Cellular injury

Repeated exposure to ethyl alcohol results in the development of a tolerance as evidenced by decreasing symptomatic reactions. It has been demonstrated that the symptoms of exposure are less clear and the time required to produce them is greater in subjects accustomed to alcohol. There is no proof, however, of physiological adaptation in humans in terms of metaboHc changes or resistance to cellular injuries. The subject of the interaction of alcohol with other dmgs has received much attention (277). 

The main types of cellular injury induced by chemical compounds are necrotic and apoptotic (programmed) cell death. Necrosis implies chaotic ending... 

Based upon theoretical considerations of the mechanisms of hypothermic-induced cellular injury, we developed the University of Wisconsin organ preservation solution (UW solution) that has had a widespread and dramatic effect on organ preservation (Table 2). Prior to the development of this solution, the liver and pancreas could be preserved for only four to six hours. Thus, there was a large time constraint on liver and pancreas transplantation and many cadaveric organs were wasted. However, the UW solution increased preservation duration to 48 to 72 hours, and dramatically increased the quality and numbers of these organs transplanted. Furthermore, this solution appears effective for the preservation of the kidney for three days and the heart for at least 15 hours. 

Physiologic stress evokes a molecular response essential to protecting the human body from cellular injury and death. Over the last two decades, molecular determinants of cellular responses to stress have become better understood, as well as their relationship to human health, development, aging, and disease. Molecular re-... 

Oxygen species are now thought to play an important role in many types of cellular injury (eg, resulting from administration of various toxic chemicals or from ischemia), some of which can result in cell death. Indirect evidence supporting a role for these species in gen-... 

Nordmann, R., Ribiere, C. and Rouach, H. (1992). Implication of free radical mechanisms in ethanol-induced cellular injury. Free Rad. Biol. Med. 12, 219-240. 

In addition to their beneficial effects, some medications may actually cause cellular injury and disease. An example of this phenomenon involves nonsteroidal anti-inflammatory drugs (NSAIDS). These drugs include aspirin (a derivative of salicylic acid), ibuprofen (arylpropionic acid, Advil ), and acetaminophen (para-aminophenol derivative, Tylenol ). Because of their beneficial pharmacological effects, consumption of these agents has increased significantly in recent years. NSAIDS have the ability to treat fever, pain, acute inflammation, and chronic inflammatory diseases such as arthritis. They are also used prophylactically to prevent heart disease, stroke, and colon cancer. 

One of the unique advantages of renal cell culture rests in making possible the study of the directional aspects of drug exposure and cellular injury that operate in vivo. The technology to grow renal epithelial cells on filter inserts for this purpose has recently been made available (Figure 17.4). This potential provides the opportunity to study compounds that interact or accumulate within the renal tubular epithelium in vivo via tubular reabsorption from the luminal surface or extraction... 

Infection 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body s defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]... 

CoUes, S.M., Irwin, K.C., Chisolm, G.M., 1996, Roles ofmultiple oxidized LDL lipids in cellular injury dominance of 7 beta-hydroperoxycholesterol,/. LipidRes. 37 2018-2028. 

These somewhat simplified descriptions of mechanisms that initiate cellular injury, and of the ways in which cells and tissues respond to these injuries will, as noted at the outset, be helpful as we describe various manifestations of toxicity and carcinogenicity. We distinguish between toxic injuries, which are typically seen in animal experiments and are usually described in the terms defined in the foregoing, and the various medical conditions we call diseases. Many toxic responses can lead to disease, but we also consider toxic injuries to be adverse effects, whether or not they are known to lead to specific diseases. 

Reynolds ES, Yee AG. 1967. Liver parenchymal cell injury. V. Relationships between patterns of chloromethane-C14 incorporation into constituents of liver in vivo and cellular injury. Lab Invest 16 591-603. 

Primary irritant-contact dermatitis results from direct cytotoxicity produced on first contact. The cellular injury is characterised by two macro-scopically visible events a reddening of the skin (erythema) and accumulation of fluid (oedema). By observing or measuring these changes, one can estimate the extent of skin damage that has occurred. The most widely used single-exposure irritancy test is based on the Draize rabbit test. ... 

Additional studies of decalin exposure in rats have characterized the specific sequence of renal alterations first the variable occurrence of light-microscopically evident proximal convoluted tubule epithelial cell necrosis, presumably a reflection of cellular injury associated with excessive protein accumulation (hyaline droplets) then the occurrence of granular casts at the junction of the inner and outer bands of the outer zone of the medulla and finally, chronic nephrosis, occurring secondary to tubular obstruction by granular casts. It is not... 

SO Bronchoconstriction. cough. Cellular injury, chlorosis, withering of leaves and abscission. Precursor to acid rain acidification of surface waters with community shifts and mortality of some aquatic organisms. Possible effect on uptake of Al and other toxic metals by plant roots. Weathering and corrosion. Defacing of monuments... 

Delayed-onset mushroom poisoning, usually caused by Amanita phalloides, A virosa, Galerina autumnalis, or G marginata, manifests its first symptoms 6-12 hours after ingestion. Although the initial symptoms usually include nausea and vomiting, the major toxicity involves hepatic and renal cellular injury by amatoxins that inhibit RNA polymerase. Atropine is of no value in this form of mushroom poisoning (see Chapter 58). 

It now seems that cytosolic calcium may not play a central role in the initiation of oxidative injury as changes in calcium homeostasis occur well after the appearance of other indications of cellular injury. However, mitochondrial lesions do occur early on in the time course of oxidative cellular damage, and calcium may indeed play a role in these. Changes in concentrations of calcium will, however, result in the activation of signaling mechanisms and alterations in cellular structure and in gene expression. Such alterations may in some instances play a critical role in cellular toxicity. For example, increases in cytosolic Ca2+ inhibit mitochondrial function. 

The cellular injury, which underlies target organ toxicity, may result from various underlying events primary, secondary, and tertiary events. Primary events result from initial damage, for example, lipid peroxidation, enzyme inhibition, covalent binding to crucial macromolecules, ischemia, and changes in thiol status. 

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