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Toxinology Introduction to the world of toxins: Definition:

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1 Toxinology Introduction to the world of toxins: Definition:
"the scientific discipline dealing with microbial, plant and animal venoms, poisons and toxins". According to Prof. Dietrich Mebs {Ref (1)}. "toxinology includes more than just the chemistry and mode of action of a toxin. It deals also with the biology of venom- or poison-producing organism, the structure and function of the venom apparatus, as well as the use of the venom or poison, the ecological role of these compounds.“ Ref (1): Mebs D (2002) Venomous and Poisonous Animals. CRC Press:Boca Raton. pg. 2 Medani A.B.

2 Definition (con) : Prof. Jurg Meier {Ref (2)}. has defined toxinology as "the science of toxic substances produced by or accumulated in living organisms, their properties, and their biological significance for the organisms involved". {Ref (2)}. Meier J & White J (1995) Handbook of Clinical Toxicology of Animal Venoms and Poisons. CRC Press:Boca Raton Medani A.B.

3 Mission Statement To maximize the health of the people handling toxins and patients receiving drugs from plant, animal or microbial origins by providing timely appropriate information in poisoning or suspected poisoning situations and by enhancing poisoning prevention. This can be achieved by expanding knowledge through more awareness, training of trainers, public groups and individuals , and making systemic contact with professionals in academic institutes and drug industrial plants and establishment of poison centers. Medani A.B.

4 Role and Philosophy of Poison Information Centers
The role of Poisons Information Centre (PIC) is to provide the public and health professionals with prompt, up-to-date and appropriate information, and advice to assist in the management of poisonings and suspected poisonings. Members of the public may be given first aid instructions, possible symptoms to watch for, advice on the need for medical attention in poisonings, and general advice on poisoning’s prevention and management, especially for people in direct contact with wildlife. Unnecessary visits to medical facilities may be avoided in minor accidental poisonings by the timely provision of advice and reassurance. Health professionals are also given poisoning advice in the management of poisoned patients. Medani A.B.

5 Clinical Toxinology Within toxinology there is a clinical subgroup, clinical toxinologists, who focus on the medical effects in humans of exposure to the toxins in animal venoms ,mivrobial or plant poisons. This includes such problems as venomous snakebite, currently considered to afflict >2.5 million people each year, with >100,000 deaths. Information on these medical consequences of toxins can be found in diverse sources, such as the Clinical Toxinology Resources Website and books such as Prof. Mebs book and the CRC book on toxinology. Clinical toxinology does not, yet, enjoy specialist status within medicine, unlike fields such as surgery and radiology. However, a training course in clinical toxinology has existed since 1997 (held in Adelaide, Australia) and efforts are under way to expand this to a true, specialist-level international training program, through an initiative of the International Society on Toxinology. Given the huge impact of toxin-based disease globally, the value of having doctors expert in this area is self evident. Medani A.B.

6 The International Society on Toxinology (IST ),was founded 1962, catering for toxinologist and their research, with an international Congress every three years and regional sectional meetings in intervening years. The society also has an official journal, Toxicon. Medani A.B.

7 Use of Toxins for Biological Therapy
Many toxins are used ,with the fast inventory advancements in drug discovory , for biological purposes. Special consideration should be directed towards the feedback from those biological uses ,though desperately needed ,in order to minimize the hazards resulting from their uses. Many examples can be given as : Medani A.B.

8 Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species.[1] It is also produced commercially for medical, cosmetic, and research use. There are two main commercial types: botulinum toxin type A and botulinum toxin type B.[2] Infection with the bacterium may result in a potentially fatal disease called botulism. Botulinum is the most acutely lethal toxin known, with an estimated human median lethal dose (LD50) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled.[3] Botulinum toxin type A and B is used in medicine for, among others, upper motor neuron syndrome, focal hyperhidrosis,blepharospasm, strabismus, chronic migraine and bruxism. It is also widely used in cosmetic treatments. The U.S. Food and Drug Administration requires a boxed warning stating that when locally administered the toxin may spread from the injection site to other areas of the body, causing symptoms similar to those of botulism. The warning was the result of deaths associated with its uses.[4][5]The commercial form is marketed under the brand name Botox, among others. Jump up^ Montecucco C, Molgó J (2005). "Botulinal neurotoxins: revival of an old killer". Current Opinion in Pharmacology 5 (3): 274–279. doi: /j.coph PMID  Jump up^ American Society of Health-System Pharmacists (October 27, 2011). "Botulinum Toxin Type A". Retrieved 4 March 2015. Jump up^ Arnon, Stephen S.; Schechter R; Inglesby TV; Henderson DA; Bartlett JG; Ascher MS; Eitzen E; Fine AD; Hauer J; Layton M; Lillibridge S; Osterholm MT; O'Toole T; Parker G; Perl TM; Russell PK; Swerdlow DL; Tonat K; Working Group on Civilian Biodefense (February 21, 2001). "Botulinum Toxin as a Biological Weapon: Medical and Public Health Management" (PDF, 0.5 MB). Journal of the American Medical Association 285 (8): 1059–1070. doi: /jama  PMID  ^ Jump up to:a b c d e FDA Notifies Public of Adverse Reactions Linked to Botox Use. Retrieved on May 6, 2012. ^ Jump up to:a b c d e f g h FDA Gives Update on Botulinum Toxin Safety Warnings; Established Names of Drugs Changed, FDA Press Announcement, August 3, 2009 Medani A.B.

9 Natural toxins are the product of a long-term evolution, and act on essential mechanisms in the most crucial and vital processes of living organisms. They can attack components of the protein synthesis machinery, act in polymerization, signal transduction pathways, intracellular trafficking of vesicles as well as immune and inflammatory responses. For this reason, toxins have increasingly being used as valuable tools for analysis of cellular physiology, and in the recent years, some of them are used medicinally for the treatment of human diseases. This review is devoted to protein toxins of bacterial origin, specifically those toxins that are currently used in therapy or those under study for their potential clinical applications. Bacterial protein toxins are all characterized by a specific mechanism of action that involves the central molecular pathways in the eukaryotic cell. Knowledge of their properties could be used for medical purposes. Fabbri A1, Travaglione S, Falzano L, Fiorentini C . Bacterial protein toxins: current and potential clinical use Medani A.B.

10 Sewage treatment  is the process of removing contaminants from wastewater, primarily from household sewage. It includes physical, chemical, and biological processes to remove these contaminants and produce environmentally safe treated wastewater (or treated effluent). A by-product of sewage treatment is usually a semi-solid waste or slurry, called sewage sludge, that has to undergo further treatment before being suitable for disposal or land application. Primary treatment consists of temporarily holding the sewage in a quiescent basin where heavy solids can settle to the bottom while oil, grease and lighter solids float to the surface. The settled and floating materials are removed and the remaining liquid may be discharged or subjected to secondary treatment. Some sewage treatment plants that are connected to a combined sewer system have a bypass arrangement after the primary treatment unit. This means that during very heavy rainfall events, the secondary and tertiary treatment systems can be bypassed to protect them from hydraulic overloading, and the mixture of sewage and stormwater only receives primary treatment. Medani A.B.

11 Secondary treatment removes dissolved and suspended biological matter
Secondary treatment removes dissolved and suspended biological matter. Secondary treatment is typically performed by indigenous, water-borne micro-organisms in a managed habitat. Secondary treatment may require a separation process to remove the micro-organisms from the treated water prior to discharge or tertiary treatment. Tertiary treatment is sometimes defined as anything more than primary and secondary treatment in order to allow rejection into a highly sensitive or fragile ecosystem (estuaries, low-flow rivers, coral reefs,...). Treated water is sometimes disinfected chemically or physically (for example, by lagoons and microfiltration) prior to discharge into a stream, river, bay, lagoon or wetland, or it can be used for the irrigation of a golf course, green way or park. If it is sufficiently clean, it can also be used for groundwater recharge or agricultural purposes. Medani A.B.

12 The Use of Bacterial Toxins in the Treatment of Cancer by A. Hoffer (M
The Use of Bacterial Toxins in the Treatment of Cancer by A. Hoffer (M.D., Ph.D.) For over two hundred years spontaneous cancer cures or regressions have been observed and recorded. They have been discussed in standard textbooks of surgery and medicine with the omission of a very important observation, i.e. that they were not spontaneous. Many of them, if not most, were preceded by a bacterial infection such as erysipelas. Many early physicians were aware that there was a relationship, but because there was no scientific explanation the connection did not become generally known. Medani A.B.

13 It had also been observed that the bacterial infection was even more beneficial if it was accompanied by fever. Helen Coley Nauts (1986) collected this imposing clinical data in the files of the Cancer Research Institute Records ( ), and in her publications (1990). Thus Vautier in 1813 discussed the cure of cancer by natural means after he had found several patients who were cured after they had developed gangrene. Nauts collected 22 such cases. The mixture of bacteria probably induced the formation of tumor necrosis factor. She published 449 cases found in 1032 worldwide references in the medical literature. Medani A.B.

14 Several toxins are "dual-use" in that they have legitimate therapeutic, pharmaceutical, or scientific applications as well as potential military utility as toxin warfare (TW) agents. The growing peaceful applications of such toxins may complicate efforts to ban their use for warfare or terrorist purposes. Worldwide consumption of toxins for medical therapy and scientific research has increased from a few grams to the current level of hundreds of grams per year, and the projected future growth of toxin therapies will require tens to hundreds of kilograms of material annually, blurring the distinction between medically useful and militarily significant quantities. As a result, a proliferator might seek to acquire an offensive TW capability under the guise of "peaceful" activities permitted by the Biological and Toxin Weapons Convention (BWC) and the Chemical Weapons Convention (CWC). To examine this problem more closely, the case of ricin--a putative toxin warfare agent with expanding scientific and medical applications--is discussed in detail. Finally, an analysis of policy options for regulating dual-use toxins concludes that precise monitoring of toxin production would be impracticable in many cases, and that international efforts to achieve greater openness and transparency offer the most realistic basis for distinguishing between the legitimate and banned uses of toxins. Jonathon,B. Trucker.(1994).Dual Use of Toxins Medani A.B.

15 Antivenoms Management of toxin-related disease is often difficult, and in many cases meticulous supportive care is all that is available. The mainstay of treatment is the use of antivenoms for many envenomations and poisoning, although these do not exist for all dangerous organisms. Unfortunately antivenoms are not an economically viable product, so development and manufacture of these agents have been limited. This is now further worsened by a current shortage of antivenom. There is a need for improvement in the prevention and management of toxin-related disease. This will require well-designed studies to define the extent of the problem, initiatives to improve the prevention and management of these conditions, and development of new, and continuation of current, antivenom supplies . Julian White, M.B.B.S, M.D., F.A.C.T.M.,, David Warrell, M.A., D.M., D.Sc., F.R.C.P., F.R.C.P.E., F.Med.Sci.,, Michael Eddleston, M.A., M.B.B.S., Ph.D., M.R.C.P.,, Bart J. Currie, F.R.A.C.P., F.A.F.P.H.M., D.T.M.H.,, Ian M. Whyte, M.B.B.S., F.R.A.C.P., F.R.C.P.E., and Geoffrey K. Isbister, B.Sc., M.B.B.S., F.A.C.E.M.(2003) Where Are We Now?Antivenoms.Clinic.Toxicol. Vol. 41, No. 3 , Pages Medani A.B.

Ι/According to origin & source 1/ Toxic plants 2/ Toxic animals 3/ Microbial natural toxins Medani A.B.

ΙΙ/According to targeted organs 1/Reproduction and Development Reproductive function - with emphasis on male reproduction. Mechanism of action of natural toxins on the male reproductive system - especially with respect to disruption of androgen biosynthesis and metabolism and also with sperm function. Expertise includes Enzymology:- radiometric assays of steroidogenic enzymes in male and female reproductive tissues and in male and female liver; Animal handling; Tissue sub-cellular fractionation; Isotope handling; Incubations; Organic extraction; Chromatography; Scintillation spectrometry; Radio-autography; Re-crystallization and Kinetic analysis Medani A.B.

18 2/ Immunotoxicology These are applied to the study of potential adverse effects of natural toxins on the immune system of humans, non-human primates and rodents. Medani A.B.

19 toxicological, genotoxic and carcinogenic effects of natural toxins
3/Genotoxicity and Carcinogenesis toxicological, genotoxic and carcinogenic effects of natural toxins 4/Mutagenicity Natural toxins with mutagenic activity and effects on DNA damage and repair mechanisms. Medani A.B.

20 g/Cardiac toxicity 5/through the toxicokinetics of natural toxins
a/ Neurotoxicity b/Renal toxicity c/ Hepatic toxicity d/Intestinal toxicity e/Pulmonary toxicity f/Haemato-toxicity g/Cardiac toxicity Medani A.B.

21 Treatment of natural toxins
At home self- care level, induction of vomiting or toxin adsorption is not a good advice. Advice can better be given through contact with poison centers. Medani A.B.

22 Medical treatment *Protect from suffocation. * Provide a ventilator
* Afford a stable intubation. * Give an antiseizure medicine in case of convulsions. * After the toxin pass the stomach,give charcoal. * Irrigate the whole gastrointestinal tract with golytely (= indicated for bowel cleansing prior to colonoscopy and barium enema X-ray examination). Medani A.B.

23 Medical treatment Some poisons have specific antidotes to prevent them from working or reverse their effects. In case of poisons with out specific antidotes, use massive supportive treatment of symptoms. Follow up the cases to get rid of subsequent harmful effects of natural poisoning. Medani A.B.

24 Treatment of natural toxins
TOXINS AS A STARTING POINT TO MEDICINES Compounds isolated from natural sources continue to inspire pharmaceutical development. A number of drugs have their origins in toxins and venoms. Constituents of snake, scorpion and spider venoms can be used as a means to destroy life, but they can also help to produce a number of potential drugs and be guides leading to new, more effective therapies. Samira Saleh. TOXINS AS A STARTING POINT TO MEDICINES. Egyptian Journal of Natural Toxins Medani A.B.

25 This article sheds some light on the uses of selectively acting toxins in drug discovery such as Curare - Botox® - The first ACE inhibitors - Exendin-4 The desintegrins, which are potent inhibitors of platelet aggregation and blood clotting. Examples: Integrilin (eptifibatide) and Ancrod - Dendrotoxins, that block neuronal K+ channels, may provide symptomatic relief in Alzheimer's disease - Activators of K+ channels could reduce abnormal electrical activity in the brain, and, hence, be useful for epilepsy - Selective M1-agonists for treating Alzheimer's disease - Toxins from scorpion venoms act selectively on sodium or potassium ion channels - Margatoxin was found to act as an immunosuppressant and Venoms from spiders and marine snails (Conus species), which selectively block different subtypes of calcium ion channels. Although many toxins are too large or too poorly absorbed to be used as drugs, advances in techniques for analyzing structures and in computer-aided drug design should make it likely that toxins will act more and more as lead compounds in drug discovery. Medani A.B.

26 Toxins from animal sources I / Toxins from amphibians
All amphibians have poisonous skin secretions, including salamanders, in fact, the skin secretion of the Pacific Newts is among the most toxic compounds known in nature. In spite of this, these animals are harmless to handle, just don’t eat them. Kids (and adults) should simply remember to wash their hands after handling them. Another important lesson to teach young (and old) amphibian lovers is to wash the hands BEFORE handling these delicate creatures, especially if those hands might be covered with sunscreen or insect repellent. These compounds can damage the skin of salamanders and frogs, and this can be deadly to them. It is a good idea to moisten your hands before holding frogs and salamanders in order to protect their skin. Medani A.B.

27 Taxonomy Order: Anura Family: Dendrobatidae
Poison Dart Frogs: Taxonomy Order: Anura Family: Dendrobatidae Habitat Poison dart frogs live in the rainforests of Central and South America and on a few Hawaiian islands. Medani A.B.

28 Medani A.B.

29 Geographical distribution
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30 Description These beautiful colors are warnings to potential predators that the frogs are poisonous. Other species, such as monarch butterflies, sport bright colors to advertise their toxicity. Several species of non-poisonous frogs evolved with similar coloring to avoid being eaten. Some scientists think that the reticulated pattern of the frogs also acts as camouflage among the forest shadows. Medani A.B.

31 Medani A.B.

32 The use of the term "frog" in common names usually refers to species that are aquatic or semi-aquatic with smooth and/or moist skins, and the term "toad" generally refers to species that tend to be terrestrial with dry, warty skin. An exception is the fire-bellied toad (Bombina bombina): while its skin is slightly warty, it prefers a watery habitat. Medani A.B.

33 Wonderful images Medani A.B.

34 Life Span They may live more than ten years in captivity.
Diet in the Wild Poison dart frogs feed mostly on spiders and small insects such as ants and termites, which they find on the forest floor using their excellent vision. They capture their prey by using their long sticky tongues. Life Span They may live more than ten years in captivity. Status Some poison dart frogs are endangered due to habitat loss, which is causing numbers to decline among many species. The possibility of new medications from these frogs' secretions is being explored.   Medani A.B.

35 1/25/2018 Medani A.B. Toxicity: Not all arrow frogs are deadly, and only three species are very dangerous to humans. The most deadly species to humans is the golden poison arrow frog (Phyllobates terribilis). Its poison, batrachotoxin, can kill many small animals or humans. Arrow frogs are not poisonous in captivity. Scientists believe that these frogs gain their poison from a specific arthropod and other insects that they eat in the wild. These insects most likely acquire the poison from their plant diet. The chemical makeup of toxins in frogs varies from irritants to hallucinogens, convulsants, nerve poisons, and vasoconstrictors. Many predators of frogs have adapted to tolerate high levels of these poisons. Others, including humans, may be severely affected. Medani A.B. Cameroon,SETAC AFRICA ,2011

36 Because frog toxins are extraordinarily diverse, they have raised the interest of biochemists as a "natural pharmacy". The alkaloid epibatidine, a painkiller 200 times more potent than morphine, is found in some species of poison dart frogs. Other chemicals isolated from the skin of frogs may offer resistance to HIV infection  Phillipe, G.; Angenot L. (2005). "Recent developments in the field of arrow and dart poisons". J Ethnopharmacol. 100(1-2): 85–91. Medani A.B.

37 Salamanders Common name: Long-Toed Salamander Scientific name: Ambystoma macrodactylum Long-toed Salamanders enjoy the typical salamander diet of insects, tadpoles, worms, beetles and small fish. Unlike tadpoles, salamander larvae are carnivores and like to munch on insects, zooplankton, and other amphibian larvae. In turn, adults and larvae are on the menu for a variety of aquatic insects, birds, fish, bullfrogs and garter snakes. Long-toed Salamanders are found in western North America in a wide variety of habitats and elevations. They range from the Alaskan panhandle throughout B.C. and down the eastern slopes of the Rocky Mountains in Alberta. They also range south through Washington and Oregon to northern California, and can be found as far east as central Idaho and the eastern slope of the Rockies in Montana. Medani A.B.

38 ii/ Archinates: i/ Spiders
Most spiders are absolutely harmless to humans. In fact, of the 20,000 different species of spiders that inhabit the Americas, only 60 are capable of biting humans. Within that small group, only four are known to be dangerous to humans: the brown recluse, the black widow, the hobo or aggressive house spider, and the yellow sac spider. Within this selected group, only the brown recluse and the black widow spider have ever been associated with significant disease and very rare reports of death. Medani A.B.

39 Medani A.B.

40 Latrodectus Kingdom: Animalia Phylum: Arthropoda Class: Arachnida
Order: Araneae Family: Theridiidae Genus: Latrodectus Medani A.B.

41 Latrodectus is a genus of spider, in the family Theridiidae, that contains approximately 31 recognized species. The common name widow spiders is sometimes applied to members of the genus due to the supposed habit of the female of eating the male after mating, although the males of most species are not actually usually eaten after mating, and can even go on to fertilize other females. The black widow spiders are perhaps the best-known members of the genus. The injection of neurotoxic venom Latrotoxin from these species is a comparatively dangerous spider bite, resulting in the condition Latrodectism which is named for the genus. The female black widow's bite is particularly harmful to humans because of its unusually large venom glands. Breene, R. G.; Sweet, M. H. (1985). "Evidence of insemination of multiple females by the male Black Widow Spider, Latrodectus mactans (Araneae, Theridiidae)" (PDF). The Journal of Arachnology 13 (3): 331–335. Medani A.B.

42 Gallary Male L. elegans from Japan Medani A.B.
Latrodectus hesperus with egg sac Europe, North Africa, the Middle East, and western Asia,female Male L. elegans from Japan Medani A.B.

43 The black widow spider: Widow spiders belong to the genus Latrodectus and include the black widow spider (Latrodectus mactans mactans) in the United States. produces a protein venom that affects the victim's nervous system. This neurotoxic protein is one of the most potent venoms secreted by an animal. Some people are slightly affected by the venom, but others may have a severe response. The first symptom is acute pain at the site of the bite, although there may only be a minimal local reaction. Symptoms usually start within 20 minutes to one hour after the bite. Local pain may be followed by localized or generalized severe muscle cramps, abdominal pain, weakness, and tremor. Large muscle groups (such as shoulder or back) are often affected, resulting in considerable pain. In severe cases, nausea, vomiting, fainting, dizziness, chest pain, and respiratory difficulties may follow. The severity of the reaction depends on the age and physical condition of the person bitten. Children and the elderly are more seriously affected than young adults. In some cases, abdominal pain may mimic such conditions as appendicitis or gallbladder problems. Chest pain may be mistaken for a heart attack. Blood pressure and heart rate may be elevated. The elevation of blood pressure can lead to one of the most severe complications. People rarely die from a black widow's bite. Life-threatening reactions are generally seen only in small children and the elderly. Ushkaryov, YA; Rohou, A; Sugita, S (2008). "alpha-Latrotoxin and its receptors".Handbook of experimental pharmacology. Handbook of Experimental Pharmacology 184(184): 171–206. Medani A.B.

44 Symptoms:The black widow spider produces a protein venom that affects the victim's nervous system. This neurotoxic protein is one of the most potent venoms secreted by an animal. Some people are slightly affected by the venom, but others may have a severe response. The first symptom is acute pain at the site of the bite, although there may only be a minimal local reaction. Symptoms usually start within 20 minutes to one hour after the bite. Local pain may be followed by localized or generalized severe muscle cramps, abdominal pain, weakness, and tremor. Large muscle groups (such as shoulder or back) are often affected, resulting in considerable pain. In severe cases, nausea, vomiting, fainting, dizziness, chest pain, and respiratory difficulties may follow. The severity of the reaction depends on the age and physical condition of the person bitten. Children and the elderly are more seriously affected than young adults. In some cases, abdominal pain may mimic such conditions as appendicitis or gallbladder problems. Chest pain may be mistaken for a heart attack. Blood pressure and heart rate may be elevated. The elevation of blood pressure can lead to one of the most severe complications. People rarely die from a black widow's bite. Life-threatening reactions are generally seen only in small children and the elderly. Medani A.B.

45 Gallary: Complications in healthy adults are uncommon. If the black widow spider bite is not treated with antivenin, symptoms may last for several days but are seldom life threatening. Medications The person bitten by a black widow spider, that has pain severe enough to seek treatment at an Emergency Department, will require narcotic pain relief. Muscle relaxants given by injection may also be of value. Although calcium gluconate given through an IV has long been advocated, it does not seem to produce much relief of symptoms. Isbister, Geoffrey K.; Page, Colin B.; Buckley, Nicholas A.; Fatovich, Daniel M.; Pascu, Ovidiu; MacDonald, Stephen P.J.; Calver, Leonie A.; Brown, Simon G.A. (2014)."Randomized Controlled Trial of Intravenous Antivenom Versus Placebo for Latrodectism: The Second Redback Antivenom Evaluation (RAVE-II) Study". Annals of Emergency Medicine.  Medani A.B.

46 Use of antivenin The antivenin available for treatment of black widow spider bites is derived from horse serum. The venom produced by various species of black widow spiders is similar, so the antivenin (antivenin) prepared against one venom is effective against the others. Antivenin is produced by gradually increasing injections of the specific venom in a horse. The horse then starts producing the antivenin, which will be used in humans. Symptoms are often not easily relieved, even with narcotics. Some experts recommend that antivenin is to be used in any severe bite because one vial of the antitoxin produces significant and rapid relief of symptoms. It can even be used if there is delay in reaching the hospital. Yet other sources recommend that antivenin be used only in children, the elderly, and those with severe underlying medical conditions. Medani A.B.

47 Brown Recluse Spider Bite: Deaths from brown recluse spiders have been reported only in children younger than seven years. The most common non-brown recluse spiders are the desert recluse .No deaths have ever been reported from non-brown recluse spiders. Bites from these cousins produce mild to moderate local skin disease. Habits: These spiders are not aggressive and bite only when threatened, usually when pressed up against the victim's skin. They seek out dark, warm, dry environments such as attics, closets, porches, barns, basements, woodpiles, and old tires. Its small, haphazard web, found mostly in corners and crevices, is not used to capture prey. Most bites occur in the summer months. Medani A.B.

48 Geographical distribution
Gallary: Geographical distribution Medani A.B.

49 Identifying the Brown Recluse Spider
One can readily learn how to identify recluse spiders with less than a minute's training. Whereas most spiders have 8 eyes, typically arranged in 2 rows of 4, the recluse spiders have 6 eyes arranged in pairs (dyads) with one anterior dyad and 2 lateral dyads .All 13 species of U.S. recluses (11 native, 2 non-native) share the same eye pattern. In many publications, the violin pattern on the cephalothorax (the first body part to which the legs attach) is mentioned as a diagnostic characteristic .Although it is quite consistent in adult brown recluses (although it can fade in preserved specimens), many recluse species and some young brown recluses have virtually no contrasting pigmentation in the violin region. In addition, recluse spiders have abdomens that are devoid of coloration pattern and their legs are covered with fine hairs but lack thickened spines. Medani A.B.

50 Close-up of the cephalothorax of the brown recluse spider, Loxosceles reclusa, showing the pattern of 6 eyes arranged in dyads .A preserved brown recluse spider showing the strongly contrasting and well-defined violin pattern on the cephalothorax as well as the patternless abdomen covered with fine hairs. A desert recluse, Loxosceles deserta, showing the lack of a strongly defined violin pattern. The cephalothorax of a preserved desert recluse showing the characteristic recluse eye pattern and a uniformly colored cephalothorax . Medani A.B.

51 Toxicity:This venom is a collection of enzymes
Toxicity:This venom is a collection of enzymes. One of the specific enzymes, once released into the victim's skin, causes destruction of local cell membranes, which disrupts the integrity of tissues leading to local breakdown of skin, fat, and blood vessels. This process leads to eventual tissue death (necrosis) in areas immediately surrounding the bite site. The venom also induces in its victim an immune response. The victim's immune system releases inflammatory agents-histamines, cytokines, and interleukins-that recruit signal specific disease-fighting white blood cells to the area of injury. In severe cases, however, these same inflammatory agents can themselves cause injury. These secondary effects of the venom, although extremely rare, can produce these more significant side effects of the spider bite: Destruction of red blood cells ,low platelet count ,blood clots in the capillaries and loss of ability to form clots where needed ,acute renal failure (kidney damage) ,coma and death Medani A.B.

52 Diagnosis: The doctor will try to make the correct diagnosis
Diagnosis: The doctor will try to make the correct diagnosis. It helps if the patient is able to produce the spider in question. That can often be difficult, because most victims don't even realize they have been bitten before developing symptoms. The doctor will ask about the bite event, time elapsed since the bite, other medical problems, medications, and allergies. Laboratory studies that may be performed include complete blood count, electrolytes, kidney function studies, blood clotting studies, and urinalysis. No specific lab findings can confirm a brown recluse bite. Therefore, a presumptive diagnosis can occur only after a careful history and examination taking into account the likelihood of a bite depending on the part of the country where the person was bitten. This diagnosis can be confirmed if the spider is available and identified as a brown recluse. Follow-up :After the initial evaluation by a doctor, the patient may expect this type of follow-up: Daily follow-up of wounds for the first 96 hours to assess the possibility or extent of necrosis of wound Medani A.B.

53 Victims may experience these symptoms:
Symptoms:Brown recluse spider bites often go unnoticed initially because they are usually painless bites. Occasionally, some minor burning that feels like a bee sting is noticed at the time of the bite. Symptoms usually develop two to eight hours after a bite. Keep in mind that most bites cause little tissue destruction. Victims may experience these symptoms: severe pain at bite site after about four hours,severe itching,nausea,vomiting, fever, and myalgias (muscle pain). Initially the bite site is mildly red and upon close inspection may reveal fang marks. Most commonly, the bite site will become firm and heal with little scaring over the next few days or weeks. Occasionally, the local reaction will be more severe with erythema and blistering, sometimes leading to a blue discoloration, and ultimately leading to a necrotic lesion and scarring. Signs that may be present include: blistering (common),necrosis (death) of skin and subcutaneous fat (less common), and severe destructive necrotic lesions with deep wide borders (rare). Medani A.B.

54 Apply ice to decrease pain and swelling.
Treatment Self-Care at Home:Home first aid care is simple. This self-care should not replace a visit to a doctor or emergency department. After a spider bite: Apply ice to decrease pain and swelling. Elevate area if possible above the level of the heart. Wash the area thoroughly with cool water and mild soap. Avoid any strenuous activity because this can spread the spider's venom in the skin. Use acetaminophen (Tylenol) for pain relief. Do not perform any of the following techniques: Do not apply any heat to the area. This will accelerate tissue destruction. Do not apply any steroid creams to the area such as hydrocortisone cream. Do not attempt to remove the spider venom with suction devices or cut out the affected tissue. Do not apply electricity to the area. Anecdotal reports of high voltage electrotherapy from common stun guns have never been shown to be effective in any scientific studies. This can also cause secondary burns and deepen tissue destruction. Do not apply a tourniquet to the extremity involved. Medani A.B.

55 Perform routine, thorough house cleaning.
Prevention Reducing the possibility of an encounter with a brown recluse spider starts with eliminating known spider habitats. Perform routine, thorough house cleaning. Reduce clutter in garages, attics, and basements. Move all firewood, building materials, and debris away from the home's foundation. Install tight-fitting window screens and door sweeps. Clean behind outside home shutters. Consider installing yellow or sodium vapor light bulbs outside entrances because these lights are less attractive to insects and draw fewer spiders to the area. Consider professional pest elimination. Medani A.B.

56 ii/Scorpions Medani A.B.

57 Sydney funnel Female funnel-web spider. Male funnel-web spider.
Medani A.B.

58 Treatment: Prehospital Care
If possible and when expedient and safe, the spider should be killed and collected for identification. A pressure immobilization bandage identical to that applied in the management of Australian snakebite should be applied immediately.6 The dressing prevents migration of venom via lymphatics to the central circulation. Simultaneous immobilization (with a splint and/or sling) diminishes the muscle-pump effect on lymphatics and venous flow. Tourniquets are to be avoided. Pressure immobilization must be maintained until the patient arrives at a hospital where antivenom is available. Supportive care, including cardiac and respiratory life support, should be performed as necessary and according to the advanced cardiac life support (ACLS) protocol. Medani A.B.

59 Emergency Department Care
Most bites do not result in severe envenomation, although local pain at the site of the bite is common. When severe envenomation occurs, resuscitation measures and antivenin therapy should be instituted as necessary. Funnel-web spider antivenom (CSL, Melbourne) is prepared by hyperimmunizing rabbits with the venom of A robustus. It has been effective in treating victims of a variety of species of Australian funnel-web spiders Antivenom has been highly successful in the treatment of A robustus envenomation. Complete resolution of symptoms has occurred in 97% of patients treated with antivenom after confirmed funnel-web spider bites. Antivenom has been used successfully in pregnant women, breastfeeding women, and children. Medani A.B.

60 Antivenom is indicated if any of the following are present:
Anaphylaxis is a risk when giving antivenom. In a recent review, adverse effects consistent with anaphylaxis occurred in 2 patients of 75 treated with antivenom. One patient of the 75 developed serum sickness within 7 days of administration of antivenom.1 Premedication with an antihistamine and steroid to prevent anaphylaxis may be considered. However, premedication with epinephrine is contraindicated because of elevated catecholamine levels induced by the venom. Administration of epinephrine is appropriate if anaphylaxis occurs. Antivenom should be given in the ED or intensive care unit with close monitoring by medical and nursing staff. The initial dose of antivenom is 2 bottles intravenously, but most cases require 4 or more bottles. Antivenom is indicated if any of the following are present: Muscle fasciculation Marked salivation or lacrimation Piloerection Significant tachycardia Hypertension in a previously normotensive patient Hypotension or shock Dyspnea Disorientation Confusion Depressed level of consciousness As with any bite, ensure that tetanus immunization status is up to date. Isbister GK, Gray MR, Balit CR, Raven RJ, Stokes BJ, Porges K, et al. Funnel-web spider bite: a systematic review of recorded clinical cases. Med J Aust. Apr ;182(8): Medani A.B.

61 This agent neutralizes the toxins from the spider bite.
Antivenin This agent neutralizes the toxins from the spider bite. Funnel-web spider antivenom Freeze-dried IgG prepared from rabbit serum, reconstituted with water for injection, and dispensed in bottles of 125 Units. Should be administered only where appropriate resuscitation facilities are immediately available. Antivenin may not be commercially available at most pharmacies. Atropine IV/IM Used for the relief of excessive airway secretions Medani A.B.

62 Further Inpatient Care
Patients who respond to antivenom may be discharged within a day or so if no complications occur. Management is more difficult if antivenom is unavailable; in such cases, the patient may need to spend many days in intensive care. Important insights into management before the availability of antivenom have been provided by Fisher et al.5 Prolonged ventilation in the intensive care unit may be required for treatment of respiratory failure. Adequate sedation is essential. Atropine has been used to provide parasympathetic blockade. In the early stages, hypertension may be treated with alpha-blockers, but massive doses may be required. Reversible agents are preferred because of the possible development of hypotension as envenomation progresses. Theoretically, beta-blockade may be lethal (because of unopposed alpha-stimulation) and is not advocated. Fisher MM, Carr GA, McGuinness R, Warden JC. Atrax robustus envenomation. Anaesth Intensive Care. Nov 1980;8(4): Medani A.B.

63 Scorpions from the family Buthidae
Out of 1500 scorpion species, 50 are dangerous to humans. Scorpion stings cause a wide range of conditions, from severe local skin reactions to neurologic, respiratory, and cardiovascular collapse. Envenomation from most scorpions results in a simple, painful, local reaction that can be treated with analgesics, antihistamines, and symptomatic/supportive care. This article focuses on scorpions that generally are considered more dangerous to humans. Almost all of these lethal scorpions, except the Hemiscorpius species, belong to the scorpion family called the Buthidae. The Buthidae family is characterized by a triangular-shaped sternum, as opposed to the pentagonal-shaped sternum found in the other 5 scorpion families. Medani A.B.

64 Buthus - Mediterranean area, from Spain to the Middle East
The lethal members of the Buthidae family include the genera of Buthus, Parabuthus, Mesobuthus, Tityus, Leiurus, Androctonus, and Centruroides. These lethal scorpions are found generally in the given distribution: Buthus - Mediterranean area, from Spain to the Middle East Parabuthus - Western and Southern Africa Mesobuthus – Throughout Asia Buthotus (ie, Hottentotta) - Across southern Africa to southeast Asia Tityus - Central America, South America, and the Caribbean Leiurus - Northern Africa and the Middle East Androctonus - Northern Africa to Southeast Asia Centruroides - Southern United States, Mexico, Central America, and the Caribbean (Centruroides exilicauda is found in the Baja California peninsula of Mexico and Centruroides sculpturatus is found in the state of Sonora, Mexico and the southwestern United States, primarily Arizona and small parts of Utah, New Mexico, Nevada, and California. The accepted taxonomy of the bark scorpion has changed over time. Either C exilicauda or C sculpturatus have been accepted at various times. However, recent evidence from biochemical, genetic, and physiologic characterization of their venom suggests that they are two different species as listed above. Medani A.B.

65 Medani A.B.

66 Centruroides species In addition to the triangular-shaped sternum, poisonous scorpions also tend to have weak-looking pincers, thin bodies, and thick tails, as opposed to the strong heavy pincers, thick bodies, and thin tails seen in nonlethal scorpions. Medani A.B.

67 Centruroides limbatus
Scorpion stings are a major public health problem in many underdeveloped tropical countries, especially Sahelian Africa, South India, the Middle East, Mexico, and South Latin America. The estimated annual number of scorpion stings is 1.2 million leading to 3250 deaths (0.27%). For every person killed by a poisonous snake, 10 are killed by a poisonous scorpion. In Mexico, 1000 deaths from scorpion stings occur per year. In the United States, only 4 deaths in 11 years have occurred as a result of scorpion stings. Furthermore, scorpions can be found outside their normal range of distribution, that is when they crawl into luggage, boxes, containers, or shoes and are unwittingly transported home via human travelers. A scorpion has a flattened elongated body and can easily hide in cracks. It has 4 pairs of legs, a pair of claws, and a segmented tail that has a poisonous spike at the end. Scorpions vary in size from 1-20 cm in length. Medani A.B.

68 Toxicity: Scorpions use their pincers to grasp their prey; then, they arch their tail over their body to drive their stinger into the prey to inject their venom, sometimes more than once. The scorpion can voluntarily regulate how much venom to inject with each sting. The striated muscles in the stinger allow regulation of the amount of venom ejected, which is usually mg. If the entire supply of venom is used, several days must elapse before the supply is replenished. Furthermore, scorpions with large venom sacs, such as the Parabuthus species, can even squirt their venom. The venom glands are located on the tail lateral to the tip of the stinger and are composed of 2 types of tall columnar cells. One type produces the toxins, while the other produces mucus. The potency of the venom varies with the species, with some producing only a mild flu and others producing death within an hour. Generally, the venom is distributed rapidly into the tissue if it is deposited into a venous structure. Venom deposited via the intravenous route can cause symptoms only 4-7 minutes after the injection, with a peak tissue concentration in 30 minutes and an overall toxin elimination half-life of hours through the urine. The more rapidly the venom enters the bloodstream, the higher the venom concentration in the blood and the more rapid the onset of systemic symptoms. Medani A.B.

69 Scorpion venom is a water-soluble, antigenic, heterogenous mixture, as demonstrated on electrophoresis studies. This heterogeneity accounts for the variable patient reactions to the scorpion sting. However, the closer the phylogenetic relationship between the scorpions, the more similar the immunological properties. Furthermore, the various constituents of the venom may act directly or indirectly and individually or synergistically to manifest their effects. In addition, differences in the amino acid sequence of each toxin account for their differences in the function and immunology. Thus, any modifications of the amino acid sequence result in modification of the function and immunology of the toxin. Medani A.B.

70 Scorpion venom may contain multiple toxins and other compounds
Scorpion venom may contain multiple toxins and other compounds. The venom is composed of varying concentrations of neurotoxin, cardiotoxin, nephrotoxin, hemolytic toxin, phosphodiesterases, phospholipases, hyaluronidases, glycosaminoglycans, histamine, serotonin, tryptophan, and cytokine releasers. The most important clinical effects of envenomation are neuromuscular, neuroautonomic, or local tissue effects. The primary targets of scorpion venom are voltage-dependent ion channels, of which sodium channels are the best studied. Venom toxins alter these channels, leading to prolonged neuronal activity. Many end-organ effects are secondary to this excessive excitation. Autonomic excitation leads to cardiopulmonary effects observed after some scorpion envenomations. Somatic and cranial nerve hyperactivity results from neuromuscular overstimulation. Additionally, serotonin may be found in scorpion venom and is thought to contribute to the pain associated with scorpion envenomation. Medani A.B.

71 The most potent toxin is the neurotoxin, of which 2 classes exist
The most potent toxin is the neurotoxin, of which 2 classes exist. Both of these classes are heat-stable, have low molecular weight, and are responsible for causing cell impairment in nerves, muscles, and the heart by altering ion channel permeability. The long-chain polypeptide neurotoxin causes stabilization of voltage-dependent sodium channels in the open position, leading to continuous, prolonged, repetitive firing of the somatic, sympathetic, and parasympathetic neurons. This repetitive firing results in autonomic and neuromuscular overexcitation symptoms, and it prevents normal nerve impulse transmissions. Furthermore, it results in release of excessive neurotransmitters such as epinephrine, norepinephrine, acetylcholine, glutamate, and aspartate. Meanwhile, the short polypeptide neurotoxin blocks the potassium channels. The binding of these neurotoxins to the host is reversible, but different neurotoxins have different affinities. The stability of the neurotoxin is due to the 4 disulfide bridges that fold the neurotoxin into a very compact 3-dimensional structure, thus making it resistant to pH and temperature changes. However, reagents that can break the disulfide bridges can inactivate this toxin by causing it to unfold. Also, the antigenicity of this toxin is dependent on the length and number of exposed regions that are sticking out of the 3-dimensional structure. Medani A.B.

72 Local tissue effects vary among species.
Clinical manifestations range from minor local tenderness to multisystem failure followed by death. Local tissue effects vary among species.  Minimal local tissue effects are present with Centruroides envenomation. Significant local tissue reaction rules out C exilicauda envenomation. Tapping over the injury site (ie, tap test) may cause severe pain after a sting by C exilicauda. Tachycardia and other dysrhythmias are caused by autonomic effects primarily, although direct myocardial toxicity with arrhythmogenic effects has been described. Hypertension or hypotension may be present. The patient may have hyperthermia. Respiratory arrest and loss of protective airway reflexes are common causes of mortality. Pulmonary edema has been described and may be secondary to cardiogenic causes and to increased capillary permeability. Autonomic effects include the following:  Sympathetic overdrive symptoms predominate, causing tachycardia, hypertension, hyperthermia, and pulmonary edema. Parasympathetic symptoms include hypotension, bradycardia, salivation, lacrimation, urination, defecation, and gastric emptying. Medani A.B.

73 Cranial nerve effects include the following:
Classic roving or rotary eye movements, blurred vision, tongue fasciculations, and loss of pharyngeal muscle control may be observed. Difficulty swallowing combined with excessive salivary secretions may lead to respiratory difficulty. Somatic effects include the following:  Restlessness and involuntary muscle jerking that can be mistaken for seizures have been described. Presence of true seizures in Centruroides envenomation is controversial and has not been proven to occur. Seizures are described in association with other scorpion envenomations. Cerebral infarction, cerebral thrombosis, and acute hypertensive encephalopathy have been described with a variety of Buthidae scorpion envenomations. Medani A.B.

74 Non-neurological predominance
The grading of these scorpion envenomations depends on whether or not neurological signs predominate and is as follows: Non-neurological predominance Mild - Local signs Moderate - Ascending local signs or mild systemic signs Severe - Life-threatening systemic signs Neurologic predominance Grade I - Local pain or paresthesia at the sting site (83%) Grade II - Pain or paresthesia that has traveled from the sting site (9.1%) Grade III - Either cranial nerve or somatic neuromuscular dysfunction (4.7%) Grade IV - Both cranial nerve and somatic neuromuscular dysfunction (3%)  Medani A.B.

75 Neurotoxic local effects
Local signs Neurotoxic local effects Local evidence of a sting may be minimal or absent in as many as 50% of cases of neurotoxic scorpion stings. In fact, tissue necrosis is rarely found. A sharp burning pain sensation at the sting site, followed by pruritus, erythema, local tissue swelling, and ascending hyperesthesia, may be reported. This paresthesia feels like an electric current (pins and needles), persists for several weeks, and is the last symptom to resolve before the victim recovers. The tap test is administered by tapping at the sting site. A positive result is when the paresthesia worsens with the tapping because the site is hypersensitive to touch and temperature. In fact, wearing clothing over the area and sudden changes in temperature exacerbate the symptoms. Tapping over the injury site (ie, tap test) may cause severe pain after a sting by C exilicauda. Cytotoxic local effects A macule (skin discolouration)or papule (small pimple or swelling of skin)appears initially at the sting site, occurring within the first hour of the sting. The diameter of the lesion is dependent on the quantity of venom injected. The lesion progresses to a purpuric plague that will necrose and ulcerate. Lymphangitis results from the transfer of the venom through the lymphatic vessels. Nonlethal local effects Pain, erythema, induration, and wheal may be present. These are secondary to venom activation of kinins and slow-releasing substances. Local tissue effects vary among species. Minimal local tissue effects are present with Centruroides envenomation. Significant local tissue reaction rules out C exilicauda envenomation. Medani A.B.

76 Neurologic signs Most of the symptoms are due to either the release of catecholamines from the adrenal glands (sympathetic nerves) or the release of acetylcholine from postganglionic parasympathetic neurons. One study by Freire-Maia et al (1974) found that the adrenergic signs occur at a low venom dose, while cholinergic signs occur at high venom dose concentrations (ie, >40 mcg/100 g in Tityus serrulatus scorpion venom). Furthermore, the adrenergic phase tended to be more dependent on the venom dose than the cholinergic phase. However, dual manifestations of the adrenergic and cholinergic signs are possible because of varying organ system sensitivities to these neurotransmitters. Geovana Novaes 1,O.L. Catanzaro 2, W.T. Beraldo 3,L. Freire-Maia 3.(1982). Effect of purified scorpion toxin (tityustoxin) on the pancreatic secretion of the rat.Toxicon,vol.20 ,P Medani A.B.

77 Nonneurologic systemic signs
Cardiovascular signs - Usually follow a pattern of a hyperdynamic phase followed by a hypodynamic phase Hypertension is described as follows: Secondary to catecholamine and renin stimulation Observed as early as within 4 minutes after the sting Lasts a few hours High enough to produce hypertensive encephalopathy Hypotension - Less common and occurs secondary to excess acetylcholine or catecholamine depletion -Tachycardia is greater than 130 beats per minute, although bradycardia can be observed. -Transient apical pansystolic murmur is consistent with papillary muscle damage. - Cardiovascular collapse occurs secondary to toxin induced myocarditis biventricular dysfunction and profuse loss of fluids from sweating, vomiting, diarrhea, and hypersalivation. Observed in 7-38% of cardiovascular cases Mild envenomation - Vascular effect with vasoconstriction hypertension Moderate envenomation - Left ventricular failure hypotension with and without an elevated pulmonary artery wedge pressure, depending on fluid status of the patient Severe envenomation - Biventricular cardiogenic shock Cardiac dysfunctions attributed to catecholamine-induced myocarditis and increases in myocardial metabolism oxygen demand (leading to myocardial ischemia–induced myocardial hypoperfusion) as well as to the direct effects of the toxin (leading to myocarditis and myocardial conduction interference) Medani A.B.

78 Respiratory signs :Tachypnea may be present.
Pulmonary edema with hemoptysis (coughing up of blood) and a normal-sized heart is observed in 7-32% of respiratory cases. This is secondary to a direct toxin-induced increased pulmonary vessel permeability effect and is also secondary to catecholamine-induced effects of hypoxia and intracellular calcium accumulation, which leads to a decrease in left ventricular compliance with resultant ventricular dilation and diastolic dysfunction. Respiratory failure may occur secondary to diaphragm paralysis, alveolar hypoventilation, and bronchorrhea. Allergic signs :Patients may have urticaria. Angioedema is reported. Patients may present with bronchospasm. Anaphylaxis is possible. Medani A.B.

79 Gastrointestinal signs
Patients may present with excessive salivation. Dysphagias (difficulty in swallowing) is possible. Nausea and vomiting are reported. Gastric hyperdistention occurs secondary to vagal stimulation. Increased gastric acid output may lead to gastric ulcers. Acute pancreatitis may lead to hyperglycemia. Liver glycogenolysis may occur from catecholamine stimulation. Toxic hepatitis Genitourinary signs Patients have decreased renal plasma flow. Toxin-induced acute tubular necrosis renal failure may occur. Rhabdomyolysis (destruction of striated muscle cells)renal failure may result from venom-induced excessive motor activity. Priapism (persistently erect penis) may occur secondary to cholinergic stimulation. One small study by Bawaskar (1982) found a positive prognostic correlation to the development of cardiac manifestations following scorpion stings. Bawaskar HS, Bawaskar PH. Scorpion sting: update. J Assoc Physicians India Jan. 60:46-55. Medani A.B.

80 Pregnancy signs - Toxin-induced uterine contraction
Hematological signs :Platelet aggregation may occur because of catecholamine stimulation. Disseminated intravascular coagulation with massive hemorrhage may result from venom-induced defibrination. Metabolic signs :Hyperglycemia may occur from catecholamine-induced hepatic glycogenolysis, pancreatitis, and insulin inhibition. Increased lactic acidosis may occur from hypoxia and venom-induced increased lactase dehydrogenase activity. Patients may have an electrolyte imbalance and dehydration from hypersalivation, vomiting, diaphoresis, and diarrhea. Pregnancy signs - Toxin-induced uterine contraction Symptoms predictive of hospital admission Priapism (odds ratio ) Vomiting (odds ratio 15.82) Systolic blood pressure (SBP) greater than 160 (odds ratio 13.38) Temperature greater than 38ºC (odds ratio 3.66) Heart rate greater than 100 beats per minute (odds ratio 3.35) Medani A.B.

81 Symptomology of specific scorpion species
Mesobuthus, Tityus, and Leiurus - Tend to cause severe cardiovascular symptoms Centruroides - Tend to cause neurological symptoms Hemiscorpius - Tend to cause tissue necrosis Generally, most lethal scorpions have an LD50 below 1.5 mg/kg. The average yield per scorpion via electrical excitation of the venom gland for a few species is listed below. Tityus species mg L quinquestriatus mg Buthus species mg Milking the venom gland produces approximately a 4-fold increase in yield amount compared to electrical excitation. Medani A.B.

82 Caulk around roof eaves, pipes and any other cracks into the home.
Control: Scorpions are difficult to control with insecticides alone. Therefore, the first control strategy is to modify the area surrounding a house. Remove all trash, logs, boards, stones, bricks and other objects from around the home. Keep grass closely mowed near the home. Prune bushes and overhanging tree branches away from the house. Tree branches can provide a path to the roof for scorpions. Store garbage containers in a frame that allows them to rest above ground level. Never bring firewood inside the house unless it is placed directly on the fire. Install weather-stripping around loose fitting doors and windows (including the garage door). Plug weep holes in brick veneer homes with steel wool, pieces of nylon scouring pad or small squares of screen wire. Caulk around roof eaves, pipes and any other cracks into the home. Keep window screens in good repair. Make sure they fit tightly in the window frame. Wear protective clothing such as shoes or gloves when working outdoors Check shoes, shake out clothing and equipment left outside prior to use. Medani A.B.

83 Treatment of scorpion poisoning
Because the clinical manifestations and severity of the symptoms vary among patients, individualize management of scorpion stings. Furthermore, frequent patient monitoring allows earlier recognition of the life-threatening problems of scorpion envenomation. Treatment generally consists of moving the patient away from the scorpion and stabilizing the patient's airway and vital signs, followed by administration of antivenin and institution of symptomatic and local treatment. Medani A.B.

84 Local treatment is discussed as follows:
A negative-pressure extraction device (i.e. the extractor) may be useful, although the benefit is unproven. The extractor creates a negative pressure of 1 atm. Apply it to the sting site after incision. Oral extraction is contraindicated. Use ice bags to reduce pain and to slow the absorption of venom via vasoconstriction. This is most effective during the first 2 hours following the sting. Medani A.B.

85 Immobilize the affected part in a functional position below the level of the heart to delay venom absorption. Calm the patient to lower the heart rate and blood pressure, thus limiting the spread of the venom. For medical delay secondary to remoteness, consider applying a lymphatic-venous compression wrap 1 inch proximal to the sting site to reduce superficial venous and lymphatic flow of the venom but not to stop the arterial flow. Only remove this wrap when the provider is ready to administer systemic support. The drawback of this wrap is that it may intensify the local effects of the venom. Medani A.B.

86 Administer local wound care and topical antibiotic to the wound.
Apply a topical or local anesthetic agent to the wound to decrease paresthesia (pins and needles) ; this tends to be more effective than opiates. Administer local wound care and topical antibiotic to the wound. Administer tetanus prophylaxis (e.g.Tetanus toxoid). Administer systemic antibiotics if signs of secondary infection occur. Administer muscle relaxants for severe muscle spasms (e.g. benzodiazepines.) Medani A.B.

87 Use invasive monitoring for patients who are unstable and hemodynamic.
Systemic treatment is instituted by directing supportive care toward the organ specifically affected by the venom.Establish airway, breathing, and circulation (i.e. ABCs) to provide adequate airway, ventilation, and perfusion. Monitor vital signs (e.g. pulse, oximetry; heart rate, blood pressure, and respiratory rate monitor). Use invasive monitoring for patients who are unstable and hemodynamic. Administer oxygen. Medani A.B.

88 Administer intravenous fluids to help prevent hypovolemia from vomiting, diarrhea, sweating, hypersalivation, and insensible water loss from the tropical environment. Perform intubation and institute mechanical ventilation with end-tidal carbon dioxide monitoring for patients in respiratory distress. For hyperdynamic cardiovascular changes, administration of a combination of beta-blockers with sympathetic alpha-blockers is most effective in reversing this venom-induced effect. Avoid using beta-blockers alone because this leads to an unopposed alpha-adrenergic effect. Also, nitrates can be used for hypertension and myocardial ischemia. Medani A.B.

89 For hypodynamic cardiac changes, a titrated monitored fluid infusion with afterload reduction helps reduce mortality. A diuretic may be used for pulmonary edema in the absence of hypovolemia, but an afterload reducer, such as prazosin, nifedipine, nitroprusside, hydralazine, or angiotensin-converting enzyme inhibitors, is better. Inotropic medications, such as digitalis, have little effect, while dopamine aggravates the myocardial damage through catecholaminelike actions. Dobutamine seems to be a better choice for the inotropic (a substance used for inculation) effect. Finally, a pressor such as norepinephrine can be used as a last resort to correct hypotension refractory to fluid therapy. Administer atropine to counter venom-induced parasympathomimetic effects. Medani A.B.

90 Insulin administration in scorpion envenomation animal experiments has helped the vital organs to use metabolic substrates more efficiently, thus preventing venom-induced multiorgan failure, especially cardiopulmonary failure. Unfortunately, no human studies have been conducted. Administer barbiturates and/or a benzodiazepine continuous infusion for severe excessive motor activity. The use of steroids to decrease shock and edema is of unproven benefit. Antivenom is the treatment of choice after stabilization and supportive care. Because of the heterogeneity of venom composition between different scorpion species, one specie’s antivenom will have limited effect on another scorpion specie’s venom. Thus, correct scorpion species identification is a prerequisite for proper antivenom treatment. Medani A.B.

91 For newer scorpion antivenom, the exact dosing has not been established as animal studies treatment amount does not translate into human studies treatment amount. In addition, the quantity to be used is determined by the patient’s clinical severity, symptom evolution, and treatment response. Unfortunately, predicting the patient’s response treatment is difficult, which makes exact antivenom dosing difficult. Furthermore, underdosing will result in limited or no effect, while overdosing increases the side effects and hypersensitivity reactions. The antivenom significantly decreases the level of circulating unbound venom within a few hours. The persistence of symptoms after the administration of antivenom is due to the inability of the antivenom to neutralize scorpion toxins already bound to their target receptors. Thus, symptomatic and supportive treatment is needed with immunotherapy. Medani A.B.

92 General time guidelines for the disappearance of symptoms after antivenom administration are as follows: -Centruroides antivenom: Severe neurologic symptoms reverse in min. Mild-to-moderate neurologic symptoms reverse in min. -Non-Centruroides antivenom: In the first hour, local pain abates (becomes less intense). In 6-12 hours, agitation, sweating, and hyperglycemia abate. In 6-24 hours, cardiorespiratory symptoms abate. Medani A.B.

93 Prpblems associated with antivenin therapy
-While an anaphylaxis reaction to the antivenom is possible, the patient is at lower risk for this than with other antivenoms for other poisonous envenomations if there is a scorpion venom—induced large release of catecholamines. -Animal-derived antivenom increases the risk of hypersensitivity reaction compared to human monoclonal-derived antivenom. -Finally, the larger the dose of antivenom, the greater the change for serum sickness. In a prospective, randomized, double-blind study, Boyer et al compared scorpion-specific F(ab') 2 antivenom (Anascorp, Centruroides [scorpion] immune F(ab) 2 intravenous [equine Anavip], Instituto Bioclon)with placebo (=regime described for pscycological benefit of the patient) in children who developed neurotoxic symptoms following scorpion envenomation.  Neuromotor abnormalities were present in all patients at baseline, and respiratory distress was present in 20%. Beginning 2 hours after treatment, symptom resolution differed significantly in the antivenom group compared with the placebo group. Plasma venom concentrations were undetectable and cessation of the neurologic syndrome occurred within 4 hours in 100% of antivenom recipients compared with 1 placebo recipient (p=0.001). Boyer LV, Theodorou AA, Berg RA, et al. Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med. 2009;360:2090–8 Medani A.B.

94 Thus, the Boyer et al study suggests that scorpion-specific F(ab') 2 antivenom successfully treated the clinical syndrome, reducing the need for concomitant sedation and reducing circulating unbound venom levels for Centruroidesenvenomation.  For Mesobuthus tamulu ( the Indian Red Scorpion) envenomations (Tamapin), horse-derived antivenom has been developed. Natu et al compared the newer antivenom treatment versus the traditional prazosin treatment in their open label study of 81 envenomated patients and found that antivenom decreased clinical recovery time to 4.14 hours +/- 1.6 hours compared to prazosin’s clinical recovery time of hours +/ hours. Natu VS, Kamerkar SB, Geeta K, Vidya K, Natu V, Sane S, et al. Efficacy of anti-scorpion venom serum over prazosin in the management of severe scorpion envenomation. J Postgrad Med. 2010;56(4):275–80.  Medani A.B.

95 Natu et al also found that the antivenom plus prazosin combination group had a recovery time of 3.46 hours +/- 1.1 hours but felt it was comparable to the antivenom group recovery time and recommended that the combination therapy be reserved for patients presenting with pulmonary edema with hypertension. Bawaskar et al compared antivenom plus prazosin versus prazosin in their open label trial of 70 patients with only grade 2 envenomations (beginning of systemic involvement) and found that 91.4% of the combination treatment group had resolution of their clinical symptoms within the 10-hour mark compared to 22.9% in the prazosin treatment group.  Both the Natu and the Bawaskar studies suggest the utility of the new Mesobuthus tamulus antivenom for systemic symptoms envenomations. Bawaskar HS, Bawaskar PH. Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion (Mesobuthus tamulus) sting: randomised open label clinical trial. BMJ. 2011;342:c7136. Medani A.B.

96 A vaccine preparation was tried in experimental animals but was not pursued because of the need to prepare different antigens according to different geographical areas and to different species of scorpions living in the same area. In some cases, be aware that meperidine and morphine may potentiate the venom. Also, the concurrent use of barbiturates and narcotics may add to the respiratory depression in patients who have been envenomated. Medani A.B.

97 Antivenins Class Summary
Composed of venom-specific F(ab’)2 fragments of immunoglobulin G (IgG) that bind and neutralize venom toxins, facilitating redistribution away from target tissues and elimination from the body. Medani A.B.

98 Ixodes holocyclus, commonly known as the Australian paralysis tick, is one of about 75 species of Australian tick fauna and is considered the most medically important. It can cause paralysis by injecting neurotoxins into its host. It is usually found in a 20-kilometre wide band following the eastern coastline of Australia. Within this range Ixodes holocyclus is the tick most frequently encountered by humans and their pets. As this area also contains the majority of Australia's most densely populated regions, incidents of bites on people, pets and livestock are relatively common. Medani A.B.

99 Tarantula hawk Kingdom: Animalia Phylum: Arthropoda Class: Insecta
Order: Hymenoptera Suborder: Apocrita Superfamily: Vespoidea Family: Pompilidae Subfamily: Pepsinae Tribe: Pepsini Medani A.B.

100 Geographical distribution
Worldwide distribution of Tarantula hawks includes areas from India to Southeast Asia, Africa, Australia, and the Americas, where these predatory wasps are also likely to be found. Tarantula hawk species have been observed from as far north as Salt Lake City, Utah in the United States, and south as far as Argentina in South America, with at least 250 species living in South America . Several species of Tarantula hawk are found in the deserts of the southwestern United States, with Pepsis formosa and Pepsis thisbe being common. The two species are difficult to distinguish, but the majority of Pepsis formosa have metallic blue bodies, reddish antennae, which separates them from Pepsis thisbe (both species have bright orange wings that become transparent near the tip). Medani A.B.

101 Toxicity:During the spiders' reproductive season, male tarantulas, which are considerably smaller than females, are usually emaciated from ignoring food while searching for females. The female tarantula hawk thus prefers the much larger female tarantulas and seeks them in their burrows. She captures, stings, and paralyzes the spider, then either drags the spider back into her own burrow or transports her prey to a specially prepared nest where a single egg is laid on the spider’s body, and the entrance is covered. When the wasp larva hatches, it rips a small hole in the spider's abdomen, then plunges into the spider's belly and feeds voraciously, avoiding vital organs for as long as possible to keep it fresh. Medani A.B.

102 After several weeks, the larva pupates
After several weeks, the larva pupates. Finally, the wasp becomes an adult, and tears open the spider's belly to get out. The wasp emerges from the nest to continue the life cycle. Tarantula wasps are "nectarivorous". The consumption of fermented fruit sometimes intoxicates them to the point that flight becomes difficult. While the wasps tend to be most active in daytime summer months, they tend to avoid the very highest temperatures. The male tarantula hawk does not hunt; instead, it feeds off the flowers of milkweeds, western soapberry trees, or mesquite trees. The male tarantula hawk has a behavior called hill-topping, where he sits atop tall plants and watches for females that are ready to reproduce. Medani A.B.

103 Sting The tarantula hawk is relatively docile and rarely stings without provocation. However the sting, particularly of Pepsis formosa, is among the most painful of any insect, but the intense pain only lasts for about 3 minutes. Commenting on his own experience Medani A.B.

104 Poisonous Birds Toxic birds are birds that use toxins to defend themselves from predators. No species of bird is known to actively inject or even produce venom, but some birds are known to be poisonous to touch or eat. These birds usually sequester toxins from animals and plants that they feed on, commonly from poisonous insects. The Africanspur-winged goose is toxic to eat as it sequesters poison in its tissues and bottom, from the blister beetles that it feeds on. Medani A.B.

105 Poisonous Birds Kingdom: Animalia Phylum: Chordata Class: Aves Order:
Passeriformes Family: Pachycephalidae Genus: Pitohui Species: P. dichrous Binomial name Pitohui dichrous Medani A.B.

106 The Hooded Pitohui, Pitohui dichrous is a songbird of New Guinea with black and orange plumage.
This species and its two close relatives, the Variable Pitohui and the Brown Pitohui, were the first documented poisonous birds. A neurotoxin called homobatrachotoxin found in the birds' skin and feathers, causes numbness and tingling in those touching the bird. Medani A.B.

107 Toxicity: Batrachotoxin affects the electrical impulses in nerves and kills by stopping the heart. Jack Dumbacher, the scientist who discovered the toxic nature of the Pitohui in 1989, experienced numbness in the mouth after sucking on a hand that had been injured by a Hooded Pitohui—clearly there was only a minute amount of batrachotoxin on his injured hand. Testing soon revealed, however, that birds in some areas have more toxin than others, with some being almost harmless while others are obnoxious to even touch. Common quail are also known to be toxic due to coturnism at certain stages in their migrations. Milius, Susan Poison Source: Toxic Birds May Get Chemical from Beetle. Science News Online 166(19)) Medani A.B.

108 Poisonous Insects Many species of arthropods (insects, arachnids and others) regularly or occasionally bite or sting human beings. Insect saliva contains anticoagulants and enzymes that cause local irritation and allergic reactions.[1] Insect venoms can be delivered by their stingers, which often are modified ovipositors, or by their mouthparts. Insect, spider and scorpion venom can cause serious injury or death. Dipterans account for the majority of insect bites, while Hymenopterans account for the majority of stings. Among arachnidsspider bites are the most common. Arthropods bite or sting humans for a number of reasons including feeding or defense. Arthropods are major vectors of human disease, with the pathogens typically transmitted by bites. Medani A.B.

109 black fly (sometimes called a buffalo gnat, turkey gnat, or white socks) is any member of the family Simuliidae of the Culicomorphainfraorder. They are related to the Ceratopogonidae, Chironomidae, and Thaumaleidae. Medani A.B.

110 Horse-flies are biting and bloodsucking members of the family Tabanidae. They are true flies in the insect order Diptera that have only one pair of membranous wings. Horse-flies are often large but agile in flight. They prefer to fly in sunlight, avoiding dark and shady areas, and are inactive at night. They are found all over the world except for some islands and the polar regions. Medani A.B.

111 Deer flies are a genus of horse-flies (Tabanidae)
Deer flies are a genus of horse-flies (Tabanidae). They are smaller than wasps, and have coloured eyes and dark bands across their wings. While female deer flies feed on blood, males instead collect pollen. When feeding, females use knife-like mandibles and maxillae to make a cross-shaped incision and then lap up the blood. Their bite can be painful, but many bites are not noticed at the time, especially if the victim is distracted. Allergic reaction from the saliva of the fly can result in further discomfort and health concerns. Pain and itch are the most common symptoms, but more significant allergic reactions can develop Medani A.B.

112 Tsetse are crudely similar to other large flies, such as the housefly, but can be distinguished by various characteristics of theiranatomy, two of which are easy to observe. Tsetse fold their wings completely when they are resting so that one wing rests directly on top of the other over their abdomen. Tsetse also have a long proboscis, which extends directly forward and is attached by a distinct bulb to the bottom of their head. Medani A.B.

113 Stomoxys calcitrans is commonly called the stable fly, barn fly, biting house fly, dog fly, or power mower fly.Unlike most members of the family Muscidae, Stomoxys calcitrans ('sharp mouth' + 'kicking') and others of its genus suck blood from mammals. Now found worldwide, the species is considered to be of Eurasian origin. Medani A.B.

114 Ceratopogonidae, or biting midges, are a family of small flies (1–4 mm long) in the order Diptera. They are also known as no-see-ums, midgies, sand flies, punkies, and others in North America, and sandflies in Australia. They are closely related to theChironomidae, Simuliidae (or black flies), and Thaumaleidae. They are found in almost any aquatic or semiaquatic habitat throughout the world, as well as in mountain areas. Females of most species are adapted to suck blood from some kind of hostanimal. Culicoides, Forcipomyia (Lasiohelea), and Leptoconops suck vertebrate blood. SomeAtrichopogon and Forcipomyia species are ectoparasites on larger insects. Dasyhelea species feed exclusively on nectar. Species in other genera are predatory on other small insects. Larvaeare always found in some damp location, such as under bark, in rotten wood, compost, mud, stream margins, tree holes, or water-holding plants (i.e., phytotelmata). Medani A.B.

115 Mosquitoes are small, midge-like flies which compose the family Culicidae. Females of most species are ectoparasites, whose tube-like mouthparts (called a proboscis) pierce the hosts' skin to consume blood. The word "mosquito" (formed by mosca and diminutive ito) isSpanish for "little fly. Thousands of species feed on the blood of various kinds of hosts, mainly vertebrates, including mammals, birds,reptiles, amphibians, and even some kinds of fish. Some mosquitoes also attack invertebrates, mainly arthropods. Though the loss of blood is seldom of any importance to the victim, the saliva of the mosquito often causes an irritating rash that is a serious nuisance. Much more serious though, are the roles of many species of mosquitoes as vectors of diseases. In passing from host to host, some transmit extremely harmful infections such as malaria, yellow fever, west nile virus, dengue fever, filariasis, and other arboviruses, rendering it the deadliest animal in the world. Medani A.B.

116 The Oestridae are a family of flies variously known as bot flies, warble flies, heel flies, gadflies, and similar names. Their larvae are internal parasites of mammals, some species growing in the host's flesh and others within the gut. The human botfly, Dermatobia hominis, is the only species of bot fly known to parasitize humans routinely, though other species of fly do cause myiasis in humans. Medani A.B.

117 Crustacean There are some 70,000 species of crustaceans and, until recently, it seemed that all of them were venom-free. The only exceptions, Speleonectes tulumensis live in coastal caves, which are connected to the ocean by underground tunnels. The remipedes were first discovered in the 1980s, and named after the Latin for “oar-footed” because of their many pairs of swimming legs. Observant scientists soon noticed that on either side of their head, behind their jaws, they had a pair of fangs —sharp, hollow-tipped and connected to glands. Others noticed them eating other crustaceans in the wild. Connecting the dots, it looked as if these creatures were venomous. Medani A.B.

118 Cephalopods A cephalopod is any member of the  molluscan class Cephalopoda "head-feet". These exclusively marine animals are characterized by bilateral body symmetry, a prominent head, and a set of arms ortentacles (muscular hydrostats) modified from the primitive molluscan foot. Fishermen sometimes call them inkfish, referring to their common ability to squirt ink. The study of cephalopods is a branch of malacology known as teuthology. Cephalopods became dominant during the Ordovician period, represented by primitive nautiloids. The class now contains two, only distantly related, extant subclasses: Coleoidea, which includes octopuses, squid, and cuttlefish; and Nautiloidea, represented by Nautilusand Allonautilus. In the Coleoidea, the molluscan shell has been internalized or is absent, whereas in the Nautiloidea, the external shell remains. About 800 living species of cephalopods have been identified. Two important extinct taxa are the Ammonoidea (ammonites) andBelemnoidea (belemnites). Medani A.B.

119 Cnidaria Box jellyfish (class Cubozoa) are cnidarian invertebrates distinguished by their cube-shaped medusae. Some species of box jellyfish produce extremely potent venom: Chironex fleckeri, Carukia barnesi and Malo kingi. Stings from these and a few other species in the class are extremely painful and can be fatal to humans. In Australia, fatalities are most often perpetrated by the largest species of this class of jellyfish, Chironex fleckeri.  Medani A.B.

120 Venomous fish  produce venom harmful to humans. The 1200 or so species of venomous fish include the  stonefish, lionfish,scorpionfish, stargazer, weever and toadfish(Daector and Thalassophryne). Medani A.B.

121 MAMMALS The European mole (Talpa europaea) is a mammal of the order Soricomorpha. It is also known as the common mole and thenorthern mole. This mole lives in an underground tunnel system, which it constantly extends. It uses these tunnels to hunt its prey. Under normal conditions the displaced earth is pushed to the surface, resulting in the characteristic molehills. It feeds mainly on earthworms, but also on insects, centipedes and even mice and shrews. Its saliva contains toxins which paralyze earthworms in particular. It has a cylindrical body and is around 12 cm (5 inches) long. Females are typically smaller than males. The eyes are small and hidden behind fur, while the ears are just small ridges in the skin. The fur is usually dark grey, but the actual range of colors is larger, as due to the subterranean habits there is no disadvantage in having off-colored fur. European moles with white, light grey, tan, taupe, andblack fur have all been reported. Mukherjee, Sarah (25 January 2008). "Searching for nature's tunnellers". BBC News. Retrieved 4 May 2010. Medani A.B.

122 Platypus venom The platypus is one of the few mammals to produce venom. Males have a pair of spurs on their hind limbs which secrete venom that is only seasonally active to breeding season, supporting the theory that the use of venom is for competition of mates only, not protection. While the spur remains available for defense outside of breeding season, the platypus's venom gland lacks secretion.[1] While the after effects are described as excruciatingly painful, this venom is not lethal to humans. Medani A.B.

123 Elliot's short-tailed shrew (Blarina hylophaga) is a small, slate grey, short-tailed species of shrew.Like other shrews, this species is insectivorous, its diet consisting primarily of beetles and slugs, along with other insects, spiders, and earthworms. They may also eat a small quantity of plants and fungi, and have been reported to eat North American deermice on occasion. Predators include owls, hawks, snakes, and swift foxes.[3] Elliot's short-tailed shrew is generally a solitary, nocturnal animal, spending the day sleeping in burrows in soft soil or leaf litter. The burrows may contain nests made from grass or leaves, and are surrounded by a network of trackways that the shrew uses while hunting for prey. They have been reported to travel across home ranges of anything from 0.06 to 0.55 hectares (0.15 to 1.36 acres), and to travel mostly around dawn and sunset. Having poor eyesight, they hunt primarily by means of echolocation. They are active throughout the year, and do not hibernate. Thompson, C.W. et al. (2011). "Blarina hylophaga (Soricomorpha: Soricidae)". Mammalian Species 43 (1): 94–103. Medani A.B.

124 The Eurasian water shrew (Neomys fodiens), known in the United Kingdom as the water shrew, is a relatively large shrew, up to 10 cm (4 in) long, with a tail up to three-quarters as long again. It has short, dark fur, often with a few white tufts, a white belly, and a few stiff hairs around the feet and tail. It lives close to fresh water, hunting aquatic prey in the water and nearby. Its fur traps bubbles of air in the water which greatly aids its buoyancy, but requires it to anchor itself to remain underwater for more than the briefest of dives. Like many shrews, the water shrew has venomous saliva, making it one of the few venomous mammals, although it is not able to puncture the skin of large animals such as humans. Highly territorial, it lives a solitary life and is found throughout the northern part of Europe and Asia, from Britain to Korea. Medani A.B.

125 The northern short-tailed shrew (Blarina brevicauda) is the largest shrew in the genus Blarina, and occurs in the northeastern region of North America.It is a semifossorial, highly active, and voracious insectivore and is present in a variety of habitats. It is notable in that it is one of the few venomous mammals. The specific epithet, brevicauda, is a combination of the Latin brevis and cauda, meaning "short tail". The saliva of the northern short-tailed shrew contains a kallikrein-like protease, used to paralyze and subdue its prey. The toxin is strong enough to kill small animals, up to sizes somewhat larger than the shrew itself, and results in painful bites to humans who attempt to handle the shrew.The venomous saliva is secreted from submaxillary glands, through a duct which opens at the base of the lower incisors, where the saliva flows along the groove formed by the two incisors, and into the prey. The toxin is very similar in structure to the one used by the Mexican beaded lizard (Heloderma horridum), but evolved independently, however, from the same precursor protein. Kita, Masaki; Nakamura, Yasuo; Ohdachi, Satoshi D.; Oba, Yuichi; Yoshikuni, Michiyasu; Kido, Hiroshi; Uemura, Daisuke (2004), "Blarina toxin, a mammalian lethal venom from the short-tailed shrew Blarina brevicauda: Isolation and characterization", PNAS 101 (20): 7542–7547, Medani A.B.

126 The Southern short-tailed shrew's diet consists of insects, annelids, hypogeous fungi, slugs and snails, centipedes, and spiders. Known predators include snakes, hawks, owls, and foxes. It has been known to store snails for the winter.[citation needed] The saliva isvenomous and is injected into the wounds of its prey by the teeth. Its venom is strong enough to kill mice, but is not lethal to humans,though it causes severe pain. McCay, T.S. (2001). "Blarina carolinensis". Mammalian Species: Number 673: pp. 1–7. Medani A.B.

127 The Cuban solenodon or almiqui (Solenodon cubanus), is a  species of soricomorph endemic to Cuba. It belongs to the familySolenodontidae along with a similar species, the Hispaniolan solenodon (Solenodon paradoxus). The solenodon is unusual among mammals in that its saliva is venomous. This species has a varied diet. At night, they search the forest floor litter for insects and other invertebrates, fungi, and roots. They climb well and feed on fruits, berries, and buds, but have more predatory habits, too. With venom from modified salivary glands in the lower jaw, they can kill lizards, frogs, small birds, or even rodents. They seem not to be immune to the venom of their own kind, and cage mates have been reported dying after fights. Medani A.B.

128 The Hispaniolan solenodon (Solenodon paradoxus), also known as the Dominican solenodon, Haitian solenodon or agouta, is asolenodon found only on Hispaniola, the island shared by Haiti and the Dominican Republic. It was first described by Brandt in A similar but smaller species, Marcano's solenodon (S. marcanoi), once lived on the island, but became extinct after European colonization. All solenodon species belong to order Soricomorpha andfamily Solenodontidae. Medani A.B.

129 A hedgehog is any of the spiny mammals of the subfamily Erinaceinae, in the order Erinaceomorpha. There are seventeen species of hedgehog in five genera, found through parts of Europe, Asia, Africa and New Zealand (by introduction). There are no hedgehogs native to Australia, and no living species native to the Americas. Hedgehogs share distant ancestry with shrews (family Soricidae), withgymnures possibly being the intermediate link, and have changed little over the last 15 million years.[2] Like many of the first mammals, they have adapted to a nocturnal way of life.[3] Hedgehogs' spiny protection resembles that of the unrelated rodent porcupines and monotreme echidnas. Medani A.B.

130 Slow lorises are a group of several species of nocturnal strepsirrhine primates which make up the genus Nycticebus. Found inSoutheast Asia and bordering areas, they range from Bangladesh and Northeast India in the west to the Sulu Archipelago in thePhilippines in the east, and from Yunnan province in China in the north to the island of Java in the south. Although many previous classifications recognized as few as a single all-inclusive species, there are now at least eight that are considered valid: the Sunda slow loris (N. coucang), Bengal slow loris (N. bengalensis), pygmy slow loris (N. pygmaeus), Javan slow loris (N. javanicus), Bornean slow loris(N. menagensis), N. bancanus, N. borneanus, and N. kayan. The group's closest relatives are the slender lorises of southern India and Sri Lanka. Their next closest relatives are the African lorisids, the pottos, false pottos, and angwantibos. A 1984 study of the Sunda slow loris indicated that its diet consists of 71% fruit and gums, and 29% insects and other animal prey. Medani A.B.

131 Reptile Venomous snakes are species of the suborder Serpentes that are capable of producing venom, which is used primarily for immobilizing prey and defense mostly via mechanical injection by fangs. Common venomous snakes include the families Elapidae, Viperidae, Atractaspididae, and some of the Colubridae. The toxicity of them is mainly indicated by murine LD50, while multifarious factors are considered to judge their potential danger to humans. Medani A.B.

132 Cobra may refer to: Naja, also known as typical or "true" cobras (known for raising the front part of the body and flattening the neck in a warning signalwhen alarmed), a group of elapids found in Africa and Asia. They include over 20 species, including Naja nivea, the cape, a moderately sized, highly venomous cobra inhabiting a wide variety of biomes across southern Africa; Cleopatra's "asp" (the Egyptian cobra, Naja haje); and the Asiatic spectacled cobra Naja naja and monocled cobra, Naja kaouthia. Spitting cobras, a subset of Naja species with the ability to squirt venom from their fangs in self-defense Hemachatus haemachatus, ringhals, rinkhals or ring-necked spitting cobra, a species of the Elapidae found in Africa Any member of the genus Boulengerina, the water cobras, a group of Elapidae found in Africa (now regarded as species in the genusNaja) Paranaja multifasciata, the burrowing cobra, an African species of the Elapidae (now regarded as a species of Naja) Any member of the genus Aspidelaps, the shield African genus in the Elapidae Any species of Pseudohaje, the tree cobras, a genus of African Elapidae Ophiophagus hannah, the king cobra, an elapid found in parts of India and southern Asia Micrurus fulvius, the American cobra or eastern coral snake, a species of the Elapidae found in the southeastern United States and in parts of Cuba. Hydrodynastes gigas, the false water cobra, a mildly venomous member of the family Colubridae. It is indigenous to parts of South America and forms a hood if disturbed, though the hood is longer and narrower than those of "true" cobras in the Elapidae. Medani A.B.

133 The Gila monster (Heloderma suspectum), is a species of venomous lizard . Although the venom is a neurotoxin as toxic as that of a coral snake, H. suspectum produces only small amounts. The Gila monster's bite is not fatal to healthy adult humans. No reports of fatalities have been confirmed after 1939, and those recorded prior to that year are possibly iatrogenic, or resulting from attempts to treat the bite itself. The Gila monster can bite quickly (especially by swinging its head sideways) and hold on tenaciously and painfully. If bitten, the victim may need to fully submerge the attacking lizard in water to break free from its bite. Symptoms of the bite include excruciating pain, edema, and weakness associated with a rapid drop inblood pressure. Gila Monster Fact Sheet". National Zoological Park. Retrieved  Medani A.B.

134 The Mexican beaded lizard (Heloderma horridum) is the most famous of the four species of venomous beaded lizards found principally in Mexico and southern Guatemala. It and its congener the Gila monster (Heloderma suspectum) are the only lizards known to have evolved an overt venom delivery system. The beaded lizard is larger than the Gila monster, but has duller coloration, black with yellowish bands of differing width depending on the species. As it is a specialized predator that feeds primarily upon eggs, the primary use of its venom is still a source of debate among scientists. However, this venom has been found to contain several enzymesuseful for manufacturing drugs in the treatment of diabetes, and research on the pharmacological use of its venom is ongoing. Medani A.B.

135 Monitor lizard is the common name of several large lizard species, comprising the genus Varanus. They are native to Africa, Asia andOceania, but are now found also in the Americas as an invasive species. Monitor lizards have long necks, powerful tails and claws, and well-developed limbs. The adult length of extant species ranges from 20 cm (7.9 in) in some species, to over 3 m (10 ft) in the case of the Komodo dragon, though the extinct varanid known as megalania (Varanus priscus) may have been capable of reaching lengths of as much as 7 m (23 ft). Most monitor species are terrestrial, but arboreal and semiaquatic monitors are also known. While most monitor lizards are carnivorous, eating eggs, smaller reptiles, fish, birds and small mammals, some also eat fruit and vegetation, depending on where they live Medani A.B.

136 LD50, mostly on rodents, is a common indicator of snakes' toxicity whose level is higher with a smaller resultant value. There have been numerous studies on snake venom with a variability of potency estimatesThere are four methods in which the LD50 test is conducted, which are injections to subcutis (SC), vein (IV), muscle (IM or IC), and peritoneum (IP). The former (SC) is most applicable to actual bites as only vipers with large fangs, such as large Bitis, Bothrops or Crotalus specimens, would be able to deliver a bite that is truly intramuscular, and snakebites rarely cause IV envenomation. Testing using dry venom mixed with 0.1% bovine serum albumin in saline, gives more consistent results than just saline alone. Belcher's sea snake (Hydrophis belcheri), which many times is mistakenly called the hook-nosed sea snake (Enhydrina schistosa), has been erroneously popularized as the most venomous snake in the world, due to Ernst and Zug's published book "Snakes in Question: The Smithsonian Answer Book" from Prominent venom expert Associate Professor Bryan Grieg Fry has clarified the error: "The hook nosed myth was due to a fundamental error in a book called 'Snakes in question'. In there, all the toxicity testing results were lumped in together, regardless of the mode of testing (e.g. subcutaneous vs. intramuscular vs intravenous vs intraperitoneal). As the mode can influence the relative number, venoms can only be compared within a mode. Otherwise, its apples and rocks. Belcher's sea snake's actual LD50 (recorded only intramuscularly) is 0.24 mg/kg] and 0.155 mg/kg,.  Studies on . and human cardiac cell culture shows that venom of the inland taipan, drop by drop, is the most toxic among all snakes. Venom Immunochemistry, Pharmacology and Emergency Response (VIPER) Institute. Frequently Asked Questions -What is the most venomous snake?. "Many experts answer that it is the Inland Taipan of Australia, because its drop-by-drop concentration of venom has great potency when measured by its ability to kill rodents" . University of Arizona. Retrieved October 14, 2013. Medani A.B.

137 Myriapoda is a subphylum of arthropods containing millipedes, centipedes, and others. The group contains over 13,000 species, all of which are terrestrial. Although their name suggests they have myriad (10,000) legs, myriapods range from having over 750 legs (the millipede Illacme plenipes)  to having fewer than ten legs. The fossil record of myriapods reaches back into the late Silurian, although molecular evidence suggests a diversification in the Cambrian Period and Cambrian fossils exist which resemble myriapods.  The oldest unequivocal myriapod fossil is of the millipede Pneumodesmus newmani, from the late Silurian P. newmani is also important as the earliest known terrestrial animal. The phylogenetic classification of myriapods is still debated. Garwood, Russell J.; Edgecombe, Gregory D. (September 2011). "Early Terrestrial Animals, Evolution, and Uncertainty". Evolution: Education and Outreach (New York:Springer Science+Business Media) 4 (3): 489–501. Medani A.B.

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