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action of vipera ammodytes venom and its fractions on the isolated rat heart. 1979524389
pharmacological study of phospholipase a from vipera ammodytes venom. 1976982478
purification and properties of a kininogenin from the venom of vipera ammodytes ammodytes.a kininogenin (ec 3.4.21.8) was purified from the venom of vipera ammodytes ammodytes (european sand viper) by a combination of gel filtration and ion-exchange chromatography. the enzyme is approximately six times more active than bovine trypsin in its ability to release vasoactive peptides from a plasma precursor. the kininogenin is a glycoprotein containing 18-20% by weight of carbohydrate. it showed a mol. wt. of 40500 on gel filtration. gel electrophoresis of the reduced sample in the presen ...19761275896
effects of sand viper (cerastes cerastes) venom on isolated smooth muscle and heart and on haematological and cardiovascular parameters in the guinea-pig.the effects of the venom of the sand viper (cerastes cerastes) on haematological and cardiovascular parameters and on isolated ileum, trachea, pulmonary artery and atrium from the guinea-pig were studied. in concentrations from 0.2 micrograms/ml to 0.6 mg/ml, snake venom caused concentration-dependent relaxation of the longitudinal ileal segments and the epinephrine-precontracted pulmonary artery rings, increased the tone of the tracheal rings and increased the rate of the spontaneously beating ...19921440630
the primary structure of ammodytin l, a myotoxic phospholipase a2 homologue from vipera ammodytes venom.a new myotoxic phospholipase a2 homologue, having a serine residue in position 49 instead of highly conserved aspartic acid, was found in the venom of vipera ammodytes. the primary structure revealed additional mutations in the positions important for enzymatic activity. tyr28 is exchanged for a histidine and gly33 for asparagine. these changes render earlier-reported weak enzymatic activity unlikely. the role of this rather abundant venom fraction is apparently in myotoxicity, which was confirm ...19911765075
neutralization of the activity of vipera ammodytes ammodytes snake venom on myocardium of rats by antitoxinum viperinum: a histopathological study.antitoxinum viperinum was tested for its ability to prevent alteration of the myocardium induced by vipera ammodytes ammodytes venom. antivenom was injected intraperitoneally either immediately, 30 min or 2 hr after the intraperitoneal injection of venom. the light microscopic examination showed that the antiserum neutralized the effects of venom and antivenom might be useful in treating v.a. ammodytes venom poisoning.19911818120
effect of venom from cerastes cerastes (egyptian sand viper) on luminol-dependent chemiluminescence of human blood phagocyte cells.cerastes cerastes venom added in vitro to human whole blood caused a marked inhibitory effect on the luminol-dependent chemiluminescence induced by phorbol myristate acetate (pma) or opsonized zymosan on phagocyte cells. the inhibitory effect produced by the venom was both dose- and time-dependent when pma was used as the stimulant of the oxidative burst. similarly, the venom produced a significant inhibitory effect when added to isolated polymorphonuclear leukocytes (pmns). incubation of the is ...19902176186
the amino acid sequence of a myotoxic phospholipase from the venom of bothrops asper.a myotoxic, basic phospholipase a2 (pi greater than 9.5) with anticoagulant activity has been purified from the venom of bothrops asper, and its amino acid sequence determined by automated edman degradation. it is distinct from the b. asper phospholipase a2 known as myotoxin i [lomonte, b. and gutierrez, j. m., 1989, toxicon 27, 725] but cross-reacts with myotoxin i rabbit antisera, suggesting that the proteins are closely related isoforms. to our knowledge, this is the first myotoxic phospholip ...19902327788
purification and characterization of phosphodiesterase (exonuclease) from cerastes cerastes (egyptian sand viper) venom.a venom exonuclease 'phosphodiesterase' (e.c. 3.1.4.1) has been purified from cerastes cerastes venom by a combination of gel filtration on sephadex g-100 superfine and ion exchange chromatography on deae-sepharose. the enzyme showed a single band on page and sds-page and had a molecular weight of 110,000. the final preparation was purified 28 fold. it had no carbohydrate and it did not have protease or 5'-nucleotidase activities. optimum temperature for enzyme activity was 56 degrees c. the enz ...19872829390
proteolysis in vitro of low and high density lipoproteins in human plasma by cerastes cerastes (egyptian sand viper) venom.envenomation by snake venoms would be expected to result in proteolysis of plasma proteins as well as of cellular constituents. incubation of human serum with crude venom from cerastes cerastes showed that the plasma lipoproteins were a target of this venom. fractionation of the crude venom by gel filtration revealed that high density lipoprotein (hdl) was susceptible almost exclusively to the highest mol. wt fraction of venom and that proteolysis was due to a metalloprotease. although hdl was d ...19883144061
development of a rapid and sensitive enzyme-linked immunosorbent assay (elisa) for measuring venom antigens after an experimental snake bite.we describe a new elisa which allows the measurement of the concentration of venom antigens in whole blood. the assay can be performed in less than 20 min and requires a 200 microliters sample of blood. it allows the accurate evaluation of concentrations of vipera ammodytes venom in quantities smaller than 1 ng/ml of blood. using this elisa, we were able to follow in rabbits the kinetics of experimental envenomation with non-lethal doses of venom. this elisa was also used to measure post mortem ...19883238700
coagulant component in cerastes cerastes (egyptian sand viper) venom.a coagulant component has been purified from cerastes cerastes venom, using gel filtration on a sephadex g 100 (fine) column followed by chromatography on a bio-rex 70 column. this compound had a proteolytic effect and could coagulate human plasma deficient in factor viii or (viii + ix) with the formation of a firm clot. it could also clot plasma deficient in factor x, but the clot formed was soft and not complete. the compound had no effect on platelet aggregation and was nontoxic. this compoun ...19863564057
amino-acid sequence of ammodytoxin b partially reveals the location of the site of toxicity of ammodytoxins.the complete amino-acid sequence of ammodytoxin b, a presynaptically toxic phospholipase a2 isolated from vipera ammodytes ammodytes venom, was determined by manual and automated protein sequencing. ammodytoxin b (i.v. ld50 = 0.58 mg/kg for white mice) is 30-fold less toxic than ammodytoxin a, the most toxic phospholipase isolated from the same venom. the two proteins (each 122 residues long) differ in only 3 residues located in positions 115, 118 and 119 (numbering according to r. renetseder et ...19863790259
[the quantities of dried venom collected from specimens of vipera ammodytes l., 1758 (reptilia, viperidae) in captivity in bulgaria].some researches have been made to obtain more data about quantities of dried venom collected from vipera ammodytes l., 1758 in captivity. the minimal quantity of dried venom collected by exemplar is 9.7 mg to 36.4 mg and the maximal quantity is 49.0 mg to 90.3 mg. from 810 exemplars of v. ammodytes of bulgaria and 9 months of investigations, 10597 samples were made, with a total of 298.164 g of dried venom (average for animal: 28.14 mg).19853834856
ammodytoxin a, a highly lethal phospholipase a2 from vipera ammodytes ammodytes venom.the amino acid sequence of ammodytoxin a, the most toxic presynaptically active phospholipase a2 isolated from vipera ammodytes ammodytes venom, was determined. the primary structure was deduced from peptides obtained by staphylococcus aureus proteinase and trypsin digestion of reduced and carboxymethylated protein and from the automated edman degradation of the n-terminal part of the non-reduced molecule. according to the sequence, the enzyme classifies to the subgroup iia of the phospholipase ...19853986212
oxygen consumption of rat brain homogenates after in vitro and in vivo addition of the basic protein from vipera ammodytes venom. 19734715497
action of a partially purified basic protein fraction from vipera ammodytes venom. 19734725560
[effect of vipera ammodytes venom on the rat electrocardiogram. i]. 19705419769
[action of vipera ammodytes venom on the rat electrocardiogram. ii]. 19705456455
[chronic excretion of salmonella and arizona bacilli by the species vipera ammodytes ammodytes (sandviper)]. 19645825935
[experimental study on the poisoning caused by the venom of the bulgarian sandviper vipera ammodytes ammodytes]. 19655846330
[on l-amino acid oxidase from venom of vipera ammodytes]. 19655885528
[activation of tissue respiration by poison of the vipera ammodytes in the golden hamster]. 19665986221
[experimental infection of snakes vipera ammodytes ammodytes with salmonella and arizona bacteria]. 19676048580
serine proteinase inhibitors from vipera ammodytes venom. isolation and kinetic studies.three protein inhibitors of serine proteinases were isolated from the crude venom of the long-nosed viper vipera ammodytes ammodytes by ion-exchange and gel chromatography. two of them strongly inhibit trypsin (ki = 3.4 x 10(-10) and 5.6 x 10(-10) m), while the third one primarily inhibits chymotrypsin (ki = 4.3 x 10(-9) m). their mr values are close to 7000, and pi is 9.8 in both trypsin inhibitors and 10.0 in the chymotrypsin inhibitor. the n-terminal group in the former inhibitors is blocked; ...19836602050
histopathological changes in rat myocardium caused by vipera ammodytes ammodytes (european viper) snake venom.the application of vipera ammodytes ammodytes snake venom, either crude venom or fractions 5 and 6 of the 11 obtained from a sephadex g-100 column, produced parenchymal degeneration of the myocardium of isolated rat hearts.19836623489
the primary structure of vipera ammodytes venom trypsin inhibitor i.the primary structure of vipera ammodytes venom trypsin inhibitor i consists of 61 amino acid residues [sequence in text]. the n-terminal group of the inhibitor is pyrrolidonecarboxylic acid. the sequential data were obtained by analysis of peptides isolated from tryptic and chymotryptic digests and by analysis of peptides derived from the hydrolysis of the aspartyl-prolyl bond of the carboxymethylated inhibitor. the primary structure of trypsin inhibitor i presented shows approximately 80% sequ ...19836639951
influence of calcium on the action of vipera ammodytes ammodytes snake venom on the myocardium.v. ammodytes ammodytes snake venom produced irreversible block of the isolated, artificially stimulated rat right ventricle or isolated rat heart. this was the result of degenerative changes of the myocardium caused by the direct effect of toxic components of the venom. an excess of ca2+ could temporarily restart the contractions.19836658810
mode of neuromuscular blocking action of toxic phospholipases a2 from vipera ammodytes venom.the effects of toxic phospholipases a2 ( fraxtions "j", "k1" and "k2") isolated from the venom of vipera ammodytes were studied on the chick biventer cervicis muscle and the mouse phrenic nerve-diaphragm preparations. in the chick muscle, all of these pla2s caused neuromuscular (n-m) blockade without producing contracture or affecting the response of the muscle to acetylcholine. in the mouse diaphragm, these pla2s inhibited completely the indirectly elicited contraction without affecting that ev ...19846732368
distribution of vipera ammodytes toxic phospholipase a in the cat and its ability to cross the blood-brain barrier.several phospholipases a could be isolated from the venom of the european viper, vipera ammodytes, having different specific activities toward egg lecithin and different lethalities. the most lethal of these enzymes is fraction "k2" having an intravenous ld50 for white mice of 0.021 mg per kg and a specific activity of 280 microm/min mg at 40 degrees c. the enzyme could be labeled with 131i without loosing its enzymatic activity and lethality. the passage of this enzyme from blood into cerebrosp ...19827080033
neuromuscular and lethal effects of phospholipase a from vipera ammodytes venom.four homogeneous proteins having phospholipase a activity were separated and studied for their i.v. lethal effects in mice and nerve-muscle activity in the guinea pig diaphragm preparation. fraction "j" had an ld50 of 0.30 mg/kg, with 3.6 microgram/ml of bath solution causing a decrease in the indirectly-elicited nerve-muscle contractions to 20% of control, without significantly changing the directly-elicited muscle contractions. fraction "k2" had an ld50 of 0.021 mg/kg and caused a similar nerv ...19827164107
bovine intracellular cysteine proteinases.cathepsins b, h and s were isolated from bovine lymph nodes and bovine spleen. it was shown that the incubation of homogenate at 37 degrees c at acid ph increased the total bana hydrolase activity and leuna activity, whereas it decreased the total activity of cathepsin s. all three enzymes are electrophoretically homogeneous and probably composed of a single polypeptide chain. they exist in multiple forms as shown by isoelectric focusing. far uv cd spectra revealed a rather high percentage of un ...19817342600
ammodytoxin a acceptor in bovine brain synaptic membranes.ammodytoxin a, the presynaptic neurotoxin from vipera ammodytes ammodytes venom, was found to bind specifically and with high affinity to bovine cortex synaptic membrane preparation. the detected ammodytoxin a high-affinity binding was characterized by equilibrium binding analysis which revealed a single high-affinity binding site with kd 4.13 nm and bmax 6.67 pmoles/mg of membrane protein. 125i-ammodytoxin a was covalently cross-linked to its neuronal acceptor using a chemical cross-linking tec ...19957570629
effect of ammodytin l from vipera ammodytes on l-6 cells from rat skeletal muscle.ammodytin l (amdl) is a myotoxic phospholipase-like protein from the venom of vipera ammodytes with a serine in position 49 instead of an aspartate, therefore this toxin is devoid of phospholipase activity, and the membrane-damaging effect does not involve any step of phospholipase activity. the aim of the present study was to analyze the effect of amdl on l-6 cells from rat skeletal muscle to investigate its mechanism of action and the role of calcium ions in its muscle-damaging activity. our d ...19957662700
identification of the neuronal acceptor in bovine cortex for ammodytoxin c, a presynaptically neurotoxic phospholipase a2.a specific, high-affinity binding site for ammodytoxin c in synaptic membranes from bovine cerebral cortex was detected and partially characterized. equilibrium binding analysis revealed a single population of [125i]ammodytoxin c acceptors with the following binding parameters: kd = 6.0 nm and bmax = 5.7 pmol/mg membrane protein. such binding was strongly inhibited by three ammodytoxins (a, b, and c) and by crotoxin b. vipera berus berus phospholipase a2 was a weaker inhibitor; nontoxic phosphol ...19947947800
a comparison of ovine and equine antivenoms.commercial antivenoms produced in horses were compared with monospecific antivenoms raised in sheep against crotalus durissus terrificus, crotalus atrox, crotalus adamanteus, micrurus fulvius fulvius, naja naja, naja kaouthia, echis ocellatus, vipera lebetina deserti, vipera berus berus and vipera ammodytes ammodytes venom. antibodies raised by immunizing sheep with c. d. terrificus venom were more effective than their equine counterparts in preventing lethal toxicity in mice (ed50), in inhibiti ...19948052997
expression of fully active ammodytoxin a, a potent presynaptically neurotoxic phospholipase a2, in escherichia coli.a cdna encoding the most presynaptically neurotoxic phospholipase a2, ammodytoxin a, from the venom of the long-nosed viper (vipera ammodytes ammodytes) has been expressed in escherichia coli. ammodytoxin a was produced as a fusion protein with the 81 n-terminal residues of adenylate kinase followed by the tetrapeptide recognition site for factor xa (iegr) just preceding the first amino acid residue of the toxin. the fusion protein was expressed under the control of tac promoter without iptg ind ...19938224227
quantitation of venom antigens from european vipers in human serum or urine by elisa.we describe an enzyme-linked immunosorbent assay (elisa) to quantitate venom antigens in human serum and urine, and thus to help evaluate the severity of envenomation due to viper bites. this assay, which is performed with commercially available polyclonal fab'2s in a double-sandwich method, is rapid, simple, and specific for antigens of european vipers (vipera aspis, vipera berus, and vipera ammodytes). no cross-reactivity was observed with other snake venoms or human serum proteins. it showed ...19938371555
some pharmacological studies on the effects of cerastes vipera (sahara sand viper) snake venom.the effects of the venom of the sahara sand viper (cerastes vipera) were studied on isolated chick biventer cervicis, isolated rat atria and vas deferens preparations, and on the electrocardiogram of anaesthetized rats. effects on 3h-noradrenaline uptake were studied using rat brain synaptosomes. at 50 micrograms/ml and 100 micrograms/ml, the venom caused a transient increase in rate and force of contractions of the rat atria followed by an irreversible depression. these effects were not prevent ...19958599181
ammodytoxin c gene helps to elucidate the irregular structure of crotalinae group ii phospholipase a2 genes.ammodytoxin c is a presynaptically neurotoxic phospholipase a2 (pla2) expressed in the venom glands of vipera ammodytes (subfamily viperinae). the gene spans more than 4 kb and consists of five exons and four introns characteristic of group ii phospholipase a2 genes. the first exon encodes the 5' untranslated region, the second exon encodes most of the signal peptide, while exons 3-5 encode three parts of the mature protein. comparison of the crotalinae and viperinae pla2 genes has shown that cr ...19968797839
effect of ammodytin l from the venom of vipera ammodytes on xenopus laevis differentiated muscle fibres and regenerating limbs.ammodytin l is a non-catalytic, phospholipase-like snake venom toxin from vipera ammodytes, which shows a cytotoxic activity on differentiated myotubes when tested in vitro. in the range of concentrations in which ammodytin l induced necrosis of myogenic cells in culture, other cell types (erythrocytes, platelets, fibroblasts) did not appear to be affected. to test the in vivo toxicity and the effective cytolytic specificity of ammodytin l we have followed the morphological changes in muscle tis ...19968835336
proliferative effect of ammodytin l from the venom of vipera ammodytes on 208f rat fibroblasts in culture.ammodytin l, purified from the venom of vipera ammodytes, triggers a rapid and dramatic lytic process in myotubes in vitro, as well as in differentiated muscle cells in vivo, through a mechanism that is not well understood. despite its great sequence similarity to phospholipase a2, it is devoid of any enzyme activity. data on artificial membranes demonstrating a direct interaction between this toxin and the hydrophobic core of the lipid bilayer suggest that the toxin also acts on the lipid micro ...19968973554
envenomation by the horned viper (vipera ammodytes l.).snake venom poisoning is a medical emergency that requires urgent therapeutic procedures. the treatment of venomous snakebites is still controversial because of unclear therapeutic modalities. choice of treatment is dictated in part by regional characteristics with regard to patient population and types of venomous snakes. the purpose of the study presented here was to report regional experience with venomous snakebites and to describe first-aid, pre-hospital, and hospital therapeutic procedures ...19979121663
preclinical assessment of immunoreactivity of a new purified equine f(ab')2 against european viper venom.the immunological and pharmacokinetic properties of a new, further purified, pasteurized preparation of equine f(ab')2 (viperfav) against vipera aspis, vipera berus, and vipera ammodytes venom were compared with the current equine f(ab')2 preparation (ipser europe). affinity constants of the v. aspis-specific f(ab')2 were determined using biosensor technology and found to be in the range of 10(8) m-1 for the four antigenic fractions of v. aspis toxins and for both f(ab')2 preparations. the impro ...19989519157
purification of a 5-ht uptake inhibitor from the venom of cerastes vipera.a protein that inhibits the re-uptake of 5-hydroxytryptamine into rat brain synaptosomes was isolated from the venom of the sahara sand viper (cerastes vipera) by gel filtration and reverse phase chromatography. it has a molecular weight of 13,739 da and an ic50 of about 50 nm for blocking uptake of 3h-5-ht into rat brain synaptosomes. it also augmented the responses to 5-ht in a smooth muscle preparation. it has phospholipase a2 activity, but it has no lytic activity as measured by its inabilit ...19989643472
an aromatic, but not a basic, residue is involved in the toxicity of group-ii phospholipase a2 neurotoxins.ammodytoxins (atxs) a, b and c are basic phospholipase a2s from vipera ammodytes ammodytes snake venom, and they exhibit presynaptic toxicity. the most toxic is atxa, followed by atxc, its naturally occurring f124-->i/k128-->e mutant, which is 17 times less toxic. two mutants of atxa have been produced in bacteria and characterized. the specific enzymic activity of the k128-->e mutant on mixed phosphatidylcholine/triton x-100 micelles is similar to that of the wild type. the k108-->n/k111-->n mu ...199910377255
pla(2) stimulation of na(+)/h(+) antiport and proliferation in rat aortic smooth muscle cells.the proliferative properties and the ability to stimulate the na(+)/h(+) antiport activity of a secretory phospholipase a(2) were studied in rat aortic smooth muscle cells in culture. the requirement of the enzymatic activity of phospholipase a(2) to elicit mitogenesis was assessed by the use of ammodytin l, a ser(49) phospholipase a(2) from the venom of vipera ammodytes, devoid of hydrolytic activity. we propose that the proliferative effect is mediated by the same transduction pathway for both ...199910516111
the amino acid region 115-119 of ammodytoxins plays an important role in neurotoxicity.quadruple (y115k/i116k/r118m/n119l) and double (y115k/i116k) mutants of ammodytoxin a, a presynaptically toxic phospholipase a(2) from vipera ammodytes ammodytes venom, were prepared and characterized. the enzymatic activity of the quadruple mutant on phosphatidylcholine micelles was threefold higher than that of atxa, presumably due to higher phospholipid-binding affinity, whereas the activity of the double mutant was twofold lower. the substantial decrease by more than two orders of magnitude ...200011027615
mrna secondary structure can greatly affect production of recombinant phospholipase a(2) toxins in bacteria.the neurotoxic activity of ammodytoxin a (atxa), a phospholipase a(2) from vipera ammodytes ammodytes venom, has been investigated by protein engineering. with the aim of obtaining atxa as a non-fused protein in the bacterial cytoplasm and avoiding problems with incomplete cleavage in vivo of the initial met preceding the first residue (ser1), a double mutant (s1a/e4q) was prepared and expressed in escherichia coli. immunoblotting of the bacterial lysate showed that the mutant was synthesized at ...200211821126
phenylalanine-24 in the n-terminal region of ammodytoxins is important for both enzymic activity and presynaptic toxicity.ammodytoxins (atxs) are group ii phospholipases a(2) (pla(2)s) with presynaptic toxicity from venom of the snake vipera ammodytes ammodytes. the molecular basis of their neurotoxicity, and that of similar pla(2) toxins, is still to be explained. to address this problem, a surface-exposed aromatic residue, phe(24), in the n-terminal region of the most potent atx, atxa, was replaced by other aromatic (tyrosine, tryptophan), hydrophobic (alanine) and polar uncharged (serine, asparagine) residues. t ...200211931665
biochemical and biological activities of the venom of a new species of pitviper from vietnam, triceratolepidophis sieversorum.biochemical and biological activities of a venom sample from a recently discovered new genus and species of pitviper from vietnam, triceratolepidophis sieversorum, were assayed and compared with those of five other viperid snakes (bothrops asper, crotalus atrox, protobothrops flavoviridis, trimeresurus insularis, and vipera ammodytes). the venom had high casein hydrolysis, arginine ester hydrolysis and haemorrhagic activities, lacked measurable phosphodiesterase and l-amino acid oxidase activiti ...200312565732
sequences and structural organization of phospholipase a2 genes from vipera aspis aspis, v. aspis zinnikeri and vipera berus berus venom. identification of the origin of a new viper population based on ammodytin i1 heterogeneity.we used a pcr-based method to determine the genomic dna sequences encoding phospholipases a2 (pla2s) from the venoms of vipera aspis aspis (v. a. aspis), vipera aspis zinnikeri (v. a. zinnikeri), vipera berus berus (v. b. berus) and a neurotoxic v. a. aspis snake (neurotoxic v. a. aspis) from a population responsible for unusual neurotoxic envenomations in south-east france. we sequenced five groups of genes, each corresponding to a different pla2. the genes encoding the a and b chains of vaspin ...200312823540
adaptive evolution in the snake venom kunitz/bpti protein family.snake venoms are rich sources of serine proteinase inhibitors that are members of the kunitz/bpti (bovine pancreatic trypsin inhibitor) family. however, only a few of their gene sequences have been determined from snakes. we therefore cloned the cdnas for the trypsin and chymotrypsin inhibitors from a vipera ammodytes venom gland cdna library. phylogenetic analysis of these and other snake kunitz/bpti homologs shows the presence of three clusters, where sequences cluster by functional role. anal ...200312860400
[on salmonella species in reptiles (new arizona species in the poisonous snake vipera ammodytes ammodytes)]. 196314166430
biochemical differences in yellow and white venoms of vipera ammodytes and russell's viper. 196514253404
protein disulphide isomerase binds ammodytoxin strongly: possible implications for toxin trafficking.ammodytoxin, a group iia secreted phospholipase a(2) from the venom of the long-nosed viper (vipera ammodytes ammodytes), is a potent presynaptically acting neurotoxin. it blocks the secretion of neurotransmitter from the nerve cell, thus hindering the communication with the neighbouring neuron or muscle cell. to express the neurotoxicity, ammodytoxin should interact with specific receptors in the axon terminal and express phospholipase activity. our previous results indicate that, following the ...200515737647
the variability of vipera ammodytes ammodytes venoms from croatia--biochemical properties and biological activity.vipera ammodytes ammodytes venom has been used for many years in croatia for immunization of horses and production of specific therapeutic anti-venoms. the neutralizing effectiveness of anti-venoms is directly dependent on the properties of the snake venom used for immunization. therefore, appropriate characterization of the whole venom is necessary prior to use in the immunization procedure. in the course of such analyses, the variability in biochemical properties and biological activity was ob ...200515907770
the c-terminal and beta-wing regions of ammodytoxin a, a neurotoxic phospholipase a2 from vipera ammodytes ammodytes, are critical for binding to factor xa and for anticoagulant effect.ammodytoxin a (atxa) from the venom of vipera ammodytes ammodytes belongs to group iia secreted phospholipase a2 (spla2), for which the major pathologic activity is presynaptic neurotoxicity. we show here that this toxin also affects hemostasis because it exhibits strong anticoagulant activity. atxa binds directly to human coagulation factor xa (fxa) with kdapp of 32 nm, thus inhibiting the activity of the prothrombinase complex with an ic50 of 20 nm. to map the fxa-interaction site on atxa, var ...200616039772
venomous snakebites in southern croatia.this retrospective study is based on the analysis of 542 snakebite envenomation cases in southern croatia, which were treated in the university hospital split over the period of 21 years. the aim of this study was to determine the incidence of venomous snakebite in southern croatia, epidemiological and clinical features of snakebite and treatment in the region. the mean annual snakebite incidence in southern croatia was 5.2 per 100,000 inhabitants. the nose- horned viper (vipera ammodytes) was r ...200616617597
binding to the high-affinity m-type receptor for secreted phospholipases a(2) is not obligatory for the presynaptic neurotoxicity of ammodytoxin a.r180, isolated from porcine brain cortex, is a high-affinity membrane receptor for ammodytoxin a (atxa), a secreted phospholipase a(2) (spla(2)) and presynaptically active neurotoxin from venom of the long-nosed viper (vipera ammodytes ammodytes). as a member of the m-type spla(2) receptors, present on the mammalian plasma membrane, r180 has been proposed to be responsible for one of the first events in the process of presynaptic neurotoxicity, the binding of the toxin to the nerve cell. to test ...200616815622
structural and pharmacological comparison of daboiatoxin from daboia russelli siamensis with viperotoxin f and vipoxin from other vipers.russell's viper (vipera russelli, also known as daboia russelli) is one of the major causes of fatal snakebites. to date, five daboia russelli subspecies have been recognized. daboiatoxin (dbtx) is the main lethal phospholipase a(2) (pla(2)) toxin in the venom of d. russelli siamensis (myanmar viper) and has strong neurotoxic, myotoxic and cytotoxic activities. dbtx and its homologous neurotoxins viperotoxin f from d. russelli formosensis (taiwan viper) and vipoxin from the bulgarian sand viper ...200717505111
molecular phylogeography of the nose-horned viper (vipera ammodytes, linnaeus (1758)): evidence for high genetic diversity and multiple refugia in the balkan peninsula.the nose-horned viper (vipera ammodytes) occurs in a large part of the south-eastern europe and asia minor. phylogenetic relationships were reconstructed for a total of 59 specimens using sequences from three mitochondrial regions (16s and cytochrome b genes, and control region, totalling 2308 bp). a considerable number of clades were observed within this species, showing a large genetic diversity within the balkan peninsula. splitting of the basal clades was evaluated to about 4 million years a ...200818267369
dose dependent effects of standardized nose-horned viper (vipera ammodytes ammodytes) venom on parameters of cardiac function in isolated rat heart.direct, dose dependent effects of the nose-horned vipers (vipera ammodytes ammodytes) venom on various parameters of cardiac action in isolated rat hearts were examined. biochemical (protein content, sds polyacrylamide gel electrophoresis) and biological (minimum haemorrhagic and necrotizing dose and lethal dose (ld(50))) characterization of the venom was performed before testing. the hearts were infused with venom doses of 30, 90 and 150 microg/ml for 10 min followed by 30 min of wash out perio ...200818313364
the role of antibodies specific for toxic spla2s and haemorrhagins in neutralizing potential of antisera raised against vipera ammodytes ammodytes venom.the contribution of antibodies directed against the two main toxic groups of proteins in the vipera ammodytes ammodytes venom, haemorrhagic metalloproteinases (h) and neurotoxic spla2s (atxs), to the overall protective efficacy of the whole venom antisera was investigated. using elisa assays we established a high correlation between the protective efficacy of the whole venom antisera in mice and their anti-atxs antibody content. as the haemorrhage is the prevailing toxic effect of the venom in h ...200818571473
neurotoxicity of ammodytoxin a in the envenoming bites of vipera ammodytes ammodytes.envenoming bites by vipera ammodytes ammodytes (the long-nosed viper) can cause life-threatening neurotoxicity, particularly in children. we investigated the mechanisms of the neurotoxicity of ammodytoxin a, the principal toxin in the venom of these snakes, in isolated nerve-muscle preparations from mice. the toxin was bound selectively to the neuromuscular junction, and at concentrations similar to those likely to be found in the circulation of young bite victims, it blocked the response of the ...200818800006
ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase a2 into mammalian motor nerve terminals.a mutant form of ammodytoxin a, a neurotoxic phospholipase a(2) from the venom of the long nosed viper vipera ammodytes ammodytes, was prepared by site-directed mutagenesis, conjugated to a nanogold particle and inoculated into the antero-lateral aspect of one hind limb of female mice. eight hours later the mice were killed, the soleus muscles of both ipsi- and contra-lateral hind limbs were removed, exposed to a silver enhancing medium and then prepared for transmission electron microscopy. sil ...200919631643
ammodytoxin content of vipera ammodytes ammodytes venom as a prognostic factor for venom immunogenicity.venoms are complex mixtures of proteins, peptides and other compounds whose biochemical and biological variability has been clearly demonstrated. these molecules have been used as antigens for immunization of anti-venom-producing animals (horses or sheep). ammodytoxins (atx) are potently neurotoxic compounds, and the most toxic compounds isolated so far from the vipera ammodytes ammodytes (vaa) venom. recently we have shown that the level of antibodies specific to vaa venom's most toxic componen ...201020139032
snakebites in adults from the diyarbakir region in southeast turkey.snake venom poisoning is a medical emergency requiring immediate attention. bites from poisonous turkish snakes can lead to local tissue damage and systemic symptoms. the vipera ammodytes species accounts for the majority of envenomation in southeast turkey.201020517744
serum il-6, tnfα levels in snakebite cases occurring in southern turkey.the snake species vipera ammodytes meridionalis and vipera lebetina obtuse are often seen in southern turkey and have venom that causes serious systemic and tissue damage. the aim of our study is to assess the relationship between tumour necrosis factor α (tnfα) and interleukin 6 (il-6) serum levels, and clinical and laboratory findings in the snakebite patients.201120595711
severe coagulopathy after vipera ammodytes ammodytes snakebite in bulgaria: a case report.the case report presents a severe coagulopathy in a 56-year-old man following envenomation by the snake (vipera ammodytes ammodytes) on his left hand. initially the man was in shock, with an extremely low blood pressure and tachycardia. local signs included a painful blister formation on the envenomation site. twenty-four hours later, the man developed acute thrombocytopenia (platelets number 10 x 10(9)/l) and ecchimoses formation on the affected limb and on the left side of his body due to a di ...201020600226
intraspecies variability in vipera ammodytes ammodytes venom related to its toxicity and immunogenic potential.vipera ammodytes is the most venomous european snake, whose venom has been used as antigen for immunization of antivenom-producing animals. same as venom of any other snake, it is a complex mixture of proteins, peptides and other compounds which biochemical and pharmacological variability has been demonstrated at interspecies and intraspecies level. in this work we demonstrated intraspecific variability between 8 venom production batches using both the conventional and the new methodology. moreo ...201020971215
cdna cloning, structural, and functional analyses of venom phospholipases a₂ and a kunitz-type protease inhibitor from steppe viper vipera ursinii renardi.snake venom phospholipases a₂ (pla₂s) display a wide array of biological activities and are each characteristic to the venom. here, we report on the cdna cloning and characterization of pla₂s from the steppe viper vipera ursinii renardi venom glands. among the five distinct pla₂ cdnas cloned and sequenced, the most common were the clones encoding a basic ser-49 containing pla₂ (vur-s49). other clones encoded either ammodytin analogs i1, i2d and i2a (designated as vur-pl1, vur-pl2 and vur-pl3, re ...201021185324
neutralization of vipera and macrovipera venoms by two experimental polyvalent antisera: a study of paraspecificity.we conducted an extensive study of neutralization of lethality of 11 species and one subspecies of snakes of the genus vipera, and of five species of macrovipera, by two experimental equine antisera. one antiserum was a trivalent preparation raised against the venoms of vipera aspis aspis, vipera berus berus and vipera ammodytes ammodytes; the other was a pentavalent preparation that also included venoms of vipera (now montivipera) xanthina and macrovipera lebetina obtusa. we measured specific n ...201121530569
ammodytagin, a heterodimeric metalloproteinase from vipera ammodytes ammodytes venom with strong hemorrhagic activity.ammodytagin, a hemorrhagic zn(2+)-dependent metalloproteinase from vipera ammodytes ammodytes (vaa) venom, is a glycosylated heterodimer of 108 kda, as determined by maldi mass spectrometry. partial amino acid sequencing by edman degradation and ms/ms analysis identified sequences belonging to metalloproteinase, disintegrin-like and cysteine-rich domains, which in addition to its heterodimeric nature allows classification into the p-iiic group of snake venom metalloproteinases (svmps). only few ...201121933678
Venom peptide analysis of Vipera ammodytes meridionalis (Viperinae) and Bothrops jararacussu (Crotalinae) demonstrates subfamily-specificity of the peptidome in the family Viperidae.Snake venom peptidomes are valuable sources of pharmacologically active compounds. We analyzed the peptidic fractions (peptides with molecular masses < 10,000 Da) of venoms of Vipera ammodytes meridionalis (Viperinae), the most toxic snake in Europe, and Bothrops jararacussu (Crotalinae), an extremely poisonous snake of South America. Liquid chromatography/mass spectrometry (LC/MS), direct infusion electrospray mass spectrometry (ESI-MS) and matrix-assisted desorption/ionization time-of-flight m ...201121959992
acute toxicity of vipoxin and its components: is the acidic component an "inhibitor" of pla2 toxicity?vipoxin is a heterodimeric neurotoxin isolated from the venom of the bulgarian long-nosed viper vipera ammodytes meridionalis. vipoxin represents a noncovalent association of two subunits - a basic and toxic phospholipase a2 enzyme, and an acidic non-enzymatic component (vipoxin's acidic component). it was postulated that the phospholipase a2 subunit was more toxic than the whole vipoxin complex and the function of the acidic component was to reduce the enzymatic and toxic activities of the basi ...201223554559
hemorrhagic stomatitis in a natural hybrid of vipera ammodytes × vipera berus due to inappropriate substrate in terrarium.a natural hybrid of vipera ammodytes × vipera berus was presented having low body weight, seizures and generalized swelling of the cephalic region. based on the history of the case and clinical examination, hemorrhagic stomatitis of traumatic origin was diagnosed. the snake was kept in a terrarium with wood chips as a substrate, and the material had induced trauma in the oral mucosa which was further complicated with salmonella arizonae and morganella morganii co-infection, abscessation and oste ...201525715871
autocatalytic acylation of phospholipase-like myotoxins.several snake venoms contain a phospholipase a2 in which position 49 in the active site is occupied by a lysine or a serine instead of the aspartate residue normally found. although these proteins do not bind ca2+ and are devoid of catalytic activity, they are still highly specific myotoxins and have recently been shown to induce membrane leakage by a new type of cytolytic mechanism. three of these toxins, myotoxin ii from bothrops asper, ammodytin l from vipera ammodytes, and the k49 protein fr ...19957718570
antigenic relationship between the venom of the night adder causus maculatus and venoms of other viperids.monovalent antivenoms were raised in mice against the venoms of causus maculatus, vipera ammodytes, echis carinatus, cerastes cerastes, bitis arietans, agkistrodon rhodostoma and bothrops atrox. these antivenoms as well as four commercially available antivenoms were tested against the venoms of 15 viperid species by means of immunoelectrophoresis and/or elisa. cross-reactive protein bands were determined by immunoblot. elisa cross-reactions of c. maculatus antivenom were low with all heterologou ...19901706897
hemorrhagin vah4, a covalent heterodimeric p-iii metalloproteinase from vipera ammodytes ammodytes with a potential antitumour activity.in the envenomation caused by a bite of vipera ammodytes ammodytes, the most venomous snake in europe, hemorrhage is usually the most severe consequence in man. identifying and understanding the hemorrhagic components of its venom is therefore particularly important in optimizing medical treatment of patients. we describe a novel high molecular mass hemorrhagin, vah4. the isolated molecule is a covalent dimer of two homologous subunits, vah4-a and vah4-b. complete structural characterization of ...201424269369
biochemical and biological properties of phospholipases a(2) from bothrops atrox snake venom.phospholipases a(2) (pla(2)s), of molecular mass 13-15kda, are commonly isolated from snake venom. two myotoxins with pla(2) activity, bapla(2)i and bapla(2)iii, with estimated molecular masses of 15kda were isolated from the venom of bothrops atrox using sephacryl s-100-hr and reverse-phase chromatography. bapla(2)i was basic, with a pi of 9.1, while bapla(2)iii was neutral with a pi of 6.9. on a molecular basis, bapla(2)iii exhibited higher catalytic activity on synthetic substrates than bapla ...200212234622
crystallographic characterization of functional sites of crotoxin and ammodytoxin, potent β-neurotoxins from viperidae venom.this review will focus on a description of the three-dimensional structures of two β-neurotoxins, the monomeric pla(2) ammodytoxin from vipera ammodytes ammodytes, and heterodimeric crotoxin from crotalus durissus terrificus, and a detailed structural analysis of their multiple functional sites. we have recently determined at high resolution the crystal structures of two natural isoforms of ammodytoxin (atxa and atxc) (saul et al., 2010) which exhibit different toxicity profiles and different an ...201222683534
neurotoxic phospholipases a2 ammodytoxin and crotoxin bind to distinct high-affinity protein acceptors in torpedo marmorata electric organ.we studied the binding of radioiodinated ammodytoxin c, a monomeric phospholipase a2 neurotoxin from vipera ammodytes, and of radioiodinated crotoxin, a dimeric phospholipase a2 neurotoxin from crotalus durissus terrificus, to presynaptic membranes from the electric organ of torpedo marmorata. in both cases, two different families of specific binding sites were identified and characterized. the high-affinity binding sites for both toxins have been shown to be proteins. the low-affinity binding s ...19979062105
a phospholipase a2-like pseudogene retaining the highly conserved introns of mojave toxin and other snake venom group ii pla2s, but having different exons.mojave toxin is a neurotoxic, heterodimeric phospholipase a2 (pla2) from the venom of the mojave rattlesnake (crotalus scutulatus scutulatus) and is characteristic of all rattlesnake presynaptic neurotoxins. here, we describe a phospholipase a2 pseudogene (psi-mtx) located 2,000 nucleotides upstream, and on the opposite dna strand, from a gene for mojave toxin acidic subunit (mtx-a). the pseudogene lacks the first exon and a few segments of noncoding dna found in functional snake venom pla2 gene ...19968769568
[the conditions in which is manifested the antitoxic action of the bile of erinaceus europaeus on the venom of vipera ammodytes]. 200615426062
[three case-reports of viperin envenoming in morocco].snake bites are responsible for a high mortality rate in africa. problems for the early care of the victims are many. we published three observations of moroccan typical viperin severe envenomings (rapidly extensive edema, necrosis, haemorrhagic shock) are presented. the overall mortality of those bites is 4%. in the maghreb, viperin syndromes are the result of the lebetin viper (vipera lebetina), the horned viper or sand viper (cerastes cerastes), sometimes bitis or echis sp. immunotherapy rema ...200818424055
the standard mouse assay of anti-venom quality does not measure antibodies neutralising the haemorrhagic activity of vipera ammodytes venom.the venom of vipera ammodytes ammodytes (vaa), like the venoms of other viperinae snakes, is largely haemorrhagic and necrotising, and only to a lesser extent neurotoxic to humans. the components most extensively studied so far, and most probably involved in generating the observed pathologies, are haemorrhagins (h), members of the metalloproteinase group of enzymes, and neurotoxic ammodytoxins (atxs), that belong to the secretory phospholipases a2. rabbit antisera were prepared containing funct ...201222445824
comparative venomics of the vipera ammodytes transcaucasiana and vipera ammodytes montandoni from turkey provides insights into kinship.the nose-horned viper (vipera ammodytes) is one of the most widespread and venomous snakes in europe, which causes high frequent snakebite accidents. the first comprehensive venom characterization of the regional endemic transcaucasian nose-horned viper (vipera ammodytes transcaucasiana) and the transdanubian sand viper (vipera ammodytes montandoni) is reported employing a combination of intact mass profiling and bottom-up proteomics. the bottom-up analysis of both subspecies identified the majo ...201829301241
sequence homology between phospholipase and its inhibitor in snake venom. the primary structure of the inhibitor of vipoxin from the venom of the bulgarian viper (vipera ammodytes ammodytes, serpentes).we are presenting the first primary structure of a snake venom inhibitor. it was isolated from the neurotoxin vipoxin of the bulgarian viper (vipera ammodytes ammodytes, serpentes) which represents a complex of a strong toxic basic protein with phospholipase a2 activity (2 isoenzymes) and the nontoxic acidic component functioning as its inhibitor. the sequence was established by automatic degradation in a liquid phase sequenator on the s-carboxymethylated chain and on the peptides obtained by tr ...19846489936
the bov-b lines found in vipera ammodytes toxic pla2 genes are widespread in snake genomes.in the fourth intron of two toxic vipera ammodytes pla2 genes a ruminantia specific 5'-truncated bov-b line element was identified. southern blot analysis of bov-b line distribution in vertebrates shows that, apart from the ruminantia, it is limited to viperidae snakes (v. ammodytes, vipera palaestinae, echis coloratus, bothrops alternatus, trimeresurus flavoviridis and trimeresurus gramineus). the copy number of the 3' end of bov-b line in the v. ammodytes genome is between 62,000 and 75,000. a ...19989792174
bov-b long interspersed repeated dna (line) sequences are present in vipera ammodytes phospholipase a2 genes and in genomes of viperidae snakes.ammodytin l is a myotoxic ser49 phospholipase a2 (pla2) homologue, which is tissue-specifically expressed in the venom glands of vipera ammodytes. the complete dna sequence of the gene and its 5' and 3' flanking regions has been determined. the gene consists of five exons separated by four introns. comparative analysis of the ammodytin l and ammodytoxin c genes shows that all intron and flanking sequences are considerably more conserved (93-97%) than the mature protein-coding exons. the pattern ...19979219538
phospholipase-like myotoxins induce rapid membrane leakage of non-hydrolyzable ether-lipid liposomes.two phospholipase-like myotoxins--ammodytin l from vipera ammodytes and myotoxin ii from bothrops asper--are shown to be able to induce leakage of liposomes made from non-hydrolyzable ether-linked phospholipids. this demonstrates that the cytolytic activity of these toxins is completely independent of any remaining enzyme activity or contamination with active phospholipases.19948110812
calcium ion independent membrane leakage induced by phospholipase-like myotoxins.the two snake venom myotoxins ammodytin l and myotoxin ii, purified respectively from vipera ammodytes ammodytes and bothrops asper, have phospholipase-like structures but lack an asp-49 in the active site and are without normal phospholipase activity. the interaction of these proteins with different types of liposomes indicated that the myotoxins were able to provoke rapid and extensive release of the aqueous content of liposomes. leakage was measured by two different methods: fluorescence dequ ...19921334427
the use of ground-borne vibrations for prey localization in the saharan sand vipers (cerastes).sand vipers of the genus cerastes are specialized semi-fossorial snakes that launch predatory strikes at rodents and lizards while partially buried in the soft sand of the saharan desert. this study attempted to document which environmental stimuli are used by these snakes as a trigger for the ambush behavior. denervating the olfactory and vomeronasal organs produced no changes in prey capture behavior in cerastes cerastes. occluding the eyes of the denervated specimens resulted in significant d ...200211907055
the presence of the wgd motif in cc8 heterodimeric disintegrin increases its inhibitory effect on alphaii(b)beta3, alpha(v)beta3, and alpha5beta1 integrins.two highly homologous dimeric disintegrins, cc5 and cc8, have been isolated from the venom of the north african sand viper cerastes cerastes. cc5 is a homodimer containing an rgd motif in its subunits. cc8 is a heterodimer. the cc8a and cc8b subunits contain rgd and wgd tripeptide sequence in their respective integrin-binding loops. both cc5 and cc8 inhibited platelet aggregation and the adhesion of cells expressing integrins alphaii(b)beta3, alpha(v)beta3, and alpha5beta1 to appropriate ligands ...200211827548
characterization of a potent platelet aggregation inducer from cerastes cerastes (egyptian sand viper) venom.a potent, proteinaceous inducer of platelet aggregation designated as iva, has been purified to homogeneity from cerastes cerastes venom by molecular sieve and ion exchange chromatography. it is composed of 2 subunits with total m(r) of 62,000 as shown by native gel chromatography and chemical cross-linking with disuccinimidyl suberate. it is not clear at the present time whether both subunits are identical gene products, however, both have identical n-terminal sequences for the first 15 amino a ...19957612660
cerastes cerastes (egyptian sand viper) venom induced platelet aggregation as compared to other agonists.the egyptian sand viper (cerastes cerastes) crude venom and subfractions were, for the first time, shown to induce platelet aggregation with agonist activities present in two subfractions. the combined activities of the crude venom components behaved in a unique fashion as compared to the platelet agonists, adp, collagen and thrombin. the action of the venom was inhibited by conditions that increased camp, partially required the formation of thromboxane a2 and was inhibited by the serine proteas ...19882829899
further characterization of the anticoagulant proteinase, cerastase f-4 from cerastes cerastes (egyptian sand viper) venom.a potent anticoagulant, cerastase f-4, was purified from the venom of cerastes cerastes. the u.v. absorption spectrum revealed a relatively high tyrosine and low tryptophan content. the molar extension coefficient and e278(0.1%) were 19,400 and 0.84, respectively. the enzyme secondary structure, as studied by circular dichroism, showed 23.6% alpha-helix, 34% beta-sheets, 19% beta-turns and 32.5% random coils. when casein was used as a substrate the optimum ph was 10.0 and the km was 1.45 g/l. ce ...19873118514
isolation and characterization of an anticoagulant proteinase, cerastase f-4, from cerastes cerastes (egyptian sand viper) venom.an anticoagulant protease, cerastase f-4, was isolated from the venom of cerastes cerastes (egyptian sand viper) by a combination of gel filtration, ion-exchange chromatography, and hplc. homogeneity of the purified anticoagulant was established by discontinuous polyacrylamide disc gel electrophoresis and by isotachophoresis. the anticoagulant enzyme is a single polypeptide chain without subunits having a molecular weight of 22,500. it consists of 28% aspartic acid residues and only 7% are basic ...19863010494
mechanism of the anticoagulant, cerastase f-4, isolated from cerastes cerastes (egyptian sand viper) venom.an anticoagulant enzyme, cerastase f-4, from the venom of cerastes cerastes was purified to homogeneity and was characterized (1). in the present report the mode of its fibrinogenolytic and fibrinolytic actions, and its effects on some other blood coagulation factors are described. cerastes f-4 was shown to readily hydrolyze the alpha a chain of fibrinogen followed by the hydrolysis of the beta b chain. the gamma-chain was relatively resistant to hydrolysis. it also degrades the three chains of ...19862939587
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