Irreversible injury

Reversible injury or irreversible injury or death Carcinogens... 

Gy, single exposure Irreversible injury throughout life, but life span was increased 50... 

Drug-induced hepatotoxicity can present in variable manifestations, such as cell death (necrosis, apoptosis), infiammation, degeneration (steatosis), fibrosis/cirrho-sis and the development of tumors. The manifestations of drug toxicity may not be mutually exclusive and may occur sequentially, or in combination. ALT and ALP can be used to generally classify the pattern of liver injury as either hepatocellular (ALT >3x ULN), cholestatic (ALP >2x ULN, ALT/ALP <2) or mixed (elevated ALP and ALT). The successful monitoring of hepatotoxicity would identify cases before irreversible injury occurs. The activity levels of ALT, AST and ALP only increase after hepatic or cholestatic injury has occurred. Waiting for activity levels to exceed the established thresholds may be too late [3]. New biomarkers are needed to monitor/predict the specific sequence of events for different classes of hepatotoxic compounds. 

The stationary phase is followed by a decline period in which cell death is not compensated by cells in proliferation. Cell death can occur by two distinct mechanisms, named necrosis and apoptosis. Necrosis occurs as a result of an irreversible injury and normal homeostasis is lost. In vivo, this form of death generally affects the neighboring cells and may result in inflammation. Autodestruction occurs by activation of hydrolases when there is a lack of nutrients and oxygen, followed by progressive disorganization and complete disintegration of the cell. 

Some patients may undergo rapid irreversible injury to larger regions of brain, presumably due to poor collateral circulation. These patients may present with large acute DWI lesions that are of similar size to the acute PI lesion (non-mismatch pattern, see Fig. 3.3). It has been suggested that this group of... 

Figure 16.2. Reversible versus irreversible cell injury. Depending on the cell and/or tissue type and the relative health of the individual, cells may adapt to stress within a limited range of homeostatic ability. If cell injury exceeds this range, the point of no return is reached (irreversible injury) and the cell dies. Note that cell death and the degradative changes associated with necrosis are at different time points.

Allard EK, Hall SJ, Boekelheide K. 1995. Stem cell kinetics in rat testis after irreversible injury induced by 2,5-hexane-dione. Biol. Reprod. 53 186-92... 

In the coronary artery-occluded Langendorff rat heart model, irreversible injury occurred within 20 min of ischemia (28). Disruption of the sarcolemma was observed in canine hearts subjected to 15(29, 30) to 20 min of coronary occlusion and reperfusion (31). 

Increases in cardiac marker proteins reflect irreversible injury... 

Necrosis is characterized by membrane disruption, massive cell swelling, cell lysis and fragmentation, and triggers the inflammatory response. The primary site of irreversible injury has been a subject of intense investigation and several hypotheses are postulated. These include the lysosomal, the mitochondrial, the metabolic end-product, calcium overload, the phospholipase, the lipid peroxidation and the cytoskeleton hypotheses, reviewed by Ganote.4... 

Cardiac MRI may have a role in risk stratification for SCD due to its ability to detect myocardial scar. The use of gadolinium, which accumulates in infarcted tissue, has allowed delayed enhancement MRI to detect scar burden. Early experiments in dog models performed by coronary artery occlusion compared acute and chronic infarcts to pathologic specimens of the dog heart postmortem (89,90). Delayed enhancement MRI was remarkably accurate in imaging the infarcted tissue in comparison to the pathologic specimen. The spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis at every stage post-MI. Reversible ischemia did not show delayed gadolinium uptake. Thus, delayed enhancement MRI can distinguish between reversible and irreversible injury, and... 

Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999 100(19) 1992-2002. 

Fieno DS, Kim RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. Contrast-enhanced magnetic resonance imaging of myocardium at risk distinction between reversible and irreversible injury throughout infarct healing. J Am Coll Cardiol 2000 36(6) 1985-91. 

Some of the urea herbicides are compounds with total action. The precondition of their total herbicidal effect is their presence during the germination or active growth stages of the plants in absorbable form with adequate quantity in the absorption zone of the roots. In the exertion of total action, one factor is the irreversible injury caused to the plant, the other the plant s inability to metabolise these herbicides into harmless compounds at a sufficient rate. 

PUHs are generally absorbed through the roots of plants and transported via the transpiration system. The mode of action of PUHs seems to be due to the combined effects of the inhibition of photosynthesis and the irreversible injury of the plant photosynthesis system via inhibition of NADPHj. ... 

In Cora Nari s case, oxygen was restored before permanent impairment of oxidative phosphorylation had occurred and the stage of irreversible injury was reached. However, reintroduction of oxygen induced ventricular fibrillation, from which she recovered. 

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