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Clinical predictors of in-hospital mortality in patients with snake bite: a retrospective study from a rural hospital in central India.

OBJECTIVE: To determine the association between selected admission risk factors and in-hospital mortality in patients admitted with venomous snake bite to a rural tertiary care hospital in central India. METHODS: Retrospective cohort study of patients aged 12 years or older admitted to a rural hospital in central India between January 2000 and December 2003 with venomous snake bites. The primary endpoint was in-hospital mortality. We used Cox proportional-hazards regression analysis to evaluate the association between risk factors (home-to-hospital distance, bite-to-hospital time, vomiting, neurotoxicity, urine albumin, serum creatinine concentration and whole-blood clotting time) and in-hospital mortality. RESULTS: Two hundred and seventy-seven patients [mean age 32 (SD 12) years; 188 men (68%)] were admitted with venomous snake bite, 29 patients (11%) died. The probability of survival at day 7 was 83%. Vomiting [hazard ratio 6.51 (95% CI 1.94-21.77), P < or = 0.002], neurotoxicity [hazard ratio 3.15 (95% CI 1.45-6.83), P = 0.004] and admission serum creatinine concentration [hazard ratio 1.35 (95% CI 1.17-1.56), P < or = 0.001] were associated with higher risk of death in the adjusted analysis. CONCLUSIONS: In our rural hospital setting, the overall mortality rate was 11 per 100 cases of snake bite. Vomiting, neurotoxicity and serum creatinine are significant predictors of mortality among inpatients with snake bite. These predictors can help clinicians assess prognosis of their patients more accurately and parsimoniously and also serve as useful signposts for clinical decision-making.

Adolescent↗

Kallikrein-kinin system in the plasma of the snake Bothrops jararaca.

1. Bothrops jararaca venom (BJV) caused a fall in the carotid artery blood pressure of the anaesthetized snake. This effect was tachyphylactic and was potentiated by captopril, a kininase II inhibitor; it was partially antagonized by promethazine plus cimetidine and was not affected by atropine. 2. Similar hypotensive effects were obtained by administration of trypsin or a partially purified BJV kininogenase to the snake. 3. Incubation of Bothrops jararaca plasma (BJP) with trypsin released a substance (or substances) that produced hypotension in the snake but not in the rat; this hypotensive effect was also potentiated by captopril. 4. The trypsinised plasma contracted Bothrops jararaca isolated uterus, a pharmacological preparation weakly sensitive to bradykinin. Trypsinised plasma was inactive on pigeon oviduct and rat uterus and displayed a weak action on the guinea-pig ileum. Similar effects were observed with incubates of a fraction of BJP, containing globulins, with a partially purified BJV kininogenase. 5. Like mammalian kinins, the substance(s) was(were) dialysable, thermostable in acid but not in alkaline pH, and inactivated by chymotrypsin but not by trypsin. Its(their) inactivation by BJP or BJP kininase II was inhibited by captopril. 6. These findings strongly suggest that, besides releasing histamine, BJV or trypsin release a kininlike substance (or substances) from the snake plasma. 7. Since BJV and other kininogenases active on mammalian plasma were shown to be unable to release kinins from BJP, in experiments conducted on pharmacological preparations suitable for the assay of mammalian kinins, these data also suggest that the snake Bothrops jararaca, like birds, may have developed its own kallikrein-kinin system.

Animals↗

A fossil snake with limbs.

A 95-million-year-old fossil snake from the Middle East documents the most extreme hindlimb development of any known member of that group, as it preserves the tibia, fibula, tarsals, metatarsals, and phalanges. It is more complete than Pachyrhachis, a second fossil snake with hindlimbs that was recently portrayed to be basal to all other snakes. Phylogenetic analysis of the relationships of the new taxon, as well as reanalysis of Pachyrhachis, shows both to be related to macrostomatans, a group that includes relatively advanced snakes such as pythons, boas, and colubroids to the exclusion of more primitive snakes such as blindsnakes and pipesnakes.

Animals↗

Diagnostic uses of snake venom.

Snake venom toxins are invaluable for the assay of coagulation factors and for the study of haemostasis generally. Thrombin-like enzymes (SVTLE) are used for fibrinogen and fibrinogen breakdown product assays as well as detecting dysfibrinogenaemias. Since SVTLE are not inhibited by heparin, they can be used for assaying antithrombin III in samples containing heparin. Snake venom prothrombin activators are utilised in prothrombin assays, whilst Russell's viper venom (RVV) can be used to assay clotting factors V, VII, X and lupus anticoagulants (LA). Activators from the taipan, Australian brown snake and saw-scaled viper have also been used to assay LA. Protein C (PC) and activated PC (APC) resistance can be measured by means of RVV, Protac (from Southern copperhead snake venom) and STA-Staclot (from Crotalus viridis helleri) whilst von Willebrand factor can be studied with Botrocetin (Bothrops jararaca). Finally, snake venom C-type lectins and metalloproteinase disintegrins are being used to study platelet glycoprotein receptors and show great potential for use in the routine coagulation laboratory.

Animals↗

Molecular basis for the partition of the essential functions of thrombin among snake venom serine proteinases: the case of thrombin-like enzymes.

Thrombin is a mammalian serine proteinase that plays a prominent role in the maintenance and regulation of hemostasis through its interaction with various substrates and/or ligands. The venoms of several snakes contain glycosylated serine proteinases that have been recognized to possess one or more of the essential activities of thrombin on fibrinogen (Fg) and/or platelets. These proteinases share about 60% sequence identity. One class of snake venom serine proteinases are those known as thrombin-like (TLE), named after their ability to directly clot Fg in order to preferentially produce fibrinopeptide A, fibrinopeptide B or both. To understand the molecular basis of this phenomenon, the corresponding amino acid sequences and molecular structures need to be analyzed. Given the absence of experimentally determined tertiary structures of snake venom, TLEs, three-dimensional molecular models should prove useful in this context. Towards this goal, we obtained models of snake venom TLEs that used TSV-PA as template, TSV-PA being the only snake venom serine proteinase whose crystal structure is known to date. Along with a comparative sequence analysis the models contribute to the identification and description of thrombin-homologous or alternative binding sites, helping thus to understand differences in specificity.

Amino Acid Sequence↗

The comparative imperative: genetics and ontogeny of chemoreceptive prey responses in natricine snakes.

Reptiles offer a rich diversity for the study of chemoreception, and snakes are a particularly appropriate group for comparative, evolutionary, genetic, developmental, and mechanistic studies. A long-term program of research is described that attempts to integrate these approaches, focusing on the widespread North American genus Thamnophis (Natricinae). Prior to their first meal, neonatal snakes respond to aqueous surface substances from species-typical prey with increased tongue-flicking and open-mouth attacks; these responses are mediated by the vomeronasal organ. Such responses predict what prey snakes will eat and can also predict relative prey preference. Species, population, litter, and individual differences exists and are important at different levels of analysis. Chemoreceptive responses are heritable, although they may show different developmental trends. Some species respond to prey types they do not eat in nature. In the earthworm specialist, T. butleri, response to fish chemicals can be interpreted as a chemoreceptive response inertially inherited from ancestral species, decoupled from prey capture techniques, and in the process of being lost. Ontogeny and experience can modify behavior of the neonate in various ways. Feeding experience can alter response to some prey more than others, and ambient prey odor may shift prey preference. Psychophysical studies show that prey preference and threshold sensitivity to prey chemicals can be independent and differ between closely related species, indicating that neural tissue is devoted to recognition of specific types of prey. In site choice tests, garter snakes can also discriminate between feces derived from conspecific snakes fed similar or different diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Odorized air current trailing by garter snakes, Thamnophis sirtalis.

The response of adult red-sided garter snakes, Thamnophis sirtalis parietalis, to airborne odor trails was studied. An airtight T-maze was used, through which a constant airflow was drawn by a vacuum pump. The arms of the 'T' provided a choice between earthworm extract and distilled water. Experiment 1 tested the snake's responses to varying concentrations of earthworm extract. Snakes accurately trailed the extract at tested concentrations (0.0, 0.01, 0.1, 1, 10, 100%). At ten percent concentration, tongue-flick rate and speed along the maze increased significantly above lower levels, suggesting the existence of a threshold concentration. A correlation between mean tongue-flick rate and mean speed was demonstrated. Experiment 2 tested the effect of differentially blocked vomeronasal ducts on a snake's ability to trail. When both ducts were blocked, no trailing was observed, suggesting that vomeronasal stimulation is required. Blocking a single duct resulted in a significant number of snakes turning to the side of the functioning duct, suggesting that the tongue-vomeronasal system may function as a chemotaxic system.

Animals↗

Brown snakes (Pseudonaja genus): venom yields, prothrombin activator neutralization and implications affecting antivenom usage.

The recent high prevalence of fatal bites by Brown snakes (Pseudonaja genus) has led to this study of venom yields from 66 brown snake milkings over 15 months. The amount of venom obtained from all species was higher than reported previously. Electrophoretic and Western blotting analyses of their venoms showed significantly lower avidity of Brown snake antivenom (BS-AV) for the prothrombin activator (PA) component (190 kD) than for other venom components, including the neurotoxins. The LD50 of P. inframacula has been determined for the first time. SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis) and Western blotting studies have shown that the Pseudonaja venoms contained proportionately more PA component than venoms of the Taipan (Oxyuranus scutellatus) or the Fierce snake (O. microlepidotus). Neutralization of the prothrombin activator of the Common Brown snake (P. textilis) (Pt-PA) by BS-AV was found to be time dependent and 40% remained unneutralized after 30 minutes incubation. Adult rats administered quantities of Pt-PA (IV) died with acute disseminated intravascular coagulation. Rats were made resistant to Pt-PA by preheparinization or by induction of tolerance to increasing quantities of Pt-PA. There is no evidence that Pt-PA has intrinsic toxicity apart from being a procoagulant. The improvement of BS-AV by addressing its deficiencies should be canvassed.

Animals↗

A 3-D kinematic analysis of gliding in a flying snake, Chrysopelea paradisi.

Flying snake species (Chrysopelea) locomote through the air despite a lack of appendages or any obvious external morphological specialization for flight. Here photogrammetric techniques were used to investigate C. paradisi's aerial trajectory in three dimensions. Two videocameras arranged in stereo were used to record head, midpoint and vent landmarks on snakes that jumped from a horizontal branch at a height of 9.62 m and landed in an open field. The coordinates of these landmarks were reconstructed in three dimensions and used to analyze patterns of position, glide angle and speed concurrently with changes in body posture in 14 glide sequences from different individuals. C. paradisi's trajectory was composed of a ballistic dive followed by a shallowing phase in which the path became more horizontal; for most glide trials, no equilibrium phase was observed. In the ballistic dive, the snake changed posture from generally straight to a wide 'S' shape in planview and began aerial undulation. Shortly after the ballistic dive, the snake's speed transitioned from an initial acceleration to stable or to a different rate of increase or decrease. Aerial undulation, in which high-amplitude traveling waves pass posteriorly down the body, was a prominent locomotor behavior. In mid-glide, this undulation occurred with the anterior body oriented approximately parallel with the ground and the posterior body cycling up and down in the vertical plane. The body angle of attack for the anterior body for one trial was 20-40 degrees . Snakes traveled a horizontal distance of 10.14+/-2.69 m (mean +/-s.d.) while reaching an airspeed of 10.0+/-0.9 m s(-1), sinking speed of 6.4+/-0.8 m s(-1) and horizontal speed of 8.1+/-0.9 m s(-1). The glide path shallowed at a rate of 20+/-6 degrees s(-1) and reached a minimum glide angle of 28+/-10 degrees , with a minimum recorded glide angle of 13 degrees . C. paradisi are surprisingly good gliders given their unconventional locomotor style, with performance characteristics that rival or surpass more familiar gliding taxa such as flying squirrels. As in other gliders, C. paradisi is potentially capable of using aerial locomotion to move effectively between trees, chase aerial prey, or avoid predators.

Animals↗

Regulation of arterial blood pressure in Australian tiger snakes.

1. Blood pressure was measured in the dorsal aorta of restrained, unanaesthetized tiger snakes (Notechis scutatus) at different body temperatures during graded, passive tilt. Aortic blood pressure in horizontal snakes showed no significant change over a range of body temperatures between 18 and 33 degrees C (mean of measurements on 16 snakes = 42.2 +/- I.98 mmHg), while heart rate increased logarithmically (Q10 approximately 2.5). Blood pressure was stable during heating and cooling between body temperatures of 15 and 30 degrees C, but the pressure was 10--50% higher during heating than during cooling. 2. Head-up tilt usually caused a brief fall in pressure at heart level followed by partial or complete recovery and tachycardia. At the cessation of tilt, there was a characteristic overshoot of the blood pressure followed by readjustment to control (pretilt) levels. Head-down tilt typically increased pressure which then either stabilized or returned toward pretilt levels. Heart rate changes during head-down tilt were not consistent in direction or magnitude. Stabilized pressures at mid-body usually increased following head-up tilt and decreased following head-down tilt, indicating physiological adjustment to posture change. Blood pressure control was evident at body temperatures ranging from 10 to 38 degrees C, but was most effective at the higher and behaviourally preferred temperatures. 3. Propranolol lowered heart rate but did not influence pressure in horizontal snakes. During head-up tilt propranolol eliminated or reduced tachycardia and sometimes reduced the efficacy of pressure compensation for tilt. Phentolamine increased heart rate, lowered blood pressure, and eliminated pressure regulation during tilt. The results suggest that sympathetically mediated reflexes assist central blood pressure regulation in the tiger snake, with vasomotor adjustments having greater importance than changes in heart rate.

Animals↗

Bites by coral snakes (Micrurus spp.) in Campinas, State of São Paulo, Southeastern Brazil.

Coral snakes (Micrurus spp.) are the main representatives of the Elapidae in South America. However, bites by these snakes are uncommon. We retrospectively reviewed the data from 11 individuals bitten by coral snakes over a 20-year period; four were confirmed (snake brought for identification) and seven were highly suspected (neuromuscular manifestations) cases of elapid envenoming. The cases were classified as dry-bite (n = 1, caused by M. lemniscatus; did not receive antivenom), mild (n = 2, local manifestations with no acute myasthenic syndrome; M. frontalis and Micrurus spp.), moderate (n = 5, mild myasthenia) or severe (n = 3, important myasthenia; one of them caused by M. frontalis). The main clinical features upon admission were paresthesia (local, n = 9; generalized, n = 2), local pain (n = 8), palpebral ptosis (n = 8), weakness (n = 4) and inability to stand up (n = 3). No patient developed respiratory failure. Antivenom was used in ten cases, with mild early reactions occurring in three. An anticholinesterase drug was administered in the three severe cases, with a good response in two. No deaths were observed. Despite the high toxicity of coral snake venoms, the prognosis following envenoming is good. In serious bites by M. frontalis or M. lemniscatus, the venom of which acts postsynaptically, anticholinesterases may be useful as an ancillary measure if antivenom is unavailable, if there is a delay in obtaining a sufficient amount, or in those patients given the highest recommended doses of antivenom without improvement of the paralysis or with delayed recovery.

Adolescent↗

Thyroid function in adrenaline-induced changes in the intermediary metabolism of the chequered water-snake (Natrix piscator).

Injection of adrenaline in ten daily doses of 100 micrograms each into the chequered water-snake, Natrix piscator, stimulated glycogenolysis and lipid esterification in the liver and lipolysis in the adipose tissue of control snakes. In both thyroidectomized and control snakes plasma protein levels decreased significantly after hormone treatment, although there was no change in concentrations of muscle glycogen and plasma lactic acid. In thyroidectomized snakes, the hormone stimulated oxidation of the free fatty acids but had no significant effect on the synthesis of the triglycerides. It is suggested that in these snakes the presence of the thyroid hormones is a prerequisite for the response of most of the metabolic processes to adrenaline.

Adipose Tissue↗

Indirect effects of large herbivores on snakes in an African savanna.

Many large mammal species are declining in African savannas, yet we understand relatively little about how these declines influence other species. Previous studies have shown that the removal of large herbivorous mammals from large-scale, replicated experimental plots results in a dramatic increase in the density of small mammals, an increase that has been attributed to the relaxation of competition between rodents and large herbivores for food resources. To assess whether the removal of large herbivores also influenced a predator of small mammals, we measured the abundance of the locally common olive hissing snake, Psammophis mossambicus, over a 19-mo period in plots with and without large herbivores. Psammophis mossambicus was significantly more abundant in plots where large herbivores were removed and rodent numbers were high. Based on results from raptor surveys and measurements of vegetative cover, differences in snake density do not appear to be driven by differences in rates of predation on snakes. Instead, snakes appear to be responding numerically to greater abundances of small-mammal prey in areas from which large herbivores have been excluded. This is the first empirical demonstration of the indirect effects of large herbivores on snake abundance and presents an interesting example of how the influence of dominant and keystone species can move through a food web.

Animals↗

Validation of a novel high-sensitivity radioimmunoassay procedure for measurement of total thyroxine concentration in psittacine birds and snakes.

OBJECTIVE: To validate a novel high-sensitivity radioimmunoassay (RIA) procedure developed to accurately measure the relatively low serum total thyroxine (T4) concentrations of birds and reptiles and to establish initial reference ranges forT4 concentration in selected species of psittacine birds and snakes. ANIMALS: 56 healthy nonmolting adult psittacine birds representing 6 species and 42 captive snakes representing 4 species. PROCEDURE: A solid-phase RIA designed to measure free T4 concentrations in dialysates of human serum samples was used without dialysis to evaluate total T4 concentration in treated samples obtained from birds and reptiles. Serum T4 binding components were removed to allow assay of undialyzed samples. Assay validation was assessed by determining recovery of expected amounts of T4 in treated samples that were serially diluted or to which T4 was added. Intra- and interassay coefficient of variation (CV) was determined. RESULTS: Mean recovery of T4 added at 4 concentrations ranged from 84.9 to 115.0% and 95.8 to 119.4% in snakes and birds, respectively. Intra- and interassay CV was 3.8 and 11.3%, respectively. Serum total T4 concentrations for 5 species of birds ranged from 2.02 to 768 nmol/L but ranged from 3.17 to 142 nmol/L for blue-fronted Amazon parrots; concentrations ranged from 0.21 to 6.06 nmol/L for the 4 species of snakes. CONCLUSIONS AND CLINICAL RELEVANCE: This new RIA method provides a commercially available, accurate, and sensitive method for measurement of the relatively low serum T4 concentrations of birds and snakes. Initial ranges for the species evaluated were established.

Animals↗

A morphological and immunohistochemical study of the ultimobranchial body in the Japanese lizard and the snake.

A morphological and immunohistochemical study of the ultimobranchial body of reptiles Japanese lizard and snake was carried out. The ultimobranchial body of the Japanese lizard was located adjacent to the left arch of the aorta between the trachea and esophagus. It was found as a cluster or group of cells with no capsule. Grimelius' silver impregnation and lead-hematoxylin staining produced positive reactions in some of the clustered cells and follicular cells. The same reaction pattern was observed with anti-calcitonin using the PAP method. The PAP reactions were positive to antiserum against pig calcitonin, but negative to antiserum against synthesized human calcitonin. Furthermore, the PAP reactions were negative to antiserum against tyrosine hydroxylase. The immunofluorescent study of the snake ultimobranchial body revealed that most of the clustered cells and some of the follicular cells were calcitonin-immunoreactive but none was tyrosine hydroxylase-immunoreactive. Certain histological similarities exist between the Japanese lizard ultimobranchial body and snake ultimobranchial body, but the distribution of calcitonin-positive cells were slightly different. In the Japanese lizard, the positive cells were scattered between the foliicles and the number was small. However, most of the cells which formed the cluster in the ultimobranchial body of snake were positive. The findings suggest that the configuration of amino acid in the Japanese lizard calcitonin and snake calcitonin are similar to that of pig calcitonin, and the reptile and the birds is a boundary of the tyrosine hydroxylase existence.

Animals↗

Effects of snake venoms on hemostasis.

Proteins found in venoms, especially of the Viperidae snake family, exert, often with a narrow specificity, activating, inactivating, or other converting effects on different components of the hemostatic and fibrinolytic systems, respectively. Some purified snake venom proteins have become valuable tools in basic research and in diagnostic procedures in hemostaseology. "Procoagulant" as well as "anticoagulant" venom components have been identified in in vitro test systems. "Procoagulant" snake venom components may cause in vivo, upon massive application as in the case of snake-bite of small prey animals, intravascular coagulation leading to circulatory arrest and rapid death. Smaller doses of procoagulant venom components applied to large organisms as in the case of snake-bite accidents in humans, may cause a consumption coagulopathy with localized or generalized bleeding. Highly purified, specific fibrinogen coagulant venom proteinases are used in human medicine to produce therapeutic defibrinogenation. These practically nontoxic venom enzymes may act synergistically with other components aggravating their toxic effects.

Animals↗

Snake bites in adults from the Asir region of southern Saudi Arabia.

One hundred thirty-two cases of snake bites in adults from the Asir region of southern Saudi Arabia occurring the period 1989-1992 were studied. Of 15 snakes killed, 10 were identified as Echis coloratus and five as were Coluber rhodorachis. The clinical presentation of those bitten by the 10 identified E. coloratus were not very different from cases in which the snake was not identified, favoring the conclusion that the commonest snakes inflicting bites in this region are the saw-scaled or carpet vipers of the genus Echis. The response of adults to bites in this region is generally benign. Patients present mainly with local swelling, pain, redness, and coagulopathy. Minor bleeding was seen in 18.2% of the patients, primarily at the bite site. No serious complications or fatal bleeding occurred. Bites are more common in males during the summer season and mainly in the low land (Tihama). Recommendations regarding management of snake bites of adults from the Asir region are outlined.

Adolescent↗

Acute, flaccid quadriplegia in three cats with suspected coral snake envenomation.

Three cats were evaluated for acute, ascending, flaccid quadriplegia; depression; and reduced nociception. Complete or partial neuromuscular junction blockade was found on nerve stimulation studies during electromyographic examinations. Two of the cases had wounds on the chin or paw compatible with coral snake bites. Although a coral snake was found in only one case, coral snake envenomation was suspected because potential for exposure, clinical signs, and electrodiagnostic findings were similar to dogs reported with this condition and to cats with tiger snake envenomation. Only one case received coral snake antivenin. All cases recovered within seven-to-10 days.

Acute Disease↗