Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.
Archis, Jennifer N; Akcali, Christopher; Stuart, Bryan L; Kikuchi, David; Chunco, Amanda J
Anthropogenic climate change is a significant global driver of species distribution change. Although many species have undergone range expansion at their poleward limits, data on several taxonomic groups are still lacking. A common method for studying range shifts is using species distribution models to evaluate current, and predict future, distributions. Notably, many sources of 'current' climate data used in species distribution modeling use the years 1950-2000 to calculate climatic averages. However, this does not account for recent (post 2000) climate change. This study examines the influence of climate change on the eastern coral snake ( Micrurus fulvius ). Specifically, we: (1) identified the current range and suitable environment of M. fulvius in the Southeastern United States, (2) investigated the potential impacts of climate change on the distribution of M. fulvius , and (3) evaluated the utility of future models in predicting recent (2001-2015) records. We used the species distribution modeling program Maxent and compared both current (1950-2000) and future (2050) climate conditions. Future climate models showed a shift in the distribution of suitable habitat across a significant portion of the range; however, results also suggest that much of the Southeastern United States will be outside the range of current conditions, suggesting that there may be no-analog environments in the future. Most strikingly, future models were more effective than the current models at predicting recent records, suggesting that range shifts may already be occurring. These results have implications for both M. fulvius and its Batesian mimics. More broadly, we recommend future Maxent studies consider using future climate data along with current data to better estimate the current distribution.
Wood, A; Schauben, J; Thundiyil, J; Kunisaki, T; Sollee, D; Lewis-Younger, C; Bernstein, J; Weisman, R
Envenomation by the Eastern coral snake is rare but may be associated with significant morbidity. While effective, acquisition of North American Coral Snake Antivenin (NACSAV) is difficult because production was discontinued for many years. The purpose of this study is to characterize coral snake exposures in Florida and determine the effects of varying treatment paradigms on patient outcomes. This study is an observational case series of cases received at Florida poison centers. Included cases were Eastern coral snake exposures occurring between January 1, 1998 and October 31, 2010. Excluded cases included those found to be unrelated or those not followed for at least 24 h post envenomation. Case comments were reviewed to obtain data. Comparisons were made between asymptomatic patients receiving empiric antivenom therapy (empiric group) and those asymptomatic patients who received antivenom upon developing signs of systemic envenomation (withhold group). Of the 553 cases identified, 387 were included in the final analysis. According to case comments, 56.3% of patients had no reported systemic symptoms. Most commonly, patients were reported to have pain (40.6%), paresthesias (28.4%), nausea (12.7%), and emesis (11.4%). NACSAV was administered to 252 patients (65%). Of those patients receiving NACSAV, 18.25% were reported to have had an adverse reaction. Patients in the withhold group (n = 106) had significantly fewer minor, moderate, and major outcomes than patients in the empiric group (n = 134, p < 0.01). While patients in the withhold group had favorable outcomes compared with those in the empiric group, this strategy cannot be applied to all patients presenting asymptomatic to healthcare facilities due to study limitations. Further studies are needed to determine what treatment strategy is most appropriate for asymptomatic patients presenting to healthcare facilities.
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
Margres, Mark J; Aronow, Karalyn; Loyacano, Jacob; Rokyta, Darin R
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
Morgan, David L; Borys, Douglas J; Stanford, Rhandi; Kjar, Dean; Tobleman, William
The clinical features of bites from Texas coral snakes (Micrurus tener) have not been well studied. Our goal was to review the largest number of victims of Texas coral snakebites to determine their characteristics, effects, treatment, and outcome. Retrospective case series of Micrurus tener exposures reported to the Texas Poison Center Network from 2000 to 2004. Eighty-two patients were included in the analysis. Most (57.3%) were 18 to 49-year-old men. Almost 90% had local swelling, pain, erythema, or paresthesias. Only 7.3% had systemic effects, and none of these were severe. Over half received coral snake antivenin, and 15.9% were given opioids for pain. No patient died and no patient required mechanical ventilation due to hypoventilation from the snakebite. There were more local findings and less severe systemic effects than previously reported. Antivenin is not needed for most of these patients, and opioids may be administered safely.
Tanaka, Gabriela D.; Furtado, Maria de Fátima D.; Portaro, Fernanda C. V.; Sant'Anna, Osvaldo Augusto; Tambourgi, Denise V.
Background Micrurus snake bites can cause death by muscle paralysis and respiratory arrest, few hours after envenomation. The specific treatment for coral snake envenomation is the intravenous application of heterologous antivenom and, in Brazil, it is produced by horse immunization with a mixture of M. corallinus and M. frontalis venoms, snakes that inhabit the South and Southeastern regions of the country. However, this antivenom might be inefficient, considering the existence of intra- and inter-specific variations in the composition of the venoms. Therefore, the aim of the present study was to investigate the toxic properties of venoms from nine species of Micrurus: eight present in different geographic regions of Brazil (M. frontalis, M. corallinus, M. hemprichii, M. spixii, M. altirostris, M. surinamensis, M. ibiboboca, M. lemniscatus) and one (M. fulvius) with large distribution in Southeastern United States and Mexico. This study also analyzed the antigenic cross-reactivity and the neutralizing potential of the Brazilian coral snake antivenom against these Micrurus venoms. Methodology/Principal Findings Analysis of protein composition and toxicity revealed a large diversity of venoms from the nine Micrurus species. ELISA and Western blot assays showed a varied capability of the therapeutic antivenom to recognize the diverse species venom components. In vivo and in vitro neutralization assays indicated that the antivenom is not able to fully neutralize the toxic activities of all venoms. Conclusion These results indicate the existence of a large range of both qualitative and quantitative variations in Micrurus venoms, probably reflecting the adaptation of the snakes from this genus to vastly dissimilar habitats. The data also show that the antivenom used for human therapy in Brazil is not fully able to neutralize the main toxic activities present in the venoms from all Micrurus species occurring in the country. It suggests that modifications in the
Full Text Available Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a ‘venomics’ approach, proteins of at least nine families were identified, with a moderate predominance of three-finger toxins (3FTx; 48.2% over phospholipase A2 (PLA2; 36.5%. Comparison of this venom profile with those of other Micrurus species suggests that it may represent a more balanced, ‘intermediate’ type within the dichotomy between 3FTx- and PLA2-predominant venoms. M. clarki venom was strongly cross-recognized and, accordingly, efficiently neutralized by an equine therapeutic antivenom against M. nigrocinctus, revealing their high antigenic similarity. Lethal activity for mice could be reproduced by a PLA2 venom fraction, but, unexpectedly, not by fractions corresponding to 3FTxs. The most abundant venom component, hereby named clarkitoxin-I, was identified as a short-chain (type I 3FTx, devoid of lethal effect in mice, whose target remains to be defined. Its amino acid sequence of 66 residues shows high similarity with predicted sequences of venom gland transcripts described for M. fulvius, M. browni, and M. diastema.
Tanaka Gabriela D
Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.
Full Text Available Conventional treatment of Naja naja oxiana (NNO envenoming requires large volumes of equine antivenin raised against NNO crude venom. The poor efficiency of this antivenin is assumed to be due to the high molecular weight non-toxic proteins, a strong immunogen, present in the crude venom. These proteins cause depression of antibody formation against the low molecular weight toxic components of venom. In the present study the low molecular weight lethal components were isolated from crude venom of NNO venom by sephadex G50 get filtration chromatography. A sera was prepared by immunizing horses with toxic fraction. One milliliter of this serum neutralized 1.8mg of NNO crude venom. This high titer antivenin is thus 2.2 times more potent than the sera obtained against NNO crude venom.
Seyedian, Ramin; Pipelzadeh, Mohammad Hassan; Jalali, Amir; Kim, Euikyung; Lee, Hyunkyoung; Kang, Changkeun; Cha, Mijin; Sohn, Eun-Tae; Jung, Eun-Sun; Rahmani, Ali Hassan; Mirakabady, Abbas Zare
Hemiscorpius lepturus envenomation exhibits various pathological changes in the affected tissues, including skin, blood cells, cardiovascular and central nervous systems. The enzymatic activity and protein component of the venom have not been described previously. In the present study, the electrophoretic profile of H. lepturus venom was determined by SDS-PAGE (12 and 15%), resulting in major protein bands at 3.5-5, 30-35 and 50-60 kDa. The enzymatic activities of the venom was, for the first time, investigated using various zymography techniques, which showed the gelatinolytic, caseinolytic, and hyaluronidase activities mainly at around 50-60 kDa, 30-40 kDa, and 40-50 kDa, respectively. Among these, the proteolytic activities was almost completely disappeared in the presence of a matrix metalloproteinase inhibitor, 1, 10-phenanthroline. Antigen-antibody interactions between the venom and its Iranian antivenin was observed by Western blotting, and it showed several antigenic proteins in the range of 30-160 kDa. This strong antigen-antibody reaction was also demonstrated through an enzyme-linked immunosorbent assay (ELISA). The gelatinase activity of the venom was suppressed by Razi institute polyvalent antivenin, suggesting the inhibitory effect of the antivenin against H. lepturus venom protease activities. Prudently, more extensive clinical studies are necessary for validation of its use in envenomed patients. Copyright 2010 Elsevier Ltd. All rights reserved.
Kisangau Daniel P
Full Text Available Abstract The success of snake bite healers is vaguely understood in Kenya, partly due to their unknown materia medica and occult-mystical nature of their practice. A comparison is made of plants used in snake bite treatments by two culturally distinct African groups (the Kamba and Luo. Thirty two plants used for snakebite treatment are documented. The majority of the antidotes are prepared from freshly collected plant material – frequently leaves. Though knowledge of snake bite conditions etiological perceptions of the ethnic groups is similar, field ethnobotanical data suggests that plant species used by the two ethnic groups are independently derived. Antivenin medicinal plants effectively illustrate the cultural context of medicine. Randomness or the use of a variety of species in different families appears to be a feature of traditional snake bite treatments. A high degree of informant consensus for the species was observed. The study indicates rural Kenya inhabitants rely on medicinal plants for healthcare.
Vega-Gonz¨¢lez Luis Roberto
All over the world there is a huge complex problem caused by the sting of poisonous animals. In many countries all around the orb there are some animal species hazardous for human beings. A case from a Mexican University R&D institute- Private firm innovation project about scorpion¡¯s antivenins health area is presented. The scientific-technological allied participant organizations performed a long life cycle innovation project, which includes research and development, knowledge transference,...
Larson, Kenneth W; Schaefer, Keith R; Austin, Cindy; Norton, Rhy; Finley, Phillip J
Although initially created for the treatment of rattlesnake (genus: Crotalus) bites, Crotalidae-Fab antivenin is used to treat many different pit viper envenomations. However, the efficacy of Crotalidae-Fab in preventing tissue loss from copperhead (Agkistrodon contortrix) or cottonmouth (Agkistrodon piscivorus) snakebites remains unclear. Recent reports show that Agkistrodon-related bites rarely require treatment beyond simple observation and pain control. The purpose of this study was to examine the amount of tissue loss in patients who received Crotalidae-Fab compared with those who did not after an Agkistrodon bite. After institutional review board approval, a retrospective study was completed at a Level 1 trauma center. Between 2009 and 2013, a total of 57 snakebites were identified. Of the 57 bites, the snake species was documented in 36 cases including 31 copperheads, 1 cottonmouth, and 4 rattlesnakes. The other 21 bites were from unknown or nonvenomous species. Of the 32 Agkistrodon-related bites, 15 patients received Crotalidae-Fab (average of 3 vials administered) and 17 did not receive Crotalidae-Fab. None of the 32 patients, regardless of treatment option, had tissue loss or required surgical interventions. Only 1 patient received Crotalidae-Fab and debridement of a vesicle associated with the bite. No clinically significant differences were observed between the groups. These findings support previous literature that failed to show added benefit of Crotalidae-Fab treatment for Agkistrodon bites beyond patient comfort and pain control. Evaluation of current protocols for Agkistrodon envenomations is warranted. Snakebite wound education in trauma physicians and nurses may decrease unnecessary use of antivenom medication.
Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.
Full Text Available Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase. N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.
Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen
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.
Rodrigo Castellari Gonzalez
Full Text Available Micrurus decoratus (Jan, 1858 is a poorly known species of coral snake, with a controversial history concerning its geographical range. The lack of consensus among researchers, since its original description, is largely due to the reporting of erroneous localities in publications. Herein we present the geographical range for the species based on the review of 184 records from 67 different municipalities in Brazil, including two new records for the state of Espírito Santo, extending its distribution to ca. 300 km northward from the previous northernmost locality. We also comment on doubtful records for the states of Rio Grande do Sul and Bahia, which contain no accurate data. We restrict the occurrence of Micrurus decoratus to the Atlantic Rainforest, with elevation range from 400 up to 1,600 m in the Brazilian states of Santa Catarina, Paraná, São Paulo, Rio de Janeiro, Minas Gerais and Espírito Santo.
Background/Aims Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells. Methodology/Principal findings Intraplantar injection of MLV (1–10 μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema. Conclusions/Significance In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms. PMID:29161255
Luciana Lyra Casais-E-Silva
Full Text Available Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells.Intraplantar injection of MLV (1-10 μg/paw in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs. MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively markedly reduced MLV-induced edema.In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms.
Sanz, Libia; Pla, Davinia; Pérez, Alicia; Rodríguez, Yania; Zavaleta, Alfonso; Salas, Maria; Lomonte, Bruno; Calvete, Juan J
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.
Dey, Abhijit; Pandey, Devendra Kumar
To determine the altitudinal variation of stigmasterol, a potential antivenin, in roots from seven populations of Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) (R. serpentina), an important herb found in Indian subcontinent which has long been used in the treatment of snakebite, blood pressure and schizophrenia. Altitudinal variation of stigmasterol content in R. serpentina roots was analyzed by high performance thin layer chromatography. Chromatography was performed on silica gel 60 F254 thin layer chromatography plates with benzene-acetone 86:14 (v/v) as mobile phase. Densitometric analysis was done at λ=366 nm after derivatization with vanillin-10% (v/v) sulphuric acid alcohol reagent. The method was validated for precision and recovery. The present experiment demonstrates a simple, rapid, precise and sensitive high performance thin layer chromatography protocol for qualitative and quantitative determination of stigmasterol from different populations of R. serpentina. Results demonstrated that in root samples stigmasterol was present at Rf value of 0.44. This investigation demonstrates that stigmasterol content in R. serpentina roots varies in different altitudes. Popular ethnomedicinal use of this herb against snakebite may be contributed by the occurrence of stigmasterol in its roots. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
Oliveira, Fabiana da Rocha; Noronha, Maria das Dores Nogueira; Lozano, Jorge Luis Lopez
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.
Castro, K L; Duarte, C G; Ramos, H R; Machado de Avila, R A; Schneider, F S; Oliveira, D; Freitas, C F; Kalapothakis, E; Ho, P L; Chávez-Olortegui, C
The main goal of this work was to develop a strategy to identify B-cell epitopes on four different three finger toxins (3FTX) and one phospholipase A2 (PLA2) from Micrurus corallinus snake venom. 3FTx and PLA2 are highly abundant components in Elapidic venoms and are the major responsibles for the toxicity observed in envenomation by coral snakes. Overlapping peptides from the sequence of each toxin were prepared by SPOT method and three different anti-elapidic sera were used to map the epitopes. After immunogenicity analysis of the spot-reactive peptides by EPITOPIA, a computational method, nine sequences from the five toxins were chemically synthesized and antigenically and immunogenically characterized. All the peptides were used together as immunogens in rabbits, delivered with Freund's adjuvant for a first cycle of immunization and Montanide in the second. A good antibody response against individual synthetic peptides and M. corallinus venom was achieved. Anti-peptide IgGs were also cross-reactive against Micrurus frontalis and Micrurus lemniscatus crude venoms. In addition, anti-peptide IgGs inhibits the lethal and phospholipasic activities of M. corallinus crude venom. Our results provide a rational basis to the identification of neutralizing epitopes on coral snake toxins and show that their corresponding synthetic peptides could improve the generation of immuno-therapeutics. The use of synthetic peptide for immunization is a reasonable approach, since it enables poly-specificity, low risk of toxic effects and large scale production. Copyright © 2014 Elsevier Ltd. All rights reserved.
Ho Paulo L
Full Text Available Abstract Background Micrurus corallinus (coral snake is a tropical forest snake belonging to the family Elapidae. Its venom shows a high neurotoxicity associated with pre- and post-synaptic toxins, causing diaphragm paralysis, which may result in death. In spite of a relatively small incidence of accidents, serum therapy is crucial for those bitten. However, the adequate production of antiserum is hampered by the difficulty in obtaining sufficient amounts of venom from a small snake with demanding breeding conditions. In order to elucidate the molecular basis of this venom and to uncover possible immunogens for an antiserum, we generated expressed sequences tags (ESTs from its venom glands and analyzed the transcriptomic profile. In addition, their immunogenicity was tested using DNA immunization. Results A total of 1438 ESTs were generated and grouped into 611 clusters. Toxin transcripts represented 46% of the total ESTs. The two main toxin classes consisted of three-finger toxins (3FTx (24% and phospholipases A2 (PLA2s (15%. However, 8 other classes of toxins were present, including C-type lectins, natriuretic peptide precursors and even high-molecular mass components such as metalloproteases and L-amino acid oxidases. Each class included an assortment of isoforms, some showing evidence of alternative splicing and domain deletions. Five antigenic candidates were selected (four 3FTx and one PLA2 and used for a preliminary study of DNA immunization. The immunological response showed that the sera from the immunized animals were able to recognize the recombinant antigens. Conclusion Besides an improvement in our knowledge of the composition of coral snake venoms, which are very poorly known when compared to Old World elapids, the expression profile suggests abundant and diversified components that may be used in future antiserum formulation. As recombinant production of venom antigens frequently fails due to complex disulfide arrangements, DNA
Full Text Available L-amino acid oxidases (LAAOs are ubiquitous enzymes in nature. Bioactivities described for these enzymes include apoptosis induction, edema formation, induction or inhibition of platelet aggregation, as well as antiviral, antiparasite, and antibacterial actions. With over 80 species, Micrurus snakes are the representatives of the Elapidae family in the New World. Although LAAOs in Micrurus venoms have been predicted by venom gland transcriptomic studies and detected in proteomic studies, no enzymes of this kind have been previously purified from their venoms. Earlier proteomic studies revealed that the venom of M. mipartitus from Colombia contains ∼4% of LAAO. This enzyme, here named MipLAAO, was isolated and biochemically and functionally characterized. The enzyme is found in monomeric form, with an isotope-averaged molecular mass of 59,100.6 Da, as determined by MALDI-TOF. Its oxidase activity shows substrate preference for hydrophobic amino acids, being optimal at pH 8.0. By nucleotide sequencing of venom gland cDNA of mRNA transcripts obtained from a single snake, six isoforms of MipLAAO with minor variations among them were retrieved. The deduced sequences present a mature chain of 483 amino acids, with a predicted pI of 8.9, and theoretical masses between 55,010.9 and 55,121.0 Da. The difference with experimentally observed mass is likely due to glycosylation, in agreement with the finding of three putative N-glycosylation sites in its amino acid sequence. A phylogenetic analysis of MmipLAAO placed this new enzyme within the clade of homologous proteins from elapid snakes, characterized by the conserved Serine at position 223, in contrast to LAAOs from viperids. MmipLAAO showed a potent bactericidal effect on S. aureus (MIC: 2 µg/mL, but not on E. coli. The former activity could be of interest to future studies assessing its potential as antimicrobial agent.
Rey-Suárez, Paola; Núñez, Vitelbina; Fernández, Julián; Lomonte, Bruno
In Colombia, nearly 2.8% of the 4200 snakebite accidents recorded annually are inflicted by coral snakes (genus Micrurus). Micrurus dumerilii has a broad distribution in this country, especially in densely populated areas. The proteomic profile of its venom was here studied by a bottom-up approach combining RP-HPLC, SDS-PAGE and MALDI-TOF/TOF. Venom proteins were assigned to eleven families, the most abundant being phospholipases A2 (PLA2; 52.0%) and three-finger toxins (3FTx; 28.1%). This compositional profile shows that M. dumerilii venom belongs to the 'PLA2-rich' phenotype, in the recently proposed dichotomy for Micrurus venoms. Enzymatic and toxic venom activities correlated with protein family abundances. Whole venom induced a conspicuous myotoxic, cytotoxic and anticoagulant effect, and was mildly edematogenic and proteolytic, whereas it lacked hemorrhagic activity. Some 3FTxs and PLA2s reproduced the lethal effect of venom. A coral snake antivenom to Micrurus nigrocinctus demonstrated significant cross-recognition of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect. The combined compositional, functional, and immunological data here reported for M. dumerilii venom may contribute to a better understanding of these envenomings, and support the possible use of anti-M. nigrocinctus coral snake antivenom in their treatment. Coral snakes represent a highly diversified group of elapids in the New World, with nearly 70 species within the genus Micrurus. Owing to their scarce yields, the biochemical composition and toxic activities of coral snake venoms have been less well characterized than those of viperid species. In this work, an integrative view of the venom of M. dumerilii, a medically relevant coral snake from Colombia, was obtained by a combined proteomic, functional, and immunological approach. The venom contains proteins from at least eleven families, with a predominance of phospholipases A2 (PLA2), followed by three
Adolfo Rafael de Roodt
. Nevertheless, the treatment of venomous snakebites in domestic animals can turn diffcult due several problems among which, the conspicuous, is the low availability or lack of antivenoms for veterinary use. As commercial pressures on the pharmaceutical industry have led to a reduction in the production of antivenins in several parts of the world, their availability is sometimes rather limited and sometimes these products are impossible to obtain. In this work, we immunized horses with venom of South American vipers to obtain hyperimmune plasma. The plasma was processed to separate whole IgG of F(ab´2 fragments using two conventional methods (caprylic acid fractionation or double saline precipitation and pepsin digestion. The obtained antivenins were tested for their biochemical and immunochemical characteristics and neutralizing potency. The SDS-PAGE of the antivenins showed, in the processed antivenin, bands in the order of 150 and 100 kDa in the whole IgG or F(ab´2 fragments, respectively. The presence of albumin or contaminants of high or low molecular weight was not detected in any of the preparations. No important differences were observed in the neutralizing potency of the antivenins, although production cost was very low with the method used to obtain pure IgG. The low production cost makes the production of antivenins for veterinary use proftable when the production of F(ab´2 fragments is not possible.
León Montero, Guillermo; Stiles, Bradley G.; Alape Girón, Alberto; Rojas Céspedes, Gustavo; Gutiérrez, José María
A comparative study was performed on the ability of IgG and F(ab')2 antivenoms to neutralize lethal and myotoxic activities of Micrurus nigrocinctus venom. Both antivenoms were adjusted to a similar neutralizing potency in experiments where venom and antivenoms were preincubated prior to injection. No significant differences were observed between IgG and F(ab')2 antivenoms concerning neutralization of lethal effect in rescue experiments, i.e., when antivenom was administered intravenously aft...
SISTEMA FIBRINOLÍTICO: MÉTODOS DE ESTUDIO Y HALLAZGOS EN VENENOS DE SERPIENTES DE LOS GENEROS Bothrops, Crotalus, Micrurus EN VENEZUELA | FIBRINOLYTIC SYSTEM: METHODS OF STUDY AND FINDINGS IN Bothrops, Crotalus, Micrurus SNAKE VENOMS IN VENEZUELA
Full Text Available En la presente revisión se muestran resultados relevantes de actividades hemostáticas, con especial énfasis a las relacionadas con la fibrinólisis, presentes en venenos de serpientes venezolanas de los géneros Bothrops, Crotalus y Micrurus, que existen en diversas localidades geográficas. Con esta descripción, se presenta además una revisión de diversos ensayos que se utilizan en investigación para estos estudios. Se han evidenciado importantes diferencias inter e intra-especies, e incluso entre ejemplares de distintos espacios geográficos, lo que debe influir en los mecanismos de acción de sus venenos y la sintomatología clínica. Estas diferencias en composición y concentración de componentes activos, deben estar asociadas a variaciones estacionales o geográficas, dieta, sexo, hábitat, edad, e inclusive variabilidades genéticas. Ello podría explicar las discrepancias en los cuadros clínicos de las víctimas y también ayudar a determinar mecanismos de acción que faciliten una mejor orientación a los médicos tratantes. Estas variables ayudarían al seguimiento y tratamiento de los pacientes, orientando a los especialistas en antivenenos, en la escogencia del inóculo, con una mezcla amplia de venenos de diferentes especies, géneros, edad, sexo y procedencia, así como con toxinas de relevancia, para la preparación y obtención de estos antivenenos con valores de gran eficacia y amplio espectro. Los componentes bioactivos aislados, como las colombienasas y la tenerplasminina-1, por sus características biológicas, representan asimismo moléculas con un uso potencial como trombolíticos y antifibrinolíticos, respectivamente.
Andreas H. Laustsen
Full Text Available Snakebite envenomings represent a neglected public health issue in many parts of the rural tropical world. Animal-derived antivenoms have existed for more than a hundred years and are effective in neutralizing snake venom toxins when timely administered. However, the low immunogenicity of many small but potent snake venom toxins represents a challenge for obtaining a balanced immune response against the medically relevant components of the venom. Here, we employ high-throughput sequencing of the immunoglobulin (Ig transcriptome of mice immunized with a three-finger toxin and a phospholipase A2 from the venom of the Central American coral snake, Micrurus nigrocinctus. Although exploratory in nature, our indicate results showed that only low frequencies of mRNA encoding IgG isotypes, the most relevant isotype for therapeutic purposes, were present in splenocytes of five mice immunized with 6 doses of the two types of toxins over 90 days. Furthermore, analysis of Ig heavy chain transcripts showed that no particular combination of variable (V and joining (J gene segments had been selected in the immunization process, as would be expected after a strong humoral immune response to a single antigen. Combined with the titration of toxin-specific antibodies in the sera of immunized mice, these data support the low immunogenicity of three-finger toxins and phospholipases A2found in M. nigrocinctusvenoms, and highlight the need for future studies analyzing the complexity of antibody responses to toxins at the molecular level.
Vivas, Jeilyn; Ibarra, Carlos; Salazar, Ana M; Neves-Ferreira, Ana G C; Sánchez, Elda E; Perales, Jonás; Rodríguez-Acosta, Alexis; Guerrero, Belsy
A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed. Copyright © 2015 Elsevier Inc. All rights reserved.
Bénard-Valle, Melisa; Carbajal-Saucedo, Alejandro; de Roodt, Adolfo; López-Vera, Estuardo; Alagón, Alejandro
The objective of this study was to identify the venom components that could play a relevant role during envenomation caused by the coral snake Micrurus tener, through its biochemical characterization as well as the analysis of its effects on a murine model. Furthermore, it aimed to evaluate crude venom, in addition to its components, for possible specificity of action on a natural prey model (Conopsis lineata). The toxicity of the crude venom (delivered subcutaneously) showed a significant difference between the Median Lethal Dose (LD₅₀) in mice (4.4 μg/g) and in Conopsis lineata (12.1 μg/g) that was not observed when comparing the Median Paralyzing Dose (PD₅₀) values (mice = 4.7 μg/g; snakes = 4.1 μg/g). These results are evidence that the choice of study model strongly influences the apparent effects of crude venom. Moreover, based on the observed physical signs in the animal models, it was concluded that the most important physical effect caused by the venom is flaccid paralysis, which facilitates capture and subduing of prey regardless of whether it is alive; death is a logical consequence of the lack of oxygenation. Venom fractionation using a C18 reverse phase column yielded 35 fractions from which 16.6% caused paralysis and/or death to both animal models, 21.9% caused paralysis and/or death only to C. lineata and 1.6% were murine specific. Surprisingly, the diversity of snake-specific fractions did not reflect a difference between the PD₅₀s of the crude venom in mice and snakes, making it impossible to assume some type of specificity for either of the study models. Finally, the great diversity and abundance of fractions with no observable effect in snakes or mice (42.7%) suggested that the observed lethal fractions are not the only relevant toxic fractions within the venom and emphasized the possible relevance of interaction between components to generate the syndrome caused by the venom as a whole. Copyright © 2013 Elsevier Ltd. All rights
Oswald Vital Brazil
Full Text Available Coral snakes, the New World Elapidae, are included in the genera Micniroides and Micrurus. The genus Mlcrurus comprises nearly all coral snake species and those which are responsible for human snake-bite accidents. The following generalizations concerning the effects induced by their venoms, and their venom-properties can be made. Coral snake venoms are neurotoxic, producing loss of muscle strenght and death by respiratory paralysis. Local edema and necrosis are not induced nor blood coagulation or hemorrhages. Proteolysis activity is absent or of very low grade. They display phospholipase A2 activity. Nephrotoxic effects are not evoked. The main toxins from elapid venoms are postsynaptic and presynaptic neurotoxins and cardiotoxins. Phospholipases A2 endowed with myonecrotic or cardiotoxin-like properties are important toxic components from some elapid venoms. The mode of action of Micrurus frontalis, M. lemniscatus, M. corallinus and M. fulvius venoms has been investigated in isolated muscle preparations and is here discussed. It is shown that while M. frontalis and M. lemniscatus venoms must contain only neurotoxins that act at the cholinergic end-plate receptor (postsynaptic neurotoxins, M. corallinus venom also inhibits evoked acetylcholine release by the motor nerve endings (presynaptic neurotoxin-like effect and M. fulvius induces muscle fiber membrane depolarization (cardiotoxin-like effect. The effects produced by M. corallinus and M. fulvius venoms in vivo in dogs and M. frontalis venom in dogs and monkeys are also reported.
Margres, Mark J; McGivern, James J; Seavy, Margaret; Wray, Kenneth P; Facente, Jack; Rokyta, Darin R
Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process and thus the genetic basis of adaptive evolution requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom gland toward toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait but also have extensive conservation and biomedical implications. C. adamanteus is currently a candidate for federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species. Copyright © 2015 by the Genetics Society of America.
Full Text Available Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2 activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2 inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.
Snake-bite is considered a neglected tropical disease that affects thousands of people worldwide. Administration of antivenom is the corner stone in the therapy of snake-bite. The study aimed to improve the production of antivenom using gamma irradiation to detoxify venom and calcium phosphate nanoparticles as alternative adjuvant. This was carried out by studying the toxicological and immunological properties of the Naja haje venom before and after exposure to 2 KGy gamma radiation. Calcium phosphate nanoparticles were selected to be used as adjuvant as they showed better entrapment efficacy than Alum or chitosan nanoparticles. In order to achieve the goal of the present study, the native, γ irradiated and nanoparticles loaded venom as well nanoparticles loaded irradiated venom were used for preparation of their specific antivenom using rabbits. Data revealed that gamma irradiation of Naja haje venom reduced its lethality to one sixth as compared to its native venom. There was no change in the antigenic reactivity between both native and γ irradiated Naja haje venoms. Inhibition in the phospholipase and proteolytic activities after gamma irradiation were shown. Furthermore, injection of γ irradiated Naja haje venom did not significantly change activities of serum LDH, CPK, CK-MB, ALT and AST as well as urea and creatinine levels compared to the normal group. In addition, the immune response of immunized rabbits was evaluated through determination of antibody titer using ELISA technique, serum titer produced with γ irradiated venom loaded on CPN showed highest titer as compared to other sera. Results indicated that the sooner antivenom was injected the higher the neutralizing capacity obtained. All the prepared antivenoms were able to neutralize the toxicological activities of Naja haje snake venom to same extent. Thus, gamma radiation is a reliable tool for detoxification of Naja haje venom without affecting its immunogenicity. Furthermore. Calcium phosphate nanoparticles are promising and safe system when applied as an adjuvant in immunization process
Ana María HENAO DUQUE; Vitelbina NÚÑEZ RANGEL
La coral “rabo de ají” es una coral bicolor larga y delgada. Esta especie está ampliamente distribuida en Colombia y es la coral que causa el mayor número de accidentes en la región Andina, por esto es importante mantener esta especie en cautiverio con fines de producción de antivenenos e investigación. No obstante, el mantenimiento de esta especie en cautiverio es difícil, debido a que se rehúsan a alimentarse voluntariamente y a que presentan alta mortalidad por el denominado síndrome de ma...
Adolfo Rafael de Roodt; Silvana Litwin; Judith Estevez; Eduardo G Gould; Jorge A Dolab; Jorge Gould
Las mordeduras producidas por serpientes venenosas son un serio problema médico en varias regiones del mundo y sobre las cuales los sistemas de salud actúan en diferentes grados en lo referente a tratamiento y prevención. Sin embargo, el tratamiento de las mordeduras de serpientes venenosas en animales domésticos puede resultar difícil por diversos motivos, siendo uno de estos la baja oferta o ausencia de antivenenos para uso veterinario. Las presiones comerciales en la industria farmacéutica...
Laustsen, Andreas Hougaard; Engmark, Mikael; Clouser, Christopher
Snakebite envenomings represent a neglected public health issue in many parts of the rural tropical world. Animal-derived antivenoms have existed for more than a hundred years and are effective in neutralizing snake venom toxins when timely administered. However, the low immunogenicity of many...
years occurred in Peru in the northern departments bordering Ecuador in 1992-1994. Sylvatic plague is endemic in the southern provinces of Loja and... Ecuador ) Micrurus bocourti (Pacific lowlands of western Ecuador ) Micrurus catamayensis (Catamayo Valley, Loja Province) Micrurus dumerilii spp...Disease Vector Ecology Profile Ecuador -~· ""’ -.. ~ """ Defense Pest Management Information Analysis Center’ Armed Forces Pest Management
Spiller, Henry A; Bosse, George M; Ryan, Mark L
In 2001, a new antivenin was introduced to the United States and became widely available in the snakebite season of 2002. We investigated what impact this may have had on snakebite treatment and medical outcome. The study used a retrospective review of all snakebites to humans reported to the National Poison Center Database System from 2000 to 2007. During the 8 years, there were 37,760 snakebites, with a mean of 4720 bites per year. There was a 27% increase in bites reported to a Poison center for the 8-year period and an overall 13.5% increase in the use of antivenin. The 2 categories primarily responsible for the increased use of antivenin were copperhead and crotaline-unknown. Rattlesnake bites remained the category most frequently treated with antivenin with a mean 52.5% treatment rate and only moderate increase for the 8 years. There was no change in the percentage or number of patients with a major outcome (mean, 3.8%) or death (mean, 0.5%). There was a decrease in patients with a minor outcome and an increase in patients with a moderate outcome. The new antivenin is reported to have a reduced potential for adverse reactions. This may have had a role in the decision of which snakebite victims received antivenin. With the introduction of a new antivenin, there has been a dramatic increase in the number of snakebite patients treated with antivenin. This has been most noticeable in snake bite categories that were less frequently treated with antivenin in the past. Copyright © 2010 Elsevier Inc. All rights reserved.
Gerardo González V.
medicine section of the Ramón González Valencia Universitary Hospital in Bucaramanga (Colombia from 1983 – 1993.40 children with diagnosis of snake bite were selected. Resulte: The major frecuency was found in the school age with a little male predominance. 95% of children carne from the rural area. The most snake genus was Bothrops (85%, we had just one case for Micrurus and the rest of them were not identified. 91%of the snake hites were in feet and legs distal thirC:. 65% of people assist for medical attention in the first 24 hours. Every patient had eye-teeth marks, and localized oedema and pain in the bite; most common haemorrhagic manifestations were ecchymosis (80% and gingival bleeding. 69% of cases were Grade II and lII. 33% of them had complicationsj the most common one was Disseminated Intravascular Coagulation. We found.prolongued PT and PTT in 85% and 63% of cases respectively. BC was not specific. 97.5% of our children received especific antivenin for treatment, 28% transfusions and 100% antibiotic and antitetanic prophylaxis.
Hospitalization average days were 5. Three of our patients (7.5% had sorne sequel andjust one died.
In conclussion there not be a good education in the community on risk about appropiatte use of shoes,
first aid, avoidiry empire treatments that to yatrogene and inmediately a consultation to the nearest clinical center should be done. The medical and paramedical personnel should be prepared about attention of patients with snake bite. It was included a protocol for the management, easy to apply in our health centers.
Zolfagharian H.; Mohammadpour Dounighi, N.
Antivenoms have been used successfully for more than a century and up to now constitute the only effectivetreatment for snakebites .The production of antivenin started long time ago when the calmette was preparedthe antivenom in 1894.The method currently used to prepare antivenom by most of the manufacturers areoriginated from the method of Pope which was develop in 1938. Several new approaches in the production ofantivenom have been proposed to produce IgG, F(ab)2, F(ab) antivenin to improve...
Conclusions: Antivenin and HBO, respectively, induced a neuroprotective effect after D. acutus envenomation by attenuating brain edema, upregulating nestin expression in SVZ, and improving coagulopathy and oxidative stress. The intervention efficacy of antivenom with HBO was maximum within 5 h after envenomation and was more efficacious than antivenom alone.
Reynoso, H.; Bucher, Enrique; Merlini, H. O.
Teniendo en cuenta las particularidades de la especie Micrurus frontalis pyrrhocryptus (coral) en lo referente a su comportamiento semifosorial, hemos considerado conveniente relacionar distintos aspectos biológicos de la especie tales como longevidad, peso y producción de veneno, con la disponibilidad de tierra en recipientes y exposición a la luz.
Full Text Available Objective: To study the incidence and epidemiology of scorpion sting cases that were referred to the health services centers of Behbahan County, Khuzistan Province, southwestern Iran, during the two yeare (2007-2008. Methods: In this descriptive retrospective research, the data has come from files of scorpionstung patients referring to the health services centers of Behbahan during study period. A special scorpion sting sheet was prepared and completed for every case of scorpion sting. Analysis of 3441 case sheets received during this period was carried out. The frequencies of medical and entomoepidemiologic parameters were turned to the percentage position. Results: A total of 3 441 cases of scorpion stings were reported during the two-year period from 2007 to 2008. The average incidence of scorpion stings was 8.8‰ in the two years. The frequency of cases was higher during August, September, June and July that 2 056 cases of scorpion stings were reported. Most stings were occurred during summer. Nearly 51.3% of the cases were men. All cases had received antivenin. Majority of scorpion sting cases (56.5% lived in the rural areas. The most common sting site was the hand. About 74.4% have received the antivenin 0-6 h after the sting. The early injection of the antivenin is very important. The most of the cases of scorpion stings (59% were occurred by yellow scorpions. Conclusions: Surveillance for cases of scorpion stings must begin at all regions of Behbahan County. Treatment of cases of scorpion stings is conducted according to a protocol set by the Ministry of Health, Treatment and Medical Education. This protocol included directions for lines of treatment and the dose of antivenin recommended. Thereafter all cases are referred to hospital for further observation and management.
Tokish, J T; Benjamin, J; Walter, F
To review a regional experience with the treatment of snakebites. Five major southern Arizona hospitals, including two Level I trauma centers. A review of all snakebite admissions over a five-year period was performed. During the period reviewed, 164 patients were admitted for snakebites. Rattlesnakes were responsible for 98 percent of identified envenomations. Thirty-six percent of the patients were transported by air to the admitting facility. Eighty percent of patients were admitted to the intensive care unit for an average of 1.6 days. Total hospital stays averaged 2.8 days. Ninety percent of patients received antivenin, usually only on the day of admission. Of those receiving antivenin, 20 percent had an anaphylactoid reaction, and 1 percent required readmission for serum sickness. Laboratory evaluation indicated abnormalities in platelet count, coagulation parameters, and fibrinogen levels, but these rarely required treatment. Thirteen percent of patients underwent surgical intervention, including a 4 percent fasciotomy rate, and a single amputation. The use of field treatment, including "cut and suck," tourniquets, and cryotherapy, increased the likelihood of surgery. The authors concluded that the intensive care unit and helicopter transport system were overused. They recommend that established objective envenomation severity scores be used to dictate patient treatment, specifically the use of antivenin.
Full Text Available McGee J Leonard,1 Catherine Bresee,2 Andrew Cruikshank1 1Animal Specialty and Emergency Center, Los Angeles, CA, USA; 2The Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: This is a retrospective multicenter study (2006–2012 examining a population of dogs with moderate to severe crotalid envenomation for protective effects of the canine rattlesnake vaccine. Five nonacademic emergency and referral veterinary hospitals in Southern California were involved in the study and contributed records regarding a total of 82 client-owned dogs that were treated for naturally occurring rattlesnake envenomation. All dogs received antivenin (Crotalidae polyvalent, with dosages ranging from one to three vials (mean: 1.3±0.6. Fourteen dogs (17% had a history of prior vaccination against crotalid venom. In univariate logistic regression modeling, cases with lower body weight (P=0.0001 or higher snakebite severity scores (P<0.0001 were associated with greater morbidity. No statistically significant difference in morbidity or mortality between vaccinated and unvaccinated dogs was found. The findings of this study did not identify a significantly protective effect of previous vaccination in the cases of moderate to severe rattlesnake envenomation that require treatment with antivenin. Keywords: rattlesnake envenomation, vaccine, antivenin, canine
Lubich, Carol; Krenzelok, Edward P
Emergency departments throughout the USA may have some familiarity with the management of envenomation from indigenous snake species such as Crotalinae (rattlesnakes) and Micrurus (coral snakes). However, venomous species may include exotic reptiles whose bites pose substantial treatment challenges due to both a lack of experience and the difficulty in obtaining antivenoms. Two pet cobra envenomation incidents illustrate the challenges that face emergency departments, especially in urban sett...
Lubich, Carol; Krenzelok, Edward P
Emergency departments throughout the USA may have some familiarity with the management of envenomation from indigenous snake species such as Crotalinae (rattlesnakes) and Micrurus (coral snakes). However, venomous species may include exotic reptiles whose bites pose substantial treatment challenges due to both a lack of experience and the difficulty in obtaining antivenoms. Two pet cobra envenomation incidents illustrate the challenges that face emergency departments, especially in urban sett...
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
Venom gland transcriptomes and proteomes of six Micrurus taxa ( M. corallinus , M. lemniscatus carvalhoi , M. lemniscatus lemniscatus , M. paraensis , M. spixii spixii , and M. surinamensis ) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2-6 toxin classes that account for 91-99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A₂ (PLA₂s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA₂s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1-2.0%) are found in all venoms except that of M. s. spixii . Other toxin families are present in all six venoms at trace levels (venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6-9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three
Steven D. Aird
Full Text Available Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs and phospholipases A2 (PLA2s comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0% are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%. Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen
Lee, H F; Lee, J D; Lee, Y C
In course of immunizing horses with snake venoms, tetanus and diphtheria toxoids, a new serum component, T-globulin, was formed and migrated between the beta- and gamma-globulins. The T-globulin content was parallel with the antibody titre after the middle course of immunization. There were many components in snake antivenin and T-globulin was composed of most of those components. The components of diphtheria T-globulin were the same as those of crude antitoxin and tetanus T-globulin except one precipitin.
Full Text Available Antivenoms have been used successfully for more than a century and up to now constitute the only effectivetreatment for snakebites .The production of antivenin started long time ago when the calmette was preparedthe antivenom in 1894.The method currently used to prepare antivenom by most of the manufacturers areoriginated from the method of Pope which was develop in 1938. Several new approaches in the production ofantivenom have been proposed to produce IgG, F(ab2, F(ab antivenin to improve their quality .Theseimprovement include complete or partial modification in the antivenom production regarding animal,immunization protocols , new adjuvants in hyperimmunization of animals , purification processes ( caprylicacid ,chromatography , diafiltration and ulterafiltration ,enzymatic digestion of IgG (pepsin, papain andfractionation of venom .When the IgG is digested enzymatically, different fragments are obtained depending on the enzyme used, that is, if papain is used, three fragments are obtained, the crystallizing fragment (Fc and two antigen-binding fragments F(ab and, if pepsin is used, one F(ab'2 fragment is obtained, while thecrystallizing fragment is digested. Fab and F(ab2 fragments conserve their capacity to specifically bind to the antigen that gave rise to them.
Full Text Available Snake bite envenomation is not uncommon in Taiwan. This study focuses on the pattern of poisonous snake bites and their management in southern Taiwan over a 5-year period. The case histories of 37 patients with poisonous snake bites admitted to the Kaohsiung Medical University Hospital between June 2001 and July 2005 were analyzed retrospectively. Three patients, bitten by unknown species of venomous snakes, were excluded from this study. The frequency of snake bites from each species of snake, the local and systemic manifestations of snake bite, treatment of complications and final outcomes were analyzed. Of the remaining 34 patients, 11 (32.4% were bitten by bamboo vipers, 10 (29.4% by Russell's pit vipers, 8 (23.5% by Taiwan cobras and 5 (14.7% by Taiwan Habu. The majority of snake bites (28 occurred between May and November. Those affected were mainly outdoor hikers (14 and workers (9. The antivenin requirements for treatment in the emergency room were in accordance with standard procedures. No mortality was noted among those envenomed by poisonous snakes. Although poisonous snake bite is not a common life-threatening emergency in the study area, we observed both an environmental risk and a seasonal incidence of snake bite. Keeping the varied clinical manifestations of snake bite in mind is important for effective management. Ready availability and appropriate use of antivenin, close monitoring of patients, institution of ventilatory support and early referral to a larger hospital when required, all help reduce mortality.
Lubich, Carol; Krenzelok, Edward P
Emergency departments throughout the USA may have some familiarity with the management of envenomation from indigenous snake species such as Crotalinae (rattlesnakes) and Micrurus (coral snakes). However, venomous species may include exotic reptiles whose bites pose substantial treatment challenges due to both a lack of experience and the difficulty in obtaining antivenoms. Two pet cobra envenomation incidents illustrate the challenges that face emergency departments, especially in urban settings, that are confronted with these exposures. It is important for emergency departments to be aware of the large underground presence of exotic venomous reptile pets and to utilise the expertise of regional poison centres that will also assist in the procurement of exotic antivenoms.
A small series of shrews collected in Guatemala and registered in the British Museum between 1843 and 1907 includes parts of type series for three species: Corsira tropicalis Gray (1843), Sorex micrurus Tomes (1862), and Blarina tropicalis Merriam (1895). These three names are now considered equivalent, but my recent review of the specimens comprising the series indicates that they include three distinct species: Cryptotis merriami Choate (1970), Cryptotis oreoryctes Woodman (2011), and Cryptotis tropicalis (Merriam 1895). I review the taxonomic history of these specimens, provide current identifications tied directly to museum register numbers, describe how to distinguish the three species, and provide revised synonymies for these species.
Se describen los signos presentados por las terneras que han llegado al laboratorio, destinadas a la vacuna, y las pruebas realizadas en vivo y a un animal muerto. Se trata de la pseudo-tuberculosis verminosa; bronquitis o bronco-pneumonía verminosa de los bovinos producida por el Strongylus micrurus. Description is made of symptoms shown by calves at the Laboratory on the vaccine and tests performed in vivo and in a dead animal; all in reference to verminous pseudo tuberculosis, bronchiti...
F. da Rocha Lagôa
Full Text Available O autor estudou a ação inativante, sôbre o complemento de cobaia, alguns venenos de serpentes brasileiras pertencentes às famílias dos Elapideos e Crotalideos. Da primeira, foi utilizado veneno de Micrurus frontalis, da segunda, foram usados venenos de espécies pertencentes aos gêneros Crotalus (C. terrificus e Bothrops (B. atrox, B. neuwiedii, B. jararaca, B. ja-raracussú, B. cotiara e B. alternata. O venenos de M. frontalis e C. terri¬ficus se revelaram incapazes de inativar o complemento, ao passo que os diversos de Bothrops empregados se mostraram altamente inativantes, destruindo sempre o 4.° componente do complemento (C4, fração idêntica à afetada pela ação da amônea.The author shows in this paper the results of the inactivation of com¬plement or alexin by some Brazilian snakes venoms of the Elapideae and Cro¬talideae families. The venom of Micrurus frontalis (Elapideae family and of Crotalus terrificus (Crotalideae family did not destroy the complement; but the venoms of Bothrops generus (B. atrox, B. neuwiedii, B. jararaca, B. jararacussú, B. cotiara e B. alternata, (Crotalideae family are highly active in the inactivation complement, always destroing the fourth component, whichis exactly the same component that is detroyed by ammonia.
William W. Lamar
Full Text Available Leptomicrurus renjifoi is described from tropical semi-deciduous forest of the eastern Colombian llanos. It is one of the smallest species in the genus, is most similar to L. scutiventris, and it may be distinguished from known congeners by a combination of color, pattern, and scale characters. Evidence for the recognition of Leptomicrurus is convincing, although its members were recently thought to comprise a closely related assemblage within Micrurus. A supposedly aberrant specimen of L. scutiventris may indicate clinal or ontogenetic variation in patternLeptomicrurus renjifoi es una nueva especie de serpiente elápida del bosque tropical semi-decíduo de los llanos orientales de Colombia. Es una de las especies más pequeñas del género, se asemeja más a L. scutiventris, y se distingue de sus congéneres por una combinación de color, patrón, y carácteres de escamación. Existe suficiente evidencia morfológica para reconocer Leptomicrurus como género independiente, aunque hasta hace poco sus miembros fueron considerados como un grupo compacto dentro del género Micrurus
Full Text Available Se ha evaluado la actividad de fosfolipasa A en seis venenos de serpientes comparando las ventajas de un método espectrofotométrico, previamente adaptado a nuestras condiciones de laboratorio, frente al método macroscópico de retardo en la coagulación de una emulsión lipoproteica. En ambos casos, la actividad de fosfolipasa A estuvo presente en los venenos de Micrurus spixii, Crotalus durissus, Bothrops brazili, Lachesis muta y Bothrops atrox y la actividad decreció en orden. En cambio, la actividad de la enzima en el veneno de Micrurus surinamensis sólo fue detectada por el método espectrofotométrico. Así mismo, los resultados basados en la cantidad de veneno utilizado para medir la actividad, mostraron una mayor sensibilidad con el método espectrofotométrico en comparación con el método macroscópico ya que se requirieron cantidades menores en el orden de 2 a 10 veces.
Full Text Available Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae. Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.
Full Text Available Aim: Evaluating the epidemiologic characteristics and management of snake bites presenting to emergency departments. Material and Method: In this retrospective study 74 cases of snakebites admitted to Emergency Department of Diyarbakir Training and Research Hospital between 2008 and 2009 were retrospectively evaluated. Results: Fourty-six (62.2% of patients were male and 28 (37.8% were female. Mean age of the study population was 34.85±19.17 (min 7- max 80 years. Most of the snakebites occurred between 18.00 to 06.00 hours and at home (73%. 79.7% of snake bites occurred to upper extremities. %93 of cases had intravenous administration of antivenin (one dose. Neither none of the patients needed recurrent administration. Discussion: Snake bites are still a major public health problem especially in rural areas. Particularly emergency care physicians should be adequately capable and sophisticated in multidisciplinary management of snake bites.
Chawla, Payal; Chawla, Amit; Vasudeva, Neeru; Sharma, Surendra Kumar
There are approximately 28 species of Aerva genus, but only a few species are medicinal of which A. persica, A. lanata and A. javanica are of great value. A number of flavonol glycosides (e.g., aervanone, kaempferol-3-galactoside, isorhamnetin-3-O-β-D-glucoside) have been reported from Aerva persica as major phytoconstituents and the minor constituents are β-cyanins (glycine betaine and trigonelline), sterols and carbohydrates. This plant is used as medicinal herb in several traditional systems of medicine all over the world, like diuretic, demulcent, purgative, emetic and tinder. Aerva plants are used to cure ulcer, lithiasis, dropsical affections, eye affection, toothache, headache, in disorders of abdomen and inflammation of internal organs. Roots and flowers are reported to possess hypoglycemic, antioxidant, anthelmintic, analgesic, antimalarial, antivenin activities and medicinal properties against rheumatism and kidney troubles.
Lee, Chi-Hsin; Lee, Yu-Ching; Liang, Meng-Huei; Leu, Sy-Jye; Lin, Liang-Tzung; Chiang, Jen-Ron; Yang, Yi-Yuan
Snake venom protein from Deinagkistrodon acutus (DA protein), one of the major venomous species in Taiwan, causes hemorrhagic symptoms that can lead to death. Although horse-derived antivenin is a major treatment, relatively strong and detrimental side effects are seen occasionally. In our study, yolk immunoglobulin (IgY) was purified from eggs, and DA protein was recognized using Western blotting and an enzyme-linked immunosorbent assay (ELISA), similar to therapeutic horse antivenin. The ELISA also indicated that specific IgY antibodies were elicited after the fifth booster, plateaued, and lasted for at least 3 months. To generate monoclonal single-chain variable fragment (scFv) antibodies, we used phage display technology to construct two libraries with short or long linkers, containing 6.24 × 10(8) and 5.28 × 10(8) transformants, respectively. After four rounds of biopanning, the eluted phage titer increased, and the phage-based ELISA indicated that the specific clones were enriched. Nucleotide sequences of 30 individual clones expressing scFv were analyzed and classified into four groups that all specifically recognized the DA venom protein. Furthermore, based on mass spectrometry, the scFv-bound protein was deduced to be snake venom metalloproteinase proteins. Most importantly, both IgY and mixed scFv inhibited the lethal effect in mice injected with the minimum lethal dosage of the DA protein. We suggest that together, these antibodies could be applied to the development of diagnostic agents or treatments for snakebite envenomation in the future. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Urbina C, Jose Nicolas; Londono M, Maria Cecilia
A total of 1840 individuals from 28 species (19 reptiles and 9 amphibians) were found in Gorgona Island, during June and July 2001. Based on 32 transects placed in four areas with different antropic perturbation degree (Prison, palm plantations, secondary forest and primary forest) it was found that the species richness was higher at the secondary forest. The species registered at primary and secondary forest where very similar as well as the species present at the prison and the palm plantations. A Canonical Correspondence Analysis (CCA) showed that Boa constricto1; Basiliscus galeritus. Ameiva bridgesii and Epipedobates boulengeri were found to be associated to open areas and their distribution was hardly affected by the environmental temperature. From the following species associated with forested areas, the canopy cover over the micro habitat influenced the distribution of Eleutherodactylus gularis. Eleutherodactylus achatinus and Bothrops atrox. While the understory cover influenced the distribution of Atelopus elegans. Bufo typhonius. Micrurus mipartitus y Enyalioides heterolepis
Full Text Available The mature ooxysts of six new species of Caryospora are described from the faeces of Brazilian snakes. They are differentiated from other species previously recorded from reptiles, largely on the size and shape of the oocyst and sporocyst, structure of the oocyst wall, and presence or absence of a polar body. C. paraensis n. sp., and C. carajasensis n. sp., are from the "false coral", Oxyrhopus petola digitalis; C. pseustesi n. sp., from the "egg-eater", Pseustes sulphureus sulphureus; C. epicratesi n. sp., from the "red boa", Epicrates cenchria cenchria; and C. micruri n. sp., and C. constancieae n. sp., from the "coral snake", Micrurus spixii spixii. A re-description is given of C. jararacae Carini, 1939, from the "jararaca" Bothrops atrox, embodying some additional morphological features.
Lunaschi, L. I.
Full Text Available The aim of this paper is to increase the knowledge on the diversity of digenean parasites in ophidians andanurans from northeastern Argentina. Specimens of the snakes Eunectes notaeus, Hydrodynastes gigas, Micrurus corallinus,Philodryas sp. and Sibynomorphus sp., and the anurans Rhinella schneideri, Phyllomedusa azurea and Leptodactylus latranswere examined. Twelve digenean species were identified: Catadiscus corderoi Mañé-Garzón, 1958, Catadiscus dolichocotyle(Cohn, 1903, Catadiscus uruguayensis Freitas & Lent, 1939, Choledocystus elegans (Travassos, 1926, Gorgoderina parvicavaTravassos, 1922, Haplometroides buccicola Odhner, 1911, Heterodiplostomum lanceolatum Dubois, 1936, Infidum similisTravassos, 1916, Mesocoelium monas (Rudolphi, 1819, Plagiorchis luehei (Travassos, 1927, Telorchis clava (Diesing, 1850and Travtrema stenocotyle (Cohn, 1902. New host species and/or new locality records from Argentina are presented.
Ivo Rohling Ghizoni-Jr.
Full Text Available The composition and geographic distribution of reptiles in Santa Catarina are little known, particularly in the open areas of its plateau (covered with ombrophylous steppe and Atlantic littoral (coastal dunes with thin, low, and predominant herbaceous vegetation known as restinga. Aiming to contribute to the knowledge of reptiles that inhabit these areas, this paper presents sixteen records of previously unknown or uncommon species in Santa Catarina: Acanthochelys spixii, Anops kingii, Cnemidophorus lacertoides, C. vacariensis, Leptotyphlops munoai, Mastigodryas b. bifossatus, Tantilla aff. melanocephala, Atractus reticulatus, Gomesophis brasiliensis, Lygophis flavifrenatus, Oxyrhopus r. rhombifer, Phalotris reticulatus, Philodryas agassizii, Xenodon dorbignyi, Micrurus altirostris and Bothrops pubescens. Aspects of the distribution and conservation of these species are discussed briefly.
Al-Sadoon, Mohammed K.
The present investigation is a retrospective review of snake bites in Riyadh province over the period (2005–2010). A total of 1019 cases of bites admitted to the Ministry of Health medical centers in Riyadh province were analyzed on the basis of age, sex, time of bite and its site on the body, outcome of treatment, antiserum dose and type of snake. Bites occurred throughout the six years with the highest frequency in 2005 and least in 2006 where most of the bite cases were mild and all evolved to cure except four patients who died following the administration of antivenom during 24 h after snake bite. Most of the patients were males (81.7%) and the most attacked age was within the range of 11–30 years (51.5%). All the bites were mainly in the exposed limbs and the most frequently bitten anatomical regions were the lower limbs (427 cases, 41.9%), principally the feet. The study incriminates Cerastes cerastes gasperettii in most of the bites indicating it as the snake of medical importance in Riyadh province. Also, the study indicates low degree of threat in spite of high rate of snake bites as a result of the availability of the medical facilities and the antivenin use in medical centers in Riyadh province. PMID:25737653
R V Bharath
Full Text Available Introduction: The present study was aimed to describe our experience with epidemiological characteristics, management options, and outcome of scorpion envenomation in children. Materials and Methods: The present retrospective study was conducted at Narayana Medical College and Hospital. The epidemiologic details including geographical locality of the event, age distribution, gender, and sting sites were noted in all hospitalized children with scorpion bite injury. Results: During the study period, a total 52 children were managed for scorpion sting. Mean age was 8.87 years. Male children were commoner victims of scorpion sting. Scorpion sting had bimodal pattern. Prazocin was used in 25 children. There was evidence of pulmonary edema in 23 cases. Seven patients required elective ventilation, and 5 of them could be weaned off within 72 hours. Mean hospital stay was 3.69 days. Two children expired in the present series. Conclusion: In present study, there was bimodal distribution of the scorpion sting cases, male children were more affected, and almost all of them improved with good outcome. We did not use anti-venin in the present study. The data from the study will serve not only to create heightened public awareness about scorpion envenomation but also to develop public awareness strategies and preventive measures.
Envenenamiento de Chelydra serpentina (Reptilia: Testudines por Tityus trivittatus (Scorpionida: Buthidae Envenomation of Chelydra serpentina (Reptilia: Testudines by Tityus trivittatus (Scorpionida: Buthidae
Adolfo R de Roodt
Full Text Available Se describe el caso de un ejemplar de tortuga mordedora (Chelydra serpentina que fue hallada con los miembros tetanizados en extensión, midriasis y poca respuesta a estímulos externos, en cuyo recinto se encontró un ejemplar de escorpión Tityus trivittatus. Ante el claro cuadro de envenenamiento, se trató al quelonio con antiveneno escorpiónico específico retornando a un estado de relajación muscular a las seis horas y encontrándoselo totalmente normal a las 24 horas sin mostrar secuelas posteriores. Este es el primer comunicado sobre el envenenamiento de quelonios por escorpiones. Se discuten algunos aspectos de este envenenamiento escorpiónico y su tratamiento con antiveneno específico.We report the case of a snapping turtle (Chelydra serpentina found tetanized, with the limbs in extension, mydriasis and poor response to external stimuli, in whose terrarium was found a Tityus trivittatus scorpion. Based on the clear clinical picture of envenoming, the turtle was treated with a specific scorpion antivenin, returning to a state of muscle relaxation after six hours of treatment and it was found totally normal at 24 hours, without envenoming sequelae. This is the first report on turtle envenomation by scorpion. The scorpion envenomation in reptiles and the treatment with specific antivenom is discussed.
Kamyab, Mostafa; Kim, Euikyung; Hoseiny, Seyed Mehdi; Seyedian, Ramin
Snakebite is a common problem especially in tropical areas all over the world including Iran. Echis carinatus as one of the most dangerous Iranian snakes is spreading in this country excluding central and northwest provinces. In this study gelatinase and fibrinogenolytic properties as two disintegrating matrix metalloproteinase enzymes were evaluated by a strong clear halo between 56-72 kDa in addition to another band located 76-102 kDa for gelatinase and one major band around 38 kDa for fibrinogenolytic enzyme respectively. The electrophorectc profile of our venom demonstrated at least one protein band between 24-31 kDa like previous reports and another two bands between 52-76 kDa and below 17 kDa stemmed probably due to the effect of natural selection in one species. According to our results Razi institute antivenin could neutralize in-vitro effects of gelatinase enzyme comprehensively. The electrophoretic profile of Iranian commercial antivenom as the main intravenous treatment of envenomed patients showed impurities in addition to F (ab') 2 weighing 96 kDa in SDS-PAGE analysis. It proposes more efforts for refinement to avoid short and long unwanted effects in envenomed patients.
Lynch Vincent J
Full Text Available Abstract Background Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Convincing examples of neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, thus they are excellent models to study the emergence of novel functions after gene duplications. Results Here, I show that positive Darwinian selection and neofunctionalization is common in snake venom phospholipase A2 genes. The pattern of gene duplication and positive selection indicates that adaptive molecular evolution occurs immediately after duplication events as novel functions emerge and continues as gene families diversify and are refined. Surprisingly, adaptive evolution of group-I phospholipases in elapids is also associated with speciation events, suggesting adaptation of the phospholipase arsenal to novel prey species after niche shifts. Mapping the location of sites under positive selection onto the crystal structure of phospholipase A2 identified regions evolving under diversifying selection are located on the molecular surface and are likely protein-protein interactions sites essential for toxin functions. Conclusion These data show that increases in genomic complexity (through gene duplications can lead to phenotypic complexity (venom composition and that positive Darwinian selection is a common evolutionary force in snake venoms. Finally, regions identified under selection on the surface of phospholipase A2 enzymes are potential candidate sites for structure based antivenin design.
Lee, Michael S Y; Sanders, Kate L; King, Benedict; Palci, Alessandro
The relationship between rates of diversification and of body size change (a common proxy for phenotypic evolution) was investigated across Elapidae, the largest radiation of highly venomous snakes. Time-calibrated phylogenetic trees for 175 species of elapids (more than 50% of known taxa) were constructed using seven mitochondrial and nuclear genes. Analyses using these trees revealed no evidence for a link between speciation rates and changes in body size. Two clades (Hydrophis, Micrurus) show anomalously high rates of diversification within Elapidae, yet exhibit rates of body size evolution almost identical to the general elapid 'background' rate. Although correlations between speciation rates and rates of body size change exist in certain groups (e.g. ray-finned fishes, passerine birds), the two processes appear to be uncoupled in elapid snakes. There is also no detectable shift in diversification dynamics associated with the colonization of Australasia, which is surprising given that elapids appear to be the first clade of venomous snakes to reach the continent.
Full Text Available The present work aimed to determine the oral microbiotic composition of snakes from São José do Rio Preto city, São Paulo State, Brazil. Ten snake species, comprising the families Boidae, Colubridae, Elapidae and Viperidae, were submitted to microbiological examination of their oral cavity, which indicated positivity for all buccal samples. Gram-negative bacilli, gram-negative cocci bacilli, gram-positive bacilli and gram-positive cocci were isolated from the snakes. Among isolated bacterium species, the occurrence of coagulase-negative staphylococci in the buccal cavity of Crotalus durissus (Viperiade, Eunectes murinus (Boidae, Mastigodryas bifossatus (Colubridae and Bacillus subtilis, common to oral cavity of Bothrops alternatus (Viperidae and Phalotris mertensi (Colubridae, was detected. It was observed higher diversity of isolated bacteria from the oral cavity of Micrurus frontalis (Elapidae and Philodryas nattereri (Colubridae, as well as the prevalence of gram-positive baccillus and gram-positive cocci. The composition of the oral microbiota of the studied snakes, with or without inoculating fangs, is diverse and also related to the formation of abscesses at the bite site in the victims of the ophidian accidents, and to pathogenic processes in the snakes that host these microorganisms.
Dantas-Torres, Filipe; Ferreira, Débora R A; de Melo, Louise M; Lima, Polly-Ana C P; Siqueira, Daniel B; Rameh-de-Albuquerque, Luciana C; de Melo, Adriana V; Ramos, Janaina A C
From 2005 to 2009, 147 ticks found on 32 wild animals from or referred to two zoobotanical parks (Parque Zoobotânico Arruda Câmara and Parque Estadual Dois Irmãos) located in northeastern Brazil were identified. Ticks found on two veterinarians working in one of the parks (i.e., Parque Estadual Dois Irmãos), after return from forested areas within the park's territory, were also identified. The following tick-host associations were recorded: Amblyomma fuscum Neumann on Boa constrictor L.; Amblyomma longirostre Koch on Ramphastos vitellinus ariel Vigors and Coendou prehensilis (L.); Amblyomma varium Koch on Bradypus variegates Schinz; Amblyomma rotundatum Koch on Chelonoidis carbonaria (Spix), Chelonoidis denticulata (L.), Micrurus ibiboboca (Merrem), Python molurus bivittatus Kuhl, Iguana iguana (L.) and B. variegatus; Amblyomma nodosum Neumann on Myrmecophaga tridactyla L. and Tamandua tetradactyla (L.); and Rhipicephalus sanguineus (Latreille) on Nasua nasua (L.). The ticks found on the veterinarians were identified as nine Amblyomma larvae. The presence of Am. nodosum in Pernambuco and Am. rotundatum and Am. varium in Paraíba is recorded for the first time and the occurrence of Am. longirostre in Pernambuco is confirmed. Ramphastos vitellinus ariel is a new host record for Am. longirostre whereas M. ibiboboca and B. variegatus are new host records for Am. rotundatum. Finally, the human parasitism by Amblyomma ticks is reported for the first time in Pernambuco, highlighting the potential of tick-borne pathogen transmission in this state.
Streicher, Jeffrey W; McEntee, Jay P; Drzich, Laura C; Card, Daren C; Schield, Drew R; Smart, Utpal; Parkinson, Christopher L; Jezkova, Tereza; Smith, Eric N; Castoe, Todd A
Strong spatial sorting of genetic variation in contiguous populations is often explained by local adaptation or secondary contact following allopatric divergence. A third explanation, spatial sorting by stochastic effects of range expansion, has been considered less often though theoretical models suggest it should be widespread, if ephemeral. In a study designed to delimit species within a clade of venomous coralsnakes, we identified an unusual pattern within the Texas coral snake (Micrurus tener): strong spatial sorting of divergent mitochondrial (mtDNA) lineages over a portion of its range, but weak sorting of these lineages elsewhere. We tested three alternative hypotheses to explain this pattern-local adaptation, secondary contact following allopatric divergence, and range expansion. Collectively, near panmixia of nuclear DNA, the signal of range expansion associated sampling drift, expansion origins in the Gulf Coast of Mexico, and species distribution modeling suggest that the spatial sorting of divergent mtDNA lineages within M. tener has resulted from genetic surfing of standing mtDNA variation-not local adaptation or allopatric divergence. Our findings highlight the potential for the stochastic effects of recent range expansion to mislead estimations of population divergence made from mtDNA, which may be exacerbated in systems with low vagility, ancestral mtDNA polymorphism, and male-biased dispersal. © 2016 The Author(s).
Viana, Lúcio André; Winck, Gisele Regina; Almeida-Santos, Marlon; Telles, Felipe Bottona da Silva; Gazêta, Gilberto Salles; Rocha, Carlos Frederico Duarte
Amblyomma rotundatum Koch is a parthenogenetic tick usually associated with reptiles and amphibians. However, relatively few studies on occurrences of ticks in wild reptile populations in Brazil have been produced. The aim of this study was to analyze the presence of ticks associated with reptile species in the Grussaí restinga, in the municipality of São João da Barra, state of Rio de Janeiro, Brazil. Between December 2010 and January 2011, 131 individuals belonging to nine species of reptiles of the order Squamata were sampled: the lizards Tropidurus torquatus (n = 51), Hemidactylus mabouia (n = 25), Mabuya agilis (n = 30), Mabuya macrorhyncha (n = 6), Cnemidophorus littoralis (n = 5) and Ameiva ameiva (n = 10); and the snakes Philodryas olfersii (n = 2), Oxyrhopus rhombifer (n = 1) and Micrurus corallinus (n = 1). The only tick species found to be associated with any of the reptiles sampled was A. rotundatum. One adult female was detected on one individual of the lizard A. ameiva, one nymph on one individual of the lizard T. torquatus and four nymphs on one individual of the snake P. olfersii. This study is the first record of parasitism of A. rotundatum involving the reptiles T. torquatus and P. olfersii as hosts. Our results suggest that in the Grussaí restinga habitat, A. rotundatum may use different species of reptiles to complete its life cycle.
Full Text Available This study aimed to evaluate the infection rates of snakes by pentastomids in the semi-arid region of Brazil. Fifteen snakes (four Micrurus ibiboboca (Merrem, 1820 and eleven Philodryas nattereri Steindachner, 1870 were collected between January and April of 2005, in the municipality of Crato (07° 14' S and 39° 24' W, State of Ceará, Brazil. Laboratorial analysis of the respiratory tracts of the sampled snakes indicated differences in host infection rates: four individuals of P. nattereri (36.4% were infected by Cephalobaena tetrapoda Heymons, 1922 (mean infection intensity 1.5 ± 0.28, 1-2 and three specimens (27.3% by Raillietiella furcocerca (Diesing, 1863 (2.3 ± 1.32, 1-5. Only one individual of M. ibiboboca (25% was infected by a non-identified species of Raillietiella sp. These are the first data on pentastomid infection in snakes in Northeastern Brazil and both snake species comprise new host records for the pentastomids. The results also indicate that the generalist parasites C. tetrapoda and R. furcocerca share their definitive hosts.
Ivo Rohling Ghizoni-Junior
Full Text Available http://dx.doi.org/10.5007/2175-7925.2009v22n3p129 A composição e a distribuição dos répteis em Santa Catarina são pouco conhecidas, particularmente em suas áreas abertas naturais do planalto (estepe ombróﬁla e do litoral (faixa litorânea de restingas com dunas. Visando contribuir com o conhecimento dos répteis nestas áreas, são apresentados registros de dezesseis espécies anteriormente desconhecidas ou com poucos registros para Santa Catarina: Acanthochelys spixii, Anops kingii, Cnemidophorus lacertoides, C. vacariensis, Leptotyphlops munoai, Mastigodryas b. bifossatus, Tantilla aff. melanocephala, Atractus reticulatus, Gomesophis brasiliensis, Lygophis ﬂavifrenatus, Oxyrhopus r. rhombifer, Phalotris reticulatus, Philodryas agassizii, Xenodon dorbignyi, Micrurus altirostris e Bothrops pubescens. São discutidos brevemente aspectos sobre a distribuição e a conservação destas espécies.
Aspectos epidemiológicos e clínicos dos acidentes ofídicos ocorridos nos municípios do Estado do Amazonas Epidemiological and clinical aspects of snake accidentes in the municipalities of the State of Amazonas, Brazil
Célio Campos Borges
municipality (70.2%. The local signs and symptoms most frequently observed in those who received medical care more than 6 hours after the accident (57.3% were edema (76.9%, pain (68.7%, erithema (10.2% and hemorrhage (9.3%. The systemic manifestation most frequently observed was hemorrhage (18.8%. Serotherapy was administered in only 65.9% of patients, the intravenous route being the route most commonly used to administer the antivenin (52.3%, while other non- recommended routes were widely used. In the majority of patients the antivenin given was antibotropic. The most frequent complications were: abscess 13.7%, necrosis 12.3%, secondary infection 8.3%, renal insufficiency 2.5% and gangrene 2.5%. The medical procedures most used in the treatment of these complications were drainage 52.6%, debridement 28.9%, amputation 10.5%, surgical cleaning 5.3% and peritoneal dialysis 2.6%. The fatality rate was 1%.
Josef E Jolissaint
Full Text Available History of present illness: While watering his lawn, a 36-year-old man felt two sharp bites to his bilateral ankles. He reports that he then saw a light brown, 2-foot snake slither away from him. He came to the emergency department because of pain and swelling in his ankles and inability to bear weight. Physical examination revealed bilateral ankle swelling and puncture marks on his left lateral heel and medial right ankle. Palpation, passive flexion and extension elicited severe pain bilaterally. Blood work including prothrombin time (PT, partial thromboplastin time (PTT, international normalized ratio (INR, and fibrinogen were within normal limits. Consultation with Poison Control indicated the snake was likely a copperhead, which is a venomous snake whose bites rarely require antivenin. Significant findings: In this case, ultrasonography of the lateral surface of the left foot revealed soft tissue edema (red arrow and fluid collection (white asterisk adjacent to the extensor tendon (white arrow. The edematous area resembles cobblestones, with hypoechoic areas of fluid spanning relatively hyperechoic fat lobules. The tendon is surrounded by anechoic fluid, expanding the potential space in the sheath. No hyperechoic foreign objects were noted. Discussion: The patient was diagnosed with soft tissue injury and extensor tenosynovitis after a snake envenomation. Snake venom contains metalloproteinases and other enzymatic proteins that cause local tissue edema and necrosis.1 After a snake bite, ultrasound can be used to assess for retained fangs, soft tissue edema, tendon sheath fluid, muscle fasciculation, and injury to deeper musculature that may not be readily apparent on physical exam.2,3 Most patients with tenosynovitis will recover with immobilization of the joint and non-steroidal anti-inflammatory medications.4 Rarely, the tendon may become infected requiring antibiotics and surgical intervention.4 Topics: Ultrasound, snake envenomation
Optimization and preliminary characterization of venom isolated from 3 medically important jellyfish: the box (Chironex fleckeri), Irukandji (Carukia barnesi), and blubber (Catostylus mosaicus) jellyfish.
Wiltshire, C J; Sutherland, S K; Fenner, P J; Young, A R
To optimize venom extraction and to undertake preliminary biochemical studies of venom from the box jellyfish (Chironex fleckeri), the Irukandji jellyfish (Carukia barnesi), and the blubber jellyfish (Catostylus mosaicus). Lyophilized crude venoms from box jellyfish tentacles and whole Irukandji jellyfish were prepared in water by homogenization, sonication, and rapid freeze thawing. A second technique, consisting of grinding samples with a glass mortar and pestle and using phosphate-buffered saline, was used to prepare crude venom from isolated nematocysts of the box jellyfish, the bells of Irukandji jellyfish, and the oral lobes of blubber jellyfish. Venoms were compared by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot test. Toxicity of some venoms was determined by intravenous median lethal dose assay in mice. Different venom extraction techniques produced significantly different crude venoms for both box and Irukandji jellyfish. Irukandji and blubber venom SDS-PAGE protein profiles were established for the first time. Analysis of Western blot tests revealed that box jellyfish antivenin reacted specifically with the venom of each jellyfish. Toxicity was found in Irukandji jellyfish venom derived by use of the mortar-and-pestle method, but not in the lyophilized venom. Glass mortar-and-pestle grinding and use of an appropriate buffer was found to be a simple and suitable method for the preparation of venom from each jellyfish species studied. This study contributes to biochemical investigations of jellyfish venoms, particularly the venom of the Irukandji jellyfish, for which there are, to our knowledge, no published studies. It also highlights the importance of optimizing venom extraction as the first step toward understanding the complex biological effects of jellyfish venoms.
Paulo Sérgio Bernarde
Full Text Available Apesar da importância dos acidentes ofídicos na Saúde Pública, são relativamente poucas as pesquisas realizadas sobre esse tema no Brasil. Devido aos poucos estudos sobre ofidismo na Amazônia e especialmente no estado do Acre, trabalhos epidemiológicos são de grande relevância. Esse estudo apresenta a lista de serpentes peçonhentas e aspectos epidemiológicos dos acidentes ofídicos em Cruzeiro do Sul, região do Alto Juruá (Acre, verificando quais gêneros de serpentes são responsáveis pelos envenenamentos e aspectos que envolvem o acidente e o atendimento hospitalar. Os dados epidemiológicos foram coligidos a partir do SINAN (Sistema de Informações de Agravos de Notificação, no setor de vigilância epidemiológica do Hospital Regional do Juruá, no município de Cruzeiro do Sul. Sete espécies de serpentes peçonhentas foram registradas nesse município: três viperídeos (Bothrops atrox, Bothriopsis bilineata e Lachesis muta e quatro elapídeos (Micrurus hemprichii, M. lemniscatus, M. remotus and M. surinamensis. Durante o período de dois anos (agosto de 2007 a julho de 2009 foram registrados 195 casos de acidentes ofídicos. Cinquenta e um por cento dos acidentes foi classificado como laquético (Lachesis, seguido pelo botrópico (Bothrops e Bothriopsis com 38% e crotálico (Crotalus com 2%. Em 9% dos casos o gênero da serpente envolvida não foi informado. A maioria dos acidentes envolveu indivíduos adultos do gênero masculino em área rural, afetados principalmente nos membros inferiores. Os casos ocorreram mais frequentemente nos meses de novembro a abril, coincidindo com os maiores níveis pluviométricos. A maioria dos acidentes foi atribuída equivocadamente à serpente L. muta, tendo sido provavelmente causados por B. atrox.Despite the importance of accidents involving snakebites, research on this theme in Brazil is relatively rare, especially in the Amazon region. Due to the poor number of studies about ophidism
Bohlen, Christopher J; Chesler, Alexander T; Sharif-Naeini, Reza; Medzihradszky, Katalin F; Zhou, Sharleen; King, David; Sánchez, Elda E; Burlingame, Alma L; Basbaum, Allan I; Julius, David
Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation. Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations. As such, venoms provide a rich and varied source of small molecule and protein pharmacophores that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain, excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH 100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain-related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception. © 2011 Macmillan Publishers Limited. All rights reserved
Lindioneza Adriano Ribeiro
Full Text Available Foram avaliados aspectos epidemiológicos de acidentes por serpentes peçonhentas no Estado de São Paulo, Brasil, com base em prontuários de 322 pacientes e em entrevistas feitas com 209 deles e/ou seus acompanhantes. Os acidentes ocorreram principalmente com pessoas de 10 a 20 anos de idade, do sexo masculino, nos meses de outubro a abril e no período diurno. As regiões anatômicas mais freqüentemente picadas foram os pés, as mãos e as pernas. Bothrops, Crotalus e Micrurus foram responsáveis por, respectivamente, 95,0%, 4,4% e 0,6% dos casos. Não ocorreram óbitos, mas 2,2% dos pacientes apresentaram seqüelas. Dentre os 209 entrevistados, a ocupação de lavrador foi a mais freqüentemente relacionada ao acidente que, em aproximadamente 60% das vezes, ocorreu durante o trabalho. O total de 160 pacientes (76,6% submeteram-se a alguma forma de tratamento antes de chegarem a um serviço de saúde: foram mais comuns o uso de torniquete (50,2%, a expressão local na tentativa de retirar parte do veneno (33,5%, a colocação das mais diversas substâncias sobre o local da picada (36,8% e a ingestão de outras (12,9%; pouco mais de um quarto dos pacientes submeteram-se a alguma forma de tratamento médico antes de chegar ao HVB sendo mais comum a antissepsia (8,2%, a administração do antiveneno (6,2%, de anti-histamínicos (5,7% e de analgésicos (5,3%.
Vidal, Bruno Prado Cortizo
Full Text Available Objetivos: Investigar a capacidade do soro antielapídico produzido no Brasil na identificação de frações do veneno de seis espécies, incluindo as que constituem o pool de inoculação: Micrurus brasiliensis, M. corallinus, M. frontalis, M. lemniscatus, M. spixii e M. surinamensis. Métodos: As amostras utilizadas fazem parte do banco de venenos do Centro de Estudos e Pesquisas Biológicas, da Pontifícia Universidade Católica de Goiás. O soro antielapídico foi cedido pela Fundação Ezequiel Dias. As metodologias empregadas foram eletroforese e imunoblotting. Resultados: Foi demonstrada uma variabilidade toxinológica e uma capacidade também variável de reconhecimento desses componentes pelo soro antielapídico. A partir da técnica de western-blotting o soro antielapídico da Fundação Ezequiel Dias foi capaz de reconhecer a maioria, mas não todos os componentes presentes nos venenos analisados. Conclusões: Os resultados sugerem uma eficácia restrita do soro antielapídico já que o mesmo possui limitações quanto as espécies Amazônicas, o que reforça a necessidade de uma revisão dos estudos intra e interespecíficos dos venenos micrúricos
Crocker, Patrick; Zad, Omid; Milling, Truman; Maxson, Todd; King, Benjamin; Whorton, Elbert
the bite patients than in controls (all P values < .05). Crotaline venom produces a broad cytokine response in human bite victims. In particular, IL-4, myeloperoxidase, and Apo A-I and C3 levels remain altered despite antivenom therapy, whereas PAI-1 and regulated upon activation, normal t-cell expressed and secreted levels seem to normalize after antivenin as other markers are affected. Understanding this profile and further study of the markers identified might lead to improved therapies and better prognostic indicators. Copyright © 2010 Elsevier Inc. All rights reserved.
Roth, Brett; Sharma, Kapil; Onisko, Nancy; Chen, Tiffany
In light of the existing controversy regarding antivenin treatment for copperhead envenomation, a more detailed analysis of the disability from this species is needed. Our objective was to prospectively determine the duration of pain, swelling, and functional disability, i.e., residual venom effects, in patients with copperhead envenomation. Patients with venomous snakebite reported to the North Texas Poison Center between April 2009 and November 2011 were assessed. Patients with confirmed envenomations were contacted by a specialist in poison information. Day zero was the day of the bite and verbal phone consent for study enrollment was obtained at that time. The patient (or their guardian) was contacted by phone daily thereafter, and asked to rate their pain, edema/swelling, and disability using the modified DASH and LEFS scales. Patients were followed to resolution of all symptoms or return to baseline. About 104 cases of venomous snakebite were followed; of which 17 were excluded due to being a dry bites (5) or for having insufficient data during follow-up (11) or due to coagulopathy (1). Overall, residual venom effects from copperhead bites for most patients last between 7 and 13 days. Median time to complete pain resolution was 7 days (mean = 10.7 days). Median length of time to resolution of swelling was 10 days (mean = 13 days) and median length of time to resolution of functional disability was 9 days (mean = 12.2 days). Residual venom effects from copperhead envenomation in this study had a slightly shorter duration than some other studies. Data are skewed due to outliers where residual venom effects lasted for up to 89 days. Initial reoccurrence of some symptoms may be seen. Antivenom (AV) is currently being used for a large percentage of patients with copperhead envenomation. Finally, no differences in duration of venom effects were seen based on age or location of bite. Our study suggests that residual venom effects from copperhead
snake charming is banned in India as part of efforts to protect India's steadily depleting wildlife, this knowledge is also rapidly disappearing in this community. Such type of ethno botanical studies will help in systematic documentation of ethno botanical knowledge and availing to the scientific world plant therapies used as antivenin by the Saperas community.
URBINA-CARDONA JOSÉ NICOLÁS
Full Text Available En la actualidad los entornos naturales se han convertido en paisajes fragmentados por actividades como la agricultura y la ganadería. La alteración antropogénica determina cambios en la diversidad de serpientes al alterar físicamente el paisaje y generar cambios en la estructura de la vegetación y el microclima. En el presente estudio se determinó la diversidad de serpientes de cuatro hábitats con diferente grado de alteración antropogénica en la Isla Gorgona. A partir de búsquedas visuales durante junio-julio 2001 y febrero-abril 2004 y a lo largo de 32 transectos lineales se registraron 51 individuos pertenecientes a 13 especies de serpientes. Se determinó una representatividad del muestreo entre el 60 y el 78% de las especies estimadas. La mayor riqueza se encontró en el bosque secundario, seguido por el primario y los cultivos. El mayor recambio de especies se presentó entre la prisión y los cultivos, y entre la prisión y el bosque primario. En el bosque secundario y primario la abundancia de serpientes se duplicó durante las lluvias mientras que en cultivos y prisión la abundancia fue mayor en época seca. Es posible que la alteración antropogénica afecte negativamente a las especies Leptophis ahaetulla, Micrurus dumerili, Oxybelis brevirostris y Tantilla longifrontalis, sin embargo, ninguna de éstas se encuentra categorizada en la lista de especies en peligro de extinción. Es necesario invertir mayor esfuerzo de captura de serpientes en ambientes conservados que en hábitats alterados, y es importante determinar la dinámica espacio- temporal en el ensamblaje de serpientes para enfocar correctamente los planes de manejo y conservación de la ofidiofauna en ambientes alterados
Valdez-Cruz, Norma A; Reynoso-Cereceda, Greta I; Pérez-Rodriguez, Saumel; Restrepo-Pineda, Sara; González-Santana, Jesus; Olvera, Alejandro; Zavala, Guadalupe; Alagón, Alejandro; Trujillo-Roldán, Mauricio A
Shake flasks are widely used during the development of bioprocesses for recombinant proteins. Cultures of recombinant Escherichia coli with orbital mixing (OM) have an oxygen limitation negatively affecting biomass growth and recombinant-protein production. With the aim to improve mixing and aeration in shake flask cultures, we analyzed cultures subjected to OM and the novel resonant acoustic mixing (RAM) by applying acoustic energy to E. coli BL21-Gold (DE3): a producer of recombinant phospholipase A2 (rPLA2) from Micrurus laticollaris snake venom. Comparing OM with RAM (200 rpm vs. 7.5g) at the same initial volumetric oxygen transfer coefficient (k L a ≈ 80 h -1 ) ~69% less biomass was obtained with OM compared with RAM. We analyzed two more conditions increasing agitation until maximal speed (12.5 and 20g), and ~1.6- and ~1.4-fold greater biomass was obtained as compared with cultures at 7.5g. Moreover, the specific growth rate was statistically similar in all cultures carried out in RAM, but ~1.5-fold higher than that in cultures carried out under OM. Almost half of the glucose was consumed in OM, whereas between 80 and 100% of the glucose was consumed in RAM cultures, doubling biomass per glucose yields. Differential organic acid production was observed, but acetate production was prevented at the maximal RAM (20g). The amount of rPLA2 in both, OM and RAM cultures, represented 38 ± 5% of the insoluble protein. A smaller proportion of α-helices and β-sheet of purified inclusion bodies (IBs) were appreciated by ATR-FTIR from cultures carried out under OM, than those from RAM. At maximal agitation by RAM, internal E. coli localization patterns of protein aggregation changed, as well as, IBs proteolytic degradation, in conjunction with the formation of small external vesicles, although these changes did not significantly affect the cell survival response. In moderate-cell-density recombinant E. coli BL21-Gold (DE3) cultures, the agitation increases in
Pinho Fábia Maria Oliveira
Full Text Available OBJETIVO: Avaliar aspectos epidemiológicos dos acidentes por serpentes peçonhentas ocorridos no Estado de Goiás. MÉTODOS: Foram analisadas ''Fichas de investigação de acidentes por animais peçonhentos'', pertencentes ao sistema de notificação da Secretaria de Saúde do Estado de Goiás, no triênio 1998-2000. RESULTADOS: Foram notificados, neste período, 3.261 acidentes por serpentes peçonhentas, com coeficiente de incidência variando entre 20 e 23/100.000 habitantes. O maior número de casos ocorreu entre os meses de outubro e abril. Dentre os 2.350 casos em que houve referência ao gênero da serpente, 78,6% foram causados por Bothrops, 20,8% por Crotalus e 6% por Micrurus. Houve predominância do sexo masculino (78,5% e com faixa etária entre 20 e 39 anos de idade. As regiões anatômicas mais freqüentemente picadas foram: pé (43,6%, pernas (23,2% e mãos (20,1%. Em relação ao tempo de atendimento, mais de 80% dos envenenamentos foram atendidos com menos de 6 horas da picada. Os envenenamentos foram classificados, de acordo com a gravidade, em leves (31,6%, moderados (47,5% ou graves (9,6%. As complicações mais comuns foram necrose tecidual no local da picada (31,8% nos envenenamentos botrópicos e insuficiência renal aguda (1,2% nos envenenamentos crotálicos. A letalidade geral foi de 0,46%, sendo a maior taxa observada entre acidentes crotálicos (1%. CONCLUSÕES: Acidentes por serpentes peçonhentas no Estado de Goiás acometem principalmente a população jovem do sexo masculino e têm sido causa de óbito.