Inhibitors against BoNT/A The detailed mechanism of BoNT pathogenicity and the structure-function relationship of BoNT provide invaluable targets for development of the antidotes and inhibitors against botulism. The BoNT molecule is divided in clear functional domains that can operate independently. This feature provides multiple targets for designing therapeutics to treat botulism. High throughput screening and the combinatorial chemistry provide another useful tool for screening the inhibitors against botulism (Cai and Singh, 2007). Early work with zinc metalloprotease inhibitors focused on the well-characterized agents captopril ((2S)-1-[(2S)-2-methyl-3-sulfanyl-propanoyl] pyrrolidine-2-carboxylic acid) and phosphoramidon (N-alpha-L-rhamno pyranosyl oxy [hydroxyl phosphinyl]-L-leucyl-L-tryptophan). These compounds, however, were found to have little inhibitory activity against BoNT (Adler et al., 1994, 1999a). Phosphoramidon analogs in which Leu–Trp was replaced by Phe–Glu to resemble the cleavage site of synaptobrevin exhibited little increase in inhibitory activity (Adler et al., 1999a). So far, numerous peptide and small molecule based inhibitors have been identified by several researchers. Schmidt et al., (1998) made single residue changes near the cleavage site of a 17-mer SNAP-25 peptide that was a minimal substrate for BoNT/A. The best inhibitors in this series had Ki values of ~2 mM in cell-free assays. With further elaboration of this approach, more potent inhibitors were developed, as exemplified by the pseudo peptide, 2-mercapto-3-phenylpropionyl-RATKML (Ki=0.33 mM; Schmidt and Stafford, 2002). Burnett et al. (2007) examined the interaction of this molecule with the active site of BoNT/A LC. Sukonpan et al. (2004) a... ... middle of paper ... ...ubstrate by non-perfectly conserved residues’ and by ‘the residues flanking the active-site region.’ This suggestion is consistent with the observation that two exosites are crucial for SNAP-25 binding to the LC of BoNT/A (Breidenbach and Brunger, 2004). The α- and ß-exosites were recognized as being potentially important in the development of specific inhibitory drugs, and targeting the peripheral sites of substrate binding has focused on a family of bis-imidazole inhibitors for BoNT/A (Merino et al., 2006). A recent study by Eubanks et al. (2007) has highlighted limitations of conventional drug development paradigms. The authors found that high-throughput screens did not consistently predict the candidates that would be most effective in their cell-based assays. Eubanks et al. (2007) also observed that efficacy in cell culture did not predict protection in vivo.
Nigam, P. K. and Anjana Nigam. “Botulinum Toxin.” Indian Journal of Dermatology 55.1 (2010): n.p. Web. 26 Jan. 2014.
Gordons, S. (2006, February 1). Drug Helps Babies Fight Deadly Botulism. HealthyDay Consumer News Service.
Its ability to inhibit phosphodiestarase type 1 leading to an increase in the concentration of cyclic AMP which is thought to result in its vasodilator effects
The Plague (French, La Peste) is a novel written by Albert Camus that is about an epidemic of bubonic plague. The Plague is set in a small Mediterranean town in North Africa called Oran. Dr. Bernard Rieux, one of the main characters, describes it as an ugly town. Oran’s inhabitants are boring people who appear to live, for the most part, habitual lives. The main focus of the town is money. “…everyone is bored, and devotes himself to cultivating habits. Our citizens work hard, but solely with the object of getting rich. Their chief interest is in commerce, and their chief aim in life is, as they call it, 'doing business’” (Camus 4). The citizens’ unawareness of life’s riches and pleasures show their susceptibility to the oncoming plague. They don’t bother themselves with matters not involving money. It is very easy for the reader to realize that they are too naive to combat the forthcoming calamity. The theme of not knowing life is more than work and habits will narrow the people’s chances of survival. Rieux explains that the town had a view of death as something that happens every day. He then explains that the town really doesn’t face towards the Mediterranean Sea. Actually it is almost impossible to see the sea from town. Oran is a town which seems to turn its back on life and freedom. The Plague was first published in 1948 in France. “Early readers were quick to note that it was in part an allegory of the German occupation of France from 1940 to 1944, which cut France off from the outside world; just as in the novel the town of Oran must close its gates to isolate the plague” (“The Plague” 202). When the plague first arrives, the residents are slow to realize the extreme danger they are in. Once they finally become aware of it...
In his novel The Plague, Albert Camus presents a pseudo-historical documentary of a plague that confines and controls the citizens of Oran within their city gates. The plague possesses the power of life and death over the people, as it determines which citizens will face their death or those who work to stop death. These latter men, personified by the characters of Rieux, Grand, and Tarrau, each struggle endlessly to master the plague's power over their lives, even with the realization they may never succeed. For Camus, this idea of an "impossible struggle" against an unseen power resonates throughout the novel and reoccurs in another "plague" which these men must contend with - the limits of human language. Camus's characters place great emphasis and importance upon the power of language and lament their inability to express themselves clearly.
From 166 A.D. to 180 A.D., The Antonine Plague spread around Europe devastating many countries. This epidemic killed thousands per day and is also known as the modern-day name Smallpox. It is known as one of deadliest plagues around the world.
Botulinum toxin serotypes A and B have been approved for both therapeutic and cosmetic purposes. (1,4) Medical treatment for conditions such as strabismus (...
No matter what, where, or who you are, water is a necessary component to keeping any organism alive. Although water is essential for life, in many places, clean drinking water is hard to find. There are many consequences to drinking contaminated water. Every year, three to five million people are attacked by water-borne diseases and over 100,000 of them die. One fatal disease that can kill within hours is cholera.
The Bubonic Plague, otherwise known as the Black Death was a raging disease. Most people thought of it as the physical Grim Reaper of their town or community. The disease lasted about six years, 1347 to 1352. The Bubonic Plague was a travesty that has traveled throughout Europe and has raged and decimated both large and small towns, putting Europe through a lot.
Anthrax is a bacterial disease caused by bacteria called Bacillus anthracis (buh-SIL-us an-THRAY-sus). The Bacillus anthracis can exist in two different forms: favorable form, when the bacteria are rod-shaped and can grow and divide, or the unfavorable form, when they form a very resistant dormant spore that helps them survive extreme environmental conditions. Like other bacteria, Bacillus anthracis is very small, only about 1 by 9 micrometers in size. It is Gram-positive, which makes the bacteria purple-pinkish rods, with a relatively long lifespan of over 70 years. Bacillus anthracis feed on iron, oxygen, water, and nutrients to survive and reproduce. Bacillus anthracis need a favorable environment, but can reproduce in many different ways, either through spore germination, asexual bacterial reproduction, or formation of new spores. Herbivore animals such as cattle, sheep, and goats are the primary target of these bacteria and can be infected when they breathe in or ingest spores in contaminated soil, plants, or water. These elliptical shaped spores have thick and layered walls which make it resistant to heat, dryness, ultraviolet light, and gamma radiations. These spores initially develop inside the rod-shaped form, causing it to be named endospore. Because the bacteria is zoonosis, which means that it affects domestic and wild animals primarily, it is very rare for people to be infected by anthrax, but it is theoretically possible when the spores get into the body either through coming in contact with infected animals or contaminated animal products. Even though people can be infected with anthrax through animal contacts, it is not contagious, meaning that it cannot be transmitted from a person to person. After the spores get ...
There are many diseases that fit into each of the four categories, if not one category, maybe two or more.
Anthrax is a bacterial disease instigated by the endospore-forming, rod-shaped bacterium Bacillus anthracis . Anthrax itself comes from the Greek word for coal, nthrax, attributable to the coal colored lesions that oftentimes develop on victims’ dermis. Though the sporadic disease most commonly affects animals in agricultural regions, it can sometimes infect humans and cause serious illness as well as both hypodermic and internal infections that can prove fatal to those infected.
Virus, Infection, and Pathogens As you begin this course, it is important for you to develop an understanding of a few key terms. These key terms are virus, infection, pathogen, and blood borne pathogen. A thorough understanding of these terms will help you better understand the concepts in subsequent sections of the course.
Handling and caring for rodents (including hamsters and gerbils) or even fish, puts humans at risk for the below-mentioned infections.
15. Table 1. A List of Commonly Used Synthetic Peptide Substrates for Caspases. From Apoptosis Methods and Protocols (pp. 21). New Jersey: Humana Press Inc.