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Lily Robinson [shoe] and ready, on the set, go: recollections.

With this case, I found myself in unfamiliar territory. I realized that my cover had been compromised and all I could think about was fleeing the scene. I was not prepared. As I ran into the studio morgue, I bumped into the autopsy table and knocked the body onto the floor. Somewhere along the line, the reptile terrarium cover must have become dislodged and the live snake escaped. In its confusion it bit into the leg of the simulated body, and thankfully not into my leg. The man who stepped out of the shadows, John Chi Leigh, saved my life. I know his name because he whispered it into my ear as he helped pick me up off the floor. As I stood in front of him, searching his face for answers, he held up the syringe which had produced the fatal blow and said 2 words before he vanished: "hundred-pacer."

CROTALID ENVENOMATION

Viperidae, subfamily Crotalinae, includes the Crotalus genus (rattlesnakes), Agkistrodon genus (copperheads and cottonmouths) and the Bothrops genus (Ferdelance). Deinagkistrodon acutus, formerly Agkistrodon acutus, is a venomous pit viper found in Southeast Asia and known by many names: the Chinese moccasin, the sharp-nosed viper, the snorkel viper and the "hundred-pace viper" ("hundred-pacer"). It is believed that after the victim is bitten, he or she will be able to walk only a hundred paces before perishing. In regions where the snakes may be more venomous, they are known as "fifty-pacers."

Pit vipers are venomous snakes with a heat-sensing pit anteroinferior to each eye, elliptical pupils (cat's eyes), and a single row of scales on their undersides--in contrast to nonvenomous snakes, which have no facial pits, round eye pupils, and 2 rows of scales on their undersides. All snakes are "cold-blooded" reptiles, that is, they maintain their body temperature approximate to that of the environment. Their forked tongues and highly developed nostrils contain receptors that can "taste" or detect odors in the air by focusing substances on the Jacobson's organ, a highly developed olfactory epithelium located in the palate. This helps to locate prey, which consists primarily of small animals and birds. Moccasins inject their venom through hollow, movable (retractable) fangs and, as with all venomous snakes, not all bites contain venom; these nonvenomous bites are known as "dry bites." To the consternation of some, venomoids are venomous snakes that have had a surgical procedure to render them incapable of administering venom with a bite (usually the removal of the venom gland). These surgically altered snakes are considered less dangerous when kept in captivity. Purists, however, feel that if one desires a less-dangerous snake, then the "keeper" should tend only nonvenomous species.

D. acutus is found in southern China, Taiwan, and northern Vietnam and resides in mainly forested mountains, rocky hillsides, or under brush. This Chinese moccasin matures to 3 to 4 feet in length and is covered with brown or reddish brown triangles overlaying a grayish or reddish brown base color.

One review of snake bites found the highest rates of bites and mortality from snake bites in South Asia (Bangladesh, Bhutan, India, Nepal Pakistan, and Sri Lanka).

India has the greatest number of snakebites per year (up to 50 000 fatalities per year) followed by Pakistan with over 8000 fatalities per year. Snake bites are usually occupational hazards in these countries as numerous workers such as fishermen, farmers, plantation workers, and herders come into contact with snakes. In addition, many of these workers live in outdoor habitats and are exposed to nocturnal snakes while sleeping.

The initial symptoms after a bite from a pit viper are usually pain and swelling around the bite, with physical signs of fang marks, hemorrhagic vesicles, and tenderness at the bite site. Patients who present to the emergency department may have a history of nausea, vomiting or diarrhea, syncope, or near syncope. While most snake bites occur on the extremities, as a result of trying to handle a snake or walking in an infested area, there have been cases reported of penetrating ocular injury caused by a venomous snakebite. In one such case, the victim was crawling along a hillside when he was bitten on his right eye. The patient presented with facial swelling, periorbital ecchymoses, subconjunctival hemorrhage, corneal edema, and exophthalmos. Although the patient received 2 vials of D. acutus antivenom, he continued to have progressive airway edema requiring intubation. Six hours after the snakebite, evisceration of the right eye was performed. The patient eventually recovered, but only after surgery, extensive supportive medical treatment, and systemic antibiotics.

Some snakes, such as those in the Elapid family (e.g., Australian death adders, African mambas, and Asian coral snakes) produce venoms containing neurotoxins that cause paralysis and death by respiratory failure. Other snakes in the Crotalid family, such as the hundred-pace viper, create venoms containing hemorrhagic and proteolytic components. These venoms produce not only extensive necrosis and hemorrhage that result in considerable tissue damage, but also coagulopathy and shock. Rapidly progressive swelling in proximity to the wound usually constitutes a more severe envenomation. In severe envenomations systemic shock is apparent with hypotension, altered mental status, respiratory difficulties, and marked coagulopathy. Laboratory studies should focus around the coagulopathies and thrombocytopenia associated with pit viper envenomations. Therefore, a complete blood count, platelet count, prothrombin time/international normalized ratio, activated partial thromboplastin time, and fibrinogen are usually included in the workup.

Snake venom proteins are the mechanism whereby animals kill or immobilize their prey. They are of considerable interest because they interact with diverse molecular targets, producing various pharmacological and physiological effects. Several snake venom proteins are used as biomedical research tools or in clinical applications. Captopril, an anti hypertensive drug, was designed on the peptide inhibitor of angiotensin-converting enzyme derived from the venom of Bothrops jararaca. Venoms of true vipers (Viperinae) and of pit vipers (Crotalinae) contain hemotoxins, e.g., serine proteases. A therapeutic peptide isolated from D. acutus is coagulation factor X-binding protein reported to induce changes in plasma membrane permeability. Other substances such as thrombin-like enzymes are used for fibrinogen and fibrinogen-breakdown product assays.

The thrombin-like protease acutobin (40 kDa) is the major coagulating fibrinogenase of D. acutus venom, and contains a single chain of 236 residues including 4 potential N-glycosylation sites. Some venoms hydrolyze fibrinogen, releasing fibrinopeptide A, B, or both, while some may affect kininogen, plasminogen, and protein C. In addition to serine proteases, metalloproteinases and C-type lectins (CSL) are found in A. acutus venom. CSL are used to investigate platelet glycoprotein receptors. Qualitative determination of snake venom by sandwich ELISA is performed in Australia for species ofsnakes native to both Australia and New Guinea (Australian CSL Snake Venom Detection Kit, CSL, Melbourne Australia).

Antivenom is used to neutralize toxins. Several countries produce specific antivenoms for individual snake species (see WHO Regional Office for South-East Asia). For example, China produces purified Agkistrodon acutus antivenin, which is the same as for D. acutus. However, one available antivenom product in the US is Crotaline Fab antivenom (CroFab, Protherics, Nashville, TN). CroFab is a purified derivative from sheep hyperimmunized with the venom of4 crotaline snakes, including an Agkistrodon species (cottonmouth snakes). However, with antivenom administration there is always the risk ofan allergic reaction.

While snakebites are less commonly fatal in the US than the rest of the world, they are nevertheless of considerable medical importance and should be identified so that the appropriate medical care can be rendered expeditiously.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition ofdata, or analysis and interpretation ofdata; (b) draftingor revising the article for intellectual content; and (c) final approval ofthe published article.

Authors' Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts ofinterest.

Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

Congratulations to Robert Cross! He submitted that the poison used in the July 2010 "Lily Robinson and Ready, On the Set, Go" came from the Deinagkistrodon acutus, a Southeast Asian pit viper. Dr. Cross is a retired professor of pathology and medicine at UNC and currently self-employed as a medicolegal consultant and expert in toxicology and pharmacology. His name was randomly drawn from dozens of entries as the winner of a $50.00 gift certificate to the AACC Bookstore.

Bibliography

* Alirol E, Sharma SK, Bawaskar H, Kuch U, Chappuis F. Snake bite in South Asia: a review. PLoS Negl Trop Dis 2010;4:1-9.

* Bush S, Lavonas E. Snake envenomation, moccasins. http://emedicine.medscape.com/article/ 771 329-overview.

* Cetaruk E. Rattlesnakes and other crotalids. In: Brent J, Wallace K, Burkhart K, Phillips S, Donovan J. Critical care toxicology. New York: Mosby; 2005. p 1075-89.

* Chen C-C, Yang C-M, Hu F-R, Lee Y-C. Penetrating ocular injury caused by venomous snakebite. Am J Ophthalmol 2005;140:544-6.

* Messmer TA, Wiscomb GW. Nonvenomous snakes. Wildlife damage management series. Logan (UT): Utah State University Cooperative Extension; 1998. 4 p.

* Miller J. Venomoids: an overview. VenomousReptiles. org; 2001. http://www.venomousreptiles.org/ articles/55.

* Morita T. Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant- and platelet-modulating activities. Toxicon 2005;45:1099-114.

* Paulchamy C. Pharmacological perspective of snake venoms from Viperidae Family. Internet J Pharmacol 2010;8:1-7.

* Qinghua L, Xiaowei Z, Wei Y, Chenji L, Yijun H, Pengxin Q, et al. A catalog for transcripts in the venom gland of the Agkistrodon acutus: identification of the toxins potentially involved in coagulopathy. Biochem Biophys Res Commun 2006;341:522-31.

* Wang YM, Wang SR, Tsai IH. Serine protease isoforms of Deinagkistrodon acutus venom: cloning, sequencing and phylogenetic analysis. Biochem J 2001;354:161-8.

* White J. Overview of snake envenoming. In: Brent J, Wallace K, Burkhart K, Phillips S, Donovan J. Critical care toxicology. New York: Mosby; 2005. p 1051-74.

* WHO. Blood safety and laboratory technology: the clinical management of snake bites in the South East Asian Region: annex 3--antivenoms for treating bites by South East Asian snakes--(listed by country of manufacture). http://www.searo.who.int/ en/Section10/Section17/Section53/Section1024_3908. htm

Received May 25, 2010; accepted May 26, 2010.

DOI: 10.1373/clinchem.2010.151100
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Title Annotation:the Clinical Chemist
Author:Robinson, Lily
Publication:Clinical Chemistry
Date:Aug 1, 2010
Words:1715
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