Toxins tissue damage

Finally, CA-MRSA produces the virulent Panton-Valentine leukcocidin toxin. It destroys leukocytes, causes severe tissue damage and necrosis, and has been associated with both necrotizing skin infections and pneumonia.14... 

It has been postulated that Chlamydia may produce a heat shock protein that causes tissue damage through a delayed hypersensitivity reaction. C. trachomatis may also possess DNA evidence of toxin-like genes that code for high-molecular-weight proteins with structures similar to Clostridium difficile cytotoxins, enabling inhibition of immune activation. This may explain the observation of a chronic C. trachomatis infection in subclinical PID. 

There is a large class of compounds that are capable of releasing histamine. They can be enzymes, toxins, morphine, d-tubocurarine, and polymers such as dextran. Moreover, tissue damage such as trauma, bites, and stress can also cause a release of histamine, and in all probability as a result, an endogenous polypeptide bradykinin is released. Action of all of these listed substances as well as a number of others can facilitate formation of anaphylactic reactions in the organism. 

Whereas the normally functioning immune response can successfully neutralize toxins, inactivate viruses, destroy transformed cells, and eliminate pathogens, inappropriate responses can lead to extensive tissue damage (hypersensitivity) or reactivity against self antigens (autoimmunity) conversely, impaired reactivity to appropriate targets (immunodeficiency) may occur and abrogate essential defense mechanisms. 

Edema toxin does not produce major tissue damage. In fact, its major role is to impair phagocyte function (Leppla, 2000). This is consistent with other toxins which fimction to elevate cAMP concentrations. Edema toxin inhibits phagocytosis of spores by human PMNs (O Brien et al, 1985) similar to LF this is in contrast to spores which promote immune cell uptake (see Table 31.1). Increased intracellular cAMP induced by EF inhibits neutrophil chemotaxis, phagocytosis, superoxide production, and microbicidal activity (Crawford et al, 2006 Turk, 2007 O Brien et al, 1985 Friedman et al, 1987 O Dowd et al, 2004 Ahmed et al, 1995). EF has been shown to inhibit TNFa and increase IL-6 production (Hoover et al, 1994). Increased cAMP levels also block LPS-induced activation... 

Exposure through breaks in the skin can result in the introduction of both toxins and pathogens. Toxins or toxic particles that are soluble in the blood plasma can be absorbed into the blood quite rapidly. For example, dermal exposure to chromic acid used in the electroplating industry can cause tissue damage, which then allows rapid uptake of hexavalent chromium ion and potential acute chromium intoxication. 

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]... 

Clinically overt nephrotoxicity is the result of the intrinsic capacity of a toxin to damage renal cells or tissue, the susceptibility of the patient, and changes in disposition of the toxin fhat result in increased delivery to the target organ or tissue. In this chapter we will examine the latter aspect of nephrotoxicity and will focus on (i) drug interactions that potentially lead to nephrotoxicity and (ii) changes in drug disposition induced by renal failure. 

Several different phospholipases can be distinguished on the basis of the site at which they hydrolyze phosphohpids (Figure 21.2). Phospholipase A2 is widely distributed in nature it is also being actively studied by biochemists interested in its structure and mode of action, which involves hydrolysis of phospholipids at the surface of micelles (Section 2.1). Phospholipase D occurs in spider venom and is responsible for the tissue damage that accompanies spider bites. Snake venoms also contain phospholipases the concentration of phospholipases is particularly high in venoms with comparatively low concentrations of the toxins (usually small peptides) that are characteristic of some kinds of venom. The lipid products of hydrolysis lyse red blood cells, preventing clot formation. Snakebite victims bleed to death in this situation. 

Mechanism. Numerous studies on the mechanism of IPO toxicity have supported the view that tissue damage by the compound is due to a highly reactive, alkylating metabolite(s) (Figure 2)(12). In vitro experiments demonstrated that this metabolic activation is catalyzed by a cytochrome P-450 enzyme system which is located in the endoplasmic reticulum of target cells(lO). This metaboliteCs) forms covalent bonds with cellular macromolecules, and it causes cell death (necrosis). The amount of cellular necrosis (measured by microscopic examination of the respective tissues 24 hours after exposure to the toxin) and the extent of protein alkylation (assayed by employing or H-IPO and measuring the amount of label... 

Often, less intense reactions are encountered. The epidermolytic, exfoliative toxins A and B attack the epidermidis causing epidermal necrosis (e.g., Sap/tytococcMX-scalded skin syndrome) [9]. Membrane-damaging toxins at infection sites (e.g., a-toxin, a-hemolysin) are a major factor in tissue damage after bacterial adherence has occurred. Other exoproteins, such as proteases, collage-nase, hyaluronidase, and lipase, act as virulence enhancers but do not actively destroy host tissues. 

By a combination of the microbial enzymes and toxins, as well as a person s immune system, or both, tissue damage occurs. 

Microcystin. An example of this type of toxin is microcystin (produced by blue-green algae), which binds covalently to a phosphatase inside liver cells this toxin does not damage other cells of the body. Unless uptake of the toxin by the liver is blocked, irreversible damage to the organ occurs within 15 to 60 minutes after exposure to a lethal dose. When this happens, the tissue damage to the liver is so severe that therapy may have little or no value. For microcystin, unlike most toxins, the toxicity is the same, no matter what the route of exposure. 

The biological effects of toxins include damage to an organ system, disruption of a biochemical process, or disturbance of an enzyme activity (Schiefer et al., 1997). Many plants and animals purposefully use toxins to protect themselves against predators and competitors. Thousands of chemicals have been isolated from plant tissues, and many of these serve to defend the plants. Alkaloids are basic organic... 

---