Local toxin

Large geographic variations in local toxins, particularly in drinking water, make it difficult to compare not only countries but also states and counties within a single country. The United States does not have a single set of standards for water purification, although the Centers for Disease Control (CDC) do make... 

Susceptibility Young infants (2-4 months of age) prior to establishment of normal intestinal flora Self-administering users of IV drugs (often black tar heroin) Antibiotic-treated patients AU exposed individuals AU exposed individuals Patients treated with local toxin ii ections... 

Natural exposure is usually the result of ingestion of food that has become contaminated with the toxin, or from local toxin production in wounds infected with C. botulinum. Exposure could also result from inhalation of the toxin in a pure form. 

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

Saxitoxin composition therefore originates as that of the local dinoflagellate population and evolves with time depending on the characteristics of the filter-feeders and subsequent consumers that accumulate and transform the toxins. 

One of the first applications of the HPLC method was the investigation of differences in toxin profiles between shellfish species from various localities ( ). It became apparent immediately that there were vast differences in these toxin profiles even among shellfish from the same beach. There were subtle differences between the various shellfish species, and butter clams had a completely different suite of toxins than the other clams and mussels. It was presumed that all of the shellfish fed on the same dinoflagellate population, so there must have been other factors influencing toxin profiles such as differences in toxin uptake, release, or metabolism. These presumptions were strengthened when toxin profiles in the littleneck clam (Prototheca Staminea) were examined. It was found that, in this species, none of the toxin peaks in the HPLC chromatogram had retention times that matched the normal PSP toxins. It was evident that some alteration in toxin structure had occurred that was unique in this particular shellfish species. 

Anatoxin-a has already proven its usefulness as a research tool in our laboratories. It is facilitating the understanding of the biophysical properties of the AChR and of the localization of the AChR in the CNS. The toxin or derivatives of it could be useful therapeutically in diseases of nicotinic receptor pathology (myasthenia gravis or Alzheimer s disease), because as a secondary amine (+)-anatoxin-a can penetrate into the CNS. 

More recent studies on the folded toxin structure by Norton and colleagues have utilized h- and C-NMR techniques (19,20). By using 2D-FT-NMR, it was possible to localize a four stranded, antiparallel )5-pleated sheet "backbone structure in As II, Ax I, and Sh I (21,22), In addition, Wemmer et al. (23) have observed an identical )5-pleated structure in Hp II. No a-helix was observed in these four variants. In the near future, calculated solution conformations of these toxins, utilizing distance measurements from extracted Nuclear Overhauser Enhancement (NOE) effects should greatly stimulate structure-activity investigations. 

In the gut, many pathogens adhere to the gut wall and produce their toxic effect via toxins which pervade the surrounding gut wall or enter the systemic circulation. Vibrio cholerae and some enteropathic E. coli strains localize on the gut wall and produce toxins which increase vascular permeability. The end result is a hypersecretion of isotonic fluids into the gut lumen, acute diarrhoea and consequent dehydration which may be fatal in juveniles and the elderly. In all these instances, binding to epithelial cells is not essential but increases permeation ofthe toxin and prolongs the presence of the pathogen. 

Tetanus occurs when Cl. tetani, ubiquitous in the soil and faeces, contaminates wounds, especially deep puncture-type lesions. These might be minor traumas such as a splinter, or major ones such as battle injury. At these sites, tissue necrosis and possibly microbial growth reduce the oxygen tension to allow this anaerobe to multiply. Its growth is accompanied by the production of a highly potent toxin which passes up peripheral nerves and diSuses locally within the central nervous system. It acts like strychnine by affecting normal function at the synapses. Since the motor nerves of the brain stem are the shortest, the cranial nerves are the first affected, with twitches of the eyes and spasms of the jaw (lockjaw). 

If we assume that those peculiarities of the toxin which cause their distribution are localized in a special group of the toxin molecules and the power of the organs and tissues to react with the toxin are localized in a special group of the protoplasm, we arrive at the basis of my side chain theory. The distributive groups of the toxin I call the haptophore group and the corresponding chemical organs of the protoplasm the receptor. . .. Toxic actions can only occur when receptors fitted to anchor the toxins are present. 

Tetanus toxin fragment C Tobacco leaves Systemic IgG and local IgA responses. Immuno- -genic in mice when administered nasally. 113... 

A case in which the toxin or appropriate metabolite is detected in urine, serum, or plasma, or detection of the specific toxin in environmental samples unless there could be a local source of the toxin (e.g., the molds that produce mycotoxins have been found in some residential and industrial settings, and the toxins have been implicated in some cases of "sick building" syndrome). 

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