Abnormal Enzymes

White blood cells, red blood cells and cultured fibroblasts are commonly used to measure enzyme activities, especially for the diagnosis of inherited enzyme abnormalities. Leukocytes may be collected by sedimentation in viscous media such as Fycol. The collection of red cells presents no problem following centrifugation of anticoagulated blood. The assay of enzymes and fibroblasts requires appropriate tissue culture facilities and extensive experience in dealing with cultured human cells. 

Neoantigens Ectopic hormones Enzyme abnormalities Increased proliferation Altered differentiation Endothelial-stimulating factors Invasion Metastasis Neoantigens Ectopic hormones Enzyme abnormalities Altered cell surface Altered cytoskeleton Chromosome abnormalities... 

R. van Wijk and W. W. van Solinge, The energy less red blood cell is lost Erythrocyte enzyme abnormalities of glycolysis. Blood 106(13), 4034 4042 (2005). 

As we soon learned, tetrahydro-aminoaeridine (THA) is less effeetive in some respeets than physostigmine in reversing seopolamine induced decrements in NF% scores (Fig. 67) but surprisingly, does seem to shorten the duration of belladonnoid intoxication. This may reflect a greater affinity for the cholinesterase enzyme. THA s tendency to cause temporaiy liver enzyme abnormalities, however, persuad us to avoid its further use. 

Hepatomegaly, jaundice, and altered liver function tests have been reported in accidental poisonings with DME An outbreak of toxic liver disease was associated with DME exposure at a fabric coating factory. Thirty-six of 58 workers had elevations of either aspartate aminotransferase or alanine aminotransferase. Serological tests excluded known infectious causes of hepatitis in all but two cases. After modification of work practices and removal of the most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms occurred in most patients. Medical surveillance of the working population for 14 months revealed no further cases of toxic liver... 

Diarrhea nausea vomiting jaundice liver enzyme abnormalities. Azotemia elevated BUN/creatinine increased serum uric acid levels (in patients predisposed to gouty arthritis) thrombocytopenia megaloblastic anemia weakness dizziness Hypokalemia headache dry mouth anaphylaxis. ... 

Adverse reactions occurring in at least 3% of patients include the following Diarrhea, dyspepsia, rash, liver enzyme abnormalities, headache. 

Hepatic function impairment Ritonavir is principally metabolized by the liver. Exercise caution when administering this drug to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. 

Sitaxsentan is a potent and selective agent which inhibits ET-1 binding to ETA receptors (IC50 = 1.4 nM), while being essentially inactive at ETB receptors (IC50 = 9.8 pM).23 In the clinic, it was found to have excellent oral bioavailability (70-100%) and a terminal elimination half-life of 10 h, and is administered as a once daily 100 mg dose. It is highly protein bound in plasma (> 99%) and extensively metabolized in the liver to inactive metabolites, predominantly by CYPs 2C9 and 3A4. Excretion is 50 60% renal, with the balance in the feces.25 Sitaxsentan inhibits CYP 2C9, and was observed to increase exposure to warfarin by over twofold. The use of cyclosporine A is also contraindicated, but no interactions were observed with sildenafil.15 Sitaxsentan was well tolerated in trials, with only minor side effects reported. Reversible liver enzyme abnormalities were also observed, but less frequently than with bosentan.15 25... 

Enzyme abnormalities may be inherited or acquired. Some of the more important inherited enzyme abnormalities are discussed below. The acquired conditions are dealt with later in this chapter under Drug Interactions. 

It is becoming increasingly evident that a number of adverse reactions to drugs are due to genetically transmitted inborn enzyme abnormalities or deficiencies. The best known example of this category is the hereditary relative deficiency of the enzyme glucose-6-phosphate-dehydrogenase (G-6-PD), which occurs in 5% to 10% of Mediterranean littoral races, blacks, Pakistanis, and Sephardic Jews. This condition renders affected individuals susceptible to acute hemolytic ane-... 

Tuberculous patients lacking in liver N-acetyl transferase who are treated with isoniazid are likely to develop polyneuritis (39). An enzyme abnormality is also responsible for the precipitation of acute intermittent porphyria by the barbiturate drugs (40). Likewise, the rare hereditary resistance to coumarin anticoagulant drugs is thought to be due to an enzyme deficiency (41). 

Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE. 1977. Neurotransmitter enzyme abnormalities in senile... 

Measurements of enzymes are used in medicine in two major ways Enzymes are measured in serum and other bodily fluids to detect injury to a tissue that makes the enzyme. Enzymes are also measured, often within a tissue, to identify abnormahties or absence of the enzyme, which may cause disease. In the first part of this chapter we discuss enzymes as markers of disease, and then describe conditions associated with abnormalities of enzymes in one readily available cell type, the erythrocyte or red blood cell. Many other abnormahties of enzymes exist, of course, and many are described in chapters of this book including Chapters 40 (Inherited Disease), 43 (Pharmacogenetics) and 55 (Inborn Errors of Amino Acid, Organic Acid, and Fastty Acid Metabolism). For descriptions of enzyme abnormalities associated with lysosomal storage disease, and tests for the related enzymes, readers are referred to the Chapter 40 Appendix that is located on this book s accompanying Evolve site, found at http //evolve.elsevier.com/Tietz/textbook/. 

Two enzyme abnormalities resulting in an overproduction of uric acid have been well described (Fig. 91-1). The first is an increase in the activity of phosphoribosyl pyrophosphate (PRPP) synthetase, which leads to an increased concentration of PRPP. PRPP is a key determinant of purine synthesis and thus uric acid production. The second is a deficiency of hypoxanthine guanine phosphoribosyl transferase (HGPRT). 

The common adverse effects of itraconazole are similar to those of terbinaflne, such as gastrointestinal disturbance, dermatologic disorders, and headache less common adverse effects include dizziness, fatigue, fever, decreased libido, and asymptomatic liver enzyme abnormalities (1% to 5% with continuous dosing and about 2% with... 

Soler, N. G., and Khardori, R., Liver enzyme abnormalities after insulin-induced hypogly-caemic coma. Br. Med. J. 291, 1541 (19850. 

IV Andersen s disease Brandling enzyme Abnormally long iinbrandied diains Liver and odier organs... 

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