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Envenomation due to terrestrial snakes is a rarity in travellers and tourists and can be readily controlled by preventive measures. It is a widely underestimated health problem of the rural population in tropical and subtropical countries, however. Prevention, First Aid, diagnostic procedures, symptomatic and specific (antivenom) treatment regimens of envenomation due to terrestrial snakes are presented.
Ten species of venomous snakes belonging to three families occur in Israel and in Jordan, some of which may pose a serious threat to humans. Specific, local antivenins are available against only two of the species, while against others regional or European preparations are used. It is suggested that in addition to the monospecific anti-Vipera palaestinae, a polyspecific antivenin be prepared against the clinically most important venomous snakes of the region, namely, Echis coloratus, Pseudocerastes fieldi, Cerastes cerastes, Walterinnesia aegyptia, and Atractaspis engaddensis.
Ritualistic serpent qua snake handling, which rests upon inveterate religious conviction arising out of literal interpretation of selected passages of the New Testament, is a rare ceremony practiced by a distinct minority of Christians predominantly in rural Appalachian regions of the United States commonly referred to as the Bible belt. The fervent, frenzied pursuit by anointed "sign-followers" of intimate contact with a variety of poisonous snakes, however, puts the handler together with sect members or bystanders at risk for lethal envenomation, particularly when prompt medical attention is held by the congregation of faith to contravene God's will. The authors report three separate cases of death due to envenomation by snakebite during a church service and the handler's faith-based refusal to seek treatment. Postmortem examination of each yielded similar physical findings attributable to various toxic sequelae of the complex venoms. A review of the injurious constituents of these chemical toxins also includes a discussion of complex pathophysiological mechanisms causing death. In addition, the authors review the history of representative legislative and judicial responses to the sensationally mortal phenomenon, all of which ineluctably grapple with fundamental Constitutional issues devolving from such controversial religious practices. We underscore the view that a thoroughly documented medicolegal investigation and autopsy are indispensable to both inform matters of public health and thereby contribute to the formulation of sound public policy.
AIMS OF STUDY: The present study was undertaken to study the relationship between the time of anti-snake venom (ASV) administration due to late arrival of patient at hospital and subsequent development of complications. MATERIAL AND METHODS: All patients of snake bite that presented to our institution over a period of 1 1/2 years were included in the present study. A detailed clinical history, clinical examination and investigations were carried out. The patients were administered ASV within 10 minutes of presentation. The bite to needle time (time between the bite and start of ASV) was noted. The patients were then followed up to note any subsequent development of complications. The end-point of the study was normalization of haematological and neurological parameters. RESULTS: Fifty patients became eligible for the study. Twenty patients (40%) had complications while remaining 30 patients (60%) were uncomplicated. An attempt was made to study relationship between bite to needle time and subsequent development of complications. It was found to be significant at 5% level of significance (p<0.05) by chi square test. CONCLUSION: Incidence of complications was directly proportional to the duration of venom in the blood prior to neutralization by ASV due to late arrival of patient at hospital. The early institution of ASV is beneficial in preventing complications however severe is the systemic envenomation.
Activation of courtship behavior in male red-sided garter snakes is independent of androgens. Only exposure to extended periods of low temperature with subsequent warming stimulates courtship in males. The pineal gland is thought to transduce temperature as well as photoperiodic information in reptiles. Therefore, we explored the relationship of the pineal and melatonin to sexual behavior in this species. Pinealectomy of male garter snakes disrupted sexual behavior upon emergence from a 17-week period of low temperature in approximately 60% of treated individuals in each of the 3 years of study. However, 40% of the males were unaffected by the pinealectomy, engaging in vigorous courtship. Administration of exogenous, chronic melatonin did not significantly modulate the effect of pinealectomy. Upon pinealectomy in the autumn (before hibernation), plasma levels of melatonin fell. However, upon emergence from hibernation, melatonin levels in pinealectomized (PINX) and sham-treated (SHAM) animals were equivalent, indicating extrapineal source(s) of melatonin. However, PINX males did not exhibit a diel cycle in melatonin levels upon emergence. Instead, melatonin remained elevated through the subsequent 24-hr period. SHAMs did exhibit a diel cycle. Ten days after emergence, PINX animals either had a disrupted/abnormal melatonin cycle and were non-courters or had a cycle similar to SHAM males and courted. Therefore, a normal diel cycle of melatonin appeared necessary for the proper expression of courtship behavior. These results suggest that the pineal in snakes 1) is part of a complex, multi-oscillator system as it is in birds and lizards and 2) may play a role in maintaining polymorphism in timing of reproductive behavior.
The zygapophyses and zygosphene-zygantrum articulations of snake vertebrae are hypothesized to restrict or eliminate vertebral torsion. This hypothesis is apparently based solely on the inference of function from structure, despite the limitations of such inferences, as well as contradictory observations and measurements. In this study, I observed and measured axial torsion in gopher snakes, Pituophis melanoleucus. To examine the structural basis of axial torsion, I measured the vertebral articulation angles along the body and the insertion angles of five epaxial muscles. To examine torsion in a natural behavior, I digitized video images and measured the degree of apparent axial torsion during terrestrial lateral undulation. Finally, I measured the mechanical capacity of the vertebral joints for actual torsion over intervals of 10 vertebrae in fresh, skinned segments of the trunk. Vertebral articulation angles vary up to 30 degrees and are associated with variation in torsional capacity along the trunk. The freely crawling P. melanoleucus twisted up to 2.19 degrees per vertebra, which produced substantial overall torsion when added over several vertebrae. The vertebral joints are mechanically capable of torsion up to 2.89 degrees per joint. Therefore, despite the mechanical restriction imposed by the complex articulations, vertebral torsion occurs in snakes and appears to be functionally important in several natural behaviors. Even in cases in which mechanical function appears to be narrowly constrained by morphology, specific functions should not be inferred solely from structural analyses.
Little is known about specific proteins involved in keratinization of the epidermis of snakes. The presence of histidine-rich molecules, sulfur, keratins, loricrin, transglutaminase, and isopeptide-bonds have been studied by ultrastructural autoradiography, X-ray microanalysis, and immunohistochemistry in the epidermis of snakes. Shedding takes place along a shedding complex, which is composed of two layers, the clear and the oberhautchen layers. The remaining epidermis comprises different layers, some of which contain beta-keratins and others alpha-keratins. Weak loricrin, transglutaminase, and sometimes also iso-peptide-bond immunoreactivities are seen in some cells, lacunar cells, of the alpha-layer. Tritiated histidine is mainly incorporated in the shedding complex, especially in dense beta-keratin filaments in cells of the oberhautchen layer and to a small amount in cells of the clear layer. This suggests the presence of histidine-rich, matrix proteins among beta-keratin bundles. The latter contain sulfur and are weakly immunolabeled for beta-keratin at the beginning of differentiation of oberhautchen cells. After merging with beta cells, the dense beta-keratin filaments of oberhautchen cells become immunopositive for beta-keratin. The uptake of histidine decreases in beta cells, where little dense matrix material is present, while pale beta-keratin filaments increase. During maturation, little histidine labeling remains in electron-dense areas of the beta layer and in those of oberhautchen spinulae. Some roundish dense granules of oberhautchen cells rich in sulfur are negative to antibodies for alpha-keratin, beta-keratin, and loricrin. The granules eventually merge with beta-keratin, and probably contribute to the formation of the resistant matrix of oberhautchen cells. In conclusion, beta-keratin, histidine-rich, and sulfur-rich proteins contribute to form snake microornamentations.
The New Guinean small-eyed snake (Micropechis ikaheka) is a cause of life-threatening envenoming. Previous studies on M. ikaheka venom have indicated the presence of neurotoxins as well as myotoxins. This study examined the in vitro myotoxic effects of M. ikaheka venom and the efficacy of a polyvalent antivenom in neutralizing these effects. Venom (50 microg/ml) produced a slowly developing contracture and inhibition of direct twitches of the chick biventer cervicis nerve-muscle preparation in the presence of tubocurarine (10 microM). Myotoxicity was confirmed by subsequent histological examination of tissues. This myotoxicity was prevented by the prior addition of polyvalent snake antivenom (30 U/ml). However, the addition of antivenom (30 U/ml) 1 h after venom administration failed to reverse or prevent the further inhibition of direct twitches. In addition, venom (1-10 microg/ml) produced concentration-dependent contractions of the guinea-pig isolated ileum. These effects were dependent on phospholipase A2 (PLA2) activity of the venom as evidenced by the ability of the PLA2 inhibitor 4-bromophenacyl bromide (4-BPB; 1.8 mM) to prevent this activity. This study indicates that M. ikaheka venom causes significant myotoxicity and that polyvalent snake antivenom may be a potential treatment for the myotoxic effects in patients envenomed by this species.
The enzyme L-amino acid oxidase (LAO) from the leaf-nosed viper (Eristocophis macmahoni) snake venom was purified to homogeneity in a single step using high performance liquid chromatography on a Nucleosil 7C18 reverse phase column. The molecular mass of the purified enzyme was 58734.0 Da, as determined by matrix-assisted laser desorption/ionization mass spectrometry. The N-terminal amino acid sequence (ADDKNPLEEAFREADYEVFLEIAKNGL) and the chemical composition of the purified LNV-LAO shows close structural homology with other L-amino acid oxidases isolated from different snake venoms. The secondary structural contents analysis of LAO, established by means of circular dichroism, revealed ca. 49% alpha-helix, 19% beta-sheet, 10% beta-turn, and 22% random coil structure. The purified LNV-LAO not only retained its specific enzymatic activity (73.46 U/mg), determined against L-leucine as a substrate, but also exhibited potent haemolytic (1-10 microg/ml), edema- (MED 4.8 microg/ml) and human platelet aggregation-inducing (ED50 33 microg/ml) properties. Unlike other haemorrhagic snake venom L-amino acid oxidases, the LNV-LAO does not produce haemorrhage. In addition to these local effects, the purified LNV-LAO showed apoptosis-inducing activity in the MM6 cell culture assay. After 18 h treatment with 25-100 microg/ml of LAO, the typical DNA fragmentation pattern of apoptotic cells was observed by means of fluorescent microscopy and agarose gel electrophoresis.
All animals that are exposed to predators must distinguish dangerous from nondangerous threats and respond correctly. In reptiles, emerging hatchlings are vulnerable to a wide range of predators, particularly if they emerge during daylight. In these experiments I tested the response of pine snake, Pituophis melanoleucus, hatchlings incubated at 22-23, 27-28, or 32-33 degreesC to visual and vibratory stimuli to examine antipredator behaviour. Emerging hatchlings were exposed to one of five conditions: (1) hawk model, (2) white head model with no facial features, (3) white head model with black eyes, (4) a person, or (5) a vibration without a visual stimulus. I tested the null hypotheses of no differences in response as a function of predator type or incubation temperature. Emergence behaviour when undisturbed was affected by incubating temperature, and antipredatory behaviour was affected by both predator type and incubation temperature. Pine snake hatchlings responded more protectively (withdrawal into tunnels) than defensively (striking), responded with less intensity to a vibration compared with visual predator stimuli, and required longer to respond to a head model without eyes than to all other predator types. Given the relatively small size of hatchlings, it is adaptive for them to withdraw into the nest rather than attack a predator. Hatchlings from eggs that were incubated at medium temperatures required less time to emerge from their underground nests when undisturbed, and had stronger protective responses than snakes incubated at other temperatures. These results suggest that hatchlings incubated at medium temperatures are generally less vulnerable to predators than hatchlings incubated at higher or lower temperatures. Copyright 1998 The Association for the Study of Animal Behaviour.
In large mating aggregations of red-sided garter snakes, Thamnophis sirtalis parietalis, in Manitoba, male courtship is directed not only to females, but also to other males with female-like skin lipids ('she-males'). We show that 'she-maleness' is an intrinsic property of a male rather than an artefact of lipid transfer from females, and that male-male courtship is very common in the field. She-males were distinctive in terms of appearance (they were heavier than other males and more often covered with mud), behaviour (they were inactive and rarely courted females) and performance (they were slow crawlers, ineffective courters and easily outcompeted by other males in mating trials). 'She-maleness' was not a characteristic of a particular subset of males, as envisaged in previous work; instead, it was a transitory phase that most (perhaps all) male snakes passed through soon after they first emerged from the winter den. Recently emerged males spent their first day or two relatively inactive, while restoring physiological functions (including locomotor performance and courtship ability). Experimental application of female skin lipids on to males dramatically decreased courtship levels of the recipient snakes. Thus, recently emerged males may derive two kinds of benefit from mimicking female skin lipids. First, female mimicry 'switches off' the male's own (energetically expensive) courtship at a time when that courtship would be unproductive. Second, it may disadvantage his rivals by distracting them from females, and increasing their energy expenditure. Copyright 2000 The Association for the Study of Animal Behaviour.
We measured the behavioural and hormonal responses to capture stress in male red-sided garter snakes. Four hours of capture stress resulted in no suppression of mating behaviour relative to control individuals. In contrast, the same stress resulted in a significant increase in plasma levels of corticosterone and a significant decrease in plasma levels of testosterone. There was a significant negative correlation between plasma levels of corticosterone and testosterone in both control and capture-stress groups, suggesting that the increase in corticosterone directly drives the decrease in testosterone. While there was no relation between body size and initial plasma levels of the two steroids, longer individuals had a significantly greater increase in corticosterone following capture stress than did shorter individuals. Snakes display indeterminate growth, suggesting that older individuals have decreased sensitivity to negative feedback in the hypothalamic-pituitary-adrenal axis and thus hypersecrete glucocorticoids. These results suggest that male red-sided garter snakes have uncoupled their behavioural stress response from their hormonal stress response to maximize reproductive opportunities. Copyright 2000 The Association for the Study of Animal Behaviour.
During the cloning of abundant cDNAs expressed in the Micrurus corallinus coral snake venom gland, we cloned an alpha-neurotoxin homologue cDNA (nxh1). Two others isoforms were also cloned (nxh3 and nxh7, respectively). The nxh1 cDNA codes for a potential coral snake toxin with a signal peptide of 21 amino acids plus a predicted mature peptide with 57 amino acids. The deduced protein is highly similar to known toxic three-finger alpha-neurotoxins, with four deduced S-S bridges at the same conserved positions. This is the first cDNA coding for a three-finger related protein described so far for coral snakes. However, the predicted protein does not possess some of the important amino acids for the nicotinic acetylcholine receptor interaction. This protein was expressed in Escherichia coli as a His-tagged protein that allowed the rapid purification of the recombinant protein. This protein was used to generate antibodies which recognized the recombinant protein in Western blot and also a single band present in the M. corallinus venom, but not in the venom of 10 other Micrurus species.
Adamalysin II, alias proteinase II, a 24 kDa zinc-endopeptidase isolated from the snake venom of the Eastern diamondback rattlesnake Crotalus adamanteus, is a prototype of the proteolytic domain of snake venom metalloproteinases and of domains found in mammalian reproductive tract proteins. Its 2.0 A crystal and molecular structure was solved by multiple isomorphous replacement using six heavy-atom derivatives, and was refined to a crystallographic R-value of 0.172. 201 of the 203 amino acid residues of adamalysin II are defined by electron density; only the first two residues are disordered and crystallographically undefined in the crystal structure. Three-quarters of these crystallographic amino acid residue assignments were confirmed by chemical sequencing. In addition, the active-site zinc-ion, a hepta-coordinated calcium ion, a fixed sulphate anion and 173 solvent molecules were localized in the structure. Adamalysin II is an ellipsoidal molecule with a relatively flat active-site cleft separating the "upper" main body from a small "lower" subdomain. The regularly folded N-terminal upper domain consists essentially of a central, highly twisted five-stranded beta-pleated sheet flanked by a long and a short surface located helix on its convex side, and by two long helices, one of which represents the central "active site helix", on its concave side. The lower subdomain, comprising the last 50 residues, is organized in multiple turns, with the chain ending in a long C-terminal helix and an extended segment clamped to the upper domain via a disulphide bridge. The catalytic zinc-ion, located at the bottom of the active-site cleft, is almost tetrahedrally co-ordinated by His142, His146 and His152, and a water molecule anchored to an intermediate glutamic acid residue (Glu143), with the three imidazole N epsilon 2 nitrogen atoms 2.1 A and the solvent oxygen atom 2.4 A away from the zinc ion. His142, Glu143 and His146 are part of the long active-site helix, which extends up to Gly149, where it turns sharply away towards His152. The importance of these residues for structure and activity of adamalysin II explains their occurrence in the HEXXHXXGXXH consensus sequence. Asp153, which is strictly conserved in these snake venom and reproductive tract metalloproteinases, is buried in the subdomain and seems to stabilize the hydrophobic active-site basement. Some residues behind, the adamalysin peptide chain folds into a characteristic 1,4-turn (the "Met-turn") containing the conserved Met166, which forms a hydrophobic basement for the three zinc-binding imidazoles.(ABSTRACT TRUNCATED AT 400 WORDS)
Acutolysin A alias AaHI, a 22 kDa hemorrhagic toxin isolated from the snake venom of Agkistrodon acutus, is a member of the adamalysin subfamily of the metzincin family and is a snake venom zinc metalloproteinase possessing only one catalytic domain. Acutolysin A was found to have a high-activity and a low-activity under weakly alkaline and acidic conditions, respectively. With the adamalysin II structure as the initial trial-and-error model, the crystal structures were solved to the final crystallographic R-factors of 0. 168 and 0.171, against the diffraction data of crystals grown under pH 5.0 and pH 7.5 conditions to 1.9 A and 1.95 A resolution, respectively. One zinc ion, binding in the active-site, one structural calcium ion and some water molecules were localized in both of the structures. The catalytic zinc ion is coordinated in a tetrahedral manner with one catalytic water molecule anchoring to an intermediate glutamic acid residue (Glu143) and three imidazole Nepsilon2 atoms of His142, His146 and His152 in the highly conserved sequence H142E143XXH146XXGXXH152. There are two new disulfide bridges (Cys157-Cys181 and Cys159-Cys164) in acutolysin A in addition to the highly conserved disulfide bridge Cys117-Cys197. The calcium ion occurs on the molecular surface. The superposition showed that there was no significant conformational changes between the two structures except for a few slight changes of some flexible residue side-chains on the molecular surface, terminal residues and the active-site cleft. The average contact distance between the catalytic water molecule and oxygen atoms of the Glu143 carboxylate group in the weakly alkaline structure was also found to be closer than that in the weakly acidic structure. By comparing the available structural information of the members of the adamalysin subfamily, it seems that, when lowering the pH value, the polarization capability of the Glu143 carboxylate group to the catalytic water molecule become weaker, which might be the structural reason why the snake venom metalloproteinases are inactive or have a low activity under acidic conditions.
Boid snakes possess unique infrared imaging pit organs. The ultrastructure of the surfaces of these organs scatter or reflect electromagnetic radiation of specific wavelengths. Pit organ epidermal surfaces of boid snakes are covered with arrays of pore-like structures called micropits. In order to determine the dimensions of this complicated surface structure, we have performed the first ultrastructural analysis on snake epidermis by high-resolution microscopy techniques. Using scanning probe microscopy and scanning electron microscopy, we found that the epidermis of pit organ, maxillary non pit organ, spectacle, and ventral scales contain arrays of micropits. These scale surfaces also contain major surface features of overlapping plate-like structures. Pit organ micropits averaged 319 nm in diameter and 46 nm in depth and were spaced an average of 808 nm from each other. These micropits were significantly deeper, of greater diameter, and spaced at greater distances apart than those of the other scales. Plate structures of the pit organs had a mean distance between plates of 3.5 microm and a mean plate step height of 151 nm. These differences serve to strengthen the argument that arrays of micropit and plate surface structures function as spectral filters or anti-reflective coatings with respect to incident electromagnetic radiation.
Published molecular phylogenetic studies of elapid snakes agree that the marine and Australo-Melanesian forms are collectively monophyletic. Recent studies, however, disagree on the relationships of the African, American, and Asian forms. To resolve the relationships of the African, American, and Asian species to each other and to the marine/Australo-Melanesian clade, we sequenced the entire cytochrome b gene for 28 elapids; 2 additional elapid sequences from GenBank were also included. This sample includes all African, American, and Asian genera (except for the rare African Pseudohaje), as well as a representative sample of marine/Australo-Melanesian genera. The data were analyzed by the methods of maximum-parsimony and maximum-likelihood. Both types of analyses yielded similar trees, from which the following conclusions can be drawn: (1) Homoroselaps falls outside a clade formed by the remaining elapids; (2) the remaining elapids are divisible into two broad sister clades, the marine/Australo-Melanesian species vs the African, American, and Asian species; (3) American coral snakes cluster with Asian coral snakes; and (4) the "true" cobra genus Naja is probably not monophyletic as the result of excluding such genera as Boulengerina and Paranaja.
The majority of snake bites in Central America are caused by Bothrops asper, whose venom induce complex local effects such as myonecrosis, edema and especially hemorrhage. These effects are only partially neutralized by the clinically used antivenom, even when administered rapidly after envenomation. Recently we screened 49 substances for antihemorrhagic activity and found that a mixture composed of CaNa2, EDTA, a B. asper serum fraction (natural antidote), and the currently used horse polyvalent antiserum is highly effective in the neutralization of local and systemic hemorrhage developing after B. asper envenomation (Borkow et al., Toxicon 35, 865-877, 1997). In the present study we screened the best six antihemorrhagic compounds for their capacity to neutralize the lethal activity in mice and the proteolytic, hemolytic, and antiattachment activities in vitro of the venom. The compounds tested included the currently used horse antivenom, rabbit antiserum against whole B. asper venom or against heated venom, B. asper and Natrix tessellata serum fractions, and CaNa2 EDTA. The constituents of the antihemorrhagic mixture were also the best inhibitors of the other examined toxic activities. Importantly, the mixture effectively neutralized toxic activities of an additional nine venoms from snakes abundant in Central America. This work suggests that the polyvalent antivenom used in Central America could be enriched with a B. asper serum fraction producing a more effective antivenom. In addition, the local application of CaNa2 EDTA to neutralize hemorrhagic toxins, immediately after a snake bite, may provide rapid inhibition of local damage caused by the venoms.