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PubMed1976

Laser Raman spectroscopy of snake venom neurotoxins: conformation.

Laser Raman spectra of neurotoxins of Pelamis platurus (yellow-bellied sea snake) and Laticauda semifasciata (broad-banded blue sea snake) were investigated. The amide I band appeared at 1672 cm-1 for both toxins, which presents an indication of anti-parallel beta structure. Since this agrees well with the result from the CD-ORD studies of snake neurotoxin, it was concluded that snake neurotoxins mainly consist of beta structure. The amide III band appeared at 1245 cm-1 for P. platurus toxin and 1248 cm-1 for L. semifasciata toxin. The four disulfide bonds present in the toxin have a very similar geometry. After vigorous heat treatment, the backbone configuration of the toxin molecule basically remained the same although it was partially denatured. The major peak at 512 cm-1 was not altered by the heat treatment but a new shoulder appeared at 546 cm-1. This suggests that a new type of S-S stretching vibration (trans-gauche-trans) was produced as a result of heat treatment. However, the majority of the S-S vibrations remained in the gauche-gauche-gauche orientation. A substantial change in the interactions between a tyrosine aromatic ring and neighboring residues was apparently the alteration caused by the heat treatment.

Amino Acids↗
PubMedDate not supplied

Ultrastructural features of cystic and merogonic stages of Hepatozoon sipedon (Apicomplexa: Adeleorina) in northern leopard frogs (Rana pipiens) and northern water snakes (Nerodia sipedon) from Ontario, Canada.

The cystic and merogonic stages of the haemogregarine Hepatozoon sipedon, infecting Northern water snakes (Nerodia sipedon sipedon) and Northern leopard frogs (Rana pipiens), respectively, in Ontario, Canada, were investigated by transmission electron microscopy. Cysts, which were observed in the liver of Northern leopard frogs (Rana pipiens) after these anurans ingested mosquitoes (Culex pipiens) containing oocysts of the parasite, harboured two cystozoites, each of which contained a large crystalloid inclusion anterior to the nucleus. Two types of meronts were observed in snakes that were fed the liver of infected frogs. Macromeronts, which matured in endothelial cells of the liver approximately 16 d after snakes ingested infected frogs, contained about 50 large macromerozoites. Macromerozoites emerged from macromeronts, entered the bloodstream of the snake, and reinfected endothelial cells. Micromeronts, which matured about 34 d post-inoculation, contained about 150 micromerozoites that infected erythrocytes and transformed into gamonts. The ultrastructural features of micromeronts and macromeronts differed only slightly: immature macromeronts and macromerozoites contained numerous amylopectin and lipid inclusions, whereas immature micromeronts and micromerozoites did not contain amylopectin inclusions and featured fewer, smaller lipid inclusions. A comparison of cystic stages among Hepatozoon species in different groups of vertebrates is presented with respect to their structure and evolutionary significance.

Animals↗
PubMed1994

Myotoxicity and nephrotoxicity of common tiger snake (Notechis scutatus) venom in the dog.

The myotoxicity and neurotoxicity of common tiger snake (Notechis scutatus) venom are major factors in the pathogenesis of envenomation in the dog. Histological examination of the tissues of experimentally envenomed dogs has demonstrated the importance of muscle damage in affecting the clinical syndrome of tiger snake envenomation. Within one hour of injection of the venom into dogs, there was selective involvement of some muscles. Cardiac and smooth muscles were not significantly affected. The severity of myofibre damage was influenced by the amount of venom injected. Immobilisation under general anaesthesia resulted in significant protection against the myotoxic effects of high doses of venom. Lesions in the kidneys of experimentally envenomed dogs were acute tubular necrosis and the variable presence of a small amount of proteinaceous material in tubules. These lesions, which were similar to those in cases of natural snake bite, were indicative of a direct nephrotoxic effect, which could be complicated by the effects of myoglobinuria. These findings emphasise the need for supportive treatment aimed at maintenance of renal function in the treatment of dogs suffering from tiger snake envenomation.

Animals↗
PubMed1996

Characteristics of shed snake skin permeability to indomethacin and fatty alcohols.

To investigate the utilities of a shed snake skin as a model membrane for preclinical studies of transdermal drug delivery, the flux of indomethacin was determined under various conditions by using a diffusion cell. The flux of fatty alcohols was determined and compared with that in human skin reported in references. The esterase activity of shed snake skin was also determined. It was found that the flux of indomethacin decreased with an increase of pH and the amount of ethanol in a vehicle. The flux of indomethacin increased by the addition of Azone, N-methyl-2-pyrrolidone and N,N-dimethyl-m-toluamide in the cream. The flux of fatty alcohols in shed snake skin was greater than that reported in human skin, and shed snake skin had similar esterase activity to human skin.

Animals↗
PubMed1988

Sodium channel distribution in normal and denervated rodent and snake skeletal muscle.

1. Sodium channel current density was measured using the loose-patch voltage clamp technique. Innervated rat, mouse and snake muscle had the highest density of Na+ channels in the end-plate region. These high Na+ channel densities were maintained in denervated muscle. 2. Perijunctional membrane had a Na+ current density 5- to 10-fold greater than the density several hundred micrometres from the end-plate. In all muscles this concentration of channels near the end-plate persisted following denervation. 3. At the tendon Na+ current density fell to low values (approximately 1 mA/cm2). The decrease in density began about 300-500 microns from the tendon. This pattern was found in all snake twitch fibres and fast-twitch (EDL) rat and mouse muscle fibres. This reduction in channel density near the tendon was not affected by denervation. 4. Sodium channels in all regions of innervated rat and snake muscle fibres were highly sensitive to tetrodotoxin (TTX). Sodium channels in snake muscle remained sensitive to TTX after denervation. Sodium channels that are relatively resistant to TTX appeared in rat muscle after denervation. TTX-resistant channels were even more concentrated near the end-plate than were TTX-sensitive channels in innervated muscle. At the tendon TTX-resistant Na+ channel density decreased. 5. We conclude that although the nerve presumably directs the localization of Na+ channels during development, the ability to maintain this distribution and to control the distribution of newly appearing channels persists long after the nerve has been removed.

Action Potentials↗
PubMed1966

Western equine encephalitis virus in Saskatchewan garter snakes and leopard frogs.

Western equine encephalitis virus was isolated from two naturally infected snakes on first bleeding and from seven others at subsequent bleedings, both with and without preliminary chilling. One snake, with neither detectable virus nor serum neutralizing antibodies when first bled, developed viremia later. Viremia in garter snakes has a cyclic rhythm independent of the temperature of the environment. Virus was isolated from 6 frogs, and 50 out of 179 had detectable serum neutralizing antibodies. Infections with this virus are widely distributed in garter snakes and leopard frogs in the agricultural area of Saskatchewan.

Animals↗
PubMed1971

Haemodialysis in poisoning by sea-snake venom.

Myoglobinuria, renal failure, and muscular weakness or paralysis were noted in two patients following sea-snake bite. A pathological study by biopsy showed renal tubular necrosis and myonecrosis. Both patients were treated by haemodialysis, and there was a remarkable improvement in the muscular symptoms. Recovery was complete in both cases. It is believed that muscular paralysis was the effect of hyperkalaemia and uraemia on the muscles sensitized by the toxic effect of the sea-snake venom. Removal of potassium and uraemic factors by dialysis thus led to the rapid improvement of the muscular activity. Haemodialysis seems to be a useful alternative method to sea-snake antivenom in the treatment of sea-snake bite poisoning.

Acute Kidney Injury↗
PubMed1993

Blood pressure during routine activity, stress, and feeding in black racer snakes (Coluber constrictor).

The pressor response to normal daily behaviors and acute stress was studied in black racer snakes (Coluber constrictor) at 30 degrees C. In addition, hematological changes during the stress response were assessed. Mean nighttime systemic arterial blood pressure (SABP) in undisturbed snakes was lower than daytime pressure (26 +/- 3 vs. 32 +/- 9 mmHg, P < 0.001). When snakes were fed mice, SABP increased 3.5- to 4-fold and heart rate increased approximately 3-fold above resting values within approximately 30 s (peak SABP, 99 +/- 18 mmHg; peak heart rate, 99 +/- 12 beats/min). Killing and ingesting the mice required 6-15 min, during which time mean SABP and heart rate were 84 +/- 16 mmHg and 92 +/- 12 beats/min. Pulmonary blood pressure also increased but remained 40-50 mmHg lower than SABP. During stress elicited by tapping the snakes for 5-8 min, heart rate was 94 +/- 6 beats/min but SABP averaged only 44 +/- 11 mmHg. Plasma norepinephrine and epinephrine increased 51- and 26-fold. Plasma glucose increased 58%, hematocrit increased 19%, and plasma volume decreased 19%. It is concluded that blood pressure is markedly affected by behavior and that the sympathetic nervous system appears to play a key role.

Animals↗
PubMedDate not supplied

Protein C activators from snake venoms and their diagnostic use.

Proteinases converting the zymogen protein C (PC) of vertebrates into activated PC have been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological, thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques. Due to this feature, the fast-acting PC activator Protac from Agkistrodon contortrix contortrix (southern copperhead snake) venom has found a broad application in diagnostic practice for the determination of disorders in the PC pathway. Recently, screening assays for the PC pathway have been introduced, based on the observation that the PC pathway is probably the most important physiological barrier against thrombosis.

Agkistrodon↗
PubMed2005

The use of snake venom-derived compounds for new functional diagnostic test kits in the field of haemostasis.

Pentapharm Ltd. has a long tradition of producing and proceeding snake venom components as APIs and tools in pharmaceutical and diagnostic applications, beginning with the snake venom-derived product Reptilase about 60 years ago. In recent years diagnostic test kits in the field of haemostasis have been developed, like Pefakit APC-R Factor V Leiden and Pefakit PiCT, which make use of one or more snake venom compounds as key reactants. The venom-derived compounds are responsible for many outstanding properties of these tests and account for their top ranking performance qualities confirmed in non-clinical and clinical studies. Both tests are on the market in Europe. Pefakit APC-R Factor V Leiden is also marketed in the US since January 2005. Research on snake venom-derived compounds for diagnostic and pharmaceutical use is ongoing.

Animals↗
PubMed2005

Two parallel prothrombin activator systems in Australian rough-scaled snake, Tropidechis carinatus. Structural comparison of venom prothrombin activator with blood coagulation factor X.

It is uncommon for similar pathways/systems to be involved in highly divergent functions within single organisms. Earlier, we have shown that trocarin D, a venom prothrombin activator, from the Australian rough-scaled snake Tropidechis carinatus, is structurally and functionally similar to the blood coagulation factor Xa (FXa). The presence of a haemostatic system in these snakes implies that they have two parallel prothrombin activating systems: one in the plasma, that participates in the life saving process of blood clotting and the other in their venom, where it acts as a toxin. Here, we report the complete cDNA sequence encoding the blood coagulation factor X (FX) from the liver of T. carinatus. Deduced T. carinatus FX sequence shows approximately 80% identity with trocarin D but approximately 50% identity with the mammalian FX. Our present study confirms the presence of two separate genes--one each for FX and trocarin D, that code for similar proteins in T. carinatus snake. These two genes have different expression sites and divergent uses suggesting that snake venom prothrombin activators have probably evolved by the duplication of the liver FX gene and subsequently marked for tissue-specific expression in the venom gland.

Amino Acid Sequence↗
PubMed1998

A clinico-epidemiological study of snake bite in Nepal.

Envenoming from snake bite is an important medical condition, frequently encountered at the emergency department of BPKIHS hospital (Dharan, Nepal). This is a retrospective study of 52 cases of suspected snake bite who presented at the department from August 1993 to November 1994. Analysis of the data showed that snake bite was more frequent between the ages of 11 to 20 years (36.7%) and 2.5 times more common in males. Fifty-seven per cent of the bites occurred between 1600 h and midnight with highest incidence (51%) occurring during the monsoon (August-October). Twenty per cent of the patients were able to identify the snake species as venomous and 90% of them presented to the hospital within 3 h of being bitten. Sixty per cent of the bites were in the lower limb. Neurotoxicity due to envenoming was recorded in nine patients (17%). No case of coagulopathy was recorded. The overall case fatality was 3.8% but mortality amongst those exhibiting signs of neurotoxicity was 22%.

Adolescent↗
PubMed2004

Independent effects of heart-head distance and caudal blood pooling on blood pressure regulation in aquatic and terrestrial snakes.

Changes in orientation in a gravitational field markedly alter the patterns of blood pressure and flow in animals, especially tall or long ones such as giraffes or snakes. Vertical orientation tends to reduce blood flow and pressure in the head for two major reasons. First, the increased vertical blood column above the heart creates a gravitational hydrostatic pressure against which the heart must work. Second, expansion of dependent vessels in the lower extremities causes blood pooling and reduces return of venous blood to the heart, thereby lowering flow and pressure. For most animals, it is difficult to separate these two effects, but snakes offer the possibility of bending the animal in the region of the heart and manipulating the two ends of the body independently. We studied baroregulatory responses in terrestrial pythons (Liasis fuscus) and aquatic file snakes (Acrochordus arafurae) by tilting only the front or rear parts and then the whole animal. Changes in head blood pressure during partial tilts added up to the change during full tilt. The vertical distance to the head had twice as much influence on head blood pressure than did blood pooling in the pythons and four times as much in file snakes. This accounts for the cephalad location of the heart in terrestrial species compared with aquatic ones.

Animals↗
PubMed2001

Autonomic control of heart rate during forced activity and digestion in the snake Boa constrictor.

Reptiles, particularly snakes, exhibit large and quantitatively similar increments in metabolic rate during muscular exercise and following a meal, when they are apparently inactive. The cardiovascular responses are similar during these two states, but the underlying autonomic control of the heart remains unknown. We describe both adrenergic and cholinergic tonus on the heart during rest, during enforced activity and during digestion (24-36 h after ingestion of 30 % of their body mass) in the snake Boa constrictor. The snakes were equipped with an arterial catheter for measurements of blood pressure and heart rate, and autonomic tonus was determined following infusion of the beta-adrenergic antagonist propranolol (3 mg kg(-1)) and the muscarinic cholinoceptor antagonist atropine (3 mg kg(-1)). The mean heart rate of fasting animals at rest was 26.4+/-1.4 min(-1), and this increased to 36.1+/-1.4 min(-1) (means +/- S.E.M.; N=8) following double autonomic block (atropine and propranolol). The calculated cholinergic and adrenergic tones were 60.1+/-9.3 % and 19.8+/-2.2 %, respectively. Heart rate increased to 61.4+/-1.5 min(-1) during enforced activity, and this response was significantly reduced by propranolol (maximum values of 35.8+/-1.6 min(-1)), but unaffected by atropine. The cholinergic and adrenergic tones were 2.6+/-2.2 and 41.3+/-1.9 % during activity, respectively. Double autonomic block virtually abolished tachycardia associated with enforced activity (heart rate increased significantly from 36.1+/-1.4 to 37.6+/-1.3 min(-1)), indicating that non-adrenergic, non-cholinergic effectors are not involved in regulating heart rate during activity. Blood pressure also increased during activity. Digestion was accompanied by an increase in heart rate from 25.6+/-1.3 to 47.7+/-2.2 min(-1) (N=8). In these animals, heart rate decreased to 44.2+/-2.7 min(-1) following propranolol infusion and increased to 53.9+/-1.8 min(-1) after infusion of atropine, resulting in small cholinergic and adrenergic tones (6.0+/-3.5 and 11.1+/-1.1 %, respectively). The heart rate of digesting snakes was 47.0+/-1.0 min(-1) after double autonomic blockade, which is significantly higher than the value of 36.1+/-1.4 min(-1) in double-blocked fasting animals at rest. Therefore, it appears that some other factor exerts a positive chronotropic effect during digestion, and we propose that this factor may be a circulating regulatory peptide, possibly liberated from the gastrointestinal system in response to the presence of food.

Adrenergic beta-Antagonists↗
PubMed1996

Bites by non-native venomous snakes in the United States.

Fifty-four consultations regarding bites by venomous snakes not native to the United States are summarized. These are from a database of 164 consultations during the period 1977- 1995. At least 29 non-native snake species were involved with cobras making up -40% of the group. There was one fatality. A high percentage of venomous snakebites in the United States involve deliberate interaction with snakes. The proportion of bites by non-native species seems to be increasing. Some of the snake species involved are discussed, and some principles for management of these bites are given.

Adolescent↗
PubMed2005

Inflammatory effects of snake venom metalloproteinases.

Metalloproteinases are abundant enzymes in crotaline and viperine snake venoms. They are relevant in the pathophysiology of envenomation, being responsible for local and systemic hemorrhage frequently observed in the victims. Snake venom metalloproteinases (SVMP) are zinc-dependent enzymes of varying molecular weights having multidomain organization. Some SVMP comprise only the proteinase domain, whereas others also contain a disintegrin-like domain, cysteine-rich, and lectin domains. They have strong structural similarities with both mammalian matrix metalloproteinases (MMP) and members of ADAMs (a disintegrin and metalloproteinase) group. Besides hemorrhage, snake venom metalloproteinase induce local myonecrosis, skin damage, and inflammatory reaction in experimental models. Local inflammation is an important characteristic of snakebite envenomations inflicted by viperine and crotaline snake species. Thus, in the recent years there is a growing effort to understand the mechanisms responsible for SVMP-induced inflammatory reaction and the structural determinants of this effect. This short review focuses the inflammatory effects evoked by SVMP.

Animals↗
PubMed2005

Medicinal plants with inhibitory properties against snake venoms.

Envenomations due to snake bites are commonly treated by parenteral administration of horse or sheep-derived polyclonal antivenoms aimed at the neutralization of toxins. However, despite the widespread success of this therapy, it is still important to search for different venom inhibitors, either synthetic or natural, that could complement or substitute for the action of antivenoms. Several plants have been utilized in folk medicine as antiophidian. However, only a few species have been scientifically investigated and still less had their active components isolated and characterized both structurally and functionally. This article presents a review of plants showing neutralizing properties against snake venoms which were assayed in research laboratories, correlating them with ethnopharmacological studies, as (i) the part of the plant used as antidote, (ii) its respective genus and family and (iii) inhibition of the main pharmacological, toxic and enzymatic activities of snake venoms and isolated toxins. Protective activity of many of these plants against the lethal action of snake venoms has been confirmed by biological assays. Compounds in all of them belong to chemical classes capable of interacting with macromolecular targets (enzymes or receptors). Popular culture can often help to guide scientific studies. In addition, biotechnological application of these inhibitors, as helpful alternative or supplemental treatments to serum therapy, and also as important models for synthesis of new drugs of medical interest, needs to be better oriented and scientifically explored.

Animals↗
PubMed1991

Pepsinogen granules in the esophageal epithelium of the rock snake.

We demonstrated a large number of pepsinogen granules in the esophageal pseudostratified ciliated epithelium of the rock snake. 1. The snake esophagus is covered with a pseudostratified ciliated epithelium. 2. This epithelium develop mostly in the upper portion of the esophagus. 3. Long supranuclear portions of the same cells are strongly PAS-positive and contain pepsinogen granules. Those cells possess cilia. 4. The strongly PAS-positive cells and pepsinogen granules decrease or are lost in the middle and lower portions of the esophagus. 5. Glands are distributed in the lamina propria mucosae of the esophagus of the Japanese lizard and gecko. Those in humans and the bird are compound tubular glands and those of the Japanese lizard and gecko are bottle-shaped. The pepsinogen granules of these glands are secreted into the excretory ducts and then discharged into the esophageal lumen. 6. However, the same granules of the snake are contained in the supranuclear portion of the epithelium and are secreted directly into the esophageal lumen. 7. The mode of pepsinogen granule secretion of the esophagus is most simple in the snake.

Animals↗