Anthrax

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Anthrax most commonly occurs in hoofed mammals and can also infect humans. 

Symptoms of disease vary depending on how the disease was contracted, but usually occur within 7 days after exposure. The serious forms of human anthrax are inhalation anthrax, cutaneous anthrax, and intestinal anthrax. 

Initial symptoms of inhalation anthrax infection tnay resemble a common cold. After several days, the. symptoms may progress to severe breathing problems and shock. Inhalation anthrax is often fatal. 

The intestinal disease form of anthrax may follow the consumption of contaminated food and is characterized by an acute inflammation of the intestinal tract. Initial signs of nausea, lo.ss of appetite, vomiting, and fever are followed by abdominal pain, vomiting of blood, and severe diarrhea. 

Direct person-to-person spread of andirax is extremely unlikely, if it occurs at all. Therefore, there is no need to immunize or treat contacts of persons ill with anthrax, such as household contacts, friends, or coworkers, unless they also were also exposed to the same source of infection. 

Spores germinate to bacillary form, multiply in macrophages, release toxins causing edema, hemorrhage, and tissue necrosis tissue damage caused by release of toxins - protective antigen, lethal toxin, edema toxin [29] 

Source Spores from infected animals, esp cattle 

Bowel movements - blood or black (melena) [G] Bowel movements - diarrhea [G] 

Breathing - difficult, rest (rest dyspnea) [I] Breathing - rapid (tachypnea) [I] 

Breath sounds, basilar - decreased Breath sounds - crackling (rales) [I] 

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More recently PCR proved to be a valuable detection and analytical tool during the terrorist inspired anthrax outbreak m the fall of 2001... 

Robert Koch, in Germany in 1881, did scientific laboratory tests on 70 different chemicals, at different concentrations and in different solvents, to assess thek abiUty to kill spores of anthrax bacteria (7). Refinement of the testing methods were made in 1897, 1903, and 1908 (8). They continued to be improved, standardized, and pubUshed under the auspices of organizations like the Association of Official Analytical Chemists (AOAC) (now called AO AC International). 

Blut rot, n. hemoglobin hematin, ruhr, /. dysentery. s ure, /, thiocyanic acid. 06s, scheibe, /. blood corpuscle. schlag, m. apoplexy. seuche, /. anthrax. stein, m. bloodstone, hematite. 

MUz-. splenic, -brand, m. anthrax, -brand-gift, n. anthrax virus. -driise,/. spleen. Mimose, /. mimosa. 

Protein toxins acting intracellularly are often composed of two subunits (A/B model). One subunit is catalytic (A-subunit) and the other is responsible for binding and cell entry (B-subunit). Following binding to an extracellular membrane receptor, the toxins are endocytosed. From the endosomes, the A-subunit is directly (pH dqDendent) transferred into the cytosol (e.g., diphtheria toxin and anthrax toxin) or the toxin is transported in a retrograde manner via the golgi to the ER (e.g., cholera toxin), where translocation into the cytosol occurs [1]. 

Another subfamily of ADP-iibosylating toxins modifies G-actin (at Argl77), thereby inhibiting actin polymerization. Members of this family are, for example, C. botulinum C2 toxin and Clostridium perfringens iota toxin. These toxins are binary in structure. They consist of an enzyme component and a separate binding component, which is structurally related to the binding component of anthrax toxin [3]. 

Anthrax toxin Lethal factor Lethal factor MEKs Endoprotease Increase in intracellular cAMP Inhibition of MAP-kinase pathways Calmodulin dependent adenylylcyclase... 

The anthrax toxin is a tripartite toxin and consists ofthe binding component protective antigen (PA), the lethal factor (LF), which is a metalloprotease, and the edema factor (EF), which is a calmodulin-dependent adenylyl-cyclase. Both enzyme components are translocated via PA into target cells. PA is activated by furin-induced cleavage and forms heptamers, which are similar to the binding components of C2 toxin and iota toxin. In the low pH compartment of endosomes, the heptamers form pores to allow translocation of LF and EF. LF cleaves six of the seven MEKs (MAPK-kinases) thereby inhibiting these enzymes. The functional consequence is the blockade of the MAPK pathways that control cell proliferation, differentiation, inflammation, stress response, and survival. Whether this is the reason for the LT-induced cell death of macrophages is not clear [1]. 

MA M34 M34.001 Anthrax lethal factor Component of anthrax toxin... 

Soelaiman S, Wei BQ, Bergson P, Lee YS, Shen Y, Mrksich M, Shoichet BK, Tang WJ. Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough. J Biol Chem 2003 278 25990-7. 

Bacillus anthracis, the causative organism of anthrax, possesses a capsule composed of polyglutamic acid the slime layers produced by other organisms are of a carbohydrate nature. 

In 1880, the bacteriologist Robert Koch had noted that anthrax spores were more rapidly killed by the same concentrahons of phenol if the temperature was elevated. A former pharmacopoeial sterilizahon process heating with a bactericide used an elevated temperature, 80-100°C, maintained for 30 minutes, to ensure that quite low concentrations of bactericides would sterilize parenteral injections and eye-drops. 

Anthrax Medium from cuitures of B. anthracis 1 Separation of protective antigen from medium 2 Adsorption 3 + 3 quantal assay in guinea-pigs using challenge with B. anthracis Exclusion of live 6. anthracis and of anthrax toxin... 

Whilst not recommended for routine administration, vaeoines additional to those represented in the juvenile programme are available for individuals in special risk categories. These categories relate to oeeupational risks or risks associated with travel abroad. Such immunization protocols include those directed against cholera, typhoid, meningitis (types A, C), anthrax, hepatitis A and B, influenza, Japanese encephahtis, rabies, tick-borne encephalitis, and yellow fever. 

Fluoroquinolones Not approved by the United States Food and Drug Administration for use in children except for anthrax (ciprofloxacin). MRSA, methicillin-resistant 5. aureus MSSA, methicillin-sensitive 5. aureus. 

Slow-acting, noncontagious biological agents. These agents, which include viruses as well as the bacterial causative agents for anthrax and tularemia, produce no initial symptoms, but cause flu-like symptoms after a... 

Slow-acting, noncontagious Bacillus anthracis (anthrax) Flu-like symptoms <7 days... 

The recruitment of zinc for a structural role, or to activate an enzyme, has been observed. The zinc ion induces the dimerization of human growth hormone (hGH), with two Zn ions associated per dimer of hGH. This is confirmed by replacement of possible zinc binding residues resulting in weakened binding of the zinc ion. Formation of a zinc-hGH dimeric complex may be important for storage of hGH in secretory granules.975 In a toxic role, anthrax lethal factor is one of the three components of the secreted toxin and is a zinc-dependent protease that cleaves a protein kinase and causes lysis of macrophages.976... 

The biological activity of a compound can often be affected dramatically by the presence of even a single fluorine substituent that is placed in a particular position within the molecule. There are diverse reasons for this, which have been discussed briefly in the preface and introduction of this book. A few illustrative examples of bioactive compounds containing a single fluorine substituent are given in Fig. 3.1. These include what is probably the first example of enhanced bioactivity due to fluorine substitution, that of the corticosteroid 3-1 below wherein Fried discovered, in 1954, that the enhanced acidity of the fluorohydrin enhanced the activity of the compound.1 Also pictured are the antibacterial (3-fluoro amino acid, FA (3-2), which acts as a suicide substrate enzyme inactivator, and the well-known anti-anthrax drug, CIPRO (3-3). 

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