Connective tissue injuries

Fibronectin, a major regulator of cell attachment to the ECM and overall cell morphology, has recently been shown to be fragmented after exposure to HO [27] while exposure to OC1- resulted in substantial cross-linking (bityrosine cross-links) [28], Exposure of fibronectin to either of these oxidants led to the formation of dysfunctional biomolecules and may provide a rational explanation for the frequently observed detachment of endothelial or epithelial cells seen during connective tissue injury. The presence of these modified forms of fibronectin in the ECM adjacent to an inflammatory focus would provide strong evidence for the role of oxidant-induced connective tissue damage, but this information is not currently available. 

The evidence for a pathophysiological role of oxidants in connective tissue injury is not confined to oxidative damage to the component macromolecules. Since there is reasonable indirect evidence that ROIs are released into the articular joint space during inflammation, it is likely that ROIs released from inflammatory cells which are adherent to or in contact with the articular cartilage surface might also damage the cellular components of articular cartilage. 

T cell activation in the lamina propria is associated with epithelial cell shedding, leading to loss of villi. It has been postulated that this is mediated by increased production of matrix metalloproteases (MMP), which, by degrading the lamina propria matrix, represent a major pathway by which T cells cause injury in the gut (Pender et al., 1997). Production of MMPs also facilitates movement of cells out of the vasculature into sites of inflammation and contributes substantially to the degradation of connective tissue during inflammatory disease (Stetler-Stevenson, 1996). Furthermore, MMPs are required for the release of soluble TNF-a from its membrane... 

In contrast, some cytokines (e.g. some CSFs and EPO) appear to be expressed constitutively. In yet other instances cytokines such as PDGF and TGF-P are stored in cytoplasmic granules and can be rapidly released in response to appropriate stimuli. Other cytokines (mainly ones with growth factor activity, e.g. TGF-P, FGF and IL-1) are found bound to the extracellular matrix in connective tissue, bone and skin. These are released, bringing about a biological response upon tissue injury. 

Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH]... 

Osteopathy was devised in 1874 by Andrew Taylor Still (1828-1917). His philosophy was that structure governs function, a belief that remains one of the basic principles of modem osteopathy. He claimed that tension in muscles and misaligned bones places unnecessary strain on the body as a whole. The initial strain can be caused by any number of factors, such as physical injury, or habitual poor posture, or by destructive emotions such as anxiety and fear. Adjusting the framework of the body would relieve that strain and enable all the systems to run smoothly so that the body would heal itself. Osteopathy is a manipulative therapy that works the body s structures (the skeleton, muscles, ligaments, and connective tissue) to relieve pain, improve mobility, and restore all-round health (Thomas, 1997 and General References). 

Liver cirrhosis is among the top 10 causes of death in the Western world. The disease occurs after chronic damage to hepatic cells, mainly hepatocytes, which can be caused by viral hepatitis, chronic alcohol abuse or toxic injury, biliary disease, and metabolic liver disorders [64], Liver cirrhosis is characterized by an abnormal deposition of connective tissue in the liver, which hampers the normal functions of the liver. Other features of the disease are general tissue damage, chronic inflammation, and the conversion of normal liver architecture into structurally abnormal nodules. Secondary to these anatomical changes are disturbances in the liver function and in the hemodynamics leading to portal hypertension and intrahepatic shunting [39, 64, 103],... 

Central nervous tissue appears to provide an especially avid environment for the occurrence of oxygen-radical generation and lipid-peroxidative reactions due to a high content of polyunsaturated fatty acids. There is now considerable biochemical, physiological and pharmacological data that supports such a connection between radical reactions and secondary CNS tissue injury. 

Proposed mechanisms and some physiological consequences of oxidative injury to connective tissue... 

Other studies have shown that other connective tissue components, including cartilage proteoglycan and collagen, are susceptible to ROI-dependent injury. Fragmentation of proteoglycan after exposure to HO -generating systems is well... 

All the major cell types (epithelial, endothelial, smooth muscle cells, pneumocytes, chondrocytes, fibroblasts) capable of producing connective tissues (e.g. cartilage, basement membrane, parenchymal stroma) are susceptible to oxidative injury in vitro [29- 33], and over the past decade the mechanism(s) of oxidative stress to these cell types has been the focus of intense research. Unfortunately, few of these studies have been specifically extended to examine the biochemical evidence for oxidative injury to connective tissue producing cells in vivo [34], Our most recent work has concentrated on determining the precise biochemical footprints of oxidative injury found within chondrocytes (also colonic epithelial cells) and attempting to correlate the presence or absence of these oxidative-injury markers seen in vitro with inflamed material from animal models and human pathological material. 

In conclusion, the evidence for the involvement of ROIs in injury to the cellular components of connective tissues is stronger than that of direct macro-molecular damage because some of the footprints of in vitro oxidative injury have been found in animal models of inflammation and from human pathological material pathological material. 

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