Types of Necrosis

Figure 16.6. The four primary types of necrosis. (A) Coagulative. On the cut surface of this canine kidney, there is a dark red, wedge-shaped area of coagulative necrosis caused by blockage of the blood supply to the area (infarction). The pale areas are older infarcts. (B) Caseous. This bovine lymph node contains a large whitish, cheese-like area of caseous necrosis characterized by loss of the normal tissue architecture. (C) Liquefactive necrosis, equine brain. There are two large areas of liquefaction with extensive loss of brain tissue. (D) Fat necrosis, bovine abdominal fat. Necrotic fat is firm and chalky white and often becomes mineralized. See color insert.

There are several potential causes for segmental necrosis of muscle fiber. The cause of this type of necrosis is not well understood but could be due to effects on the plasma membrane or the outer boundary of the muscle fiber. Aminocaproic acid (an antifibrinolytic medication used in the treatment of a subarachnoid hemorrhage), clofibrate (used to treat hyperlipedemia), emetine (found in ipecac syrup), cardiac glycosides, heroin, and phencyclidine have been associated with necrotizing myopathies. 

A nucleic acid can never code for a single protein molecule that is big enough to enclose and protect it. Therefore, the protein shell of viruses is built up from many copies of one or a few polypeptide chains. The simplest viruses have just one type of capsid polypeptide chain, which forms either a rod-shaped or a roughly spherical shell around the nucleic acid. The simplest such viruses whose three-dimensional structures are known are plant and insect viruses the rod-shaped tobacco mosaic virus, the spherical satellite tobacco necrosis virus, tomato bushy stunt virus, southern bean mosaic vims. 

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

Yellow phosphorus was the first identified liver toxin. It causes accumulation of lipids in the liver. Several liver toxins such as chloroform, carbon tetrachloride, and bromobenzene have since been identified. I he forms of acute liver toxicity are accumulation of lipids in the liver, hepartxiellular necrosis, iii-trahepatic cholestasis, and a disease state that resembles viral hepatitis. The types of chrome hepatotoxicity are cirrhosis and liver cancer. 

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

Although toxic agents have the potential to cause necrosis, some of them can interfere with intracellular signaling pathways and induce apoptosis instead of necrosis. It seems that organotin(IV) compounds exert their toxic effects involving all these processes. The precise balance of these actions and their outcomes may differ radically from one cell type to another and among different organisms. 

The major types of drug therapy used in IBD include aminosalicylates, glucocorticoids, immunosuppressive agents (azathioprine, mercaptopu-rine, cyclosporine, and methotrexate), antimicrobials (metronidazole and ciprofloxacin), and agents to inhibit tumor necrosis factor-a (TNF-a) (anti-TNF-a antibodies). 

NO acts as an autocrine factor that mediates HIV-1 replication as at the molecular level, NO seems to stimulate long-terminal repeat-mediated transcription [125]. It was noted that exogenous NO increases replication of HIV-1 T-tropic isolates in primary T cells or T-cell lines, and inhibitors of iNOS partly block HIV-1 replication, especially that induced by tumor necrosis factor a [125]. The contrasting effects of exogenous NO, particularly NO donors, may depend on the type of NO donors, their releasing kinetics, and the dose used in the study design. 

Cytokines produced by lymphocytes are called lymphokines, and those produced by monocytes are termed monokines. Lymphocytes and monocytes are different types of white blood cells. The major lymphokines are interferons (IFNs) and some interleukins (ILs). Monokines include other interleukins and tumor necrosis factor (TNF). 

Tumor Necrosis Factor There are two types of tumor necrosis factor TNF-a and TNF- 8. Of the two, TNF-a has been studied in more detail. TNF-a is a 157 amino acid polypeptide. It is a mediator of immune regulation, including the activation of macrophages and induction of the proliferation of T cells. Another TNF-a function is its cytotoxic effects on a number of tumor cells. Recent research, however, concentrates on its property in the stimulation of inflammation, particularly in the case of rheumatoid arthritis. Clinical trials are being conducted with drugs to block TNF-a with anti-TNF-a monoclonal antibodies. These antibodies target the excessive levels of TNF-a in the synovial fluid of joints and provide relief to sufferers of rheumatoid arthritis (Exhibit 4.10). 

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... 

Chemical injuries to the liver depend on the type of toxic agent, the severity of intoxication, and the type of exposure, whether acute or chronic. The six basic types of liver damage are fatty liver, necrois, hepatobiliary dysfuntions, viral-hke hepatitis, and (on chronic exposure) cirrhosis and neoplasia. A number of organic chemicals and drugs induce fatty liver and hver necrosis. 

At least four types of cytokine receptors can be differentiated on the basis of sequence homology (Fig. 11.2). Many members of the cytokine receptors of type 1 regulate growth and transmit mitogenic signals to the cell nucleus. The cytokine receptors of type 2 include the receptors for the interferons a and p. Type 3 includes the receptors for tiunor necrosis factor TNF and for CD 40 and Fas protein, which are foimd on T lymphocytes. 

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