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December 1985, Volume 35, Issue 12

Letter to the Editor

CREATINE KINASE ACTIVITIES IN SERA OF CIRRHOTICS

Sir,
Creatine Kinase (CK) E.C. 2.7.3.2. is separable into three different isoenzymes by a number of methods.1-4 Each isoenzyme is a dimer composed of two subunits (Bor M) each having a relative molecular mass of 40,0001. These isoenzymes are widely distributed in tissues, CK-MM and CK-MB are found mainly in the skeletal and heart muscles and CK-BB in G.l. tract and the brain with small amounts also found in the kidneys, lungs and the liver5-6 . In recent years many investigators have discussed diagnostic and clinical significance of CK-iso enzymes in acute myocardial infarction7. In the last few years, a number of case reports have appeared that deal with the presence of CK-BB or Macro CK and CK-MB in sera of patients with malignancies thought to be produced by neoplastic cells8-14 .
These reports stimulated us to study CK-levels in histologically proven cirrhotics to screen for abnormal values of CK if any. We evaluated total CK and CK activities after
Immunoinhibition of the M moiety to determine CK-MB or CK-BB values. In a total of thirty cases we found that total CK values were higher than normal controls though within the normal range (Table 1).

The activity after inhibition of M fraction show higher values than controls and the difference was significant ( p < 0.001 ) (Table 1). The M inhibited CK values in many cirrhotics were similar to controls, however, twelve cases had much higher mean values (87.75 ± 32.3 U/L with a range 58-1 48 U/L). Though from these raised values and over technical methods it is difficult to interpret whether the raised activity in cirrhotics are due to CK-MB or CK-BB or both. The fact that they are raised with no evidence of myocardial injury, raises interesting questions. Are these raised values suggestive or indicative of neoplastic changes not seen histologically? If so can these values be used as prognostic or tumour indicators? Interestingly many of the cases who had raised values after M inhibition had a histological diagnosis of macronodular cirrhosis, a type more often associated with primary liver cancer. These fmdings are interesting but -would become pertinent when isoenzyme patterns are evaluated in such cases to ascertain if CK-BB or CK-MB or both are raised and if such raised values are found in cases of primary liver cancer.
Total CK and Ck activities after immunohibition of M moiety was evaluated in sera of 30 histo­logically diagnosed cirrhotics and 14 normal controls. Both activities were determined by optinilsed standard methods using 340 rat assay by Boehringer kits. Normal Ck range (24-195).

ACKNOWLEDGEMENT

We are grateful to Dr. Sarwar Zuberi and Dr. Huma Qureshi of the PMRC Research Centre Jinnah Postgraduate Medical Centre Karachi for providing the sera and clinical and histological data on these patients to make the study possible.
Mirza Naqi Zafar and lftikhar Ahmed Zafar Research and Diagnostic Center, 7/14 Clinic Side, Rirnpa Plaza, Karachi.

REFERENCES

1. Dawson, D.M., Eppenberger, H.M. and Kaplan, N.O. The comparative enzymology of creatun kinases. II. Physical and chemical properties. J. Biol. Chem., 1967; 242: 210.
2. Somer, H. and Konttinen, A. Demonstration of serum creatine kinase isoenzymes by a flourescence technique. Clin. Chim. Acta, 1972; 40 : 133.
3. Jockers-Wretove and Pfleiderer, G. Quantitation of creatune kinase isoenzymes in human tissues and sera by an immunological method. Clin. Chim.Acta, 1975;58: 223.
4. Smith, A.F. Separation of tissue and serum creatinine kinase isoenzymes on polyacrylamide gel slabs. Clin. Chhn. Acta, 1972; 39 : 351.
5. Tsung, S .H. Creatinune kinase isoenzyme patterns in human tissues obtained at surgery. Clin. Chem., 1976;22 : 173.
6. Takahashi, K., Shutta, K., Matsuo, B. et al. Serum creatin kinase isoenzymes in Duchenne muscular dystrophy. Clin. Chim. Acta, 1977;75 : 435.
7. Yuv, H. Diagnostic significance of serum creatine kinase isoenzyme MB fraction (CK-MB) in acute myocardial infarction. Jpn. Soc. Intern. Med., 1978; 67 :576.
8. Annesley, T.M. and McKenna, B.J. Ectopic creatine kinase MB production in metastatic cancer. Am. J. Chin. PathoL, 1983; 77 : 255.
9. Heinz, J.W., O’Donnell, NJ. and Lott, J.A. Apparent mitochondrial creatine kinase in the serum of a patient with metastatic cancer of the liver. Chin. Chem., 1980; 26 : 1908.
10. Yuv, H., Takagi, Y., Senju, 0., Hosoya, J., Gomi, K. and Ishii, T. Creatinine kinase isoenzyme of high relative molecular mass in serum of a cancer patient. Clin. Chem., 1978; 24 : 2054.
11. Zweig, M.H. and Van Sterirteghem, A.C. Assessment of radioimmunoassay of serum creatine kinase BB (CK-BB) as a tumour marker; studies in patients with various cancers and a comparison of CK-BB concentrations to prostate acid phosphatase concentrations. JNCI., 1981; 66 : 659.
12. Liu, T.Z., Shen, J.T., Lee, Y.T. and Shohet, S.B. A typical cathode migrating creatine kinase isoenzyme and human breast carcinoma; a specific marker. Chin. Chem., 1980; 26 : 1765.
13. Meyer, 1.J., Thompson, J.A., Kiser, E.J. and Haven, G.T. Observation of a variant creatine kinase isoenzyme in sera and breast tumour cytosols. Am. J. Clin. PathoL, 1980; 74 : 332.
14. Silverman, L.M., Dermer, G.B., Zweig, M,H., van Steirteghem, A.C. and Tokes, Z.A. Creatine kinase BB; a new tumour-associated marker. CIin.Chem.,1979;25 :1432.

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