Chronic fibrosis

Hepatic - Methotrexate has the potential for acute (elevated transaminases) and chronic (fibrosis and cirrhosis) hepatotoxicity. Chronic toxicity is potentially fatal it generally occurs after prolonged use (generally 2 years or more) and after a total dose of at least 1.5 g. 

Lung fibrosis occurs with a buildup of fibrous material inside lung cavities. The fibers are rich in collagen, the tough, fibrous protein that gives strength to bone and connective tissue. Chronic fibrosis can result from pulmonary exposure to aluminum dust, aluminum abrasives, chromium(VI), coal dust, kaolin clay dust, ozone, phosgene, silica, and finely divided mineral talc. 

Hepatic fibrosis is seen with chronic exposure to hepatoxicants that cause increasing damage to hepatocytes and is part of the wound healing response. Chronic fibrosis leads to severe disruption of the liver architecture by the deposition of extracellular matrix (ECM). Advanced fibrosis disrupts the proper blood flow and results in scarring of the liver that can lead to irreversible liver damage known as cirrhosis. Chronic exposure to the hepatoxins CCI4, monocrotaline, and alcohol are examples of compounds that cause excessive fibrosis. 

Hepato toxicity Liver, bile duct, and gall bladder. The liver is particularly susceptible to xenobiotics due to its large blood supply and its role in metabolism Steatosis (lipid accumulation in hepatocytes) Chemical hepatitis (inflammation of the liver) Hepatic necrosis (death of the hepatocytes) Hepatic cancer (cancer of the liver) Hepatic cirrhosis (chronic fibrosis) Hypersensitivity (immune reaction resulting in hepatic necrosis)... 

The mechanism of action of talc in pleurodesis has not been fully elucidated, although it is thought to stimulate a typical local inflammatory response, with reduced fibrinolytic activity, mesothelial cell injury, and fibroblast proliferation. Pneumonitis or respiratory failure can be secondary to downstream inflammatory mediators from more proximal talc injury (7). This acute-phase inflammatory response is dose-related (8,9) and is inhibited by glucocorticoids (10). Talc may also have an adhesion stimulating quality, since empyema alone stimulates a typical inflammatory response but does not lead to pleurodesis (11). In fact, talc stimulates intercellular adhesion molecule-1 in mesothelial cells (12). The mechanism of chronic fibrosis may involve continuous fibroblast activation by foreign body giant cell released mediators or macrophages. 

Hawkins, RA., Claman, H.N., Clark, RA.F. and Steigerwald, J.C. (1985). Increased dermal mast cell populations in progressive systemic sclerosis a link in chronic fibrosis Ann. Intern. Med. 102, 182-186. 

In 1959, radiographic changes characteristic of diffuse pulmonary fibrosis were reported in 87% of 31 patients who had taken phenytoin for 2 years or more. Since then, studies have been conflicting. If phenytoin does produce chronic fibrosis, it would appear to be a relatively rare event. 

Mouse (CD-1) once Dermal 5000 M (late chronic fibrosis) Randall and Coggle 1995 "Sr Y... 

Silica is the main component of most rocks and is a crystalline substance made of silicon and oxygen. It occurs in quartz (found in granite), sand and flint, which are present in a wide variety of construction materials. Harm is caused by the inhalation of silica dust which can lead to silicosis (acute and chronic), fibrosis and pneumoconiosis. Activities which can expose workers and members of the public to silica dust include ... 

B. In Vitro Release of Mediators Associated with Acute Inflammation and Chronic Fibrosis... 

Epidemiological studies of nickel-producing and nickel-using workers seldom indicate excess mortaUty from nonmalignant respiratory disease. Evidence for such effects exists mainly as a few reports of isolated incidents of asthma, pulmonary fibrosis, chronic bronchitis, and emphysema in nickel workers. Nickel may or may not play a causal role in these incidents (131). 

Chronic Pulmonary Toxicity Chronic damage to the lungs may be due to several subsequent exposures or due to one large dose that markedly exceeds the capacity of pulmonary defense, clearance, and repair mechanisms. Chronic pulmonary toxicity includes emphysema, chronic bronchitis, asthma, lung fibrosis, and lung cancer. The single most important reason for chronic pulmonary toxicity is tobacco smoke, which induces all types of chronic pulmonary toxicity, with the exception of fibrosis. 

These drug are prescribed as replacement therapy for those with pancreatic enzyme insufficiency. Conditions or diseases that may cause a decrease in or absence of pancreatic digestive enzymes include cystic fibrosis, chronic pancreatitis, cancer of the pancreas,... 

Earci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R, Serra G, Lai ME, Loy M, Caruso L, Desmet V, PurceU RH, Balestrieri A (2004) Long-term benefit of interferon alpha therapy of chronic hepatitis D regression of advanced hepatic fibrosis. Gastroenterology 126 1740-1749... 

Detailed sub-analyses of a variety of clinical trials have provided information about host and viral factors influencing the virologic response in the treatment of chronic hepatitis C. The most important factors include the HCV genotype, HCV RNA concentration at baseline, age, weight, gender, ethnicity, liver enzymes, and stage of fibrosis (Mihm et al. 2006 Pawlotsky 2005). 

Cystic fibrosis (CF) is a recessive genetic disorder prevalent among whites in North America and certain parts of northern Europe. It is characterized by chronic bacterial infections of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to abnormal development of the vas deferens, and elevated levels of chloride in sweat (> 60 mmol/L). 

In experimental animals, vitamin E deficiency results in resorption of femses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic fiver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premamre infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally fragile as a result of peroxidation, which leads to hemolytic anemia. 

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