Chapter V - Medical Biology - course content Ecology 2023-2024 (2).pdf

Excercise 5. Topic: Selected organisms of medical significance. Glossary: Alkaloids - alkaline chemical compounds containing nitrogen. Allergen - an antigen that triggers an allergic reaction in sensitive people. Anaphylaxis - a severe, life-threatening, systemic or generalized type I hypersensitivi...

Excercise 5. Topic: Selected organisms of medical significance. Glossary: Alkaloids - alkaline chemical compounds containing nitrogen. Allergen - an antigen that triggers an allergic reaction in sensitive people. Anaphylaxis - a severe, life-threatening, systemic or generalized type I hypersensitivity reaction (immediate hypersensitivity). Antibiotics - natural, secondary metabolites produced by microorganisms that have the ability to inhibit growth or destruct other microorganisms (bacteria, fungi, protozoa). Arthrospores – fungal exospores formed as a result of fragmentation of hypha or pseudohypha. Bioaerosol – very small airborne (0.001 to 100 μm)particles (biotic and abiotic) released from terrestrial and marine ecosystems into the atmosphere. Blastospores – fungal exospores usually formed singly by budding from mycelium stem cells. Cardiotoxins – toxins causing diseases of the heart and the circulatory system. Chlamydospores – thick-walled spherical or cylindrical spores formed in hunger conditions or in the normal life cycle of some fungi. Disseminated mycosis – the occurrence of multiple loci of invasion in the organism with the presence of fungi in the blood. Endogenous mycosis – mycosis caused by a fungal strain belonging to the host's natural microbiota; e.g. by an excessive increase in the fungal population in the gastrointestinal tract after long-term antibacterial therapy. Endospores – fungal spores formed inside the spore-forming cell. Exogenous mycosis - mycosis caused by a fungal strain originating from the external environment; e.g. by inhaling spores into the lungs or penetrating of the mycelium elements through damaged skin. Exospores – fungal spores formed outside the spore-forming cell. Fruiting body – mycelium product made of clumpy hyphae of pseudogeneous tissue; produces spores. Fungemia– the presence of fungi in the blood. Glycosides – organic compounds made of sugar and a glycone parts. Hepatotoxins – toxinsthat damage the liver. Hyphae –a group of filamentous which are comprised of hypha - the long filamentous branches found in fungi and actinobacteria. Hyphae are important structures required for growth and are referred to mycelium. Immunotoxins– toxins that adversely affect the organism's immunity. Monofocal mycosis – the presence of a fungal strain within one organ / tissue. Multifocal mycosis – thepresence of a fungal strain in several organs / tissues. Mycelium – thallus of fungi. Mycosis – plant,animal and human disease caused by microscopic pathogenic fungi. Nephrotoxins – toxins damaging the kidneys. Neurotoxins – toxins that cause damage to the central nervous system. Opportunistic mycosis – mycosis developing in people with severely reduced immunity. Phytotoxins – fungi-derived compounds toxic to plants. Pseudohyphae – a group of cells formed in yeasts by budding and lengthening to filamentous forms; they lie one behind the other, but do not have a common wall, unlike hyphae Spores – single- or multicellular cells used for fungi (also some microorganisms and plants) reproduction; arising as a result of mitotic divisions (asexual spores) or meiotic divisions (sexual spores). Thallus – vegetative body of the organism, that lacks differentiation into distinct parts. Zootoxins – a toxic substance of animal origin Mycotoxins - compounds of fungal origin toxic to animals and humans Fungi Fungi belong to heterotrophic organisms (they do not have chloroplasts), they live saprophytically or parasitically. Their thalluses consist of filamentous, vegetative cells called hyphae. The organisms reproduce asexually by various spores, and sexually by isogamy, anisogamy and oogamy. Many fungi occur not as hyphae but as unicellular forms called yeasts, which reproduce vegetatively by budding. Fungi are one of the most numerous taxonomic units, accounting for about 1.5 million species in the world, including both microscopic fungi and Macromycetes (mushrooms).Fungi can cause diseases affecting people, animals and plants. It is estimated that about 300 species are potentially pathogenic to humans. Diseases caused by fungi: 1. Allergic diseases - hypersensitivity to fungal antigens, e.g. spores inhaled with air. 2. Mycoses - diseases of plants, animals and humans caused by microscopic pathogenic fungi. 3. Mycotoxicosis - acute or chronictoxicological syndrome caused by the consumption of fungal toxins a) from microscopic fungi, usually moulds, contaminating food; "mycotoxicoses"; b) alkaloids of Claviceps purpurea sclerotium (ergot) - human ergotism; c) present in consumed fruiting bodies of poisonous mushrooms. Allergic diseases – inhaled allergens Allergic diseases constitute a growing medical problem in developed countries and concern about 30% of people. Of the inhaled allergens, the fungal spores occupy the third place in terms of frequency after grass pollens and other dust allergens (dust mites, cockroaches, mold, pollen, pet hair, flaky epidermis, feathers). The air is an important reservoir of potentially pathogenic fungi for humans. Over 80 genuses of fungi can cause allergy symptoms in humans; those most important from the clinical point of view are Alternaria, Aspergillus, Cladosporium, Mucor, PenicilliumandRhizopus. One of the factors that determine allergenicity of fungal spores is their size. Depending on the size, the elements of bioareosol (including fungal spores) can reach particular parts of the upper and/or lower respiratory tract, causing characteristic symptoms: grass pollen, large fungal spores (e.g. Alternaria sp.) are retained in the nasopharyngeal cavity - they can cause irritation of the nose and eyes, hay fever; spores of such fungi as Cladosporium sp., Mucor sp. or Rhizopus sp. are retained in the bronchi - they may be associated with the development of bronchitis / alveolitis, as well as with the etiopathogenesis of bronchial asthma; the majority of bacteria and very small fungal spores (e.g. Aspergillus sp., Penicillium sp.) reach the bronchioles and alveoli; they cause allergic alveolitis and bronchial asthma. Fungi (spores, morphic elements of mycelium) present in the atmospheric air, apart from allergic reactions,can also cause mycoses, most often in immunocompromised people. Mycoses can be divided based on the origin of the etiological factor and location in the human body; division for clinical use (Figure 1). Figure 1. Diagram of the division of fungal infections. Mycoses from the point of view of the diagnosis of the etiological factor can be further divided into those that are caused by yeasts, by moulds and dermatophytes (fungi groups taking into account morphological differences). Potentially pathogenic yeasts: Yeasts are quite heterogeneous group both morphologically and taxonomically. Their common feature is asexual reproduction in the form of budding. Until recently, this group was divided into: - true yeasts, i.e. fungi representing the phylum Ascomycota, reproducing asexually by budding, and reproducing sexually with forming ascospores; - yeast-like fungi, i.e. fungi reproducing asexually by budding and representing both the phylumAscomycota (for which no sexual reproduction was found) and Basidiomycota (reproducing sexually by basidiospores). Candida albicans On the Sabouraud medium, the colonies are cream-colored, glossy, usually smooth, wrinkled with age,of yeastlike smell.Budding cells are (sub)spherical, pseudohyphae are present, with blastoconidia (blastospores) in dense grapelike arrangement. Dark, spherical chlamydospores mostly terminal, often on a slightly swollen subtending cells. Germinating blastospores in the presence of serum, especially the human serum, form short pseudohyphae - the socalled “germ tubes”. Pathogenicity: An opportunistic pathogen in patients with impaired immunity. The oesophageal candidiasis (candidosis) is one of the most common symptoms of acquired immune deficiency syndrome (AIDS) and is considered an indicator disease of HIV infectionC. albicans is the most common aetiological factor of systemic and disseminated mycoses. Candida tropicalis Colonies cream-coloured, off-white, soft, glossy, with slightly convex centre, smooth and creamy or wrinkled near the margin. Budding cells ellipsoidal. Pseudomycelium (pseudohyphae) abundant, consisting of long, poorly branched elements, often narrowing towards a sterile apex; oval or circular blastospores arranged in small groups around the middle of each cellular element. Pathogenicity: An opportunistic pathogen in patients with impairedimmunity. Rhodotorula rubra / mucilaginosa Colonies coral red to pink (salmon-coloured), glossy, smooth or rough, soft, mucous. Budding cells ellipsoidal, unipolar; it does not form hyphae or pseudohypahe. It synthetizes and accumulates carotenoids, hence the colour of the colonies. Pathogenicity: It may cause systemic and disseminatedmycoses in patients with immunosuppression. Geotrichum candidum Colonies white to cream-coloured, smooth, not glossy, flat or with cottony aerial mycelium and somewhat fimbriate margin. In the course of the growing process, colonies become fluffy. Expanding hyphae often with di- or trichotomous branching;. Lateral branches soon disarticulating into short-cylindrical cells which are slightly inflated. It forms vegetative cells, true hyphae and arthrospores (arthroconidia), sometimes it forms blastospores and pseudohyphae. Some strains are used in food technology. Pathogenicity:Geotrichosisof the skin, nails, digestive tract, the respiratory and reproductive systemsin patients with immunosuppression. Case I Patient: 3-month-old boy Symptoms: the child is restless, reluctant to take in food; visible changes in the mouth, on the tongue, on the palate, extensive white-cream, soft coatings (a few millimetres in diameter), after removal of the coating the inflamed ground appears in the form of erythema or bleeding erosion. Diagnostics: an oral swab was collected. Photo by. K. Góralska Culture on the Sabouraud medium: cream-colored colonies with a smooth edge, do not grow into the medium, smooth and shiny, with the characteristic smell of yeast. The direct preparation shows pseudohyphae and numerous blastospores that form clusters around pseudohyphae. Diagnosis: candidiasis of the oral cavity caused by Candida albicans. Mould fungi: Alternaria alternata and Cladosporium spp. So-called outside-home fungi: colonize superficial layers of soil, plant debris. The peak of the sporulation season for the genus Alternaria falls in July and August/September. Spores of these fungi are large, multicellular, so-called dry;their release to the environment is passive, dependent on meteorological factors, particularly on wind speed. Alternaria spore allergens are the most common cause of allergic rhinitis and asthma among fungal allergens. The concentration of Alternaria alternata spores with a value of 100 in 1m3 of the air is considered a threshold concentration responsible for the occurrence of disease symptoms in people allergic to this agent in Poland.Alternaria spp. is becoming an increasingly recognized pathogen in patients with reduced immunity. Skin changes are the most commonly observed signs, however, pneumonia, asthma, sinusitis may also occur. The level of a daily concentration of Cladosporium spores in 1m3 of the air varies considerably throughout the year, from zero to several thousand spores. The presence of 3000 Cladosporium herbarum spores in 1m3 of the air is considered to be the concentration responsible for the occurrence of allergic disease symptoms in people allergic to this agent. The season of the most abundant sporulation of the genus Cladosporium, and thus the most severe symptoms in people who are allergic, covers the period from May/June to August. It is worth noting that the periods of grass pollination coincide with the peak of sporulation of fungi of the genus Cladosporium and Alternaria. Aspergillus fumigatus A saprophytic species, widely distributed in the environment. It grows at 37 ° C - 50 ° C (conidia survive up to70°C - temperature occurring in composters). Forms hyphae and conidiophores withsmall spores(diameter of 2-3 m)which spread easily in the airand are the most common aetiological factor of aspergillosis. A. fumigatus belongs to opportunistic pathogens (it does not cause mycosis in people with normal immunity), which in non-immunocompetent persons may cause, among others, aspergillosis of the lungs and allergic respiratory diseases (e.g. alveolitis allergica). Aspergillus niger, Penicillium spp. Spores of these fungi are commonly found in the atmospheric air. These species belong to the so-called indoor fungi that thrive in the microenvironment of enclosed spaces, with high humidity, limited ventilation and poor access to light. Their spores are present in the air, usually in similar amounts throughout the year. In the external environment, the highest concentrations of spores are recorded in spring and winter, both in urban and rural areas. Phytophthora infestans - potato late blight It is a microscopic fungus which causes root rot of a wide variety of plant species including potatoes. Infection often results in the death of a plant, with earlier symptoms including wilting, yellowing and darkening of stems, leaves and roots. The effects of Phytophthora infestans in Ireland in 1845-57 were one of the factors which caused over one million people to starve to death and forced another two million to emigrate from the affected countries (the Great Irish Famine). Case II Patient: 71-year-old man Symptoms: the patient was admitted to a dermatological ward with symptoms on the skin (around the ankle of the left leg) in the form of erythema and scaly foci with a diameter of Photo by K. Góralska about 5 cm. An immunocompetent patient with no underlying disease, negative HIV test. Diagnostics: swab and scrapings were taken from the skin lesions, cultures were carried out on a microbiological medium. Culture on the medium: suede colonies, mealy, grey-olive colour. In the microscopic preparation large, pale brown club-shaped conidia with a thick, uneven wall and numerous transverse and longitudinal or oblique septa are visible. At the top of the hypha, the spores occur singly or in chains. Diagnosis: skin lesions caused by Alternaria alternata. Mycotoxins The term “mycotoxins” was first introduced in 1962 after an occurrence of mass deaths of turkeys on poultry farms in England in 1960. The first identified mycotoxin derived from Aspergillus flavus and was classified in the aflatoxin group. Currently, about 400 types of mycotoxins are known. Mycotoxins are secondary metabolites of microscopic fungi that have toxic effects on animals (including humans), plants and bacteria. They can be stored as endotoxins in mycelium and conidia or also secreted as exotoxins into the medium. They cause contamination of food industry products, forage and food of animal origin. The ability to produce mycotoxins is a natural feature of many mould fungi; most frequently they are produced by species of the genera Penicillium, Aspergillus and Fusarium. Mycotoxins are characterized by a low molecular weight and good solubility in water. Classification of fungal metabolites: - zootoxins - toxic to animals and humans – mycotoxinssensu stricte (Table 1); - phytotoxins - toxic to plants; - antibiotics - toxic to microorganisms (bacteria, fungi, protozoa).Table 1. Mycoxins produced by fungi (according to Grajewski 2006). Genus Mycoxin Aspergillus Aflatoxin B1, G1, M1, ochratoxin A, sterigmatocystin, cyclopiazonic acid Penicillium Ochratoxin A, citrinin, patulin, cyclopiazonic acid, penitrem A Fusarium Trichothecenes (e.g., deoxynivalenol, nivalenol, T-2 toxin, HT-2 toxin, diacetoxyscirpenol), zearalenone, fumonisins, moniliformine Alternaria Tenuazonic acid, alternariol, alternariol methyl ether Mycotoxins showing: carcinogenic, cytotoxic, embryotoxic, teratogenic and mutagenic activity (Table 2). Table 2. Effects of mycotoxins on the human body (according to Grajewski 2006). Potential action Mycotoxin Carcinogenic Aflatoxins, ochratoxin A, fumonisins Mutagenic Aflatoxins, sterigmatocystin Embryotoxic and teratogenic Ochratoxin A Weakening of the immune system Aflatoxins, ochratoxin A Mycotoxicosis is an acute or chronic poisoning caused by the consumption of fungal toxins. Examples of mycotoxicoses in humans: - ergot poisoning – ergotism (see the section on Claviceps purpureaalkaloids); - yellow rice disease –the nervous system palsy and paralysis (similar to beriberi) - caused by the metabolites of fungi of the genus Penicillium (citreoviridin, luteoscirin, islanditoxin, citrinin and others); - toxic dietary leukaemia –the nervous system palsy and the hematopoietic system dysfunction (mortality 60%) - caused by the metabolites of fungi of the genus Fusarium, among others: F. sporotrichioides and F. poae (trichothecenes, predominantly T-2 toxin); - endemic Balkan nephropathy – severe kidney disease - the cause is ochratoxin A; - liver cancer – long-term consumption of aflatoxin-containing peanuts. The accumulation of mycotoxins in food products is related to the so-called post-harvest diseases of cereal grains, oil plants, fruits and vegetables. Moulding of agricultural productsleads to their contamination with mycotoxins, which when consumed with food pose a threat to human and animal health (Figure 2). Fungal metabolites present in the fodder adversely affect livestock production (economic losses). Indoor fungi can produce volatile organic compounds that are products of their primary and secondary metabolism. The type of volatile compounds produced depends on the type of a substrate on which fungi grow. A bioaerosol may also contain large amounts of a mixture of mould fungi spores (mycotoxin source). Volatile compounds may be toxic and cause mucous membrane irritation or neurological symptoms (disorientation, prolonged reaction time, dizziness). Figure 2. Sources of mycotoxins for humans (according to Grajewski 2006). Characteristics of selected groups of mycotoxins: - aflatoxins - produced by many fungi species from genus Aspergillus,e.g. A. flavus,A. fumigatus,A. parasiticus Action: hepatotoxic, carcinogenic (liver cancer), mutagenic, genotoxic (aflatoxin B1), immunotoxic (affects the CD4+ T cell-dependent immune response) Characteristic features: they do not decompose at high temperature;they are destroyed by ultraviolet light and atmospheric oxygen Occurrence / presence detected on/in: peanuts, oilseeds, maize grains, milk (aflatoxin M1 and M2), chicken eggs, figs, almonds, spices (chili, paprika, nutmeg, curry) - ochratoxin A - produced, among others, by Aspergillus sp. (A. ochraceus), Penicillium sp. Action: neurotoxic, carcinogenic, teratogenic, embryotoxic Characteristic features: it does not decompose during cooking and frying Occurrence: grains of cereals (wheat, oats, barley, rye, maize), coffee beans, poorly dried herbal products (Figure 3) tea 1% wine, champagne beer 2% fruit juices 5% 11% bread 28% cocoa 1% coffee 16% meat, cold cuts, cheese 8% nuts, dried fruit, chocolate 5% rolls 9% cereals, muesli 4% flour, cakes, pizza 6% pasta 4% Figure 3. Sources of ochratoxin A in the human diet (according to Grajewski 2006). - patulin - produced, among others, byPenicillium sp., Aspergillus sp. Action: genotoxic Occurrence/ presence detected on/in: fruits, mainly apples (juices, mousses, purees) - trichothecenes - produced byFusarium sp. Action: haemorrhagic, cytotoxic, dermatotoxic, inhibition of protein synthesis in cells Characteristic features: produced by parasitic fungi of crops Occurrence/ presence detected on/in: cereal grains Examples: deoxynivalenol, T-2 toxin, HT-2, nivalenol - fumonisins - produced by Fusarium sp. (Fusarium moniliforme) Action: neurotoxic, hepatotoxic, pneumotoxic, carcinogenic (cancer of the oesophagus, liver cancer) Occurrence/ presence detected on/in:: maize (grain, flour, semolina) - zearalenone - produced by Fusarium sp., Giberella sp. Action: causes oestrogenic syndrome in animals (female infertility, male feminization) Occurrence / presence detected on/in:: cereal grains (oats, rye, wheat, rice, maize, sorghum). Claviceps purpurea alkaloids Claviceps purpurea is afungus that grows on the ears of rye and related cereal and forage plants.Its ergot, called Secale cornutum,contains a set of alkaloids - lysergic acid derivatives that paralyze the sympathetic nerve endings and stimulate contraction of smooth muscles (uterine, peripheral blood vessels). There are two groups of alkaloids: peptide (ergotamine, ergotoxine); amide (ergometrine). Consumption of ergot alkaloid-contaminated plant material, such as grains,can cause ergotism in humans and other mammals. In the case of such intoxication, the central nervous system is stimulated. Poisoning symptoms include abdominal pain, vomiting, diarrhoea, dizziness and headaches, sensory disorders (dysaesthesia) and visual disturbances, convulsions, shortness of breath (dyspnoea), and respiratory paralysis. First aid includes:induction of vomiting, administrationof activated charcoal and a person should be transported to the hospital. In medicine, alkaloids of Secale cornutum are used as ingredients of complex preparations in obstetrics,gynaecology and to treat vegetative neuroses and migraines. Poisoning with Macromycetes (cup mushrooms) The fruiting bodies of mushrooms picked in the environment can cause food poisoning. The fungi known as deadly poisonous are Amanita phalloides (deathcap) and its varieties, Amanita virosa (destroying angel), Amanita verna (fool's mushroom), Gyromitra esculenta (brain mushroom, turban fungus, elephant ears), Cortinarius orellanus (fools webcap), Inocybe erubescens (deadly fibrecap, brick-red tear mushroom, red-staining Inocybe), Galerina sp.and some species of Macrolepiota. Depending on the mechanism of action of toxic compounds, the following groups of Macromycetes toxins are distinguished classified as: 1. showing cytotoxic activity (toxic agents: amanitin, orelanin, gyromitrine) - they damage parenchymal organs (the liver, kidneys, central nervous system); e.g. Amanita phalloides, Galerina sp., Cortinarius sp., Gyromitra esculenta. 2. blocking the metabolism of ethyl alcohol (toxic agent: coprine), e.g. species of the genus Coprinus - young fruiting bodies are edible but after consumption of alcohol in 3 to 48 (or even 72) hours after the consumption of these fungi, poisoning symptoms and even death may occur; 3. showing peripheral muscarinic cholinergic activity (toxic agent: muscarine) – they cause stimulation of the parasympathetic nervous system; e.g. Inocybe sp., Clitocybe sp.,Suillellus luridus (lurid bolete), Rubroboletus satanas (Satan's bolete), Amanita muscaria (fly agaric, red toadstool); 4. showing the central atropin-like action (toxic agent: muscimol) – they cause CNS depression and hallucinations; e. g. Amanita gemmata (gemmed Amanita, jonquil Amanita), Amanita pantherina (panther cap, false blusher); 5. hallucinogenic (toxic agents: psilocybin, psilocin); e.g. species representing the genera Panaeolus and Stropharia (roundheads); 6. showing gastroenterotoxic action (various toxic agents), e.g. Paxillus involutus (brown roll-rim, poison pax), Entoloma sinuatum (livid entoloma, livid agaric, livid pinkgill, leaden entoloma, lead poisoner), Scleroderma citrinum (common earthball,pigskin poison puffball,common earth ball), Agaricus xanthodermus (yellow-staining mushroom, yellow-stainer), Amanita citrina (false death cap, Citron Amanita), Russula emetica (the sickener, emetic russula, vomiting russula), Tricholoma pardinum (spotted tricholoma, tiger tricholoma, tigertop, leopard knight, or dirty trich). Mushrooms representinga specific group may also have an effect typical of other groups. Usually they all cause gastrointestinal disturbances. Amanita phalloides– deathcap The deathcap occurs throughout Europe, northern Africa and in many parts of Asia. In other regions of the world, including USA, Australia and South America Amanita phalloides is an introduced species. Toxic substances contained in the deathcap are phallotoxins, virotoxinsand cyclic peptides called amatoxins (e.g. α-, β-, γ-amanitin, amanin). Amatoxins are inhibitors of RNA polymerase II, enzyme of the formation of messenger RNA (mRNA), microRNA, and small nuclear RNA (snRNA) synthesis. They inhibit protein synthesis, rapidly leading to cell necrosis and cause damage of the gastrointestinal tract mucous membrane, necrosis of the liver and renal tubules; lethal dose is 0.1 mg / kg body weight). These substances are classified as heat stable; they are not sensitive to high temperature (temperature of decomposition of phallotoxins is 280-282 ° C, of amatoxins is 242 ° C). Morphological characteristics of the deathcapfruiting body: a smooth yellow-green or olive-green cap (almost white when immature) white gills, white stem, a large, weakly striated ring on the stem, bulbous, thickened base of the stem surrounded by a high and protruding volva, ellipsoidal to subglobose, spores with appendage (apiculus), colourless, with a smooth surface, 7-12x6-8 μm (featuresimportant in the sporological diagnosis of vomit in case of spore print: white, not distinctive odour when young; old specimens have a very unpleasant sickly sweet smell. The deathcapfruiting bodyis most often misidentified(especially young specimens)as Russula sp., Tricholoma equestre (T. flavovirens, man on horseback, yellow knight), Macrolepiota procera (parasol mushroom)orAgaricus campestris (field mushroom, meadow mushroom). Fatal poisoning may occur after eating about 50g of the fungus (medium-sized fruiting body). Toxins penetrate cells within 4-6hoursfollowing consumption. After 8-40 hours nausea, abdominal pain, vomiting and diarrhoea occur, then dehydration causes cardiovascular shock, tachycardia, decrease in blood pressure. On the third or fourth day liver damage occurs: jaundice, haemorrhagic diathesis, renal failure, metabolic acidosis; death may also occur. In the case of poisoning with deathcaps, the pre-medical procedure includes administration of activated charcoal and fast-acting laxative (doubtful efficacy) as well ascollection of vomits for mycological examination. Treatment methods include gastric lavage (it is important in the first few dozen of minutes after consumption of the fungus), electrolyte replenishment, administration of glucose and vitamin K and haemodialysis. In the case of a severe liver damage (a life threatening condition),liver transplantation is necessary. Paxillus involutus – brown roll-rim A cosmopolitan fungus. It is found in most regions of Europe, it also commonly occurs in Asia, North America, Australia and New Zealand. Until the end of the 1980s, the brown roll-rim was considered to be an edible fungus. Now it is known to be toxic. Symptoms of poisoning may appear after a few or several (even 10-15) years because the toxin - involutin - accumulates in the organism and causes the development of haemolytic syndrome (symptoms of anaemia similar to the leukaemia syndrome). Morphological characteristics of the fruiting body: initially convex, ochre cap soon becomes centrally depressed and gradually turns chestnut brown; the margin remains inrolled and it usually has a fluted edge; downy in dry weather, the cap surface is viscid when wet, gills pale ochre at first, gradually turn brown with age, stem light ochre at first, becoming chestnut brown with age or if bruised, ellipsoidal, smooth spores, 7.5-9 x 5-6µm; spore print: sienna, odour not distinctive; acidic taste. Rusula emetica – the sickener, emetic russula, vomiting russula It is very common and widespread in coniferous woodlands throughout Europe, however, it also occurs in northern Africa, some Asian countries and in many parts of North America. Early symptoms of poisoning are nausea and vomiting, accompanied by severe stomach pains and followed by diarrhoea. Poisoning by this mushroom is unlikely to be fatal, except the case of very young children or immunecompromised people. Morphological characteristics of the fruiting body: a scarlet cap with a smooth surface, convex, sometimes becoming slightly depressed when fully mature; margin knobbly and slightly striated, white gills, white stem, sometimes slightly yellowing with age; the base slightly clavate, ellipsoidal spores, colourless, with a rough surface, 8-11 x 7.5-8.5µm; spore print: white or very pale cream faint fruity odour; very hot and peppery taste. Mushroom poisoning - epidemiological data The greatest number of poisonings is recorded after the consumption of Amanita phalloides and Paxillus involutus. It is estimated that there are 600-1000 mushroom poisoning cases per year in Poland, the majority of them with gastric symptoms.The National Poison Data System in United States has reported (doi: 10.1080/00275514.2018.1551669. Epub 2018 Dec 12) over the 18 years (to 2016) 133 700 cases (7428/year) of mushroom exposure, mostly by ingestion. Approximately 704 (39/year) exposures have resulted in major harm. Fifty-two (2.9/year) fatalities have been reported, mostly from cyclopeptide (68–89%)-producing mushrooms ingested by older adults unintentionally. Agaricus campestris– field mushroom A field mushroom is world-wide distributed. It occurs throughout most of Europe, North Africa, Asia (including India, China and Japan), in the USA, Canada and Australia. t is very closely related to the familiar supermarket button mushroom (Agaricus bisporus). Morphological characteristics of the fruiting body: a creamy white cap, sometimes developing small scales as it matures; usually the margin remains down-turned or slightly in-rolled even when the cap has expanded fully, gills, at first deep pink, turn dark brown and eventually almost black as it matures, the white stem is smooth above the single, delicate ring and somewhat scaly below, ovoid spores, 6.5-9 x 4-6µm, spore print; deep chocolate brown, not distinctive odour and taste. Plants of medical significance Plants (whole plant or some of plant parts) contain different chemical compounds that may affect the human body most often they represent alkaloids and glycosides. Such substances are designed to protect the plant against herbivorous animals and parasites - they are harmful / toxicto these organisms. Used in humans, depending on the dose, these substances can induce the desired therapeutic effects or cause disturbances in the body's vital functions (intoxication) and even death. In the immediate vicinity of humans (gardens, parks and also ) there are many species of poisonous plantse.g. lily of the valley (Convallaria majalis), common ivy (Hedera helix), wild privet (Ligustrum vulgare), guelder rose (Viburnum opulus), common yew(Taxus baccata), deadly nightshade (Atropa belladonna), jimsonweed (Datura stramonium), purple foxglove(Digitalis purpurea) and woolly foxglove (Digitalis lanata).Many plants that are toxic when ingested are also grown indoors as ornamental plants. Alkaloids are alkaline nitrogen-containing organic compounds that exhibit diverse biological activity.It is evaluated that about 10 to 25% of higher (vascular) plants (Tracheophyta) contain alkaloids. Examples of plant alkaloids are: atropine, nicotine, cocaine, morphine, strychnine, capsaicin, caffeine, theobromine, theophylline, colchicine. Glycosides are organic compounds of sugar and aglycone parts (a non-sugar component e.g. carboxylic acids, methanol, glycerol, sterols, phenols linked to sugar with a C-glycosidic, N-glycosidic, O-glycosidic or S-glycosidic bond). Examples of plants of medical significance: Atropa belladonna -belladonna, deadly nightshade The alkaloids present in the plant include: L-hyoscyamine, atropine, scopolamineand belladonnine. Alkaloids paralyze the parasympathetic nerves of the autonomic nervous system. Symptoms of poisoning (most often after administration by a herbalist for medicinal purposes or after accidental ingestion ofbelladonnafruit – 2-3 fruits for child)appear within 15 minutes.They include redness of the face, drying of the mucous membranes, acceleration of the pulse (tachycardia), dilation of the pupils (mydriasis), stimulation of the central nervous system (psychomotor agitation), anxiety, hallucinations, convulsions, fits of madness, death due to respiratory paralysis. Use in medicine: atropine (cause relaxation of the smooth muscles) is used in the treatment of bronchial asthma, control of gastrointestinal cramps occurring, e.g. in peptic ulcer disease. It is used in combating the symptoms of motion sickness due to antiemetic properties.Atropine is also used in bradycardia in order to restore normal heart rate.In ophthalmology, it is used in the diagnostics forprolonged pupil dilation, it causes relaxation of the orbicularis oculi muscles andit is also applied in the treatment of choroidal and retinal inflammatory. Datura stramonium- jimsonweed, devil's snare, common name - thornapple It contains alkaloids such as Atropa belladonna but it has a higher amount of scopolamine which paralyzes the central nervous system and peripheral parasympathetic nerves (parasympatolytic activity). Symptoms of poisoning: agitation from euphoric states to fits of madness, nausea, redness of the skin, hallucinations, stupor, mydriasis, vision disorder, death due to respiratory paralysis. Application in medicine: as an anti-asthmatic agent, it relieves asthma attacks. Digitalis purpurea - foxglove, common foxglove, purple foxglove, lady's glove It contains cardenolides (cardiac glycosides, including purpureaglicosides A and B, digitoxin, verodoxin, glucogitaloxin). The primary glycoside is digitoxin, characterized by almost 100% absorption from the gastrointestinal tract and the ability to bind strongly to proteins in the blood serum; it is slowly eliminated and shows a high degree of accumulation in the organism. Digitalis lanata - woolly foxglove, Grecian foxglove It contains cardenolides (cardiac glycosides, e.g. lanatosides A, B, C, D, E, digitoxin, digoxin, diginatin, acetyl digitoxin) that exhibit: "+" (positive) inotropic and tonotropic action (increase in contraction force and myocardial tone); "-" (negative)chronotropic and dromotropic action (decrease in frequency of heart contractions and conductivity). Symptoms of poisoning: decrease in heart rate, nausea, vomiting, gastrointestinal colics, visual disturbances, paralysis, spasms; death occurs as a result of cardiac arrest. Application in medicine: Cardiac glycosides are one of the most toxic drugs. The natural cardiac glycosides of Digitalis purpurea are on the one hand a source of drugs, while on the other hand they can cause poisoning. After exceeding its therapeutic dose by only 1.5-3 times poisoning symptoms, often life-threatening, may occur. Currently, pharmacotherapy uses mainly the most pharmacokinetically stable woolly foxglove’s cardiac glycosides (they are four times more potent than those derived from purple foxglove leaves), which accumulate less due to a faster absorption and elimination from the organism. They are used in circulatory insufficiency, heart failure, arrhythmia (atrial fibrillation), myocardial infarction. Convallaria majalis- Lily of the valley The most important active compounds found in this plant are cardenolide glycosides (including convallatoxin, convallatoxol) which have a toning effect on the heart muscle, strengthen the muscle contraction and slightly slow down heart rate. Glycosides accumulate poorly – they act quickly and briefly; this reduces the likelihood of excessive accumulation and the occurrence of toxic effects. Symptoms of poisoning: nausea, vomiting, diarrhoea, heart arrhythmia, first increase and then decrease in blood pressure, weakness and cardiac arrest. Application in medicine: in the weakening of the cardiac muscle (myocardium). Animals of medical significance Particularly dangerous to human are venomous animals which have the ability to produce toxic compounds and its active transmission to the tissues of other animals including humans. Aculeata Aculeata are insects belonging to the order Hymenoptera, including bees, bumblebees and Vespidae family (wasp, hornet).At the posterior end of the abdomen, the female insects have an ovipositor, an egg-laying device.In theAculeata species, the ovipositor has become modified as a stinger, and the eggs are laid from the base of the structure, rather than from the tip, which is used only to inject venom. Components of the Aculeata venom are:  low-molecular substances (histamine, serotonin, acetylcholine, catecholamines),  peptides (including melittin, apamine, kinins),  enzymes (hyaluronidase, phospholipase, phosphatase). The venom of common wasp (Vespula vulgaris) and honeybee (Apis mellifera) differ from each other, although some of their components have a very similar structure, such as hyaluronidase or, to a lesser extent, phospholipase. An important peptide strongly damaging cells, melittin, occurs only in bee venom, while the protein antigen 5 - is present only in Vespidae venom. There is a very large similarity between venom components within the Apidae family (bees, bumblebees) and individual Vespidae species (Table 3). Table 3. Comparison of Aculeatavenom components. Common wasp venom Honey bee venom  more immunogenic  less immunogenic  main allergen is antigen 5 (protein), phospholipase A,  melittin, apamine, MCD peptide, phospholipase A2, acid hyaluronidase, kinins phospholipase, hyaluronidase Characteristics of selected venom components:  Phospholipase A2 (10-12% of bee venom) shows a strong allergenic activity, destroys erythrocytes, hydrolyzes phospholipids in cell membranes, reduces blood pressureand blocks blood coagulation processes.  Apamine causes disturbances of water and electrolyte balance, smooth muscle and transverse striated muscles contractions. The DL50 is approximately 4mg / kg body weight.  Melittin causes haemolysis, inflammation, pain, bronchospasm, weakening of blood clotting; it also causes cell lysis, acts on the central nervous system. In high doses it causes, among others, bradycardia, impaired conduction, arrhythmia and it increases intestinal peristalsis. The DL50 is 3.5mg / kg body weight.  The MCD peptide (50-55% bee venom) releases heparin and histamine from mast cells;it is responsible for systemic muscle contractions, pains, it causes hyperactivity. The DL50 is approximately 40mg / kg body weight.  Hyaluronidase has a strong allergenic activity, causes hyperaemia and increases the permeability of blood vessels, facilitates the spread of venom in the organism.  Acid phosphatase has a strong allergenic activity.  Kinins strongly reduce blood pressure, cause severe skin hyperaemia and strong local pain (hornet venom kinins are less active than those of wasp venom). Female worker bees can sting only once and then dies; in the human skin leaves a fragment of the abdomen with a stinging apparatus (stinger with barbs venom sac, a ganglion and muscles acting as a pump). The structure and mechanism of the stinging apparatus action cause its further penetration into the skin and injection of venom remaining in the sac. Wasps do not leave stingers in the skin, so they can sting repeatedly, and the portion of venom is several times smaller than in the case of bees.Stingers of wasps and bees have harpoon-shaped barbs bent backwards, the wasp’s stinger, however, has much smaller barbs than the bee’s and the stinger is released in a sheath, while that of a bee Degree Characteristics Extensive local reaction Symptoms Swelling in the sting site exceeding 10cm in diameter and lasting for over 24 hours General 1st degree symptoms of low generalized urticaria, pruritus of the skin, weakness, anxiety intensity 2nd degree 3rd degree 4th degree General reaction Acute general reaction Shock reaction any of the above symptoms and at least 2 of the following: angioneurotic oedema, tightness in the chest, nausea, vomiting, diarrhoea, abdominal pain, dizziness any of the above symptoms and at least 2 of the following: dyspnoea, wheezing, stridor, speech disorders, hoarseness, weakness, confusion, fear of death any of the above symptoms and at least 2 of the following: decrease in blood pressure, collapse, loss of consciousness, incontinence of urine and stool, cyanosis protrudes from the sheath during stinging. Removing of the bee’s stinger: never do it with two fingers, because by squeezing the venom sac you introduce the venom into the body; it is best to pry with the blade of the knife or with a fingernail and pull it out ("scrape") without squeezing it with your fingers. It is important to remove the venom as soon as possible (in 30 seconds), because after about 1 minute the entire amount of venom from the stinger apparatus is released. Vespa crabro - European hornet It is common throughout the world except Australia, New Zealand and cold climatic zones. The insect belongs to the Vespidae family. The sting of the hornet is more painful than the sting of a bee or wasp because of the larger and deeper penetrating stinger. The composition of the hornet's venom is similar to that of a wasp. Hornet, similarly to a bee or bumblebee, attacks only if it is provoked. Only the wasp can sting if not attacked. Reactions of the human body to the Aculeata venom The Aculeata insects sting is painful and in most cases causes a limited local reaction. Particularly dangerous stings are those in the area of the head and neck (effects of venom action on the central nervous system) and in the larynx and throat area (oedema, suffocation) (Table 4).In about 20% of the population extensive allergic reactions may occur; they may be of various severity, e.g. hives (urticaria), anxiety, symptoms from the digestive system, bewilderment, dyspnoea, swelling of the joints. Table 4. Symptoms of Hymenoptera venom allergy (assessment of the severity of reaction according to Müller 1990) There are three types of reactions to Aculeata stings: - normal reaction - it is the result of the action of a small amount of toxins contained in the venom; it occurs in not allergic people. The main symptoms are pain, redness, slight oedema, feeling hot at the sting site. The reaction of this type usually lasts several dozen minutes (rarely a few hours); - toxic reaction –it occurs when a large amount of toxic substances contained in the venom gets to the body (multiple stings); general symptoms appear, including muscle cramps, headache and high temperature; - allergic reaction – occurs in people who are allergic. There are two types of reactions, i.e. an extensive local reaction (a significant oedema occurs in the sting site, it may cover the entire limb and last for several hours or sometimes days) and a generalized reaction (includes also other parts of the body apart from the sting site). In some patients, as a result of Hymenoptera sting, rare unusual reactions develop which appear in a few hours to several days after the sting, including:  serum sickness(an immune-complex-mediated hypersensitivity reaction),  neurological changes, i.e. cranial peripheral nerve damage, epileptic seizures, hemiplegia (hemiparesis, unilateral paresis), and organopathic syndrome,  acute renal failure,  haemorrhagic diathesis (thrombocytopenia),  disseminated intravascular coagulation (DIC),  myocardial infarction,  heart arrhythmia. People who are hypersensitive should be provided with a pre-filled syringe containing adrenaline (Anapen, Fastject). It is very important to know the biology of insects, which allows the application of measures to reduce the risk of re-sting (not performing sudden movements, not wearing clothes in vivid colours, not using perfumes that irritates the insects, avoiding the consumption of sweets in the open air). It should be remembered that the insects become more aggressive as the temperature and humidity increase. Scorpions Scorpions are free-living predatory arachnids (class: Arachnida, order: Scorpiones)found in tropical and subtropical climates. They range in size from 9 cm to 23 cm, have eight legs and a pair of grasping pedipalps. The body of these animals is divided into cephalothorax (the head and thorax fused together) and the abdomen with a narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger. They lead the nocturnal lifestyle, they are viviparous and can survive adverse environmental conditions owing to their ability to hibernate. Venoms of various species of scorpions are a mixture of compounds (neurotoxins, enzyme inhibitors, etc.) and cause different effects. Of approximately 2000 known scorpions species, only some have a venom capable of killing a man. Vast majority of the species do not represent a serious threat to humans and in most cases healthy adults do not need any medical treatment after being stung (although people who are allergic to scorpion venom may react in various ways). Leiurus quinquestriatus – deathstalker This scorpion occurs in desert and shrubland habitats in North Africa and the Middle East. Itis yellow, 30–77 mm long. It is one of the most dangerous species of scorpion. Its venom contains neurotoxins that cause rapid general reactions without prior local reactions. The DL50 value of venom varies from 0.16 to 0.50 mg /kg body weight. Within 2448 hours it can lead to death due to circulatory insufficiency or respiratory failure, especially in children, elderly people,those with a heart condition or allergics. Venomous spiders The most deadly spiders in the world: 1. Funnel-web spiders (family Dipluridae) 2. Widow spiders (Latrodectus sp.) 3. Wolf spider (family Lycosidae) 4. American yellow sac spider (Cheiracanthium inclusum) 5. Brazilian wandering spiders(Phoneutria fera, P. nigriventer) 6. Brown recluse spider (Loxosceles reclusa) Venomous spiders in Poland: Meta menardi–European cave spider It has a natural range of occurrence extending from Scandinavia to North Africa and from Europe to Korea; there are also transplanted populations as far apart as Japan and Madagascar. It occurs in sewage wells, telecommunications wells, caves, basements, as well as at the outlets of railway tunnels (because the adult spiders are photophobic and live in places free from light). It is a long-jawed orb-weaving spider which reaches a large size - the abdomen is only 1.5 cm long, but with its legs, its body is about 5 cm. It is the most venomous spider in Poland. Its venom is not a threat to human life, however, the bite is painful (it is compared to the hornet stings). Cheiracanthium punctorium–yellow sac spider It occurs in Europe (mainly in Germany, France, Switzerland, Italy and former Yugoslavia, in Poland (in the southern part of the country) and Asia; it prefers high temperatures. It is a medium-sized spider representing the family of Miturgidae; reaches a length of about 10-15 mm and has large jaws. It hunts for insects from his tubular web. It is one of the few spiders in Poland whose bite causes poisoning symptoms. Following the bite, burning pain and inflammation occur. The venom contains haemolysins; it is deadly to insects, while in humans it causes long-lasting pain, weakness and chills. Bite symptoms (increased heart rate, fainting and vomiting) can last up to two weeks. There were no cases of deaths after the bite of the yellow sac spider. Araneus It is a genus of common orb-weaving spiders, including the European garden spider and the barn spider. Usually they are not dangerous species for humans; in the case of a bite, in extreme cases, on the body there may be swelling and tissue necrosis in the form of two small points. Poisonous reptiles Bufo bufo - common toad It is an amphibian found throughout most of European countries (with the exception of Ireland, Iceland, andsome Mediterranean islands), in the western part of North Asia, and in a small part of Northwest Africa. It is one of the largest amphibians found in Poland. On the back, neck and shoulder of toads are skin glands that secrete a number of alkaloid substances known as bufotoxins (they act as neurotoxins to deter predators). The venom glands are clustered to form warts on the toad's skin. Larger clusters of glands on the head are the parotid (paratoid) glands.The toxic substances found in toads can be divided by chemical structure in two groups: 1. bufadienolides, which are cardiac glycosides (e.g., bufotalin) 2. tryptamine-related substances (e.g., bufotenin) At low doses they stimulate the activity of the myocardium (effects resemble those of Digitalis sp.), in high doses - they inhibit myocardial activity. In traditional Chinese medicine, dried toads were used to treat heart diseases. Venomous snakes The most venomous snakes of the world: 1. Inland taipan – Australia 2. Dubois' sea snake - Coral Sea, Arafura Sea, Timor Sea, Tar River, and Indian Ocean 3. Eastern brown snake - Australia, Papua New Guinea, Indonesia 4. Yellow bellied sea snake - Tropical oceanic waters 5. Peron's sea snake - Gulf of Siam, Strait of Taiwan, Coral sea islands, and other places 6. Many-banded krait - Mainland China, Taiwan, Vietnam, Laos, Burma Venomous snakes in Poland: Vipera berus –common European adder,common European viper It occurs in Europe and North Asia. It is the only poisonous snake in Poland, and belongs to the species under partial protection. The viper is most active at night.During the day, it can stay in well-sunlit places, because it is a thermophilic animal. It lives in forests, especially among dense bushes , as well as in glades.It feeds on rodents, shrews, moles, nestlings, lizards and frogs. It kills the victim with a bite and devours it dead. In Europe, the number of snake bite cases, mainly from the Viperidae family, is estimated at 15-25 thousand, and the number of deaths between 1 and 7 per year.Most cases of the snake bites have a mild course (70-80% asymptomatic or only local symptoms). Deaths affect children, the elderly and people with cardiovascular diseases. Mortality is below 1%. In the place of the bite there occur two small points after the venom teeth (about 1 cm away from each other). After the bite, there is usually severe pain and worsening painful swelling, bruising and enlargement of the nearest lymph nodes (under the armpit or groin of the bitten limb). Two characteristic, painful points are visible on the skin, and the skin at the site of the bite turns blue-red; petechiae and skin necrosis may appear. At the same time, systemic symptoms may appear, such as: - nausea, - abdominal pain, - vomiting, - diarrhoea, - excessive sweating, - fever, - thirst, - dizziness, - bleeding from the gums, haematuria, - symptoms of shock: hypotension, tachycardia, cold sweats, paleness, disturbances of consciousness. Urticaria, angioneurotic oedema and anaphylactic shock may occur in people hypersensitive to venom components. The main components of viper venom: - haemorrhagin damages the blood vessel walls,it causes bleeding from the nose, haematuria, extravasation of blood; - haemolysin leads tolysis of erythrocytes, it causes aenemia and jaundice; - neurotoxin affects the nervous system, it causes dizziness, nausea, vomiting; - hyaluronidase (an enzyme digesting the hyaluronic acid polymer) decomposes the main component of the connective tissue core - facilitates the spread of venom. Viper bite - first aid: comfortably arrange a bitten person, cover the wound with sterile gauze, immobilize the limb,and place below the level of the heart Currently, dressings or tourniquets are not recommended as this may increase the risk of limb necrosis. A tourniquet can be applied above the bite site only when the transport of the patient to the hospital takes> 30 minutes, but it requires periodic control of the blood supply to the limb. It is also not recommended to cover the bite with ice or to cut it. put the patient in a hospital as soon as possible, slowly administer a venom viper antitoxin (specific horse immunoglobulin G - obtained from horses immunized with a viper venom), intravenously (not in a sick limb!). An intradermal allergic test should be performed prior to administration of the antitoxin, and if it is not possible, the viper antitoxin should be administered together with anti-shock agents (adrenaline injection). Due to the foreign protein contained in the preparation, anaphylactic reactions including shock may occur after administration of the antitoxin. Early anaphylactic reactions occur within 10-180 minutes following the injection; they include fever, pruritus, urticaria, dry cough, nausea and vomiting, diarrhoea, abdominal colic, tachycardia. Some people may have life-threatening bronchoconstriction, hypotension, and angioneurotic oedema. Examples of the use of animal venoms in medicine Bee venom In the treatment with the use of bee venom, controlled stinging, ointments, injection solutions and chemoacupuncture can be applied (venom introduced directly into the human body is the most effective, in other cases the effectiveness of the therapy is lower). The venom introduced into the body in appropriate doses has a therapeutic effect (locally and generally), causes the dilation of the arteries and capillaries, increases the blood flow, has a beneficial effect on the hematopoietic system, reduces the viscosity and density of the blood. In addition, the use of apitoxin therapy reduces blood pressure, stimulates the heart muscle, activates metabolism, reduces blood cholesterol. It has an auxiliary effect in the treatment of tongue mucositis and periodontitis, postoperative scars and wounds that are difficult to heal. Indications for bee venom therapy include rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis; post-traumatic pain syndromes, discopathies; diseases of the nervous system, e.g. neuralgia (sciatica, lumbago = low back pain); bursitis and tenosynovitis, sprains; diseases of the heart and peripheral vessels. Ant venom Ant venom contains formic acid (acidum formicum) which is the main component of the formic spirit. It has a vasodilating effect on blood vessels, paralyzes sensory and pain receptors, has antirheumatic, antiarthritic and warming properties. The preparation is mainly used for pain relief in sciatica, lumbar and sacral pain, as well as joint pain. Deathstalkervenom The chlorotoxin contained in the scorpion's venom connects to cancer cells. The preparation called Tumor Paint BLZ-100 based on chlorotoxin adheres to tumour cells and behaves like a dye that shines under the influence of infrared radiation. When using a specialized camera during surgery, the doctor can distinguish a healthy tissue from cancer; this preparation is in the phase of clinical trials. Peruvian green velvet tarantula (Thrixopelma pruriens) venom The venom of the spider (found in Chile and Peru) contains the ProTx-II peptide which binds to the cell membrane of nerve cells and blocks the NAV1.7 pain receptor. Potentially, this substance can become a painkiller. Sydney funnel-web spider (Atrax robustus) venom Hi1 proteins found in the venom of this spider (found in Australia) have a neuroprotective effect, blocking pHsensitive ion channels in the cell membranes of neurons - the activity of these channels plays an important role in the process of dying of the hypoxic cell. Research on laboratory animals suggests that in the future Hi1a could be administered in the early stages of stroke treatment. Brazilian wandering spider (Phoneutria nigriventer) venom The venom of the spider (found in tropical parts of North and South America) contains a Tx2-6 toxin that causes erection of the penis in bitten men. Research on the use of this toxin in the treatment of erectile dysfunction is being carried out. Magical cone (Conus magus) venom On the basis of snail (found in the seas and oceans in tropical and subtropical zones) venom ziconotide was produced, acts as a specific blocker of calcium channels in neurons and is used in the treatment of chronic pain. Viper venom It is used in medicine as an ingredient in ointments of analgesic, anti-inflammatory, reducing blood clotting and regenerating properties, which are used to treat injuries, contusions and hematomas. It can also be used as a warming agent, reducing muscle tension, in the prevention of rheumatic changes, osteoarthritis changes and inflammation of the musculoskeletal system. Neurotoxic properties of venom make it successfully used in cosmetology - relaxation and immobilization of mimic muscles (smoothing effect). Jararaca, yarara (Bothrops jararaca) venom The BPF protein present in the venom of the snake (found in South America) causes a reduction in blood pressure and became the basis for the group of drugs - angiotensin-converting-enzyme (ACE) inhibitors obtained in the 70's. The active substance has undergone clinical trials and under the name captopril has been approved as a drug for hypertension. The annual production of captopril is around 1000 tons. Gila monster (Heloderma suspectum) venom The saliva of this lizard (found in the southwestern United States and the northwestern Mexican state of Sonora) contains a compound that regulates blood sugar levels and suppresses appetite. Exenatide is a synthetic version of a protein, exendin-4, derived from the Gila monster's saliva; it is the precursor of incretins and it is used in medicine as a drug for the treatment of type 2 diabetes and supporting the maintenance of normal body weight. Some components of snake venom have been used in diagnostics of haemostatic disorders. The Ecarin prothrombin activator obtained from the Indian saw-scaled viper (Echis carinatus - found in North Africa, the Arabian Peninsula and Central Asia) is used to detect an abnormal type of prothrombin; serine protease Protac® - from the copperhead (Agkistrodon contortrix– endemic to Eastern North America) venom is used to detect protein C and protein S; RVV-X metaloprotease from the Russell's viper (Daboia russelii - found in Southeast Asia) venom is used for the screening test for lupus anticoagulants. Integrilin® (Eptifibatide) and Aggrastad® (Triofiban) anticoagulants based on snake toxin are used to prevent heart attacks and blood clotting. Eptifibatide is a cyclic heptapeptide derived from protein present in a venom of a snake from pit viper subspecies (Sistrurus miliarius barbouri - endemic to the southeastern United States). Celtic Biotech Iowa Inc. develops new products for the treatment of cancer and pain based on crotoxin obtained from the tropical rattlesnake (Crotalus durissus terrificus- found in Latin America and Mexico) and cardiotoxin from Chinese cobra (Naja atra– found in the areas of south-eastern China, Laos and Taiwan). References: 1. De Hoog G. S., Guarro J., Figueras M. J., Atlas of clinical fungi, Centraalbureau voor Schimmelcultures, Universitat Rovira i Virgili, Utrecht, Netherlands 2000 2. Utkin N.Y. Animal venom studies: current benefits and future developments. World Journal of Biological Chemistry, 2015; 6(2):28-33 3. Campbell N.A., Reece J.B.: Biology. Pearson, Benjamin Cummings, Seventh Edition 2005