Impact of Cyanobacteria Toxins

Impact of Cyanobacteria Toxins Introduction Cyanobacteria, or also known as blue-green algae is one of the bacteria phylum. It was classified as blue-green algae because it resembles eukaryotic green algae. Cyanobacteria are photosynthetic prokaryotes which have the ability to synthesize chlorophyll a. Chlorophyll a primarily absorbs most red and blue light, which allow cyanobacteria to obtain energy. This energy was then used to synthesize carbohydrate from carbon dioxide and water. Water is used as electron donor during the photosynthesis process and produces oxygen as a byproduct. Thus, the ability of cyanobacteria underwent the process of photosynthesis leading to the evolution of oxygen as they play an important role in increasing the amount of oxygen in Earth. Besides, cyanobacteria also called blue-green algae because of its ability to form the phycobilin pigment (phycocyanin). Phycocyanin is an accessory pigment where it works in conjunction with chlorophyll a. Phycocyanin pigment is the one that give bluish colour to cyanobacteria. According to Dittmann and Wiegand (2006), the lyses of a cyanobacterial bloom leads to release of high amounts of blue pigmented. However, the colour can degrade under condition of high exposure to light and heat (Jespersen et al., 2005). Because cyanobacteria are prokaryote, it is usually small and unicellular. Usually individual cyanobacteria are round, oval, globular or string-like in shape. However, cyanobacteria often growth in colonies and, thus are large and easily to view. These colonies are built of many layers and can form filaments, sheets or even hallow ball depend on its species and environmental condition. Cyanobacteria have been classified into five groups based on their morphologies. There are chrooccales (I), pleurocapsales (II), oscillatoriales (III), nostacales (IV) and stigonematales (V). Group l is unicellular cyanobacteria that divide by binary fusion or budding, while group II is unicellular form that divide by multiple fission. Then, group III is filamentous colonies that reproduce by trichome breakage (Henson, 2002). However, only groups IV and V are supported by phylogenetic studies and make up the heterocystous cyanobacteria. They have the ability to fix Nitrogen such as genera of Anabaena, Nostoc, and etc. Cyanobacteria are extremely successful organism that can adapt in any condition depend on its species. The fossil record shows their existence since 3.5 billion years ago and it are still around. According to Hitzfeld et al. (2000), the cyanobacteria inhabitants vary from hot springs to temporary frozen ponds in Antarctica. Cyanobacteria are gram negative that has cell wall made up of peptidoglycan and lipopolysaccharide layers that surrounded by gelatinous and mucilaginous sheath. The presence of the gelatinous sheath may help in survival of cyanobacteria during extreme conditions and desiccation (Duy et al., 2000). Cyanobacteria mostly found in brackish, freshwater, rivers, lakes, ponds and some reservoirs. They commonly live in such condition to get access of water and sunlight, as they do the photosynthesis process. The high accumulation of cyanobacteria is due to nutrient enrichment (eutrophication). The eutrophication is the process of water bodies gets the excess of nutrient a nd this promotes extremely growth of cyanobacteria. This nutrient may come from many sources, such as fertilizers applied to agriculture, erosion of soil containing nutrients and etc. The excess of nutrient lead to massive population of cyanobacteria, include the blooms, scums, and mats and biofilms (Codd et al., 2005). The existence of cyanobacteria bloom can reduce dissolved oxygen in water and may cause other aquatic organisms died. Alperdoorn et al. (2007) suggest that complex interaction of high concentration of nutrients, sunlight, warm temperature, turbidity, pH, conductivity, salinity, carbon availability and slow-flowing stagnant water are involved in production of blooms. Besides, the bloom of cyanobacteria is related with toxins released. Purpose of study The purpose of study is to analyze the type of toxins produced by bloom of cyanobacterial. Growth of cyanobacteria bloom is favored by nutrient enrichment. The increase of mass population of cyanobacteria will lead to high amount of toxin produced. Then, relate how these toxins act in order to affect humans and animals health. Objectives of study Production and mode of action of cyanobacteria Occurrence of cyanobacterial toxins in affects humans and animals -example case Routes of exposure Diseases in Humans and Animals Conclusion further work Production and mode of action of cyanobacteria toxins Properties of cyanobacterial toxins There are around 150 genera with about 2000 species of cyanobacteria has been recognized, as according to the current taxonomy. However, out of them, only 40 genera have been identified to produce toxins (Hitzfeld et al., 2000). The toxins produced by bloom of cyanobacteria are sometimes called cyanotoxins. The genera that release toxins from cyanobacteria bloom are include Microcystis, Anabaena, Anabaenopsis, Plankthothrix, Aphanizomenon, Cylindrospermopsis, Raphidiopsis and Nodularia (Codd et al., 2005). Cyanotoxins are classified into two grouped, where one is based on their modes of toxin affect the animals cells or cell system, and the other one is based on their chemical composition and structure (Codd et al.,1999). The first grouped are divided into four types, which are hepatotoxins, neurotoxins, cytotoxin and irritant toxins (Codd et al., 2005). However, the second grouped is classify into three different chemical structure which are cyclic peptides, alkaloids and lipopolysa ccharides (LPS) (Sivonen Jones 1999). The production of cyanotoxin are highly variable depends on time and an individual bloom itself. Besides, the arrangement of the genes and their expression under certain environmental condition also contribute in released the toxins. Hepatotoxins-cyclic peptides Hepatotoxins class has the chemical structure of cyclic peptides. These kinds of toxins are released by bloom of cyanobacteria that ranging from freshwater to oceans. Among the common hepatotoxins produced are mycrocystins and nodularins. Microcystin is first found in the early 1980 and isolated from Microcystis aeruginosa. Thus, the toxins were named as microcystin (Sivonen Jones 1999). Then, it was identified that microcystins also have been produced from the genera of Anabaena, Microcystis, Planktothrix, Nostoc and Anabaenopsis (Hitzfeld et al., 2000). Differ from microcystins, where nodularins only produced by the genera of Nodularia and were names as nodularins after its producer, Nodularia spumigena (Falconer 1998). Both are widespread cyanotoxins because the presence of gas vesicle that provides buoyancy. Gas vesicles enable them to float up or sink in order to get sunlight and reach the site of nutrient-rich layers (Dittmann Wiegand 2006). Enough of nutrient and sunlight en able the cyanobacteria to undergo the photosynthesis process and lead to excess growth. Therefore, the cyanotoxins of microcystins and nodularins could be produce enormously and can disturb the ecosystems Microcystins are difference from nodularins based on their chemical structure of cyclic peptides. The chemical structures of microcystins have been identified as cyclic heptapeptides, while nodularins has chemical structure of cyclic pentapeptides (Codd et al., 1999). Cyclic heptapeptides refer to microcystins that contain seven peptide-linked amino acids. There are five common amino acids and another two L-amino acids are varied (Park et al., 1993). The five common amino acids are D-erythro-ÃŽ ²-methylaspartic acid, D-alanine, N-methyldehydroalanine, D-glutamate and Adda-3-amino-9-methoxy-2, 6, 8-trimethyl- 10-phenyldeca-4, 6-dienoic acid. The variable L amino acids are located at position 2 and 4. The variable of L amino acids increased the variations in microcsytins structure and so far there are about 70 structural variables have been identified (Codd et al., 2005). Besides that, demethylation of D-erythro-ÃŽ ²-methylaspartic acid and N-methyldehydroalanine amino acids also give variation in microcystin structure. In contrast, only about 6 variant of nodularins structure have been recognized (Codd et al. 1999). Both microcystins and nodularins only release from cyanobacteria bloom once it was lyses. These toxins are potent inhibitors of eukaryotic protein phosphotases activity (Park et al., 1993). According to Codd et al, (2005), this inhibition can change the membrane integrity and causing tumor production and liver damage. Liver is the main targeting organ in this action of toxins. Neurotoxin-alkaloids Neurotoxins contain the chemical structure of alkaloids. Alkaloids are chemical compound that contains any basic nitrogen atoms and produced by cyanobacteria. It cause toxic that act on nerve cell (neuron). So far, three known families of neurotoxins are anatoxin-a, anatoxin-a(S) and saxitoxins. Anatoxin-a acts by mimic acetylcholine, while anatoxin-a(S) inhibit acetylcholinesterase. Next, saxitoxins which relatively associated with paralytic shellfish poisons (PSP) are works by block the sodium channels. These toxins have been reported found mostly in area of North America, Europe and Australia (Sivonen Jones 1999). Devlin et al. (1977), identified anatoxins-a as a secondary amine 2-acetyl-9-azabicyclo (4-2-1)non-2-ene. Anatoxin-a is usually released by Anabaena flos-aquae, Anabaena spp, Anabaena planktonica, Oscillatoria, Aphanizomenon and Cylindrospermum (Sivonen and Jones, 1999). This toxins cause symptoms such as fasciculation, gasping and convulsion, when infection occurred in animals (Mazur et al., 2003). In contrast, Anatoxin-a(S) is guanidine methyl phosphate ester and produced by Anabaena flos-aquae and Anabaena lemmermannii (Codd et al., 2005). However, its structure still h as not been recognized. Sanitoxins are group of carbonate alkaloids and about 20 of structural variations has been recognized (Codd et al., 2005). Sanitoxins are produced by species of Anabaena, Aphanizomenon, Cylindrospermopsis, Lyngbya, Planktothrix and Trichodesmium (Carmichael et al., 2001) Cytotoxin-alkaloids Cylindrospermopsin is the example of cytotoxin released and has been found in tropical and subtropical water such as in lakes, rivers and water supply reservoir (Falconer 1998). According to Hitzfeld et al (2000) and Codd et al (1999), cylindrospermopsin could also be categorized as hepatotoxins because it affects liver damage. However, Codd et al (2005) and Falconer (1998) have categorized it under cytotoxin class because its action as an inhibitor of protein synthesis. This inhibition cause damage to tissue that rapidly synthesize protein such as pituitary gland, epithelia including gut lining, the pancreas, lymphoid tissue and the prostate gland, as well as the kidneys and liver (Falconer 1998). This toxin is also genotoxic, which can cause loss of chromosome and break of DNA strand (Humpage et al 2000). Cylindrospermopsin is a cyclic guanidine alkaloid and has been isolated mainly from cylindrospermopsis raciborskii and also from Aphanizomenon ovalisporum, Umezakia natans, Aphani zomenon flosaquae and Raphidiopsis curvata (Falconer and Humpage, 2006). Irritant toxins Irritant toxins are usually related with skin irritant (dermatoxin). Aplysiatoxin and lyngbyatoxin is alkaloid structure and both are the most toxins that cause skin irritation. Aplysiatoxin is produced by genera of Lyngbya, Oscillatoria and Schizothrix whereas Lyngbyatoxin is produced by Lyngbya (Codd et al 1999). Aplysiatoxin also is potent tumour promoters and Lyngbyatoxin also caused severe oral and gastrointestinal inflammation (Sivonen and Jones, 1999). LPS endotoxin released by cyanobacteria is less potent than released by bacteria, such as Salmonella (Codd et al 1999). LPS is localized at outer membrane wall of cyanobacteria and contain lipid A that responsible for much of toxicity of cyanobacteria. LPS endotoxin in cyanobacteria is produced by Microcystis, Oscillatoria and Anabaena (Codd et al 1999). The signs and symptoms of this toxin are fever, rigors, headache, nausea, mild amnesia and diarrhea (Stewart et al., 2006). According to Codd et al (2005), it may contribute to inflammatory and gastrointestinal incidents. Toxin Chemical structure Producer Genera Primary target organ Hepatotoxins Microcystins Cyclic heptapeptides Microcystis, Anabaena, Planktothrix, Nostoc Anabaenopsis Liver Nodularins Cyclic pentaptides Nodularia Liver Neurotoxins Anatoxin-a Alkaloids Anabaena, Oscillatoria and Aphanizomenon, Cylindrospermum Microcystis Nerve synapse Anatoxin-a(s) Alkaloids Anabaena Nerve synapse Saxitoxins Alkaloids Aphanizomenon, Anabaena, Lyngbya Cylindrospermopsis Nerve axon Cytotoxins Cylindrospermosin Cyclic guanidine alkaloids Cylindrospermopsis, Aphanizomenon, Umezakia Rhapidiopsis Tissue damage include liver and kidney Irritant toxins Lyngbyatoxin Alkaloids Lyngbya Skin, GI tract Aplysiatoxin Alkaloids Lyngbya, Oscillatoria Schizothrix Skin Endotoxins LPS Microcystis, Oscillatoria Anabaena Potential irritant affect any exposed tissues Table 1: Updated from Codd et al. (1999) and Sivonen Jones (1999). This shows the summaries of general features of cyanotoxins. Occurrence of cyanobacterial toxins The cases of cyanotoxins affect humans and animals have been reported occurred throughout the world. This include part of Europe (such as Belgium, France, Germany, UK, etc), America (at least 27 states), Middle East and Asia (such as Bangladesh, Saudi Arabia, Thailand), Australasia (such as Australia, New Zealand), Africa (Botswana, Morocco) and also Marine Atlantic Ocean (Baltic Sea, Caribbean sea) and Antarctica (McMurdo Ice Shelf) (Codd et al., 2005). From the case reported, cyanatoxins affect animals, include wild and domestic mammals, birds, amphibians and fish, while human cases ranging from acute to chronic (Hitzfeld et al., 2000). The first case of cyanotoxins occurred in animals was the death of cattle, sheep, dogs, horses and pigs. This took placed in Lake Alexandrina, Australia in 1878. The death of these animals was due to drink the water that contains a scum of Nodularia spumigena (Francis, 1878) . After this case, numerous cases have been reported and most commonly involved death of farm animals after drinking the contaminated water with cyanobacterial bloom (Hitzfeld et al., 2000). For example, in 1991 the death of sheep has been recorded in Darling River, Australia. This death occurred after drinking from a farm dam contaminated with saxitoxins, released by Anabaena circinalis (Goodman et al., 1999). Besides, the cases of dog deaths after swimming in, or eating, cyanobacteria also occurred. In 1992, death of dogs at Loch Insh, Scotland happened after swimming was due to release of Anatoxin-a by Oscillatoria sp. into the water (Edwards et al., 1992). Among the earliest reported cases involving acute effect in humans was a series of town along the Ohio River, US in 1931. It start when the water of a side branch of the river develop a cyanobacteria bloom because of low rainfall. This water was then washed into the main river and caused a series of gastroenteritis once it moves downstream (Tisdale 1931). However, the toxins caused this outbreak is unknown and the organism that released this toxins was unspecified. Then, another case involving the same diseased, (gastroenteritis) was reported in Harare, Zimbabwe in 1966. This time Microcystis aeruginosa was the one that has been identified responsible in this case, but the toxins released was still not known (Hitzfeld et al., 2000). Children living in this area developed gastroenteritis each year as they use the water reservoir which contains a natural bloom of Microcystis (Zilberg 1966). The case of chronic effects in humans may be present due to short exposure to toxins (Goodman et al., 1999). The incidence in China, 1995 due to microcystins have lead to chronic of liver injury, hepatocellular carcinoma. This is primary cancer of the liver and most are secondary to hepatitis B infection. From the case analyzed, cyanobacteria are abundant in surface waters of south east China, where the incidence of hepatocellular carcinoma is highest. Thus, it has been concluded that microcystins in the drinking water are responsible for the increased of liver cancer (Falconer 1998). Compare to all cyanotoxins, cyclic peptides (mostly microcystins) has high risk because of their potential to develop diseases in long term time, even when exposed to low concentration of cyanotoxins. This was confirmed after examined all the cases reported, where the major injury is hepatotoxicosis, cause liver damage. In contrast, neurotoxin mostly shows acute effect in mammals (Goddman et al., 1999). Routes of exposure There are many ways where humans and animals can be exposed to cyanotoxins. From the cases reported, animals usually infected by cyanotoxins orally via drinking contaminated water. For instance, the case reported of cattle deaths in Alpine Lakes, Switzerland (1974-1994). The cattle died because of liver damage after drinking the water which contains bloom of cyanobacteria (Hitzfeld et al., 2000). Besides, human can get infection of cyanotoxins during the recreational activity involving direct contact with water such as swimming, canoeing and paddling (Apeldoorn et al., 2007). In 1989, UK, some of army recruits showed symptoms of infected by cyanotoxins after swimming and canoes training in water with dense bloom of Mocrocystis. The signs of symptoms were vomiting, diarrhea, blistering of the lips, sore throat and central abdominal pain (Turner et al., 1990). The person that worked in the area of water such as boatmen and environmental scientists are also easily to get infection. Acco rding to Dittmann and Wiegand (2006), the consumption of blue green algae containing food and dietary supplements, such as pills or capsules, also can lead to gain the toxicity of cyanobacteria. According to Codd et al (1999), there are four routes of exposure where human can get infection of cyanotoxins (Table 2). The first one is via oral routes, taken by ingestion during recreational activity, drinking water, food and dietary supplements that contain dried cyanotoxins. The oral route has caused the outbreak of many diseased, such as gastroenteritis and hepatoenteritis after drinking water (Codd et al 1999). Infection by pulmonary route occurs either by inhalation of cyanobacteria bloom during recreational activity or work practices in industrial spray water (Codd et al., 1999). Next, dermal route is associated with skin or mucosal contact the contaminated water. This can lead to skin irritation and allergic reaction. Lastly, haemodialysis route can occurred via water used in haemodialysis treatment. Among the cases of this route, is the case of major fatal incident at haemodialysis clinic in Caruaru, Brazil. This case happened in 1996, where the patients with dialysis tre atment were treated with water from local reservoir. All patients experienced symptoms of nausea, vomiting, muscle weakness and painful hepatomegaly. Then, these patients developed acute liver failure and acute neurotoxicity signs. From all the treated patients, 60 have been recorded as dead. Microcystins released by Aphanizomenon and Oscillatoria have been recognized as the toxins that responsible for this death (Codd et al., 1999). Exposure route Exposure medium Oral (ingestion) drinking water, recreational water, food (shellfish, finfish if toxin if toxin accumulation has occurred during production), dietary supplements (pills, capsules) if contains dried cyanobacterial cells with toxins. Pulmonary (inhalation, aspiration) water: aerosols, spray during recreation, work, showering Dermal water during recreation, work, showering (skin, mucosal contact) Haemodialysis water used for haemodialysis Table 2: Taken from Codd et al., 2005. This figure summaries the human exposure route and exposure medium for cyanotoxins. Diseases in Animals and Humans Hepatoenteritis Liver damage Hepatoenteritis is described as hepatitis-like illness, where associated with liver problem. This diseased can infect both human and animals. The outbreak of hepatoenteritis disease was reported in 1979 and occurred in Palm Island of the Queensland, Australia. Thus, this case also name as â€Å"Palm Island Mystery Disease† because the water drinking is supply from Palm Island reservoir (Ohtani et al., 1992). Investigation have shown that the reservoir contain the bloom of Cylindrospermopsis raciborskii. This species released cylindrospermopsin and responsible for developed of severe hepatoenteritis among the 140 children and 10 adults. The common symptoms of this disease are malaise, anorexia, vomiting, painful liver enlargement, dehydration and bloody diarrhea. This toxin is very water soluble and infect into body by oral route via drinking water. According to Falconer and Humpage (2006), the mechanism of action for cylindrospermopsin is relatively slow. It work by inhibit pr otein synthesis at ribosome during the peptide chain elongation step. Besides, the toxins also released CYP450 oxidation that work to inhibit the glutathione synthesis. Both inhibitions caused major changes in liver, particularly hepatocytes. First, accumulation of ribosomes in the cytoplasm of hepatocytes and followed by membrane proliferation. Next, the accumulation of lipid in the central portion of hepatic lobules and all this lead to severe liver necrosis (Duy et al., 2000). Kidney, lung, heart, spleen and thymus also might be affects. The toxins of microcystins are majorly involved in liver damage. Most of microcystins types are hydrophilic and thus, not able to penetrate vertebrate cell membrane. It only can uptake into cell membrane via transporter. Once the microcystins are uptake by mammals, it is transport into the blood from the ileum via bile acid type transporter, that present in hepatocytes (Apeldoorn et al 2007). As a result, the present of microcystins is higher in liver due to active uptake by hepatocytes. Once inside the hepatocytes, microcystins act as potent inhibitor of eukaryotic protein phosphatases 1 and 2A. These inhibitions cause changes in cytoskeletal proteins, and thus results in deformation of hepatocytes. The liver may undergo changes in term of a disruption of hepatocytes structure due to damage of cytoskeleton, loss of sinusoidal structure, increased in liver weight because of intrahepatic haemorrhage, heart failure and death. Gastroenteritis Gastroenteritis is inflammation of the gastrointestinal tract, where involved stomach and intestine. This diseased can be cause by infection from cyanobacteria bloom of Microcystis sp and Anabaena sp. Acording to Hitzfeld et al (2000), the cases of gastroenteritis that have been recorded due to cyanobacteria bloom were occured in Ohio River, US (1931), Harare, Zimbabwe (1966) and Itaparica Dam, Brazil (1993). However, the toxins that responsible for this diseased still remain unknown because lack of available toxin analysis method and knowledge of candidate toxins at the time (Codd et al., 1999). Recently, there is case where LPS endotoxin is responsible for gastroenteritis incidents (Codd et al., 2005). Gastroenteritis is categorized under acute effect and mostly results in diarrhea. Besides, the symptoms shows are nausea and vomiting, loss of appetite, fever, headaches and abnormal pain. Respiratory problem Neurotoxins effects can lead to progressive paralysis and death because of respiratory failure. The case of livestock death in Europe and the US have been reported due to anatoxin-a, released from the genera of Oscillatoria, Aphanizomenon and Anabaena (Falconer, 1998). Anatoxin-a acts as a potent postsynaptic depolarizing neuromuscular blocking agent, where it binds to neuronal nicotinic acetylcholine receptors of neuromuscular junction (Goodman et al., 1999) .This cause postsynaptic sodium channel of neuron is remain open and lead to continuous stimulation of sodium ion influx and continuously generates action potential. Consequently, the muscle contraction is over react and might be followed by fatigue and respiratory failure (Dittmann and Wiegand, 2006). This toxin can cause rapidly death depending on the species and amount of toxin ingested. The clinical sign of this infection are muscle fasciculation, decreased movement, abdominal breathing, cyanosis, and death by respiratory fa ilure. Saxitoxins are another type of neurotoxins that can infect both human and animals. As mention before, the case of Darling River in Australia (1990-1991) involved the deaths of sheep and cattle due to saxitoxins. Then, in human, saxitoxins have been the cause of paralytic shellfish poisoning (PSP). Saxitoxins acts as a blocking agent of sodium channel in nerve axons. In mammals, this induces muscle paralyzed (respiratory muscle) and can follow by death due to respiratory failure (Apeldoorn et al., 2007). Skin irritation and allergic Lyngbya majuscula is one of the cyanobacteria that released aplysiatoxin and lyngbyatoxin. These toxins act as potent skin tumour promoters. Both toxins, especially aplysiatoxin, cause skin irritation after contact with bloom of Lyngbya majuscula. Swimmers of Hawaii and Okinawa got acute dermatitis (causing itch), erythematous wheals and desquamation after contact with Lyngbya majuscule (Codd et al., 1999). Besides, symptoms have included rashes, blisters, allergic reaction, asthma, conjunctivitis, and eye irritation. Conclusion The development of cyanobacterial bloom tends to be favored by nutrient enrichment (eutrophication). Therefore, enough nutrients will provide extremely growth of cyanobacteria bloom and thus, lead to high production of cyanotoxins once it is lyses. The most clearly study of toxins is microcystins due to widespread of its production among the cyanobacteria blooms. Besides, their existences that usually can be found in lakes, rivers and water supply reservoirs also lead to increased the chance to affect humans and animals health compare to the other toxins. As mention above, there are four routes where infection of cyanotoxins could occurs, which are by oral route, dermal route, pulmonary route and lastly via haemodialysis route. Once the toxins get inside humans and animals, they will start reacts and disturb the system inside the body according to its modes of actions. Therefore, it leads to outbreak of many diseased such as hepatoenteritis, gastroenteritis, respiratory problem and s kin irritation and allergic. However, till now there are some mechanism of toxins that still not understood, such as lyngbyatoxins (Goodman et al., 1999).Then, further work also need to be done in order to solve the cases of unknown toxic affect humans and animals that have been recorded. For example, the case of the outbreak of gastroenteritis diseased occurred in Ohio River, US (1931), Harare, Zimbabwe (1966) and Itaparica, Dam, Brazil (1993), where no actual toxins have been identified (Hitzfeld et al., 2000). All the features of cyanobacterial cell include their type of the toxins released and their mode of action is needed to understand clearly, in order to monitor and control their growth from continuously affect humans and animals. Thus, guidelines and regulatory standard could be developed to increased awareness of actual and potential of cyanotoxins. References APELDOORN, M. E., EGMOND, H. P., SPEIJERS, G. J. A. BAKKER, G. J. I. 2007. Toxins of cyanobacteria. Mol. Nutr. Food Res, 51, 7-60. CARMICHAEL, W. W., AZEVEDO, S., AN, J. I., MOLICA, R., J.R, JOCHIMSEN, E. M., LAU, S., RINEHART, K. L., SHAW, G. R. EAGLESHAM, G. K. 2001. Human Fatalities from Cyanobacteria: Chemical and Biological Evidence for Cyanotoxins. Environ Health Perspect, 109, 663-668. CODD, G. A., BELL, S. G., KAYA, K., WARD, C. J., BEATTIE, K. A. METCALF, J. S. 1999. Cyanobacterial toxins, exposure routes and human health. European Journal of Phycology, 34, 405-415. CODD, G. A., MORRISON, L. F. J.S, M. 2005. Cyanobacterial toxins: risk management for health protection. Toxicology and Applied Pharmacology, 203, 264-272. DEVLIN, J.P., EDWARDS, O.E., GORHAM. P.R., HUNTER. M.R., PIKE, R.K. STAVRIC, B. 1977.  Anatoxin-a, a toxic alkaloid from Anabaena flos-aquae NCR-44h. J. of Chem, 55, 1367-1371. DITTMANN, E. WIEGAND, C. 2006. Cyanobacterial toxins occurrence, biosynthesis, and impact on human affairs. Molecular Nutrition Food Resources, 50, 7-17. DUY, T.N., LAM, P.K.S., SHAW, G.R CONNELL, D.W. 2000. Toxicology and risk assessment of freshwater  cyanobacterial (Blue green algae) toxins in water. Rev Environ Contam Toxicol, 163, 113-186. EDWARDS, C., BEATTIE, K., SCRIMGOUR, C. Codd, G. 1992. Identification of anatoxin-a in benthic  cyanobacteria (blue-green algae) and in associated dog poisonings at Loch lnsh, Scotland.  Toxicon, 30, 1165-1175. FALCONER, I. R. 1998. An Overview of Problems Caused by Toxic Blue-Green Algae (Cyanobacteria) in Drinking and Recreational Water. John Wiley Sons, Inc. Environ Toxicol, 14, 5-12. FALCONER, I. R. HUMPAGE, A. R. 2006. Cyanobacterial (Blue-Green Algal) Toxins in Water Supplies: Cylindrospermopsins. Wiley Periodicals, Inc. Environ Toxicol, 21, 299-304. FRANCIS, G. 1878. Poisonous Australian Lake. Nature, 18, 11-12. GOODMAN, T., FALCONER, I. FITZGERALD, J. 1999. Human Health Aspects. In: BARTRAM, I. C. A. J. (ed.) Toxic Cyanobacteria in Water: A guide to their public health consequences,monitoring and management. World Health Organization. HENSON, B. J., WATSON, L.E., BARNUM, S.R. 2002. Molecular Differentiation of the Heterocystous Cyanobacteria, Nostoc and Anabaena, Based on Complete NifD Sequences. Current Microbiology, 45, 161-164. HITZFELD, B. C., HOGER, S. J. DIETRICH, D. R. 2000. Cyanobacterial Toxins: Removal during Drinking Water Treatment, and Human Risk Assessment. Environmental Health Perspect

Vivid Atmosphere

Vivid Atmosphere: Tennis Slowly, I kneel down to tie my shoe for the fourth time this match. The sweat creeps down my face as if mocking me in saying that I should have taken the cardio sessions more seriously. At this point I was doing everything I could just to keep my body from collapsing to the ground. The feel of the sun beating down makes me wonder if it is purposely driving all of its energy to sap mine. Glancing up across the court I see my water bottle filled with mountain dew.At that very moment the sugary, citrusy scent flows through my nose increasing my thirst even more. I could care less if everyone knows that my shoe really wasn’t untied, and they did. This was too much, the constant sprinting back and forth while trying to place the ball in that perfect spot. Why would anyone participate in something like this willingly? Somehow I always pick the best hobbies. It’s been about a minute now and my hand tightens around the sticky tape of my racket as I use every ounce of energy I have left to stand to my feet.Standing there my weight now shifts back and forth between my tired and blistered feet. She serves. My fast reflexes allow me to throw my racket to where the ball is going and my jaw tenses as I brace myself for impact. The vibrations tingle up my arm as I strategically swing through the ball at the perfect speed and angle. Well, almost perfect. The disappointment of another return into the net. A smirk on my opponent’s face shows her attempt at hiding the satisfaction she has in winning†¦. again.

Slides

Because they contain N functions, the dyes were screened in vitro for antibacterial activity; of over 0,000 tested dyes none showed any antibiotic activity However, In vivo studies with mice, that had been infected with a bacterial culture, showed that several dyes counteracted gram-positive bacterial Intections. HDR. F. 2013 Prontosll Gerhard Domagk (Nobel Prize, 1939) was a research scientist at l. c. Farbenlndustrle,a German manufacturer of dyes and other chemicals. He carried out studies that showed Prontosil to be an effective antibacterial agent.When Domagk's daughter developed a streptococcal Infection (having cut her finger), and was in danger of having an arm amputated (or worse), she was the first patient to receive rontosil and be cured by it (1935). Prontosil received wider tame when it was used to save the lite ot Franklin D. Roosevelt, Jr. , son of the US president. HDR-F-2013 infected with a bacterial culture. Several dyes were found to counteract gram-positive bacteri al infections. NH2 o s Prontosil Later it was discovered that, in living organisms, Prontosil is converted to sulfanilamide, and that sulfanilamide was the actual active compound.Sulfanilamide inhibits the synthesis of folic acid, which is an essential chemical compound for bacterial growth. Penicillin bacterial infections in 1941. By 1943, penicillin was being produced for the military and was first used for war casualties in Sicily and Tunsia. CH3 Penicillins act by modifying an enzyme involved in the synthesis ofa a bacterium's cell wall. the synthesis of bacterium's cell wall. Actively growing bacteria die because they areare Actively growing bacteria die because they unable to produce a a functional cell wall. unable to produce functional cell wall.Penicillins have no effect on mammalian cells because they are not enclosed by cell walls. The first penicillin was isolated in in 1938 and The first penicillin was isolated 1938 and ound to cure bacterial infections in in mice. was found to cure bacterial infections mice. It It was used successfully in nine cases ofof human used successfully in nine cases human Hormones Hormones are chemical messengers – organic compounds synthesized in glands and delivered by the bloodstream to target tissues in order to stimulate or inhibit some biochemical process. Many hormones are steroids.Remember: All steroids contain a tetracyclic ring system. The most abundant member of the steroid family in anlmals (ana numans) Is cnolestero of all other steroids. Steroids c t Is tne precursor Steroids are organic compounds that contain four cycloalkane rings, three cyclohexane rings and one cyclopentane ring; they are Joined (fused) in a specific way. The steroid core has 20 C atoms, 17 form the four rings, plus three methyl groups. sack to HORMONES Sex The sex hormones are divided into three groups: (1) the male sex hormones, or androgens; (2) the female sex hormones, or estrogens; (3) the pregnancy hormones, or progestins.A ll sex hormones are steroids. ster010s perTorm many Tunctlons n Function Regulation of secondary sexual characteristics Reproduction and control of the reproductive cycle Regulation of metabolism Examples Estradiol (an estrogen); testosterone (an androgen) Progesterone and the gestagens Digestion of fat Cell membrane component Cholic acid; bile salts Cholesterol Cortisol; cortisone derivatives This is the basic carbon skeleton for all steroids. 10. 7 Testosterone, the principal male sex hormone, is responsible for male secondary sex characteristics.Synthetic testosterone analogs (anabolic steroids) are used in medicine to promote muscle and tissue growth, e. g. , patients with muscular atrophy. Anabolic steroids are used illegally, most commonly by â€Å"body builders† and athletes. The health risks are numerous, including liver cancer, coronary neart Olsease, ana s er Estradiol is the principal female sex hormone. It is responsible for the development of the female secondary sex characteristics and participates in the control of the menstrual cycle.Progesterone is an example of a progestin: it prepares the uterus for the implantation of a fertilized egg. Synthetic analogs of progesterone and estradiol are the active agents in the birth control pill, allowing for control of the menstrual cycle and ovulation. An estimated 50 to 60 million women worldwide use â€Å"the pill† as the primary form of ontraception. Drug Use RU-486, The Abortion Pill RI-J-486 acts as an antagonist – a drug that fits into a receptor site, but does not have the customary effect as does another drug; in this case the other drug is progesterone.Cortisone Cortisone, used extensively in the treatment of rheumatoid inflammations, is one of the adrenocortical hormones produced in the outer part of the adrenal gland. These hormones participate in regulating the electrolyte and water balance in the body, as well as in protein and carbohydrate metabolism. Ethics of Methotre xate is a prescription drug used in the reatment of breast cancer. It can be used to block the action of folic acid, which is required for normal cell Olvlslon ana growtn 0T an emoryo.LIKe RI-J-486, it can be used to induce abortion in the weeks of pregnancy. Once a drug is approved by the FDA, a physician can prescribe it for purposes not originally intended by the drug manufacturer. Medicines Prescription, Generic, and the pioneer drug, but cannot Prescription, is chemically equivalent to Over-the-counter be A generic drug Generic, and Over-the-counter marketed until the patent protection on the pioneer drug has run out after 20 ears.A generic drug is chemically equivalent to the pioneer drug, but cannot be A generic drug is chemically equivalent to the pioneer drug, but cannot be marketed until the patent protection on the pioneer drug has run The lower priced drug protection on the pioneer its generic name,out after 20 marketed until the patent commonly marketed under drug has r un out in this20 after case alprazolam instead of Xanax. The lower priced drug commonly marketed under its generic name, in this The lower priced druginstead of Xanax. case alprazolam commonly marketed under its generic name, in thisPrescription, Generic, and Over-the-counter A generic drug is chemically equivalent to the pioneer drug, but cannot be marketed until the patent protection on the pioneer drug has run out after 20 years. 10. 10 The lower priced drug commonly marketed under its generic name, in this case alprazolam instead of Xanax. 10. 1 Heroal Remeales 10. 11 Ephedra Ephedra – used safely for thousands of years as herbal remedy known as Ma Huang. In 2003, several deaths related to the ingredients led the FDA (in 2004) to ban ephedra products. At this time, there are ongoing discussions to make the product available again.The herb contains the amphetamine-like alkaloids – ephedrine and the less active pseudoephedrine. Pseudoephedrene is used as a decongesta nt Ephedrine is a bronchodilator (opens the airways), and a stimulant Drugs of Abuse Ephreda was responsible for the deaths of over 80 people. An ephreda manufacturer challenged the FDA ban in court, claiming that the FDA had failed to prove that ephreda was not safe at low doses. In 2006, the US Court of Appeals for the Tenth Circuit upheld the FDA's ban on ephreda. Heroin Morphin diacetylmorphin, alkaloid in opium â€Å"chemically modified† high the â€Å"abused† natural drugTetrahydrocannabinol – Marijuana A9-tetrahydrocannabinol is the principal psychoactive component of the cannabis plant (marijuana), the most commonly abused illicit drug in the US; effects include euphoria and anxiety. Medical uses are being discussed; legal in some states; the Federal Government is opposed. One way to look at drugs is to classify them by their medical usefulness and their potential of abuse. Drugs of abuse can also be classified by their tendency to lead to physical depen dence (addiction) vs. the physical harm they inflict on the user. Many addictive drugs are also highly detrimental to uman health.OxyconBn OxyContin contains oxycodone Oxycodone has been used safely for many years. But this formulation includes a time-released mechanism for long-lasting treatment of chronic pain. Drug abusers quickly determined how to get around the time-release and were able to rapidly ingest large amounts of oxycodone. The effects were said to be similar to heroin. Over-prescribed in the Appalachian areas in late 1990s and early 2000s. Many became addicted. An Amino Acid serotonin Tryptophan is converted to serotonin, an antidepressant, which is converted to melotonin, inducing drowsiness

Studio Business Plan Essay - 4772 Words

The Cage Recording Studio P.O. Box 240092 Montgomery, AL 36124-0092 (334) 260-3739 Fax: (425) 650-5190 Email: cagestudio@yahoo.com www.cagestudio.itgo.com Business Plan Prepared by Eric Gwin Owner and Operator Executive Summary ....................................................................... 2 Purpose of Business....................................................................... 3 Mission Statement:..................................................................................................................................... 3 Our History................................................................................................................................................. 3 Description of†¦show more content†¦Our target market is primarily independent musicians who are not signed by record labels, singer/songwriters who are looking for ways of recording their music, choirs, and other church groups. We will focus on our specialization of vocal and acoustic production and we will also offer other resources for musicians such as equipment rentals, web promotion, and sheet music publishing. As far as our studio business is concerned, we will concentrate on the area around Montgomery, Alabama, where we are located, and we will strive to meet the needs of the above target market, as well as the growing need for recording services among the col lege and artistic community in Montgomery. The owner will provide all financing. He has accumulated a significant sum of money through his previous endeavors in the recording business as a studio engineer and session vocalist. In this business plan, we have tried to include everything anyone might ever want to know about The Cage, as well as the recording industry as a whole. 2 Purpose of Business Mission Statement: Whether you are a musician longing to express your creativity in a recorded work, a business owner looking to advertise with a commercial jingle, or a promoter in need of a sound system for your next event, our mission is to meet your creative needs with quality professional audio productionShow MoreRelatedBusiness Plan for a Multimedia Studio2978 Words   |  12 Pages BUSINESS PLAN FOR KING STUDIOS 28, Pound Road Magodo 01-XXX6634 1.0 Executive Summary 1 2.0 Company Summary 2 3.0 Services 4 4.0 Market Analysis Summary 4 5.0 Strategy and Implementation Summary 8 6.0 Management Summary 12 7.0 Financial Plan 13 1.0 Executive Summary King Studios, located in Magodo, Lagos will serve small and medium-sized businesses and non-profits for all of their studio photography needs by  creating beautiful shots that serve the clients needs, offering  excellentRead MoreCareer Research : I Became A Dance Teacher1422 Words   |  6 Pagesme to teach high school in the day but own my own dance studio. 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Conclusion†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.. Executive summary: The blush hair and beauty studio (salon) is located in Ringwood