Cell necrosis

Historical Inhalation Agents. Diethyl ether produces excellent surgical anesthesia, but it is flammable (see Ethers). Chloroform is a nonflammable, sweet smelling, colorless Hquid which provides analgesia at nonanesthetic doses and can provide potent anesthesia at 1% (see Chlorocarbons AND CHLOROHYDROCARBONs). However, a metabohte causes hepatic cell necrosis. Tdlene, a nonflammable colorless Hquid, has a slower onset and recovery and a higher toxicity and chemical reactivity than desirable. Cyclopropane is a colorless gas which has rapid induction (2 —3 min) and recovery characteristics and analgesia is obtained in the range of 3—5% with adequate skeletal muscle relaxation (see Hydrocarbons). The use of cyclopropane has ceased, however, because of its flammabiHty and marked predisposition to cause arrhythmias. 

Systemic treatment of 13-cis retinoic acid frequently leads to cheilitis and eye irritations (e.g., unspecific cornea inflammation). Also other symptoms such as headache, pruritus, alopecia, pains of joints and bone, and exostosis formation have been reported. Notably, an increase of very low density lipoproteins and triglycerides accompanied by a decrease of the high density lipoproteins has been reported in 10-20% of treated patients. Transiently, liver function markers can increase during oral retinoid therapy. Etretinate causes the side effects of 13-cis retinoid acid at lower doses. In addition to this, generalized edema and centrilobulary toxic liver cell necrosis have been observed. 

Troponins T or I Proteins found predominantly in cardiac muscle that regulate calcium-mediated interaction of actin and myosin troponins I and T are released into the blood from myocytes at the time of myocardial cell necrosis after infarction. These biochemical markers become elevated and are used in the diagnosis of myocardial infarction. 

After administration of mercuric chloride to mice, cell necrosis was found to be severest in the S2 and proximal S3 [228] segments of the proximal tubules corresponding to the preferential accumulation of mercury, engaging the convoluted part of the proximal tubular segment [229]. Very large mercury-containing lysosomes developed in the distal S3 segment. 

Micro-Thromboses Platelets and leucocytes, like other cells, are known to carry surplus negative charge, and can be electrophoretically deposited at (or around) the anode10 owing to the positive electrode potential. These microthromboses in capillaries in or near the treatment site will result in decreased blood flow and may contribute to a local dystrophy of the tissue. A more pronounced version of this effect can be seen sometimes as electrocoagulation and vascular occlusion (i.e., shut, closed or obstructed vasculature) of the tumor tissue. In other words, ECT cuts off the blood supply to the tumor and causes the tumor cell necrosis. 

Hepatic Effects. Hepatic effects have been reported in humans exposed orally or by the dermal and inhalation routes to toxic doses of 1,2-dibromoethane (Letz et al. 1984 Olmstead 1960 Saraswat et al. 1986). These effects consist of hepatocellular and Kupffer cell necrosis. Results in humans are supported by animal studies in which the liver is also a target organ for toxic effects of 1,2-dibromoethane following exposure by a variety of routes (Botti et al. 1986 Brandt et al. 1987 Broda 1976 NTP 1982 Rowe et al. 1952). 1,2-Dibromoethane, as well as inducing necrosis, can also act as a hepatocellular mitogen in rats (Ledda-Columbano et al. 1987a). 

Liver toxicity related to 1,2-dibromoethane depends on the metabolic pathway utilized and the amount of damage induced in cellular protein and membrane structures. Humans exposed to low levels of 1,2-dibromoethane are at potential risk of having toxic events occurring within hepatocytes whether these effects will be subcellular or result in cell necrosis may depend on internal dose and a variety of factors. Liver damage that is severe enough to cause clinical disease in humans from low-level exposure is unlikely. 

Toxicologists classify hepatic toxicants according to the type of injuries they produce. Some cause accumulation of excessive and potentially dangerous amounts of lipids (fats). Others can kill liver cells they cause cell necrosis. Cholestasis, which is decreased secretion of bile leading to jaundice (accumulation of gruesome looking pigments that impart a yellowish color to the skin and eyes) can be... 

Figure 20.34 A simple representation of the processes of necrosis and apoptosis leading to the death of cells. Necrosis is initiated by a decrease In the ATP/ADP concentration ratio, which slows ion pumps, which leads to cation imbalance (e.g. ca ion entry into the cytosol) and hence intracellular damage, entry of water and lysis which can lead to local inflammation. Apoptosis is initiated by specific extracellular or intracellular factors, which lead to cell shrinkage and disruption into apoptotic bodies which are removed by phagocytes.

Available data on chronic exposure to 1,4-dichlorobenzene in animal studies include a 76-week inhalation study in rats that resulted in increased liver and kidney weights (Riley et al. 1980) a 2-year oral study in mice that resulted in liver effects (NTP 1987), such as hepatocellular degeneration, and cell necrosis and renal effects such as nephropathy and renal tubular degeneration and a 2-year oral study in rats that resulted in a high rate of mortality and renal effects including nephropathy and degeneration of the renal tubules (NTP 1987). No animal studies of chronic dermal contact with 1,4-dichlorobenzene have been located. 

Cell necrosis (not shown) should be distinguished from apoptosis. In cell necrosis, cell death is usually due to physical or chemical damage. Necrosis leads to swelling and bursting of the damaged cells and often triggers an inflammatory response. 

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... 

The carcinogenic properties of hexachlorobutadiene are proposed to result from binding of the sulfenic acid degradation product or a thioketene intermediate to cellular DNA (Dekant et al. 1990b Henschler and Dekant 1990). Cell necrosis is thought to stimulate replication of cells with altered DNA, enhancing tumorigenesis. 

Adenosine 3 receptor ADORA3 Agonism Immunosuppression, hypotension, anti-ischaemic (cardioprotective), pro-ischaemic (cerebral), cell necrosis, cell proliferation and angiogenesis. Antagonism might cause myocardial ischaemia, proinflammatory effects, hypertension and interfere with the regulation of cell growth. 

Cell necrosis in liver Hepatic toxicity in humans... 

Inhibitors of the microsomal enzymes decreased the covalent binding and the Clara cell necrosis and increased the LD50, even though the blood and pulmonary levels of ipomeanol... 

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