Friday, March 28, 2008

2nd paper

Anthrax

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Biological warfare is the use of bacteria, viruses, or toxins to destroy things such as people or crops. The use of biological toxins extracted from plants and animals on arrow heads or poison darts to kill enemies and prey predates recorded history as we know it [1]. This technology is still being used by some African and South American cultures. In the developing world, there are many forms of biological (germ) warfare. Anthrax is one of the oldest recorded diseases used in biological warfare. It has infected animals such as cows, sheep, and other grazing herds. It has also affected humans who work with these animals and their by parts [2].

Cases of humans using biological warfare have been well recorded in history. During the middle ages, it was common to catapult dead bodies infected with smallpox or the bubonic plague over opposing city walls in battle [1]. In 1763, British troops gave Indians blankets used by people with smallpox. Japan contaminated food and released plague-infected ticks during their conflict with China during World War 2 [3]. In 1969 President Nixon terminated the U.S. biological weapons program. The program had two lethal biological agents, Bacillus anthrax and Francisella tularensis (tularemia), these were already standardized and weaponized [1]. Bacillus anthracis is the bacterium that causes anthrax [2]. In 2001, an anthrax letter in the United States infected twenty-two people and killed five [3].

Several differences set biological weapons apart from other weapons of mass destruction like nuclear and chemical weapons. Biological and chemical weapons share characteristics that are distinct from nuclear weapons [4]. The materials needed to create a weapon can be easily acquired because they either have other legitimate uses or occur in nature. An aspect that differs biological and chemical weapons is that once the agent is released it may not be immediately detectable [3]. There are systems that detect biological agents, but most have a delay between acquiring the agent and identifying it. The effects of an attack are not immediately detectable. People may become exposed to an agent soon after its release, but the infection requires time to cause illness. Thus, one of the first indicators of a biological weapon attack could be the outbreak of the disease [3].

Anthrax is commonly found in the ground or on a surface. Anthrax spores are relatively harmless, but once they come into contact with the right environment they begin to germinate. They need an environment that is rich in amino acids, nucleotides and glucose. These elements are also found in the blood and other tissues in humans and animals [2]. Anthrax can enter the body through the intestines through ingestion, the lungs through inhalation, or skin through cuts. An infected human will usually be quarantined. However, anthrax usually does not spread from an infected human to a non-infected human [5]. Repertory infection comes with cold or flu-like symptoms followed by severe respiratory collapse. This disease can rarely be treated, even if it is caught in early stages of infestation. Inhalation of anthrax is almost 100% fatal [5].

Intestinal infection is most often caused by eating anthrax-infected meat. It is characterized by serious intestinal difficulty, vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Some lesions have been found in the intestines and in the mouth and throat. After the bacterium enters the bowel system, it spreads through the bloodstream throughout the body, making even more toxins on the way. Intestinal infections can be treated but usually result in fatality rates of 25% to 60%, depending upon how soon treatment begins.

Anthrax that shows up as a boil- like skin lesion that eventually forms an ulcer with a black center. The black center often shows up as a large, painless, ulcer, beginning as an irritating and itchy skin lesion or blister that shows up as a black dot at the site of infection. This type of infection is the least fatal form of anthrax infection if treated. But without treatment, approximately 20% of all types of the skin infection cases may progress to toxemia and death [5].

Viewed at the cellular level, an anthrax bacterium looks like a jointed rod. When it enters the body and finds the environment it needs, it moves to the lymph nodes. From there it begins to multiply and produce a toxin that attacks human cells resulting in swelling, a drop in blood pressure, and ultimately death [2].

The way it attacks the cells and exactly what it does, was in question for many years. In the mid 1980s, some interesting facts about the behavior of the anthrax bacterium when it finds a host were discovered. Researchers found that there are three proteins that are created by the anthrax bacteria. These proteins are harmless individually, but together can be deadly. These proteins are referred to as: Protective antigen (PA), Edema factor (EF), Lethal factor (LF) [2].

The Protective Antigen is the main part of the three part toxin we know as anthrax. After the PA activation on the surface of the cell, it forms a membrane inserter called the heptamer. The heptamer transfers the toxic enzymes. The Protective Agent can also translate other heterologous proteins[6]. The protective antigen is made up of anti-parallel beta sheets with four domains. The amino-terminal domain has two calcium ions and a proteases activation site. The heptamerization domain has a large loop in the membrane insertion. The third domain has an unknown function. The carboxy-terminal receptor-binding domain is also one of the four domains.

The lethal factor is a zinc dependent that creates a specific bond in signaling proteins, which also destroys the signaling ability [7]. Proteins of the mitogen-activated protein kinase family, gets cleaved by the lethal factor. The crystal structure of the lethal factor is very complex.

The edema factor is a calmodulin-dependant. It is the main factor in the skin infections of anthrax. The role of the edema factor has been uncovered by the crystal structure, coupled with calmodulin. When it enters the cell, it creates more AMP and complexes the calmodulin [7].

When these proteins are released, the protective antigen binds to the cell surface and forms a channel in the cell membrane that allows the edema factor and lethal factor to enter the cell. The edema factor, combined with the protective antigen, forms a toxin known as the edema toxin. The lethal factor, when combined with the protective antigen, forms a toxin known as the lethal toxin. It is the lethal toxin that does the most damage within the cell [2]. With what we know about anthrax, we can now cure 70% of all anthrax infections.

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