Instruct: Given a question, retrieve passages that answer the question.
Query: How do anti toxins work?
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria. Although they are most effective in neutralizing toxins, they can kill bacteria and other microorganisms. Antitoxins are made within organisms, but can be injected into other organisms, including humans. This procedure involves injecting an animal with a safe amount of a particular toxin. Then, the animal’s body makes the antitoxin needed to neutralize the toxin. Later, the blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing passive immunity. To prevent serum sickness, it is often best to use antitoxin generated from the same species (e.g. use human antitoxin to treat humans).
Lizards such as the Gila monster produce toxins with medical applications. Gila toxin reduces plasma glucose; the substance is now synthesised for use in the anti-diabetes drug exenatide (Byetta). A toxin from Gila monster saliva has been studied for use as an anti-Alzheimer's drug.
In CKD numerous uremic toxins accumulate in the blood. Even when ESKD (largely synonymous with CKD5) is treated with dialysis, the toxin levels do not go back to normal as dialysis is not that efficient. Similarly, after a kidney transplant, the levels may not go back to normal as the transplanted kidney may not work 100%. If it does, the creatinine level is often normal. The toxins show various cytotoxic activities in the serum and have different molecular weights, and some of them are bound to other proteins, primarily to albumin. Uremic toxins are classified into three groups as small water-soluble solutes, middle molecular-weight solutes, and protein-bound solutes. Hemodialysis with high-flux dialysis membrane, long or frequent treatment, and increased blood/dialysate flow has improved removal of water-soluble small molecular weight uremic toxins. Middle molecular weight molecules are removed more effectively with hemodialysis using a high-flux membrane, hemodiafiltration and hemofiltration. However, conventional dialysis treatment is limited in its ability to remove protein-bound uremic toxins.
When a polymorphic toxin with anti-bacterial activity is produced by a bacterial strain, this strain is protected by a specific immunity protein encoded by a gene immediately downstream of the toxin gene.
The toxins responsible for most shellfish poisonings are water insoluble, heat and acid-stable, and ordinary cooking methods do not eliminate the toxins. The principal toxin responsible for PSP is saxitoxin. Some shellfish can store this toxin for several weeks after a harmful algal bloom passes, but others, such as butter clams, are known to store the toxin for up to two years. Additional toxins are found, such as neosaxitoxin and gonyautoxins I to IV. All of them act primarily on the nervous system.
Lizards such as the Gila monster produce toxins with medical applications. Gila toxin reduces plasma glucose; the substance is now synthesised for use in the anti-diabetes drug exenatide (Byetta). Another toxin from Gila monster saliva has been studied for use as an anti-Alzheimer's drug.
Presynaptic neurotoxins, commonly known as β-neurotoxins, affect the presynaptic regions of the neuromuscular junction. The majority of these neurotoxins act by inhibiting the release of neurotransmitters, such as acetylcholine, into the synapse between neurons. However, some of these toxins have also been known to enhance neurotransmitter release. Those that inhibit neurotransmitter release create a neuromuscular blockade that prevents signaling molecules from reaching their postsynaptic target receptors. In doing so, the victim of these snake bite suffer from profound weakness. Such neurotoxins do not respond well to anti-venoms. After one hour of inoculation of these toxins, including notexin and taipoxin, many of the affected nerve terminals show signs of irreversible physical damage, leaving them devoid of any synaptic vesicles.
Anthrax is a disease caused by "Bacillus anthracis", a spore-forming, Gram positive, rod-shaped bacterium (Fig. 1). The lethality of the disease is caused by the bacterium's two principal virulence factors: (i) the polyglutamic acid capsule, which is anti-phagocytic, and (ii) the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: (i) protective antigen (PA), (ii) edema factor (EF), and (iii) lethal factor (LF).
In 1992, Stevens worked with researchers at Gilead on the structural studies of neuraminidase inhibitors that eventually became Tamiflu, and later partnered with Roche. After the initial experience with structure based drug discovery from 1992–1997 with Gilead and Tamiflu, Stevens focused on understanding the basic mechanism of how Botox (botulinum toxin) works, and on ways to use this scaffold for next generation protein therapeutics. In parallel to the work on botulinum toxin, Stevens worked on the enzymes involved in the catecholamine biosynthetic pathway, specifically the three aromatic amino acid hydroxylases including phenylalanine hydroxylase. From 1999-2004 Stevens was involved in the startup of Syrrx that developed the marketed drug Nesina for type II diabetes. From 2000–2010, Stevens has worked with BioMarin Pharmaceutical to develop Kuvan (tetrahydrobiopterin) and assisted in the design and development of PEG-PAL (pegylated Phenylalanine ammonia-lyase) as treatments for mild and classical phenylketonuria (PKU). In 2008 Stevens started Receptos that developed an S1P1 agonist for multiple sclerosis and inflammatory bowel disease and in 2011 he started RuiYi that developed an anti-CB1 antibody for liver fibrosis.
Type IV toxin-antitoxin systems are similar to type II systems, because they consist of two proteins. Unlike type II systems, the antitoxin in type IV toxin-antitoxin systems counteracts the activity of the toxin, and the two proteins do not directly interact.
Every toxic injury or expsoure to a toxin has different effects and symptoms. Some toxic effects do not necessarily cause permanent damage and can be reversible. However, some toxins can cause irreversible permanent damage. Depending on the intensity of the poison of the substance it can affect just one particular organ system or they may produce generalized toxicity by affecting a number of systems. A variety of symptoms occur depending on how and where the toxic injuries affect the body. Generally, if the toxins affect the respiratory system the symptoms are coughing, tight chest, difficulty in breathing and nose and throat irritation. Miscarriage or infertility can occur if it occurs in the ovaries or testes.Depression, severe headaches and dizziness are the symptoms for toxins affecting the spinal cord and brain. Visible reactions such as skin rashes, and swelling and eye redness are common. Exposure to asbestos can lead to Mesothelioma which is a cancer that can cause serious damage to the lining of the lungs. The symptoms include shortness of breath, cough, night sweats and fever.
Epistemological particularism is the belief that one can know something without knowing how one knows that thing. By this understanding, one's knowledge is justified before one knows how such belief could be justified. Taking this as a philosophical approach, one would ask the question "What do we know?" before asking "How do we know?" The term appears in Roderick Chisholm's "The Problem of the Criterion", and in the work of his student, Ernest Sosa ("The Raft and the Pyramid: Coherence versus Foundations in the Theory of Knowledge"). Particularism is contrasted with Methodism, which answers the latter question before the former. Since the question "What do we know" implies that we know, particularism is considered fundamentally anti-skeptical, and was ridiculed by Kant in the "Prolegomena".
In 2002, investigators' attention was drawn to the highly toxic Brazilian "Lonomia obliqua" caterpillar setae and their enzymatic fibrinolysin toxin. A caterpillar defense mechanism based on specific setal toxins made more biological sense than a defense based on intestinal cyanide content. More importantly, if the ETC abortions were due to an enzyme or toxin, it should be possible to vaccinate horses against the toxin, an approach already explored with reference to the "Lonomia" toxin. In June 2002, conception of this ETC enzymatic setal toxin hypothesis was recorded as an intellectual property (IP) disclosure with the University of Kentucky IP office in which creation of an anti-ETC abortifacient toxin vaccine was proposed.
The existence of automimicry in the form of non-toxic mimics of toxic members of the same species (analogous to Batesian mimicry) poses two challenges to evolutionary theory: how can automimicry be maintained, and how can it evolve? For the first question, as long as prey of the species are, on average, unprofitable for predators to attack, automimicry can persist. If this condition is not met, then the population of the species rapidly crashes. The second question is more difficult, and can also be rephrased as being about the mechanisms that keep warning signals honest. If signals were not honest, they would not be evolutionarily stable. If costs of using toxins for defence affects members of a species, then cheats might always have higher fitness than honest signallers defended by costly toxins. A variety of hypotheses have been put forth to explain signal honesty in aposematic species. First, toxins may not be costly. There is evidence that in some cases there is no cost, and that toxic compounds may actually be beneficial for purposes other than defence. If so, then automimics may simply be unlucky enough not to have gathered enough toxins from their environment. A second hypothesis for signal honesty is that there may be frequency-dependent advantages to automimicry. If predators switch between host plants that provide toxins and plants that do not, depending on the abundance of larvae on each type, then automimicry of toxic larvae by non-toxic larvae may be maintained in a balanced polymorphism. A third hypothesis is that automimics are more likely to die or to be injured by a predator's attack. If predators carefully sample their prey and spit out any that taste bad before doing significant damage ("go-slow" behaviour), then honest signallers would have an advantage over automimics that cheat.
Along with Venom, Anti-Venom, Hybrid and his sister Scorn, Toxin is mentioned as being the next option to stop Carnage's rampage in the Midwest after the Avengers are defeated. However, the US military is unable to find Toxin, leaving it up to the hybrid symbiotes and Scorn to stop Carnage.
ParD is a plasmid anti-toxin that forms a ribbon-helix-helix DNA binding structure. It stabilises plasmids by inhibiting ParE toxicity in cells that express ParD and ParE. ParD forms a dimer and also regulates its own promoter (parDE). As with CcdB the toxin target is DNA gyrase. Induction of ParE toxin results in inhibition of cell division but not cell growth.
Recently, studies have shown that alpha-toxin plays a role in inducing apoptosis in certain human immune cells. Incubation of T-cells, monocytes, and peripheral blood lymphocytes with either purified alpha-toxin or S. aureus cell lysate resulted in the induction of apoptosis via the intrinsic death pathway. This activity was inhibited when two different anti-alpha-toxin antibodies were introduced. In the same study, alpha toxin was shown to activate caspase 8 and caspase 9, which in turn activate caspase 3, which causes massive DNA degradation and apoptosis. This activity was shown to be independent of the death receptor pathway.
The TxpA/RatA toxin-antitoxin system was first identified in "Bacillus subtilis". It consists of a non-coding 222nt sRNA called RatA (RNA anti-toxin A) and a protein toxin named TxpA (Toxic protein A).
Shiga toxin, also known as Stx, is a toxin that is produced by the rod shaped "Shigella dysenteriae" and "Escherichia coli" (STEC). Food and drinks contaminated with these bacteria are the source of infection and how this toxin is spread. Symptoms include abdominal pain as well as watery diarrhea. Severe life-threatening cases are characterized by hemorrhagic colitis (HC). The discovery of shiga toxin is credited to Dr. Kiyoshi Shiga in 1898.
Technically, CAT-3888 is an anti-CD22 immunotoxin fusion protein between a murine anti-CD22 disulfide-linked Fv (dsFv) antibody fragment and an edited copy of bacterial Pseudomonas exotoxin PE38. The toxin is activated intracellularly, by the low pH of the lysosome into which the entire protein was internalized via the CD22 receptor. The toxin kills the targeted cell through ribosome inactivation.
It has been proposed that chromosomal homologues of plasmid toxin-antitoxin systems may serve as anti-addiction modules, which would allow progeny to lose a plasmid without suffering the effects of the toxin it encodes. For example, a chromosomal copy of "the ccdA" antitoxin encoded in the chromosome of "Erwinia chrysanthemi" is able to neutralize the "ccdB" toxin encoded on the F plasmid and thus, prevent toxin activation when such a plasmid is lost. Similarly, the "ataR" antitoxin encoded on the chromosome of is able neutralize the "ataT" toxin encoded on plasmids found in other enterohemorragic "E. coli".
Certain novel treatment strategies, such as the use of anti-induction strategies to prevent toxin production and the use of anti-Shiga toxin antibodies, have also been proposed.
In order for these types of toxins to take effect, post-ingestion toxin producers have to be consumed by a grazer. Post-ingestion toxins, also known as suicide toxins, are not beneficial to individual cells because unlike terrestrial plants, phytoplankton do not have sacrificial tissue. However, if internal toxins do result in the death, decrease growth rate, infertility, or deterrence of a predator the remaining representatives of the plankton community may benefit. Community defense is most beneficial in a clonal population where toxigenic species are abundant, for example during a monospecific phytoplankton bloom.
The complete covalent structure of several such toxins has been deduced: They comprise around 66 amino acid residues forming a three stranded anti-parallel beta sheet over which lies an alpha helix of approximately three turns. Four disulfide bridges cross-link the structure of the long-chain toxins whereas the short toxins contain only three. BmKAEP, an anti-epilepsy peptide isolated from the venom of the Manchurian scorpion, shows similarity to both scorpion neurotoxins and anti-insect toxins.
Toxin-antitoxin systems are typically classified according to how the antitoxin neutralises the toxin. In a type I toxin-antitoxin system, the translation of messenger RNA (mRNA) that encodes the toxin is inhibited by the binding of a small non-coding RNA antitoxin that binds the toxin mRNA. The toxic protein in a type II system is inhibited post-translationally by the binding of an antitoxin protein. Type III toxin-antitoxin systems consist of a small RNA that binds directly to the toxin protein and inhibits its activity. There are also types IV-VI, which are less common. Toxin-antitoxin genes are often inherited through horizontal gene transfer and are associated with pathogenic bacteria, having been found on plasmids conferring antibiotic resistance and virulence.