model of MPTP/probenecid, we show that bee venom provides sustained protection in an animal model that mimics the chronic degenerative process of PD. Apamin, however, reproduced these protective effects only partially, suggesting that other components of bee venom enhance the protective action of the peptide. PMID:23637888

  1. Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

    PubMed Central

    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

  2. Venomic and antivenomic analyses of the Central American coral snake, Micrurus nigrocinctus (Elapidae).

    PubMed

    Fernández, Julián; Alape-Girón, Alberto; Angulo, Yamileth; Sanz, Libia; Gutiérrez, José María; Calvete, Juan J; Lomonte, Bruno

    2011-04-01

    The proteome of the venom of Micrurus nigrocinctus (Central American coral snake) was analyzed by a "venomics" approach. Nearly 50 venom peaks were resolved by RP-HPLC, revealing a complex protein composition. Comparative analyses of venoms from individual specimens revealed that such complexity is an intrinsic feature of this species, rather than the sum of variable individual patterns of simpler composition. Proteins related to eight distinct families were identified by MS/MS de novo peptide sequencing or N-terminal sequencing: phospholipase A(2) (PLA(2)), three-finger toxin (3FTx), l-amino acid oxidase, C-type lectin/lectin-like, metalloproteinase, serine proteinase, ohanin, and nucleotidase. PLA(2)s and 3FTxs are predominant, representing 48 and 38% of the venom proteins, respectively. Within 3FTxs, several isoforms of short-chain α-neurotoxins as well as muscarinic-like toxins and proteins with similarity to long-chain κ-2 bungarotoxin were identified. PLA(2)s are also highly diverse, and a toxicity screening showed that they mainly exert myotoxicity, although some are lethal and may contribute to the known presynaptic neurotoxicity of this venom. An antivenomic characterization of a therapeutic monospecific M. nigrocinctus equine antivenom revealed differences in immunorecognition of venom proteins that correlate with their molecular mass, with the weakest recognition observed toward 3FTxs.

  3. Delayed polymorphonuclear leukocyte infiltration is an important component of Thalassophryne maculosa venom pathogenesis.

    PubMed

    Pareja-Santos, Alessandra; Oliveira Souza, Valdênia Maria; Bruni, Fernanda M; Sosa-Rosales, Josefina Ines; Lopes-Ferreira, Mônica; Lima, Carla

    2008-07-01

    Thalassophryne maculosa fish envenomation is characterized by severe pain, dizziness, fever, edema and necrosis. Here, the dynamic of cellular influx, activation status of phagocytic cells, and inflammatory modulator production in the acute inflammatory response to T. maculosa venom was studied using an experimental model. Leukocyte counting was performed (2 h to 21 days) after venom injection in BALB/c mice footpads. Our results showed an uncommon leukocyte migration kinetic after venom injection, with early mononuclear cell recruitment followed by elevated and delayed neutrophil influx. The pattern of chemokine expression is consistent with the delay in neutrophil recruitment to the footpad: T. maculosa venom stimulated an early production of IL-1beta, IL-6, and MCP-1, but was unable to induce an effective early TNF-alpha and KC release. Complementary to these observations, we detected a marked increase in soluble KC and TNF-alpha in footpad at 7 days post-venom injection when a prominent influx of neutrophils was also detected. In addition, we demonstrated that bone marrow-derived macrophages and dendritic cells were strongly stimulated by the venom, showing up-regulated ability to capture FITC-dextran. Thus, the reduced levels of KC and TNF-alpha in footpad of mice concomitant with a defective accumulation of neutrophils at earlier times provide an important clue to uncovering the mechanism by which T. maculosa venom regulates neutrophil movement.

  4. Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones

    PubMed Central

    Macrander, Jason; Broe, Michael; Daly, Marymegan

    2016-01-01

    Cnidarians represent one of the few groups of venomous animals that lack a centralized venom transmission system. Instead, they are equipped with stinging capsules collectively known as nematocysts. Nematocysts vary in abundance and type across different tissues; however, the venom composition in most species remains unknown. Depending on the tissue type, the venom composition in sea anemones may be vital for predation, defense, or digestion. Using a tissue-specific RNA-seq approach, we characterize the venom assemblage in the tentacles, mesenterial filaments, and column for three species of sea anemone (Anemonia sulcata, Heteractis crispa, and Megalactis griffithsi). These taxa vary with regard to inferred venom potency, symbiont abundance, and nematocyst diversity. We show that there is significant variation in abundance of toxin-like genes across tissues and species. Although the cumulative toxin abundance for the column was consistently the lowest, contributions to the overall toxin assemblage varied considerably among tissues for different toxin types. Our gene ontology (GO) analyses also show sharp contrasts between conserved GO groups emerging from whole transcriptome analysis and tissue-specific expression among GO groups in our differential expression analysis. This study provides a framework for future characterization of tissue-specific venom and other functionally important genes in this lineage of simple bodied animals. PMID:27389690

  5. Protein Discovery: Combined Transcriptomic and Proteomic Analyses of Venom from the Endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae)

    PubMed Central

    Teng, Zi-Wen; Xiong, Shi-Jiao; Xu, Gang; Gan, Shi-Yu; Chen, Xuan; Stanley, David; Yan, Zhi-Chao; Ye, Gong-Yin; Fang, Qi

    2017-01-01

    Many species of endoparasitoid wasps provide biological control services in agroecosystems. Although there is a great deal of information on the ecology and physiology of host/parasitoid interactions, relatively little is known about the protein composition of venom and how specific venom proteins influence physiological systems within host insects. This is a crucial gap in our knowledge because venom proteins act in modulating host physiology in ways that favor parasitoid development. Here, we identified 37 possible venom proteins from the polydnavirus-carrying endoparasitoid Cotesia chilonis by combining transcriptomic and proteomic analyses. The most abundant proteins were hydrolases, such as proteases, peptidases, esterases, glycosyl hydrolase, and endonucleases. Some components are classical parasitoid venom proteins with known functions, including extracellular superoxide dismutase 3, serine protease inhibitor and calreticulin. The venom contains novel proteins, not recorded from any other parasitoid species, including tolloid-like proteins, chitooligosaccharidolytic β-N-acetylglucosaminidase, FK506-binding protein 14, corticotropin-releasing factor-binding protein and vascular endothelial growth factor receptor 2. These new data generate hypotheses and provide a platform for functional analysis of venom components. PMID:28417942

  6. Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom.

    PubMed Central

    Barros, S F; Friedlanskaia, I; Petricevich, V L; Kipnis, T L

    1998-01-01

    We have provided evidence that: (a) lethality of mice to crude Bothrops venom varies according the isogenic strain (A/J > C57Bl/6 > A/Sn > BALB/c > C3H/HePas > DBA/2 > C3H/He); (b)BALB/c mice (LD50=100.0 microg) were injected i.p. with 50 microg of venom produced IL-6, IL-10, INF-gamma, TNF-alpha and NO in the serum. In vitro the cells from the mice injected and challenged with the venom only released IL-10 while peritoneal macrophages released IL-10, INF-gamma and less amounts of IL-6; (c) establishment of local inflammation and necrosis induced by the venom, coincides with the peaks of TNF-alpha, IFN-gamma and NO and the damage was neutralized when the venom was incubated with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops atrox venom is genetically dependent but MHC independent; that IL-6, IL-10, TNF-alpha, IFN-gamma and NO can be involved in the mediation of tissue damage; and that the major venom component inducers of the lesions are haemorrhagins. PMID:9883969

  7. Factor X activating Atractaspis snake venoms and the relative coagulotoxicity neutralising efficacy of African antivenoms.

    PubMed

    Oulion, Brice; Dobson, James S; Zdenek, Christina N; Arbuckle, Kevin; Lister, Callum; Coimbra, Francisco C P; Op den Brouw, Bianca; Debono, Jordan; Rogalski, Aymeric; Violette, Aude; Fourmy, Rudy; Frank, Nathaniel; Fry, Bryan G

    2018-05-15

    Atractaspis snake species are enigmatic in their natural history, and venom effects are correspondingly poorly described. Clinical reports are scarce but bites have been described as causing severe hypertension, profound local tissue damage leading to amputation, and deaths are on record. Clinical descriptions have largely concentrated upon tissue effects, and research efforts have focused upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances suggestive of procoagulant functions have been reported in some clinical cases, yet this aspect has been uninvestigated. We used a suite of assays to investigate the coagulotoxic effects of venoms from six different Atractaspis specimens from central Africa. The procoagulant function of factor X activation was revealed, as was the pseudo-procoagulant function of direct cleavage of fibrinogen into weak clots. The relative neutralization efficacy of South African Antivenom Producer's antivenoms on Atractaspis venoms was boomslang>polyvalent>saw-scaled viper. While the boomslang antivenom was the most effective on Atractaspis venoms, the ability to neutralize the most potent Atractaspis species in this study was up to 4-6 times less effective than boomslang antivenom neutralizes boomslang venom. Therefore, while these results suggest cross-reactivity of boomslang antivenom with the unexpectedly potent coagulotoxic effects of Atractaspis venoms, a considerable amount of this rare antivenom may be needed. This report thus reveals potent venom actions upon blood coagulation that may lead to severe clinical effects with limited management strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Accessing Novel Conoidean Venoms: Biodiverse Lumun-lumun Marine Communities, An Untapped Biological and Toxinological Resource

    PubMed Central

    Seronay, Romell A.; Fedosov, Alexander E.; Astilla, Mary Anne; Watkins, Maren; Saguil, Noel; Heralde, Francisco M.; Tagaro, Sheila; Poppe, Guido T.; Aliño, Porfirio M.; Oliverio, Marco; Kantor, Yuri I.; Concepcion, Gisela P.; Olivera, Baldomero M.

    2010-01-01

    Cone snail venoms have yielded pharmacologically-active natural products of exceptional scientific interest. However, cone snails are a small minority of venomous molluscan biodiversity, the vast majority being tiny venomous morphospecies in the family Turridae. A novel method called lumun-lumun opens access to these micromolluscs and their venoms. Old fishing nets are anchored to the sea bottom for a period of 1–6 months and marine biotas rich in small molluscs are established. In a single lumun-lumun community, we found a remarkable gastropod biodiversity (155 morphospecies). Venomous predators belonging to the superfamily Conoidea (36 morphospecies) were the largest group, the majority being micromolluscs in the family Turridae. We carried out an initial analysis of the most abundant of the turrid morphospecies recovered, Clathurella (Lienardia) cincta (Dunker, 1871). In contrast to all cDNA clones characterized from cone snail venom ducts, one of the C. cincta clones identified encoded two different peptide precursors presumably translated from a single mRNA. The prospect of easily accessing so many different morphospecies of venomous marine snails raises intriguing toxinological possibilities: the 36 conoidean morphospecies in this one net alone have the potential to yield thousands of novel pharmacologically-active compounds. PMID:20005243

  9. Irradiation of the Crude Venom of Bothrops jararacussu to Obtain Toxoid

    NASA Astrophysics Data System (ADS)

    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.

  10. Characterization of the venom from the spider, Araneus gemma: search for a glutamate antagonist

    SciTech Connect

    Early, S.L.

    1985-01-01

    Venom from three spiders, Argiope aurantia, Neoscona arabesca, and Araneus gemma have been shown to inhibit the binding of L-(/sup 3/H)glutamate to both GBP and synaptic membranes. The venom from Araneus gemma was shown to be the most potent of the three venoms in inhibiting the binding of L-(/sup 3/H)glutamate to GBP. Therefore, Araneus gemma venom was selected for further characterization. Venom from Araneus gemma appeared to contain two factors which inhibit the binding of L-(/sup 3/H)glutamate to GBP and at least one factor that inhibits L-glutamate-stimulated /sup 35/SCN flux. Factor I is thought to be L-glutamic acid, based on:more » (1) its similar mobility to glutamic acid in thin-layer chromatography and amino acid analysis, (2) the presence of fingerprint molecular ion peaks for glutamate in the mass spectrum for the methanol:water (17:1) extract and for the fraction from the HPLC-purification of the crude venom, and (3) its L-glutamate-like interaction with the sodium-dependent uptake system. Factor II appears to be a polypeptide, possibly 21 amino acids in length, and does not appear to contain any free amino groups or tryptophan. While the venom does not appear to contain any indoleamines, three catecholamines (epinephrine, epinine, dopamine) and one catecholamine metabolite (DOPAC) were detected.« less

  11. The transcriptome recipe for the venom cocktail of Tityus bahiensis scorpion.

    PubMed

    de Oliveira, Ursula Castro; Candido, Denise Maria; Dorce, Valquíria Abrão Coronado; Junqueira-de-Azevedo, Inácio de Loiola Meirelles

    2015-03-01

    Scorpion venom is a mixture of peptides, including antimicrobial, bradykinin-potentiating and anionic peptides and small to medium proteins, such as ion channel toxins, metalloproteinases and phospholipases that together cause severe clinical manifestation. Tityus bahiensis is the second most medically important scorpion species in Brazil and it is widely distributed in the country with the exception of the North Region. Here we sequenced and analyzed the transcripts from the venom glands of T. bahiensis, aiming at identifying and annotating venom gland expressed genes. A total of 116,027 long reads were generated by pyrosequencing and assembled in 2891 isotigs. An annotation process identified transcripts by similarity to known toxins, revealing that putative venom components represent 7.4% of gene expression. The major toxins identified are potassium and sodium channel toxins, whereas metalloproteinases showed an unexpected high abundance. Phylogenetic analysis of deduced metalloproteinases from T. bahiensis and other scorpions revealed a pattern of ancient and intraspecific gene expansions. Other venom molecules identified include antimicrobial, anionic and bradykinin-potentiating peptides, besides several putative new venom components. This report provides the first attempt to massively identify the venom components of this species and constitutes one of the few transcriptomic efforts on the genus Tityus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Direct injection of venom by a predatory wasp into cockroach brain.

    PubMed

    Haspel, Gal; Rosenberg, Lior Ann; Libersat, Frederic

    2003-09-05

    In this article, we provide direct evidence for injection of venom by a wasp into the central nervous system of its cockroach prey. Venomous predators use neurotoxins that generally act at the neuromuscular junction, resulting in different types of prey paralysis. The sting of the parasitoid wasp Ampulex compressa is unusual, as it induces grooming behavior, followed by a long-term lethargic state of its insect prey, thus ultimately providing a living meal for the newborn wasp larvae. These behavioral modifications are induced only when a sting is inflicted into the head. These unique effects of the wasp venom on prey behavior suggest that the venom targets the insect's central nervous system. The mechanism by which behavior modifying compounds in the venom transverse the blood-brain barrier to induce these central and long-lasting effects has been the subject of debate. In this article, we demonstrate that the wasp stings directly into the target ganglia in the head of its prey. To prove this assertion, we produced "hot" wasps by injecting them with (14)C radiolabeled amino acids and used a combination of liquid scintillation and light microscopy autoradiography to trace radiolabeled venom in the prey. To our knowledge, this is the first direct evidence documenting targeted delivery of venom by a predator into the brain of its prey. Copyright 2003 Wiley Periodicals, Inc. J Neurobiol 56: 287-292, 2003

  13. Pelagia noctiluca (Scyphozoa) Crude Venom Injection Elicits Oxidative Stress and Inflammatory Response in Rats

    PubMed Central

    Bruschetta, Giuseppe; Impellizzeri, Daniela; Morabito, Rossana; Marino, Angela; Ahmad, Akbar; Spanò, Nunziacarla; La Spada, Giuseppa; Cuzzocrea, Salvatore; Esposito, Emanuela

    2014-01-01

    Cnidarian toxins represent a rich source of biologically active compounds. Since they may act via oxidative stress events, the aim of the present study was to verify whether crude venom, extracted from the jellyfish Pelagia noctiluca, elicits inflammation and oxidative stress processes, known to be mediated by Reactive Oxygen Species (ROS) production, in rats. In a first set of experiments, the animals were injected with crude venom (at three different doses 6, 30 and 60 µg/kg, suspended in saline solution, i.v.) to test the mortality and possible blood pressure changes. In a second set of experiments, to confirm that Pelagia noctiluca crude venom enhances ROS formation and may contribute to the pathophysiology of inflammation, crude venom-injected animals (30 µg/kg) were also treated with tempol, a powerful antioxidant (100 mg/kg i.p., 30 and 60 min after crude venom). Administration of tempol after crude venom challenge, caused a significant reduction of each parameter related to inflammation. The potential effect of Pelagia noctiluca crude venom in the systemic inflammation process has been here demonstrated, adding novel information about its biological activity. PMID:24727391

  14. Antivenom potential of ethanolic extract of Cordia macleodii bark against Naja venom.

    PubMed

    Soni, Pranay; Bodakhe, Surendra H

    2014-05-01

    To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity. Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities of Naja venom was investigated as recommended by WHO. At the dose of 400 and 800 mg/kg ethanolic extract of Cordia macleodii bark significantly inhibited the Naja venom induced lethality, hemorrhagic lesion, necrotizing lesion and edema in rats. Ethanolic extract of Cordia macleodii bark was effective in neutralizing the coagulant and defibrinogenating activity of Naja venom. The cardiotoxic effects in isolated frog heart and neurotoxic activity studies on frog rectus abdominus muscle were also antagonized by ethanolic extract of Cordia macleodii bark. It is concluded that the protective effect of extract of Cordia macleodii against Naja venom poisoning may be mediated by the cardiotonic, proteolysin neutralization, anti-inflammatory, antiserotonic and antihistaminic activity. It is possible that the protective effect may also be due to precipitation of active venom constituents.

  15. Antivenom potential of ethanolic extract of Cordia macleodii bark against Naja venom

    PubMed Central

    Soni, Pranay; Bodakhe, Surendra H.

    2014-01-01

    Objective To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity. Methods Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities of Naja venom was investigated as recommended by WHO. Results At the dose of 400 and 800 mg/kg ethanolic extract of Cordia macleodii bark significantly inhibited the Naja venom induced lethality, hemorrhagic lesion, necrotizing lesion and edema in rats. Ethanolic extract of Cordia macleodii bark was effective in neutralizing the coagulant and defibrinogenating activity of Naja venom. The cardiotoxic effects in isolated frog heart and neurotoxic activity studies on frog rectus abdominus muscle were also antagonized by ethanolic extract of Cordia macleodii bark. Conclusions It is concluded that the protective effect of extract of Cordia macleodii against Naja venom poisoning may be mediated by the cardiotonic, proteolysin neutralization, anti-inflammatory, antiserotonic and antihistaminic activity. It is possible that the protective effect may also be due to precipitation of active venom constituents. PMID:25183127

  16. Stenotrophomonas-Like Bacteria Are Widespread Symbionts in Cone Snail Venom Ducts.

    PubMed

    Torres, Joshua P; Tianero, Maria Diarey; Robes, Jose Miguel D; Kwan, Jason C; Biggs, Jason S; Concepcion, Gisela P; Olivera, Baldomero M; Haygood, Margo G; Schmidt, Eric W

    2017-12-01

    Cone snails are biomedically important sources of peptide drugs, but it is not known whether snail-associated bacteria affect venom chemistry. To begin to answer this question, we performed 16S rRNA gene amplicon sequencing of eight cone snail species, comparing their microbiomes with each other and with those from a variety of other marine invertebrates. We show that the cone snail microbiome is distinct from those in other marine invertebrates and conserved in specimens from around the world, including the Philippines, Guam, California, and Florida. We found that all venom ducts examined contain diverse 16S rRNA gene sequences bearing closest similarity to Stenotrophomonas bacteria. These sequences represent specific symbionts that live in the lumen of the venom duct, where bioactive venom peptides are synthesized. IMPORTANCE In animals, symbiotic bacteria contribute critically to metabolism. Cone snails are renowned for the production of venoms that are used as medicines and as probes for biological study. In principle, symbiotic bacterial metabolism could either degrade or synthesize active venom components, and previous publications show that bacteria do indeed contribute small molecules to some venoms. Therefore, understanding symbiosis in cone snails will contribute to further drug discovery efforts. Here, we describe an unexpected, specific symbiosis between bacteria and cone snails from around the world. Copyright © 2017 American Society for Microbiology.

  17. Venom-based peptide therapy: insights into anti-cancer mechanism

    PubMed Central

    Ma, Rui; Mahadevappa, Ravikiran; Kwok, Hang Fai

    2017-01-01

    The 5-year relative survival rate of all types of cancer has increased significantly over the past three decades partly due to the targeted therapy. However, still there are many targeted therapy drugs could play a role only in a portion of cancer patients with specific molecular alternation. It is necessary to continue to develop new biological agents which could be used alone and/or in combination with current FDA approved drugs to treat complex cancer diseases. Venom-based drugs have been used for hundreds of years in human history. Nevertheless, the venom-origin of the anti-cancer drug do rarely appear in the pharmaceutical market; and this is due to the fact that the mechanism of action for a large number of the venom drug such as venom-based peptide is not clearly understood. In this review, we focus on discussing some identified venom-based peptides and their anti-cancer mechanisms including the blockade of cancer cell proliferation, invasion, angiogenesis, and metastasis (hallmarks of cancer) to fulfill the gap which is hindering their use in cancer therapy. Furthermore, it also highlights the importance of immunotherapy based on venom peptide. Overall, this review provides readers for further understanding the mechanism of venom peptide and elaborates on the need to explore peptide-based therapeutic strategies. PMID:29246030

  18. [Treatment of Rheumatoid Arthritis by Bee-venom Acupuncture].

    PubMed

    Chen, Shi-Yun; Zhou, Peng; Qin, Ye

    2018-04-25

    To study the clinical efficacy and safety of bee-venom acupuncture therapy for rheumatoid arthritis (RA). A total of 120 cases of RA patients were randomized into bee-sting acupuncture group (treatment) and western medicine group (control) in accordance with the random number table. The patients of the control group were treated by oral administration of Methotrexate (10 mg, once a week) and Celecoxlb (0.2 g, once a day), and those of the treatment group treated by 5 to 15 bee stings of Ashi -points or acupoints according to different conditions and corporeity, and with the bee-sting retained for about 5 min every time, once every other day. The treatment lasted for 8 weeks. The therapeutic effect was assessed by examining symptoms and signs of the affected joints as morning stiffness duration, swollen/tender joint counts (indexes), handgrip strength, 15 m-walking time, visual analogue scale (VAS), Disease Activity Score including a 28-joint count (DAS 28), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibody (ACCPA); and for assessing the safety of bee-venom acupuncture, the patients' responses of fever, enlargement of lymph nodes, regional red and swollen, itching, blood and urine tests for routine were examined. Findings of DAS 28 responses displayed that of the two 60 cases in the control and bee-venom acupuncture groups, 15 and 18 experienced marked improvement, 33 and 32 were effective, 12 and 10 ineffective, with the effective rates being 80% and 83. 33%, respectively. No significant difference was found between the two groups in the effective rate ( P >0.05). After the treatment, both groups have witnessed a marked decrease in the levels of morning stiffness duration, arthralgia index, swollen joint count index, joint tenderness index, 15 m walking time, VAS, RF, ESR, CRP and ACCPA, and an obvious increase of handgrip strength relevant to their own levels of pre-treatment in each

  19. Risk Associated with Bee Venom Therapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Park, Jeong Hwan; Yim, Bo Kyung; Lee, Jun-Hwan; Lee, Sanghun; Kim, Tae-Hun

    2015-01-01

    Objective The safety of bee venom as a therapeutic compound has been extensively studied, resulting in the identification of potential adverse events, which range from trivial skin reactions that usually resolve over several days to life-threating severe immunological responses such as anaphylaxis. In this systematic review, we provide a summary of the types and prevalence of adverse events associated with bee venom therapy. Methods We searched the literature using 12 databases from their inception to June 2014, without language restrictions. We included all types of clinical studies in which bee venom was used as a key intervention and adverse events that may have been causally related to bee venom therapy were reported. Results A total of 145 studies, including 20 randomized controlled trials, 79 audits and cohort studies, 33 single-case studies, and 13 case series, were evaluated in this review. The median frequency of patients who experienced adverse events related to venom immunotherapy was 28.87% (interquartile range, 14.57–39.74) in the audit studies. Compared with normal saline injection, bee venom acupuncture showed a 261% increased relative risk for the occurrence of adverse events (relative risk, 3.61; 95% confidence interval, 2.10 to 6.20) in the randomized controlled trials, which might be overestimated or underestimated owing to the poor reporting quality of the included studies. Conclusions Adverse events related to bee venom therapy are frequent; therefore, practitioners of bee venom therapy should be cautious when applying it in daily clinical practice, and the practitioner’s education and qualifications regarding the use of bee venom therapy should be ensured. PMID:25996493

  20. NEUTRALIZATION OF TWO NORTH AMERICAN CORAL SNAKE VENOMS WITH UNITED STATES AND MEXICAN ANTIVENOMS

    PubMed Central

    Sánchez, Elda E.; Lopez-Johnston, Juan C.; Rodríguez-Acosta, Alexis; Pérez, John C.

    2009-01-01

    Elapid snakes throughout the world are considered very lethal containing neurotoxic venoms that affect the nervous system. When humans are envenomated it is considered a serious medical emergency, and antivenom is the main form of treatment considered, in spite of the fact that some patients may only survive under intensive therapy treatment such as respiratory support. Coral snakes are part of the family Elapidae and envenomations by these snakes are very low (< 2% of total snakebites) in most countries from southeastern United States to Argentina. In the United States there are only two species of coral snakes of medical importance which belong to the Micrurus genera: Micrurus fulvius fulvius (Eastern coral snake) and M. tener tener (Texas coral snake). In 2006, Wyeth pharmaceutical notified customers that the production of the North American Coral Snake Antivenin (NACSA) in the U.S. was discontinued and adequate supplies were available to meet historical needs through the end of October 2008; and therefore, it is of utmost important to consider other antivenoms as alternatives for the treatment of coral snake envenoming. One logical alternative is the coral snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to compare neutralization between NACSA and Coralmyn antivenoms with the North American coral snake venoms, the venom lethal doses (LD50) and antivenom effective doses (ED50) were determined in 18–20 g, female, BALB/c mice. Additionally, venom comparisons were determined through a non reduced SDS-PAGE for M. f. fulvius, M. t. tener and the Mexican coral snake venom, M. nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize 3 LD50 doses of all venom from both M. t. tener and M. f. fulvius, while Wyeth antivenom only neutralized M. f. fulvius venom and was not effective in neutralizing 3 LD50 doses of M. t. tener venom. Coralmyn is effective in the neutralization of both clinically important coral snake

  1. Neutralization of two North American coral snake venoms with United States and Mexican antivenoms.

    PubMed

    Sánchez, Elda E; Lopez-Johnston, Juan C; Rodríguez-Acosta, Alexis; Pérez, John C

    2008-02-01

    Elapid snakes throughout the world are considered very lethal, containing neurotoxic venoms that affect the nervous system. When humans are envenomated it is considered a serious medical emergency, and antivenom is the main form of treatment considered, in spite of the fact that some patients may only survive under intensive therapy treatment such as respiratory support. Coral snakes are part of the family Elapidae and envenomations by these snakes are very low (<2% of total snakebites) in most countries from southeastern United States to Argentina. In the United States, there are only two species of coral snakes of medical importance that belong to the Micrurus genera: Micrurus fulvius fulvius (Eastern coral snake) and Micrurus tener tener (Texas coral snake). In 2006, Wyeth pharmaceutical notified customers that the production of the North American coral snake antivenin (NACSA) in the US was discontinued and adequate supplies were available to meet historical needs through the end of October 2008; and therefore, it is of utmost important to consider other antivenoms as alternatives for the treatment of coral snake envenoming. One logical alternative is the coral snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to compare neutralization between NACSA and Coralmyn antivenoms with the North American coral snake venoms, the venom lethal doses (LD(50)) and antivenom effective doses (ED(50)) were determined in 18-20 g, female, BALB/c mice. Additionally, venom comparisons were determined through a non-reduced SDS-PAGE for M.f.fulvius, M.t.tener and the Mexican coral snake venom, Micrurus nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize three LD(50) doses of all venom from both M.t.tener and M.f.fulvius, while Wyeth antivenom only neutralized M.f.fulvius venom and was not effective in neutralizing three LD(50) doses of M.t.tener venom. Coralmyn is effective in the neutralization of both clinically important

  2. Antisnake Venom Activity of Hibiscus aethiopicus L. against Echis ocellatus and Naja n. nigricollis.

    PubMed

    Hasson, S S; Al-Jabri, A A; Sallam, T A; Al-Balushi, M S; Mothana, R A A

    2010-01-01

    The objective of the study is to investigate whether the Hibiscus aethiopicus L. plant has neutralization activity against venoms of two clinically important snakes. The H. aethiopicus was dried and extracted with water. Different assays were performed to evaluate the plant's acute toxicity and its anti-snake venom activities. The results showed that H. aethiopicus extract alone had no effect on the viability of C(2)C(12) muscle cells, but significantly (P < .05) protected muscle cells against the toxic effects of E. ocellatus venom at 55, 150, and 300 mug/mL. The maximum protective effect of the extract was exhibited at 75 mug/mL. The extract significantly (P < .001) inhibited the cytotoxic effects of E. ocellatus venom at 300 mug/mL. All rabbits (n = 10) and guinea pigs (n = 10) were alive after the two weeks of given the lethal dosage 16 g/Kg of the H. aethiopicus extract herbal solution. No abnormal behaviour was observed of both groups of animals. All guinea pigs (n = 3) treated with venoms alone (5 mg/kg) died. However, all guinea pigs (n = 21) treated with venom (5 mg/kg) and the extract (400 to 1000 mg/kg) survived. Guinea pigs (n = 3) treated with Naja n. nigricollis venom alone (2.5 mg/kg) and guinea pigs (n = 21) venom with the extract (400 to 1000 mg/kg) died. The H. aethiopicus completely (100%) blocked the haemorrhagic activity of E. ocellatus in the egg embryo at 3.3 mg/mL of extract. These findings suggest that H. aethiopicus may contain an endogenous inhibitor of venom-induced haemorrhage.

  3. Snake-venom resistance as a mammalian trophic adaptation: lessons from didelphid marsupials.

    PubMed

    Voss, Robert S; Jansa, Sharon A

    2012-11-01

    Mammals that prey on venomous snakes include several opossums (Didelphidae), at least two hedgehogs (Erinaceidae), several mongooses (Herpestidae), several mustelids, and some skunks (Mephitidae). As a group, these taxa do not share any distinctive morphological traits. Instead, mammalian adaptations for ophiophagy seem to consist only in the ability to resist the toxic effects of snake venom. Molecular mechanisms of venom resistance (as indicated by biochemical research on opossums, mongooses, and hedgehogs) include toxin-neutralizing serum factors and adaptive changes in venom-targeted molecules. Of these, toxin-neutralizing serum factors have received the most research attention to date. All of the toxin-neutralizing serum proteins discovered so far in both opossums and mongooses are human α1B-glycoprotein homologs that inhibit either snake-venom metalloproteinases or phospholipase A(2) myotoxins. By contrast, adaptive changes in venom-targeted molecules have received far less attention. The best-documented examples include amino-acid substitutions in mongoose nicotinic acetylcholine receptor that inhibit binding by α-neurotoxins, and amino-acid substitutions in opossum von Willebrand factor (vWF) that are hypothesized to weaken the bond between vWF and coagulopathic C-type lectins. Although multiple mechanisms of venom resistance are known from some species, the proteomic complexity of most snake venoms suggests that the evolved biochemical defences of ophiophagous mammals are likely to be far more numerous than currently recognized. Whereas most previous research in this field has been motivated by the potential for medical applications, venom resistance in ophiophagous mammals is a complex adaptation that merits attention from comparative biologists. Unfortunately, evolutionary inference is currently limited by ignorance about many relevant facts that can only be provided by future research. © 2012 The Authors. Biological Reviews © 2012 Cambridge

  4. A rational design for the nanoencapsulation of poisonous animal venoms in liposomes prepared with natural phospholipids.

    PubMed

    da Costa, Maria Helena Bueno; Sant'Anna, Osvaldo A; Quintilio, Wagner; Schwendener, Reto Albert; de Araujo, Pedro Soares

    2012-11-01

    Liposomes have been used since the 1970's to encapsulate drugs envisaging enhancement in efficacy and therapeutic index, avoidance of side effects and increase in the encapsulated agent stability. The major problem when encapsulating snake venoms is the liposomal membrane instability caused by venom phospholipases. Here the results obtained encapsulating Crotalus durissimus terrificus and a pool of Bothropic venoms within liposomes (LC and LB, respectively) used to produce anti-venom sera are presented. The strategy was to modify the immunization protocol to enhance antibody production and to minimize toxic effects by encapsulating inactivated venoms within stabilized liposomes. Chemically modified venoms were solubilized in a buffer containing an inhibitor and a chelating agent. The structures of the venoms were analyzed by UV, CD spectroscopy and ELISA. In spite of the differences in the helical content between natural and modified venoms, they were recognized by horse anti-sera. To maintain long-term stability, mannitol was used as a cryoprotectant. The encapsulation efficiencies were 59 % (LB) and 99 % (LC), as followed by filtration on Sephacryl S1000. Light scattering measurements led us to conclude that both, LB (119 ±47 nm) and LC (147±56 nm) were stable for 22 days at 4 °C, even after lyophilization. Genetically selected mice and mixed breed horses were immunized with these formulations. The animals did not show clinical symptoms of venom toxicity. Both, LB and LC enhanced by at least 30 % the antibody titers 25 days after injection and total IgG titers remained high 91 days after immunization. The liposomal formulation clearly exhibited adjuvant properties.

  5. Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis.

    PubMed

    Suzuki, M; Tanaka, T

    2006-06-01

    Ultrastructural studies on the reproductive tract and venom apparatus of a female braconid, Meteorus pulchricornis, revealed that the parasitoid lacks the calyx region in its oviduct, but possesses a venom gland with two venom gland filaments and a venom reservoir filled with white and cloudy fluid. Its venom gland cell is concaved and has a lumen filled with numerous granules. Transmisson electron microscopic (TEM) observation revealed that virus-like particles (VLPs) were produced in venom gland cells. The virus-like particle observed in M. pulchricornis (MpVLP) is composed of membranous envelopes with two different parts: a high-density core and a whitish low-density part. The VLPs of M. pulchricornis is also found assembling ultimately in the lumen of venom gland cell. Microvilli were found thrusting into the lumen of the venom gland cell and seem to aid in driving the matured MpVLPs to the common duct of the venom gland filament. Injection of MpVLPs into non-parasitized Pseudaletia separata hosts induced apoptosis in hemocytes, particularly granulocytes (GRs). Rate of apoptosis induced in GRs peaked 48h after VLP injection. While a large part of the GR population collapsed due to apoptosis caused by MpVLPs, the plasmatocyte population was minimally affected. The capacity of MpVLPs to cause apoptosis in host's hemocytes was further demonstrated by a decrease ( approximately 10-fold) in ability of host hemocytes to encapsulate fluorescent latex beads when MpVLPs were present. Apparently, the reduced encapsulation ability was due to a decrease in the GR population resulting from MpVLP-induced apoptosis.

  6. Evaluation of pro-inflammatory events induced by Bothrops alternatus snake venom.

    PubMed

    Echeverría, Silvina; Leiguez, Elbio; Guijas, Carlos; do Nascimento, Neide Galvão; Acosta, Ofelia; Teixeira, Catarina; Leiva, Laura C; Rodríguez, Juan Pablo

    2018-02-01

    Inflammation is a major local feature of envenomation by bothropic snakes being characterized by a prominent local edema, pain, and extensive swelling. There are reports demonstrating that whole Bothrops snake venoms and toxins isolated from them are able to activate macrophages functions, such as phagocytosis, production of reactive oxygen, cytokines and eicosanoids, however, little is known about the effects of Bothrops alternatus (B.a.) venom on macrophages. In this work, we evaluated the proinflammatory effects of B.a. venom with in vivo and in vitro experiments using the Raw 264.7 cell line and mouse peritoneal macrophages. We detected that B.a. venom augments cell permeability (2-fold), and cellular extravasation (mainly neutrophils), increase proinflammatory cytokines IL1 (∼300-fold), IL12 (∼200-fold), and TNFα (∼80-fold) liberation and induce the expression of enzymes related to lipid signaling, such as cPLA 2α and COX-2. Additionally, using lipidomic techniques we detected that this venom produces a release of arachidonic acid (∼10 nMol/mg. Protein) and other fatty acids (16:0 and 18:1 n-9c). Although much of these findings were described in inflammatory processes induced by other bothropic venoms, here we demonstrate that B.a. venom also stimulates pro-inflammatory pathways involving lipid mediators of cell signaling. In this sense, lipidomics analysis of macrophages stimulated with B.a. venom evidenced that the main free fatty acids are implicated in the inflammatory response, and also demonstrated that this venom, is able to activate lipid metabolism even with a low content of PLA 2 . Copyright © 2017. Published by Elsevier B.V.

  7. Comparative Study of Biological Activities of Venom from Colubrid Snakes Rhabdophis tigrinus (Yamakagashi) and Rhabdophis lateralis

    PubMed Central

    Komori, Yumiko; Hifumi, Toru; Yamamoto, Akihiko; Sakai, Atsushi; Sawabe, Kyoko; Nikai, Toshiaki

    2017-01-01

    Rhabdophis lateralis, a colubrid snake distributed throughout the continent of Asia, has recently undergone taxonomic revisions. Previously, Rhabdophis lateralis was classified as a subspecies of R. tigrinus (Yamakagashi) until 2012, when several genetic differences were discovered which classified this snake as its own species. To elucidate the toxicity of venom from this poorly studied colubrid, various biological activities were compared between the venom from the two snake species. The components of their venom were compared by the elution profiles of reversed-phase HPLC and SDS-PAGE, and gel filtrated fractions were tested for effects on blood coagulation. Proteolytic activities of these fractions were also assayed by using synthetic substrates, fibrinogen, and matrix proteins. Similar to the R. tigrinus venom, the higher molecular weight fraction of R. lateralis venom contained a prothrombin activator. Both prothrombin time (PT) and activated partial thromboplastin time (APTT) of human plasma were shortened by the addition of R. lateralis and R. tigrinus venom. The thrombin formation was estimated by the uses of SDS-PAGE and chromogenic substrates. These venom fractions also possessed very specific proteinase activity on human fibrinogen, but the substrates for matrix metalloproteinase, such as collagen and laminin, were not hydrolyzed. However, there were some notable differences in reactivity to synthetic substrates for matrix metalloproteinase, and R. tigrinus venom possessed relatively higher activity. Our chemical investigation indicates that the components included in both venoms resemble each other closely. However, the ratio of components and proteolytic activity of some ingredients are slightly different, indicating differences between two closely-related snakes. PMID:29149042

  8. Antitoxin activity of aqueous extract of Cyclea peltata root against Naja naja venom

    PubMed Central

    Sivaraman, Thulasi; Sreedevi, N. S.; Meenatchisundaram, S.; Vadivelan, R.

    2017-01-01

    OBJECTIVES: Snakebites are a significant and severe global health problem. Till date, anti-snake venom serum is the only beneficial remedy existing on treating the snakebite victims. As antivenom was reported to induce early or late adverse reactions to human beings, snake venom neutralizing potential for Cyclea peltata root extract was tested for the present research by ex vivo and in vivo approaches on Naja naja toxin. MATERIALS AND METHODS: Ex vivo evaluation of venom toxicity and neutralization assays was carried out. The root extracts from C. peltata were used to evaluate the Ex vivo neutralization tests such as acetylcholinesterase, protease, direct hemolysis assay, phospholipase activity, and procoagulant activity. Gas chromatography-mass spectrometry (GC-MS) analysis from root extracts of C. peltata was done to investigate the bioactive compounds. RESULTS: The in vivo calculation of venom toxicity (LD50) of N. naja venom remained to be 0.301 μg. C. peltata root extracts were efficiently deactivated the venom lethality, and effective dose (ED50) remained to be 7.24 mg/3LD50 of N. naja venom. C. peltata root extract was found effective in counteracting all the lethal effects of venom. GC-MS analysis of the plant extract revealed the presence of antivenom compounds such as tetradecanoic and octadecadienoic acid which have neutralizing properties on N. naja venom. CONCLUSION: The result from the ex vivo and in vivo analysis indicates that C. peltata plant root extract possesses significant compounds such as tetradecanoic acid hexadecanoic acid, heptadecanoic acid, and octadecadienoic acid which can counteract the toxins present in N. naja. PMID:29326487

  9. Antitoxin activity of aqueous extract of Cyclea peltata root against Naja naja venom.

    PubMed

    Sivaraman, Thulasi; Sreedevi, N S; Meenatchisundaram, S; Vadivelan, R

    2017-01-01

    Snakebites are a significant and severe global health problem. Till date, anti-snake venom serum is the only beneficial remedy existing on treating the snakebite victims. As antivenom was reported to induce early or late adverse reactions to human beings, snake venom neutralizing potential for Cyclea peltata root extract was tested for the present research by ex vivo and in vivo approaches on Naja naja toxin. Ex vivo evaluation of venom toxicity and neutralization assays was carried out. The root extracts from C. peltata were used to evaluate the Ex vivo neutralization tests such as acetylcholinesterase, protease, direct hemolysis assay, phospholipase activity, and procoagulant activity. Gas chromatography-mass spectrometry (GC-MS) analysis from root extracts of C. peltata was done to investigate the bioactive compounds. The in vivo calculation of venom toxicity (LD 50 ) of N. naja venom remained to be 0.301 μg. C. peltata root extracts were efficiently deactivated the venom lethality, and effective dose (ED 50 ) remained to be 7.24 mg/3LD 50 of N. naja venom. C. peltata root extract was found effective in counteracting all the lethal effects of venom. GC-MS analysis of the plant extract revealed the presence of antivenom compounds such as tetradecanoic and octadecadienoic acid which have neutralizing properties on N. naja venom. The result from the ex vivo and in vivo analysis indicates that C. peltata plant root extract possesses significant compounds such as tetradecanoic acid hexadecanoic acid, heptadecanoic acid, and octadecadienoic acid which can counteract the toxins present in N. naja .

  10. Mast cells and IgE in defense against venoms: Possible "good side" of allergy?

    PubMed

    Galli, Stephen J; Starkl, Philipp; Marichal, Thomas; Tsai, Mindy

    2016-01-01

    Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus) Venoms.

    PubMed

    Chaisakul, Janeyuth; Rusmili, Muhamad Rusdi Ahmad; Hodgson, Wayne C; Hatthachote, Panadda; Suwan, Kijja; Inchan, Anjaree; Chanhome, Lawan; Othman, Iekhsan; Chootip, Krongkarn

    2017-03-29

    Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait ( Bungarus candidus ) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the in vivo and in vitro cardiovascular effects of B. candidus venoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. B. candidus venoms (50 µg/kg-100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg-100 µg/ml) induced concentration-dependent relaxation (EC 50 = 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration-response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by B. candidus venoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.

  12. The putative serine protease inhibitor Api m 6 from Apis mellifera venom: recombinant and structural evaluation.

    PubMed

    Michel, Y; McIntyre, M; Ginglinger, H; Ollert, M; Cifuentes, L; Blank, S; Spillner, E

    2012-01-01

    Immunoglobulin (Ig) E-mediated reactions to honeybee venom can cause severe anaphylaxis, sometimes with fatal consequences. Detailed knowledge of the allergic potential of all venom components is necessary to ensure proper diagnosis and treatment of allergy and to gain a better understanding of the allergological mechanisms of insect venoms. Our objective was to undertake an immunochemical and structural evaluation of the putative low-molecular-weight serine protease inhibitor Api m 6, a component of honeybee venom. We recombinantly produced Api m 6 as a soluble protein in Escherichia coli and in Spodoptera frugiperda (Sf9) insect cells.We also assessed specific IgE reactivity of venom-sensitized patients with 2 prokaryotically produced Api m 6 variants using enzyme-linked immunosorbent assay. Moreover, we built a structural model ofApi m 6 and compared it with other protease inhibitor structures to gain insights into the function of Api m 6. In a population of 31 honeybee venom-allergic patients, 26% showed specific IgE reactivity with prokaryotically produced Api m 6, showing it to be a minor but relevant allergen. Molecular modeling of Api m 6 revealed a typical fold of canonical protease inhibitors, supporting the putative function of this venom allergen. Although Api m 6 has a highly variant surface charge, its epitope distribution appears to be similar to that of related proteins. Api m 6 is a honeybee venom component with IgE-sensitizing potential in a fraction of venom-allergic patients. Recombinant Api m 6 can help elucidate individual component-resolved reactivity profiles and increase our understanding of immune responses to low-molecular-weight allergens

  13. Low-molecular-weight compounds with anticoagulant activity from the scorpion Heterometrus laoticus venom.

    PubMed

    Thien, Tran Vu; Anh, Hoang Ngoc; Trang, Nguyen Thi Thuy; Trung, Phung Van; Khoa, Nguyen Cuu; Osipov, A V; Dubovskii, P V; Ivanov, I A; Arseniev, A S; Tsetlin, V I; Utkin, Yu N

    2017-09-01

    Low-molecular-weight compounds with anticoagulant activity were isolated from the scorpion Heterometrus laoticus venom. The determination of the structure of the isolated compounds by nuclear magnetic resonance and mass spectrometry showed that one of the isolated compounds is adenosine, and the other two are dipeptides leucyl-tryptophan and isoleucyl-tryptophan. The anticoagulant properties of adenosine, which is an inhibitor of platelet aggregation, is well known, but its presence in scorpion venom is shown for the first time. The ability of leucyl-tryptophan and isoleucyl-tryptophan to slow down blood clotting and their presence in scorpion venom are also established for the first time.

  14. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword

    PubMed Central

    Chen, Jun; Lariviere, William R.

    2010-01-01

    Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. PMID:20558236

  15. Venom Profiling of a Population of the Theraphosid Spider Phlogius crassipes Reveals Continuous Ontogenetic Changes from Juveniles through Adulthood.

    PubMed

    Santana, Renan C; Perez, David; Dobson, James; Panagides, Nadya; Raven, Robert J; Nouwens, Amanda; Jones, Alun; King, Glenn F; Fry, Bryan G

    2017-03-25

    Theraphosid spiders (tarantulas) are venomous arthropods found in most tropical and subtropical regions of the world. Tarantula venoms are a complex cocktail of toxins with potential use as pharmacological tools, drugs and bioinsecticides. Although numerous toxins have been isolated from tarantula venoms, little research has been carried out on the venom of Australian tarantulas. We therefore investigated the venom profile of the Australian theraphosid spider Phlogius crassipes and examined whether there are ontogenetic changes in venom composition. Spiders were divided into four ontogenic groups according to cephalothorax length, then the venom composition of each group was examined using gel electrophoresis and mass spectrometry. We found that the venom of P. crassipes changes continuously during development and throughout adulthood. Our data highlight the need to investigate the venom of organisms over the course of their lives to uncover and understand the changing functions of venom and the full range of toxins expressed. This in turn should lead to a deeper understanding of the organism's ecology and enhance the potential for biodiscovery.

  16. Venom Profiling of a Population of the Theraphosid Spider Phlogius crassipes Reveals Continuous Ontogenetic Changes from Juveniles through Adulthood

    PubMed Central

    Santana, Renan C.; Perez, David; Dobson, James; Panagides, Nadya; Raven, Robert J.; Nouwens, Amanda; Jones, Alun; King, Glenn F.; Fry, Bryan G.

    2017-01-01

    Theraphosid spiders (tarantulas) are venomous arthropods found in most tropical and subtropical regions of the world. Tarantula venoms are a complex cocktail of toxins with potential use as pharmacological tools, drugs and bioinsecticides. Although numerous toxins have been isolated from tarantula venoms, little research has been carried out on the venom of Australian tarantulas. We therefore investigated the venom profile of the Australian theraphosid spider Phlogius crassipes and examined whether there are ontogenetic changes in venom composition. Spiders were divided into four ontogenic groups according to cephalothorax length, then the venom composition of each group was examined using gel electrophoresis and mass spectrometry. We found that the venom of P. crassipes changes continuously during development and throughout adulthood. Our data highlight the need to investigate the venom of organisms over the course of their lives to uncover and understand the changing functions of venom and the full range of toxins expressed. This in turn should lead to a deeper understanding of the organism’s ecology and enhance the potential for biodiscovery. PMID:28346332

  17. [Toxicological and immunological aspects of scorpion venom (Tytius pachyurus): neutralizing capacity of antivenoms produced in Latin America].

    PubMed

    Barona, Jacqueline; Otero, Rafael; Núñez, Vitelbina

    2004-03-01

    The toxicity and immunochemical properties of Tityus pachyurus Pocock scorpion venom was characterized, as well as the neutralization capacity against it by three anti-scorpion antivenoms (Alacramyn, Instituto Bioclón, México; Suero antiescorpiónico, Instituto Butantán, Sao Paulo, Brasil; and Suero antiescorpiónico, Centro de Biotecnología, Universidad Central de Venezuela, Caracas, Venezuela). The venom yield, obtained by manual milking, 680+/-20 microg venom, a 50% lethal dose in mice was 4.8 microg/kg (90 microg for an 18-20 g mouse). The most common symptoms of venom poisoning in mice were sialorrhea, respiratory distress, profuse sweating, ataxia, behavior alterations (restlessness, somnolence) and hyperglycemia at 3 and 24 hours after subcutaneous venom injection (0.5 LD50). The neutralizing capacity of Bioclón (México City) and Butantán (Sao Paulo) antivenoms (for a 50% effective dose) was 330 and 292 microg venom/ml antivenom, respectively. The Biotecnología (Caracas) antivenom did not neutralize the lethal effect of venom. By electrophoresis (SDS-PAGE) was demonstrated that the venom contains proteins from less than 14 kd to 97 kd. The Western blots indicated immunological reactivity of the three antivenoms with most of venom components, including proteins of low molecular mass (<14 kd). The results allow to conclude that T. pachyurus venom is neutralized efficiently by anti-scorpion antivenoms produced in México and Brasil.

  18. Sexually dimorphic venom proteins in long-jawed orb-weaving spiders (Tetragnatha) comprise novel gene families

    PubMed Central

    Zobel-Thropp, Pamela A.; Bulger, Emily A.; Cordes, Matthew H.J.; Binford, Greta J.; Gillespie, Rosemary G.

    2018-01-01

    Venom has been associated with the ecological success of many groups of organisms, most notably reptiles, gastropods, and arachnids. In some cases, diversification has been directly linked to tailoring of venoms for dietary specialization. Spiders in particular are known for their diverse venoms and wide range of predatory behaviors, although there is much to learn about scales of variation in venom composition and function. The current study focuses on venom characteristics in different sexes within a species of spider. We chose the genus Tetragnatha (Tetragnathidae) because of its unusual courtship behavior involving interlocking of the venom delivering chelicerae (i.e., the jaws), and several species in the genus are already known to have sexually dimorphic venoms. Here, we use transcriptome and proteome analyses to identify venom components that are dimorphic in Tetragnatha versicolor. We present cDNA sequences including unique, male-specific high molecular weight proteins that have remote, if any, detectable similarity to known venom components in spiders or other venomous lineages and have no detectable homologs in existing databases. While the function of these proteins is not known, their presence in association with the cheliceral locking mechanism during mating together with the presence of prolonged male-male mating attempts in a related, cheliceral-locking species (Doryonychus raptor) lacking the dimorphism suggests potential for a role in sexual communication. PMID:29876146

  19. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom.

    PubMed

    Olmedo, Hidekel; Herrera, María; Rojas, Leonardo; Villalta, Mauren; Vargas, Mariángela; Leiguez, Elbio; Teixeira, Catarina; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo; Montero, Mavis L

    2014-01-01

    The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.

  20. Crude venom from nematocysts of Pelagia noctiluca (Cnidaria: Scyphozoa) elicits a sodium conductance in the plasma membrane of mammalian cells

    NASA Astrophysics Data System (ADS)

    Morabito, Rossana; Costa, Roberta; Rizzo, Valentina; Remigante, Alessia; Nofziger, Charity; La Spada, Giuseppa; Marino, Angela; Paulmichl, Markus; Dossena, Silvia

    2017-01-01

    Cnidarians may negatively impact human activities and public health but concomitantly their venom represents a rich source of bioactive substances. Pelagia noctiluca is the most venomous and abundant jellyfish of the Mediterranean Sea and possesses a venom with hemolytic and cytolytic activity for which the mechanism is largely unknown. Here we show that exposure of mammalian cells to crude venom from the nematocysts of P. noctiluca profoundly alters the ion conductance of the plasma membrane, therefore affecting homeostatic functions such as the regulation and maintenance of cellular volume. Venom-treated cells exhibited a large, inwardly rectifying current mainly due to permeation of Na+ and Cl-, sensitive to amiloride and completely abrogated following harsh thermal treatment of crude venom extract. Curiously, the plasma membrane conductance of Ca2+ and K+ was not affected. Current-inducing activity was also observed following delivery of venom to the cytosolic side of the plasma membrane, consistent with a pore-forming mechanism. Venom-induced NaCl influx followed by water and consequent cell swelling most likely underlie the hemolytic and cytolytic activity of P. noctiluca venom. The present study underscores unique properties of P. noctiluca venom and provides essential information for a possible use of its active compounds and treatment of envenomation.

  1. Identification and characterization of novel reptile cathelicidins from elapid snakes.

    PubMed

    Zhao, Hui; Gan, Tong-Xiang; Liu, Xiao-Dong; Jin, Yang; Lee, Wen-Hui; Shen, Ji-Hong; Zhang, Yun

    2008-10-01

    Three cDNA sequences coding for elapid cathelicidins were cloned from constructed venom gland cDNA libraries of Naja atra, Bungarus fasciatus and Ophiophagus hannah. The open reading frames of the cloned elapid cathelicidins were all composed of 576bp and coded for 191 amino acid residue protein precursors. Each of the deduced elapid cathelicidin has a 22 amino acid residue signal peptide, a conserved cathelin domain of 135 amino acid residues and a mature antimicrobial peptide of 34 amino acid residues. Unlike the highly divergent cathelicidins in mammals, the nucleotide and deduced protein sequences of the three cloned elapid cathelicidins were remarkably conserved. All the elapid mature cathelicidins were predicted to be cleaved at Valine157 by elastase. OH-CATH, the deduced mature cathelicidin from king cobra, was chemically synthesized and it showed strong antibacterial activity against various bacteria with minimal inhibitory concentration of 1-20microg/ml in the presence of 1% NaCl. Meanwhile, the synthetic peptide showed no haemolytic activity toward human red blood cells even at a high dose of 200microg/ml. Phylogenetic analysis of cathelicidins from vertebrate suggested that elapid and viperid cathelicidins were grouped together in the tree. Snake cathelicidins were evolutionary closely related to the neutrophilic granule proteins (NGPs) from mouse, rat and rabbit. Snake cathelicidins also showed a close relationship with avian fowlicidins (1-3) and chicken myeloid antimicrobial peptide 27. Elapid cathelicidins might be used as models for the development of novel therapeutic drugs.

  2. Follow-up of venom immunotherapy (VIT) based on conventional techniques and monitoring of immunoglobulin E to individual venom allergens.

    PubMed

    Carballada, F; Boquete, M; Núñez, R; Lombardero, M; de la Torre, F

    2010-01-01

    To assess the efficacy of venom immunotherapy (VIT) and monitor changes in in vivo and in vitro test results after 5 years of treatment and subsequent follow-up. To study the profile of immunoglobulin (Ig) E to individual allergens prior to treatment and 1 year afterwards. We studied 562 patients with hymenoptera venom allergy (438 to bee, 124 to wasp), all of whom underwent immunotherapy with Apis or Vespula extract. The patients were followed up using conventional in vivo and in vitro tests, and in 51 cases, specific IgE against the main hymenoptera allergens was measured before starting and after 1 year of treatment. Of the 387 patients who completed VLT, 130 sensitized to Apis and 68 to Vespula suffered spontaneous re-stings during treatment. Of these, 123 (94.6%) did not suffer any reaction and 64 (94.1%) suffered only a local reaction. Sixty-two patients sensitized to Apis and 14 sensitized to Vespula suffered spontaneous re-stings after stopping treatment. Only 3 patients suffered a systemic reaction (grade I Müller). At the end of treatment, the results of skin tests and specific IgE to whole extract improved significantly. Reductions in IgE to the main allergens were observed after 1 year of treatment (median differences in Ves v 5, -238.0, P = .0425; and in Api m 1, -183.0, P = .0024). The high rate of spontaneous re-stings shows that efficacy is maintained for years after completing treatment in a real-world setting. Determination of IgE to individual venom allergens may offer new perspectives in the diagnosis and follow-up of these patients.

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

    PubMed

    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

  4. Venom characterization of the Amazonian scorpion Tityus metuendus.

    PubMed

    Batista, C V F; Martin