Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that in the chloramphenicol-induced aplastic anemia nitrosochloramphenicol may be involved as a toxic intermediate. We found that aminochloramphenicol, which reportedly is formed from chloramphenicol by intestinal bacteria, is N-oxygenated by liver microsomes of untreated rats with apparent Km = 0.4 mM and Vmax = 0.28 nmole/min/mg protein. These values are in close agreement with those reported for aniline N-oxygenation. Reductive reactions, however, eliminate the N-oxygenation products at markedly higher rates. As judged from hemoglobin-free single-pass liver perfusion experiments, N-hydroxy-chloramphenicol is reduced at rates faster than 300 nmole/min/g liver wet, and nitrosochloramphenicol is eliminated at rates faster than 1.5 mumole/min/g liver. At least two NADPH- and two NADH-dependent cytosolic enzymes are responsible for nitrosochloramphenicol reduction. Determination of the kinetic parameters of these enzymes by stop-flow analysis revealed the contribution of enzymes, one of it being alcohol dehydrogenase, with Michaelis constants in the micromolar range. Despite this high reducing capacity, about 10% of nitrosochloramphenicol reacted with GSH under formation of glutathionesulfinamidochloramphenicol and GSSG released from the liver into bile and venous effluent. At high nitrosochloramphenicol load these reactions led to glutathione depletion of the liver, caused membrane damage, and impaired bile production. At low nitrosochloramphenicol load, i.e. below 0.5 mumole/min/g, no relevant nitrosochloramphenicol passed the liver. These data together with the previously reported reactions of nitrosochloramphenicol within human blood suggest that nitrosochloramphenicol, if formed at all in the intestine or liver, is rather unlikely to be transferred to the critical target.
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PMID:Formation and disposition of nitrosochloramphenicol in rat liver. 405 15

Studies of the composition of coal tar, which began in Prussia in 1834, profoundly affected the economies of Germany, Great Britain, India, and the rest of the world, as well as medicine and surgery. Such effects include the collapse of the profits of the British indigo monopoly, the growth in economic power of Germany based on coal tar chemistry, and an economic crisis in India that led to more humane tax laws and, ultimately, the independence of India and the end of the British Empire. Additional consequences were the development of antiseptic surgery and the synthesis of a wide variety of useful drugs that have eradicated infections and alleviated pain. Many of these drugs, particularly the commonly used analgesics, sulfonamides, sulfones, and local anesthetics, are derivatives of aniline, originally called "blue oil" or "kyanol." Some of these aniline derivatives, however, have also caused aplastic anemia, agranulocytosis, and methemoglobinemia (that is, "blue people"). Exposure to aniline drugs, particularly when two or three aniline drugs are taken concurrently, seems to be the commonest cause of methemoglobinemia today.
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PMID:Blue gods, blue oil, and blue people. 806 94