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integrated "omics" profiling indicates that mirnas are modulators of the ontogenetic venom composition shift in the central american rattlesnake, crotalus simus simus.understanding the processes that drive the evolution of snake venom is a topic of great research interest in molecular and evolutionary toxinology. recent studies suggest that ontogenetic changes in venom composition are genetically controlled rather than environmentally induced. however, the molecular mechanisms underlying these changes remain elusive. here we have explored the basis and level of regulation of the ontogenetic shift in the venom composition of the central american rattlesnake, c ...201323575160
snake venomics and antivenomics of bothrops atrox venoms from colombia and the amazon regions of brazil, perú and ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism.the venom proteomes of bothrops atrox from colombia, brazil, ecuador, and perú were characterized using venomic and antivenomic strategies. our results evidence the existence of two geographically differentiated venom phenotypes. the venom from colombia comprises at least 26 different proteins belonging to 9 different groups of toxins. pi-metalloproteinases and k49-pla(2) molecules represent the most abundant toxins. on the other hand, the venoms from brazilian, ecuadorian, and peruvian b. atrox ...200919665598
comparison of the effect of crotalus simus and crotalus durissus ruruima venoms on the equine antibody response towards bothrops asper venom: implications for the production of polyspecific snake antivenoms.antivenoms are preparations of immunoglobulins purified from the plasma of animals immunized with snake venoms. depending on the number of venoms used during the immunization, antivenoms can be monospecific (if venom from a single species is used) or polyspecific (if venoms from several species are used). in turn, polyspecific antivenoms can be prepared by purifying antibodies from the plasma of animals immunized with a mixture of venoms, or by mixing antibodies purified from the plasma of anima ...201021130107
snake venomics of the central american rattlesnake crotalus simus and the south american crotalus durissus complex points to neurotoxicity as an adaptive paedomorphic trend along crotalus dispersal in south america.we report a comparative venomic and antivenomic characterization of the venoms of newborn and adult specimens of the central american rattlesnake, crotalus simus, and of the subspecies cumanensis, durissus, ruruima, and terrificus of south american crotalus durissus. neonate and adult c. simus share about 50% of their venom proteome. the venom proteome of 6-week-old c. simus is predominantly made of the neurotoxic heterodimeric phospholipase a(2) (pla(2) crotoxin) (55.9%) and serine proteinases ...201019863078
neotropical rattlesnake (crotalus simus) venom pharmacokinetics in lymph and blood using an ovine model.the most abundant protein families in viper venoms are snake venom metalloproteases (svmps), snake venom serine proteases (svsps) and phospholipases (pla2s). these are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (pk) of whole venom (wv) and its protein families. we studied the pathophysiology, pk profile and differential absorption of representative toxins from venom of neotropical rattlesnake (c ...202032708875
detection and quantification of a β-neurotoxin (crotoxin homologs) in the venom of the rattlesnakes crotalus simus, c. culminatus and c. tzabcan from mexico.snake venom may vary in composition and toxicity across the geographic distribution of a species. in the case of the three species of the neotropical rattlesnakes crotalus simus, c. culminatus and c. tzabcan recent research has revealed that their venoms can contain a neurotoxic component (crotoxin homologs), but is not always the case. in the present work, we detected and quantified crotoxin homologs in venom samples from three species distributed across mexico, to describe variation at the ind ...201932550564
epidemiology of snakebites in el salvador (2014-2019).this study describes the basic epidemiological features of snakebites in el salvador for the period 2014-2019 on the basis of data provided by the national system of information on morbidity and mortality (sistema de morbi-mortalidad via web, simmow) of the ministry of health of el salvador. the total number of cases per year ranged from 161 (2017) to 215 (2016). incidences ranged from 2.52 cases to 3.38 cases per 100,000 population per year, corresponding to the years 2017 and 2016, respectivel ...202032738247
neutralizing potency and immunochemical evaluation of an anti-crotalus mictlantecuhtli experimental serum.snakebite in mexico is commonly treated with an antivenom which uses bothrops asper and crotalus simus venoms as immunogens. current taxonomic recommendations for the c. simus species complex suggest a novel endemic species from mexico: crotalus mictlantecuhtli. the aim of this report was to evaluate the immunogenic properties of c. mictlantecuhtli venom and its potential to generate polyclonal antibodies capable of neutralizing other pitviper venoms. we generated an experimental anti-crotalus m ...202032891663
toxicological profile of medically relevant crotalus species from mexico and their neutralization by a crotalus basiliscus/bothrops asper antivenom.specimens of the crotalus genus represent a potential snakebite problem in mexico, and despite the great number of species of crotalus present in this country, only a few of them are relevant from a medical point of view. crotalus envenomed patients can present a range of signs and symptoms, depending on the species involved, and their treatment is indistinctly with either of the anti-viperid antivenoms available in the mexican public health system. one of these antivenoms is produced by immuniz ...202032345455
thrombelastographic characterization of the thrombin-like activity of crotalus simus and bothrops asper venoms.: annually, thousands suffer venomous snake-bite from crotalus simus and bothrops asper vipers in central and south america. the goals of the present study were to generally characterize the thrombin-like effects of venom from these snakes in human plasma with viscoelastic methods. human plasma was exposed to the venom of three different c. simus subspecies and venoms obtained from b. asper vipers located in three different locations in mexico. to characterize the factor x-activating and thrombi ...201727314863
effects of pi and piii snake venom haemorrhagic metalloproteinases on the microvasculature: a confocal microscopy study on the mouse cremaster muscle.the precise mechanisms by which snake venom metalloproteinases (svmps) disrupt the microvasculature and cause haemorrhage have not been completely elucidated, and novel in vivo models are needed. in the present study, we compared the effects induced by bap1, a pi svmp isolated from bothrops asper venom, and csh1, a piii svmp from crotalus simus venom, on cremaster muscle microvasculature by topical application of the toxins on isolated tissue (i.e., ex vivo model), and by intra-scrotal administr ...201627992592
proteomic, toxicological and immunogenic characterization of mexican west-coast rattlesnake (crotalus basiliscus) venom and its immunological relatedness with the venom of central american rattlesnake (crotalus simus).the venom of the mexican west-coast rattlesnake (crotalus basiliscus) was characterized for its protein composition, toxicological profile and immunogenic properties. this venom is composed of 68% zn2+-dependent metalloproteinases (svmps), 14% phospholipases a2(pla2s), 11% serine proteinases, 4% svmps-inhibitor tripeptides (svmp-its), 2% bradykinin-potentiating peptides (bpps), 0.6% cysteine-rich secretory proteins (crisps), and 0.2% l-amino acid oxidases (laaos). svmps present in the venom are ...201728238904
integrated venomics and venom gland transcriptome analysis of juvenile and adult mexican rattlesnakes crotalus simus, c. tzabcan, and c. culminatus revealed mirna-modulated ontogenetic shifts.adult rattlesnakes within genus crotalus express one of two distinct venom phenotypes, type i (hemorrhagic) and type ii (neurotoxic). in costa rican central american rattlesnake, ontogenetic changes in the concentration of mirnas modulate venom type ii to type i transition. venomics and venom gland transcriptome analyses showed that adult c. simus and c. tzabcan expressed intermediate patterns between type ii and type i venoms, whereas c. culminatus had a canonical type i venom. neonate/juvenile ...201728731347
cross-reactivity and cross-immunomodulation between venoms of the snakes bothrops asper, crotalus simus and lachesis stenophrys, and its effect in the production of polyspecific antivenom for central america.a mixture of the venoms of bothrops asper, crotalus simus and lachesis stenophrys is used as immunogen to produce the polyspecific central american antivenom (polival-icp). in this work, we studied the ability of each of these venoms to modulate the antibody response induced by the other two venoms included in the immunization mixture. for that, equine monospecific, bispecific and polyspecific antivenoms were prepared and compared regarding their ability to neutralize the phospholipase a2, coagu ...201728803057
contributions of the snake venoms of bothrops asper, crotalus simus and lachesis stenophrys to the paraspecificity of the central american polyspecific antivenom (polival-icp).polival-icp antivenom is produced from plasma of horses immunized toward the venoms of bothrops asper, crotalus simus and lachesis stenophrys. the antibody response induced by these venoms confers polival-icp the capacity to neutralize the venoms of the most important central american viperids, including not only homologous venoms (i.e., venoms used as immunogen), but many heterologous venoms (i.e., venoms not used as immunogen). in this work, the individual contributions of homologous venoms to ...201829407870
citrus bioflavonoid, hesperetin, as inhibitor of two thrombin-like snake venom serine proteases isolated from crotalus simus.around 5.5 million people suffer from snakebites per year, with about 400,000 cases with some type of sequelae, such as amputation, and 20,000 to 125,000 cases with the fatal end. usually, the victim outcome depends on correct, agile and many times in situ intervention based on the proper identification of the snake venom type and its potential effects, among other factors. therefore, knowledge on the snake venom composition and a research on inhibitors of snake venom target components might ame ...201829337219
snake venomics and antivenomics of bothrops colombiensis, a medically important pitviper of the bothrops atrox-asper complex endemic to venezuela: contributing to its taxonomy and snakebite management.the taxonomic status of the medically important pitviper of the bothrops atrox-asper complex endemic to venezuela, which has been classified as bothrops colombiensis, remains incertae cedis. to help resolving this question, the venom proteome of b. colombiensis was characterized by reverse-phase hplc fractionation followed by analysis of each chromatographic fraction by sds-page, n-terminal sequencing, maldi-tof mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of ...200919457355
disintegrins of crotalus simus tzabcan venom: isolation, characterization and evaluation of the cytotoxic and anti-adhesion activities of tzabcanin, a new rgd disintegrin.disintegrins are small non-enzymatic proteins common in the venoms of many viperid snakes. these proteins have received significant attention due to their ability to inhibit platelet aggregation and cell adhesion, making them model compounds in drug development and design investigations. the present study used a combination of molecular and proteomic techniques to screen the venom of the middle american rattlesnake (crotalus simus tzabcan) for novel disintegrins. six disintegrin isoforms were id ...201526163300
identification of linear b-cell epitopes on myotoxin ii, a lys49 phospholipase a₂ homologue from bothrops asper snake venom.knowledge on toxin immunogenicity at the molecular level can provide valuable information for the improvement of antivenoms, as well as for understanding toxin structure-function relationships. the aims of this study are two-fold: first, to identify the linear b-cell epitopes of myotoxin ii from bothrops asper snake venom, a lys49 phospholipase a₂ homologue; and second, to use antibodies specifically directed against an epitope having functional relevance in its toxicity, to probe the dimeric as ...201222677805
preclinical assessment of a polyspecific antivenom against the venoms of cerrophidion sasai, porthidium nasutum and porthidium ophryomegas: insights from combined antivenomics and neutralization assays.a polyspecific antivenom is used in central america for the treatment of envenomings by viperid snakes. this antivenom is generated in horses hyperimmunized with a mixture of venoms from bothrops asper, crotalus simus and lachesis stenophrys. the present study analyzed the ability of this antivenom to neutralize the venoms of three central american viperid species of the 'porthidium group', i.e. porthidium nasutum, porthidium ophryomegas and cerrophidion sasai, formerly classified as cerrophidio ...201323313380
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.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 l ...201323727490
immunological profile of antivenoms: preclinical analysis of the efficacy of a polyspecific antivenom through antivenomics and neutralization assays.parenteral administration of animal-derived antivenoms constitutes the mainstay in the treatment of snakebite envenomings. despite the fact that this therapy has been available for over a century, the detailed understanding of the neutralizing and immunoreactivity profiles of the majority of antivenoms is pending. currently, a combination of preclinical neutralization tests and 'antivenomics', i.e. a proteomic-based assessment of antivenom immunoreactivity, provides a powerful analytical platfor ...201424583507
the use of ecological niche modeling to infer potential risk areas of snakebite in the mexican state of veracruz.many authors have claimed that snakebite risk is associated with human population density, human activities, and snake behavior. here we analyzed whether environmental suitability of vipers can be used as an indicator of snakebite risk. we tested several hypotheses to explain snakebite incidence, through the construction of models incorporating both environmental suitability and socioeconomic variables in veracruz, mexico.201424963989
proteomic and toxicological profiling of the venom of bothrocophias campbelli, a pitviper species from ecuador and colombia.detailed snake venom proteomes for nearly a hundred species in different pitviper genera have accumulated using 'venomics' methodologies. however, venom composition for some lineages remains poorly known. bothrocophias (toad-headed pitvipers) is a genus restricted to the northwestern portion of south america for which information on venom composition is lacking. here, we describe the protein composition, toxicological profiling, and antivenom neutralization of the venom of bothrocophias campbell ...201425091349
isolation and characterization of four medium-size disintegrins from the venoms of central american viperid snakes of the genera atropoides, bothrops, cerrophidion and crotalus.four disintegrins were isolated from the venoms of the central american viperid snakes atropoides mexicanus (atropoimin), bothrops asper (bothrasperin), cerrophidion sasai (sasaimin), and crotalus simus (simusmin). purifications were performed by reverse-phase hplc. the four disintegrins have biochemical characteristics, i.e. molecular mass and location of cys, which allow their classification within the group of medium-size disintegrins. all of them present the canonical rgd sequence, which det ...201425457103
the disintegrin tzabcanin inhibits adhesion and migration in melanoma and lung cancer cells.integrins play an essential role in cancer survival and invasion, and they have been major targets in drug development and design. disintegrins are small (4-16kda) viperid snake venom proteins that exhibit a canonical integrin-binding site (often rgd). these non-enzymatic proteins inhibit integrin-mediated cell-cell and cell-extracellular matrix interactions, making them potential candidates as therapeutics in cancer and numerous other human disorders. the present study examined the cytotoxic, a ...201627060015
full-length venom protein cdna sequences from venom-derived mrna: exploring compositional variation and adaptive multigene evolution.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 ...201627280639
accessing cryptic diversity in neotropical rattlesnakes (serpentes: viperidae: crotalus) with the description of two new species.members of the crotalus durissus species complex are widely distributed from mexico to argentina in areas with mainly seasonally dry tropical deciduous forest. although four species (c. culminatus, c. durissus, c. simus and c. tzabcan) are currently recognized, species limits remain to be tested. previous genetic studies suggest that c. durissus and c. simus may be paraphyletic and that at least one cryptic species may be present. we analyzed 2596 bp of dna sequence data from three mitochondrial ...202032229836
morphological alterations caused by manual venom extraction on the main venom gland of bothrops asper and crotalus simus snakes (serpentes: viperidae): long-term implications for antivenom production.the only scientifically validated treatment for snakebite envenomation is the administration of antivenoms. for their production, small quantities of snake venom are injected in animals to elicit a specific antibody response. snakes are kept in captivity, and their venom is regularly extracted to assure antivenom access. it has already been reported that the pressure exerted upon the venom gland during this extraction can cause tissue damage and fibrosis, leading to a decrease in the venom yield ...201931689424
biochemical and immunochemical characterization of venoms from snakes of the genus agkistrodon.in the present work, venoms from five species of the genus agkistrodon were evaluated in terms of their enzymatic (phospholipase a2 and caseinolytic) and biological (edema forming, hemorrhagic, procoagulant and lethal) effects. horses were used to produce monovalent hyperimmune sera against each of three venoms (a. bilineatus, a. contortrix and a. piscivorus) and their neutralizing potency, expressed as median effective dose (ed50), was determined against the venoms of all five species. in terms ...201932550570
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