Cerebral Complications of Snakebite Envenoming: Case Studies.

There are an estimated 5.4 million snakebite cases every year. People with snakebite envenoming suffer from severe complications, or even death. Although some review articles cover several topics of snakebite envenoming, a review of the cases regarding cerebral complications, especially rare syndromes, is lacking. Here, we overview 35 cases of snakebite by front-fanged snakes, including Bothrops, Daboia, Cerastes, Deinagkistrodon, Trimeresurus, and Crotalus in the Viperidae family; Bungarus and Naja in the Elapidae family, and Homoroselaps (rare cases) in the Lamprophiidae family. We also review three rare cases of snakebite by rear-fanged snakes, including Oxybelis and Leptodeira in the Colubridae family. In the cases of viper bites, most patients (17/24) were diagnosed with ischemic stroke and intracranial hemorrhage, leading to six deaths. We then discuss the potential underlying molecular mechanisms that cause these complications. In cases of elapid bites, neural, cardiac, and ophthalmic disorders are the main complications. Due to the small amount of venom injection and the inability to deep bite, all the rear-fanged snakebites did not develop any severe complications. To date, antivenom (AV) is the most effective therapy for snakebite envenoming. In the six cases of viper and elapid bites that did not receive AV, three cases (two by viper and one by elapid) resulted in death. This indicates that AV treatment is the key to survival after a venomous snakebite. Lastly, we also discuss several studies of therapeutic agents against snakebite-envenoming-induced complications, which could be potential adjuvants along with AV treatment. This article organizes the diagnosis of hemotoxic and neurotoxic envenoming, which may help ER doctors determine the treatment for unidentified snakebite.

Venom Ophthalmia and Ocular Complications Caused by Snake Venom.

Little is known about the detailed clinical description, pathophysiology, and efficacy of treatments for ocular envenoming (venom ophthalmia) caused by venom of the spitting elapid and other snakes, as well as ocular complications caused by snake venom injection. In this paper, we review clinical information of case reports regarding venom ophthalmia and snake venom injection with associated ocular injuries in Asia, Africa, and the United States. We also review the literature of snake venom such as their compositions, properties, and toxic effects. Based on the available clinical information and animal studies, we further discuss possible mechanisms of venom ophthalmia derived from two different routes (Duvernoy's gland in the mouth and nuchal gland in the dorsal neck) and the pathophysiology of snake venom injection induced ocular complications, including corneal edema, corneal erosion, cataract, ocular inflammation, retinal hemorrhage, acute angle closure glaucoma, as well as ptosis, diplopia, and photophobia. Finally, we discuss the appropriate first aid and novel strategies for treating venom ophthalmia and snake envenoming.

Comparison of sea snake (Hydrophiidae) neurotoxin to cobra (Naja) neurotoxin.

Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins were determined, and then compared to cobra neurotoxins by computer modeling. This allowed for easy comparison of the similarities and differences between the two types of postsynaptic neurotoxins. Comparison of computer models for the toxins of sea snakes and cobra will reveal the three dimensional difference of the toxins much clearer than the amino acid sequence alone.

Isolation and chemical characterization of a toxin isolated from the venom of the sea snake, Hydrophis torquatus aagardi.

Sea snakes (family: Hydrophiidae) are serpents found in the coastal areas of the Indian and Pacific Oceans. There are two subfamilies in Hydrophiidae: Hydrophiinae and Laticaudinae. A toxin, aagardi toxin, was isolated from the venom of the Hydrophiinae snake, Hydrophis torquatus aagardi and its chemical properties such as molecular weight, isoelectric point, importance of disulfide bonds, lack of enzymatic activity and amino acid sequence were determined. The amino acid sequence indicated a close relationship to the primary structure of other Hydrophiinae toxins and a significant difference from Laticaudinae toxins, confirming that primary toxin structure is closely related to sea snake phylogenecity.

Isolation of anticoagulant from the venom of tick, Boophilus calcaratus, from Uzbekistan.

Boophilus calcaratus is a tick found in Central Asia and a common parasite to domestic animals. Venom from this tick was fractionated by two-step column chromatography, Sephadex G-75, and DEAE-Sephadex A-25. The homogeneity of the anticoagulant was examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified component is named calcaratin and has a molecular weight of 14,500. The effect of the purified anticoagulant component (calcaratin) on various sites of the blood coagulation cascade scheme was examined and compared with crude venom. The chromogenic substrates S-2238 (H-D-Phe-Pip-Arg-pNA 2HCl) for thrombin and S-2765 (N-alpha-Z-D-Arg-Gly-Arg-pNA 2HCl) for factor Xa were also investigated. Activated partial clotting times were all prolonged, suggesting the anticoagulation nature of the purified component and crude venom. Prolongation of fibrinogen clotting time (FCT) is highly suggestive of the antithrombin property of the purified component and its original venom.

Geographic variations, cloning, and functional analyses of the venom acidic phospholipases A2 of Crotalus viridis viridis.

Geographic venom samples of Crotalus viridis viridis were obtained from South Dakota, Wyoming, Colorado, Oklahoma, Texas, New Mexico, and Arizona. From these samples, the phospholipases A(2) (PLA(2)s) were purified and their N-terminal sequences, precise masses, and in vitro enzymatic activities were determined. We purified two to four distinct acidic PLA(2)s from each sample; some of them displayed different inhibition specificities toward mammalian platelets. One of the acidic PLA(2)s induced edema, but had no anti-platelet activity. There was also a common basic PLA(2) myotoxin in all the samples. We have cloned five acidic PLA(2)s and several hybrid-like nonexpressing PLA(2)s. Molecular masses and N-terminal sequences of the purified PLA(2)s were matched with those deduced from the cDNA sequences, and the complete amino acid sequences of five novel acidic PLA(2)s were thus solved. They share 78% or greater sequence identity, and a cladogram based on the sequences of many venom acidic PLA(2)s of New World pit vipers revealed at least two subtypes. The results contribute to a better understanding of the ecogenetic adaptation of rattlesnakes and the structure-activity relationships and evolution of the acidic PLA(2)s in pit viper venom.

Extremely low nerve growth facior (NGF) activity of sea snake (Hydrophiidae) venoms.

Sea snake venoms contain less protein than those of land snakes (Toom et al., 1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live in salty water, and their venoms may be different from those of land snakes. Because of the difficulty in obtaining sea snake venoms, information about sea snake venoms is quite incomplete. NGF is commonly present in the venoms of land snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini, 1956; Lipps, 2002). It is therefore of interest to investigate the presence or absence of NGF in sea snake venoms. In order to investigate the presence or absence of NGF, five sea snake venoms were selected. Lapemis hardwickii (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda semifasciata (broad band blue sea snake) venom was also examined and the venom was obtained from Gato Island in the Philippines.

The effect of snake venoms and their components on adrenomedullary cells: catecholamine efflux and cell damage.

The effects of snake venom on the cholinergic system have been well-studied; however, no similar studies have been performed on the adrenergic system. Adrenomedullary cells secrete catecholamine (CA) on stimulation; thus they are an ideal system to study the effect of snake venoms on CA secretion or inhibition. Snake venoms from different Families and Genera were investigated. All snake venoms investigated, caused CA efflux. CA can be released when cytolysis takes place; so in order to assert CA efflux was not due to cytolysis, venoms were added after the cells were treated with KCl. Most venom, with the exception of sea snake (Hydrophiidae) venom, was found to induce CA release due to cytolysis. The effects of purified components such as phospholipase A2, neurotoxin I, and cardiotoxin were also investigated. Neurotoxin I caused neither cytolysis nor CA efflux. Cardiotoxin caused marked cytolysis, but with slightly less damaging effects than that of cobra venom. Some ion channel blockers prevented cytolysis induced by cardiotoxin. The CA efflux induced by cardiotoxin may be mediated through Ca2+ channels because the efflux could be completely depressed by a Ca2+ channel blocker (1 mM CdCl2).