Tissue injury

Soft Tissue Injuries. Some of the more common soft tissue injuries are sprains, strains, contusions, tendonitis, bursitis, and stress injuries, caused by damaged tendons, muscles, and ligaments. A sprain is a soft tissue injury to the ligaments. Certain sprains are often associated with small fractures. This type of injury is normally associated with a localized trauma event. The severity of the sprain depends on how much of the ligament is torn and to what extent the ligament is detached from the bone. The areas of the human body that are most vulnerable to sprains are ankles, knees, and wrists. 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

The potential for normal brain tissue injury is one of the limiting factors in the use of XRT for brain tumors. Pentobarbital is a cerebral radioprotectant in rodent and primate models after single doses, but is associated with significant risks. Of alternative barbiturates, thiopental given to tats receiving 70-Gy (7000-rad) whole-brain irradiation in a single fraction enhances the 30-day survival similarly to pentobarbital, whereas ethohexital and phenobarbital show no radioprotective activity (250). 

Chemical Pathology. Also referred to as clinical chemistry, this monitoring procedure involves the measurement of the concentration of certain materials in the blood, or of certain enzyme activities in semm or plasma. A variety of methods exist that allow (to variable degrees of specificity) the definition of a particular organ or tissue injury, the nature of the injurious process, and the severity of the effect (76). 

Urinalysis. Urine is collected at various times and examined with respect to its volume, specific gravity, and the presence of abnormal constituents. The results may indicate kidney damage or suggest tissue injury at other sites (77). 

For the above reasons, chronic exposure studies are frequently designed in such a way that it is possible to combine observations for tumorigenesis and noimeoplastic tissue injury. Chronic studies are usually extensively monitored. It is common practice to sacrifice animals at intervals during the study in order to detect the onset of any tissue injury. For two-year exposure studies, it is most meaningful to have interim sacrifices at 12 and 18 months. 

Physiological Effects. The sulfur and nitrogen mustards act first as cell irritants and finally as a cell poison on all tissue surfaces contacted. The first symptoms usually appear in 4—6 h (4). The higher the concentration, the shorter the interval of time between the exposure to the agent and the first symptoms. Local action of the mustards results in conjunctivitis (inflammation of the eyes) erythema (redness of the skin), which may be followed by blistering or ulceration and an inflammatory reaction of the nose, throat, trachea, bronchi, and lung tissue. Injuries produced by mustard heal much more slowly and are much more Fable to infection than bums of similar intensity produced by physical means or by other chemicals. 

Tissue Conditioners. Tissue conditioners are gels designed to alleviate the discomfort from soft-tissue injury, eg, extractions. Under a load, they exhibit viscous flow, forming a soft cushion between the hard denture and the oral tissues. The polymer in tissue conditioners is often the same as that used for resilient liners. The liquid is a plasticizer containing an alcohol of low volatility (219,220). 

Thrombolytic Enzymes. Although atherosclerosis and the accompanying vascular wall defects are ultimately responsible for such diseases as acute pulmonary embolism, arterial occlusion, and myocardial infarction, the lack of blood flow caused by a fibrin clot directly results in tissue injury and in the clinical symptoms of these devastating diseases (54). Thrombolytic enzyme therapy removes the fibrin clot by dissolution, and has shown promise in the treatment of a number of thrombo-occlusive diseases (60). 

Airway surfaces, like skin, are continually exposed to the ambient environment. In contrast to skin submucosal vessels, however, w hich shed excess heat by vasodilating when heated and conserve heat by vasoconstricting when chilled, it is unclear how the airway vasculature responds to temperature extremes. Inspiring cold air poses two challenges to conducting airway tissues the risk of tissue injury should inadequate heat reach the airway surface and excessive body heat loss due to increasing the radial temperature gradient. Vasodilation would protect airway tissue but increase heat loss, while vasoconstriction would produce the opposite effect. 

Further neutrophil influx and amplification of inflammation and tissue injury... 

Mice that are homozygous for a disrupted Bx or B2 receptor gene are healthy, fertile and normotensive. In Bx-deficient mice, bacterial lipopolysaccharide-induced hypotension is diminished and the recruitment of polymorphonuclear leukocytes to the sites of tissue injury is impaired, and the animals show signs of hypoalgesia. Deletion of the B2 gene in mice leads to salt-sensitive hypertension and altered nociception. 

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

Initiation of the fibrin clot in response to tissue injury is carried out by the extrinsic pathway. How the intrinsic pathway is activated in vivo is unclear, but it involves a negatively charged surface. The intrinsic and extrinsic pathways converge in a final common path-vray involving the activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen to form the fibrin clot. The intrinsic, extrinsic, and final common pathways are complex and involve many different proteins (Figure 51-1 and Table 51-1). In... 

The model concerning wound healing occurs in two phases (1) pro-inflammatory responses (Glaser and Kiecolt-Glaser 2005 Moore 1999 Tidball 2005 Whelan et al. 2005) which are needed to ensure adequate clearance of pathogen at the site of tissue injury, as well as, (2) re-epithelialization and neovascularization events (Frantz et al. 2005 Moore 1999 Naldini and Carraro 2005 Olah and Caldwell 2003 Whelan et al. 2005) to ensure proper wound closure. It is important to note that the resolution of pathogen clearance is essential in order for the wound closure processes to take place (Robson 1997). 

Following tissue injury, the innate immune response is the first line of defense against possible pathogen infections. Through evolutionary pressures, the body automatically assumes infection which will be present post injury. Innate immunity... 

Gutteridge, J.M.C. (1988) In Oxygen Radicals and Tissue Injury (ed. B. Halliwell) pp. 9-19, Upjohn and Federal American Societies for Experimental Biology, Bethesda, MD. 

Sadrzadeh, S.M.H. and Eaton, J.W. (1992). Hemt obin-induced oxidant damage to the central nervous system. In Free Radical Mechanisms of Tissue Injury (eds. M.T. Moslen and C.V. Smith) pp. 24—32. CRC Press, Boca Baton. 

Mulligan, M.S., Hevel, J.M., Morletta, M.A. and Ward, P.A. (1991). Tissue injury caused by deposition of immune complexes is L-aiginine dependent. Proc. Natl. Acad. Sci. USA 88, 6338-6342. 

Maestro, R, Thaw, H., Bjork, J., Blanker, M. and Arfors, K.E. (1980). Free radicals as mediators of tissue injury. Acta Physiol. Scand. 492 (Suppl.), 43-57. 

McCord, J.M. (1985). Oxygen-derived free radicals in postischaemic tissue injury. N. Engl. J. Med. 312, 159-163. 

Free-radical-induced oxidation of low-density lipoprotein (LDL) may be another mechanism that leads to tissue injury. Following incubation with endothelial or smooth muscle cells, LDL oxidizes and becomes toxic to proliferating fibroblasts (Morel et al., 1983a). 

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

Ward, P.A., Till, G.O., Kunkel, R. and Beauchamp, C. (1983). Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury. J. Clin. Invest. 72, 789-801. 

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