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Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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370<br />

Chapter | 12 Diagnostic Enzymology <strong>of</strong> <strong>Domestic</strong> <strong>Animals</strong><br />

In long-distance sled dog races, there are marked interindividual<br />

variations with activity ranging from unchanged<br />

to more than 13-fold increase. However, there is minimal<br />

increase in serum CK activity following exercise in<br />

untrained beagle dogs ( Chanoit et al. , 2002 ). In horses, it<br />

has been concluded through kinetic studies that the amount,<br />

in grams, <strong>of</strong> striated muscle damaged is negligible following<br />

exercise ( Volfinger et al. , 1994 ). It has been reported that<br />

increases tend to occur more frequently in fillies, younger<br />

animals, and untrained horses ( Harris et al. , 1998 ).<br />

In all species, CK has the advantage over serum aspartate<br />

aminotransferase in being specific for muscle injury<br />

and not affected by hepatocellular injury. The short halflife<br />

<strong>of</strong> the enzyme may tend to reduce the diagnostic sensitivity<br />

<strong>of</strong> the test, but it also <strong>of</strong>fers an effective means <strong>of</strong><br />

monitoring response to therapy.<br />

K . Other Enzymes<br />

As mentioned in the introduction, numerous other enzymes<br />

have been investigated for use in diagnosis and prognosis<br />

<strong>of</strong> disease and organ dysfunction in nonhuman animals.<br />

Some <strong>of</strong> these have been dropped altogether or receive<br />

limited use, such as lactic acid dehydrogenase, 5 nucleotidase,<br />

glutathione S-transferase, leucine aminopeptidase,<br />

arginase, aldolase, and acid phosphatase, among others.<br />

The reasons for their limited use vary but include relatively<br />

poor diagnostic accuracy, diagnostic redundancy with<br />

already established tests, and a lack <strong>of</strong> readily available<br />

test kits. For example, serum lactic acid dehydrogenase<br />

(LDH) activity originates from several tissues including<br />

liver, skeletal muscle, heart muscle, and erythrocytes. This<br />

resulting decreased test sensitivity and specificity limits<br />

the diagnostic accuracy <strong>of</strong> serum LDH activity. Although<br />

LDH isoenzyme analysis may improve tissue specificity,<br />

the tests are relatively time consuming, expensive, and still<br />

only provide a subjective assessment <strong>of</strong> the contribution <strong>of</strong><br />

each organ to the total serum activity. In addition, the test<br />

does not <strong>of</strong>fer a substantial improvement over assays to<br />

other enzymes such as alanine aminotransferase or creatine<br />

kinase. A few laboratories still <strong>of</strong>fer 5 nucleotidase, but it<br />

provides much <strong>of</strong> the same information as ALP and perhaps<br />

has lost favor as a result. Arginase is highly specific<br />

for injury to hepatocytes but suffers from a short half-life<br />

and is not readily available for autoanalyzers.<br />

V . FUTURE OF SERUM ENZYMOLOGY<br />

Although the number <strong>of</strong> studies investigating enzyme activity<br />

assays for diagnostic purposes has decreased since the<br />

1990s, they are still <strong>of</strong> immense importance to diagnostic<br />

medicine. The currently increasing interest in identifying<br />

protein and peptide markers <strong>of</strong> organ injury or dysfunction<br />

will require immunoassays to determine their concentrations<br />

in serum. This is <strong>of</strong>ten problematic to veterinarians, as<br />

appropriate antibodies to these markers in domestic animals<br />

are frequently unavailable. The divergence <strong>of</strong> human<br />

biomarker research away from classical serum enzymology<br />

has the unintended consequence <strong>of</strong> limiting the universality<br />

<strong>of</strong> new biomarker application across species. Although this<br />

continues to be a deterrent, there is increased interest in the<br />

development and utilization <strong>of</strong> immunoassays in veterinary<br />

medicine as evidenced by the assays for trypsin-like immunoreactivity<br />

and pancreatic lipase immunoreactivity in<br />

dogs and cats, as well as immunoassays for nonenzymatic<br />

proteins, such as the natruretic peptides and troponins.<br />

Problems regarding the availability <strong>of</strong> immunoassays and<br />

long turnaround time from submission to obtaining laboratory<br />

results are increasingly being addressed. For example,<br />

the development <strong>of</strong> automated analyzers for immunoassays<br />

has allowed test results to be available on the same day as<br />

sample submission. Canine TLI is available on the Immulite<br />

system from Diagnostic Products Corporation, and more<br />

are expected in the future. The fields <strong>of</strong> serum enzymology<br />

and serum protein markers have merged in human medicine<br />

as evidenced by the topic section “ Proteomics and Protein<br />

Markers ” in the table <strong>of</strong> contents <strong>of</strong> the journal <strong>Clinical</strong><br />

Chemistry. The development <strong>of</strong> this merger in nonhuman<br />

animal medicine is almost certain to happen.<br />

REFERENCES<br />

Abraham , G. , Gottschalk , J. , and Ungemach , F. R. ( 2005 ). Evidence<br />

<strong>of</strong> ototopical glucocorticoid-induced decrease <strong>of</strong> hypothalamicpituitary-adrenal<br />

axis response and liver function . Endocrinology<br />

146 , 3163 – 3171 .<br />

Aktas , M. , Auguste , D. , Concordet , D. , Vinclair , P. , Lefebvre , H. ,<br />

Toutain , P. L. , and Braun , J. P. ( 1994 ). Creatine kinase in dog plasma:<br />

preanalytical factors <strong>of</strong> variation, reference values and diagnostic<br />

significance . Res. Vet. Sci. 56 , 30 – 36 .<br />

Aktas , M. , Auguste , D. , Lefebvre , H. P. , Toutain , P. L. , and Braun , J. P.<br />

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353 – 369 .<br />

Aktas , M. , Lefebve , H. P. , Toutain , P. L. , and Braun , J. P. ( 1995 ).<br />

Disposition <strong>of</strong> creatine kinase activity in dog plasma following intravenous<br />

and intramuscular injection <strong>of</strong> skeletal muscle homogenates .<br />

J. Vet. Pharmacol. Ther. 18 , 1 – 6 .<br />

Allen , L. C. V. , Allen , M. J. , Greur , G. J. , H<strong>of</strong>fmann , W. E. , and<br />

Richardson , D. C. ( 2000 ). A comparison <strong>of</strong> two techniques for the<br />

determination <strong>of</strong> serum bone-specific alkaline phosphatase activity in<br />

dogs . Res. Vet. Sci. 68 , 231 – 235 .<br />

Allen , M. J. , H<strong>of</strong>fmann , W. E. , Richardson , D. C. , and Breur , G. J. ( 1998 ).<br />

Serum markers <strong>of</strong> bone metabolism in the dog . Am. J. Vet. Res. 59 ,<br />

250 – 254 .<br />

Anderson , H. C. , Sipe , J. B. , Hessle , L. , Dhanyamraju , R. , Atti , E. ,<br />

Camacho , N. P. , and Millan , J. L. ( 2004 ). Impaired calcification<br />

around matrix vesicules <strong>of</strong> growth plate and bone in alkaline<br />

phosphatase -deficient mice . Am. J. Path . 164 , 841 – 847 .<br />

Archer , F. J. , and Taylor , S. M. ( 1996 ). Alkaline phosphatase bone isoenzyme<br />

and osteocalcin in the serum <strong>of</strong> hyperthyroid cats . Can. Vet. J.<br />

37 , 735 – 739 .

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