Serum Guanase Activity Research Articles

Determination of guanase activity in patients with prolonged treatment with simvastatin

In this study, 28 patients suffering from hyperlipidemia who were on simvastatin ,were included for determination serum guanase activity. Guanase activity was observed at high level in those patients (n = 16) who were on prolonged treatment with simvastatin (more than 30 days) but its activity remained within normal when simvastation was administrated at interrupted intervals . The results were compared with two control groups the first (n=10) with hyperlipidemia but with no simvastatin and the second (n=10) was normal individuals with no history of hyperlipidemia. However, guanase activity was found to be normal in both control groups .
 Besides, this study was found that alkaline phosphatase was also increased in some patients , However , guanase activity was observed earlier than alkaline phosphatase which have suggested that simvastatine could cause liver injuries when used for a long time . This study is the first study conducted to predict liver injuries as a result of simvastatin through guanase elevation .

Clinical significance of serum guanase activity in various liver diseases.

Serum guanase activity was measured using a sensitive colorimetric method in patients with liver diseases. Guanase activity was correlated with GPT, GOT in acute viral hepatitis and chronic hepatitis, however, in liver cirrhosis and hepatocellular carcinoma it was correlated with total bilirubin as well as aminotransferases. In addition, the GPT-to-guanase ratio differed chronic hepatitis from liver cirrhosis. These findings suggest that determination of guanase and aminotransferases in useful in differentiation of liver diseases as well as assessing liver damage.

A Basic Study on the Automated Assay of Serum Guanase Activity and an Application of This Assay to Hepatobilliary and Pancreatic Diseases

A Basic Study on the Automated Assay of Serum Guanase Activity and an Application of This Assay to Hepatobilliary and Pancreatic Diseases

Simple ultraviolet spectrophotometric method for the determination of serum guanase activity

We describe a simple, kinetic method for the determination of serum guanase activity that involves enzymatic coupling to xanthine oxidase and measurement of the rate of uric acid formation by spectrophotometric monitoring of the absorption at 300 nm. At this wavelength, the absorption of uric acid is about 80% of its maximal absorption at 293 nm, but the difference in molar extinction coefficient between guanine and uric acid is similar (9,000 at 293 nm vs 8,400 at 300 nm). There are three advantages to the use of the higher wavelength: first, the absorption of serum proteins is only one third of the absorption at 293 nm resulting in a significant reduction in noise level. Second, the lower absorption of serum proteins allows increasing sensitivity of the assay by increasing the amount of serum in the reaction mixture. Third, the higher wavelength allows the use of automated centrifugal analyzers that are generally not designed for measurements below 300 nm. The between-day coefficient of variation was 5.8% (n = 27) at an activity of 17 U/L and 8.2% at an activity of 2 U/L. The reference range for 50 sera from males and females was 0.4 to 1.8 U/L (n = 50; mean +/- 2SD). The method is linear to 40 U/L.

Simple, rapid determination of serum guanase activity with the Hitachi 736 automated discrete analyzer.

We present a detailed analysis both of tryptic peptides and amino-terminal sequences of the subunits of two collagenous fragments (HMW and LMW) previously isolated from pepsin extracts of chicken cartilage (Reese, C.A., and Mayne, R. (1981) Biochemistry 20, 5443-5448). This analysis and a comparison with the nucleotide sequence of the cDNApYN1738 (Ninomiya, Y., and Olsen, B.R. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 3014-3018) shows that HMW and LMW are pepsin-resistant fragments of a unique collagen composed of molecules with three different polypeptide chains (alpha-chains). This collagen has been assigned the type number IX, and the alpha-chain encoded by pYN1738 has been given the designation alpha 1 (IX). Type IX collagen contains three triple-helical domains and at least two sets of interchain disulfide bridges. At the amino and carboxyl ends are noncollagenous domains which do not appear to be homologous to amino and carboxyl propeptides of interstitial collagens.

Clinical evaluation of serum guanase activity in liver diseases

We measured serum guanase (EC 3.5.4.3) activity in patients with various diseases and in healthy controls, and evaluated the clinical usefulness of this enzyme in liver diseases. The reference range, which showed no significant difference between sexes and ages over the range studied, was 0 to 1.8 U/L. The mean guanase activities for patients with various liver diseases, including acute hepatitis, chronic hepatitis, liver cirrhosis, hepatoma and metastatic carcinoma, were above the upper limit of the reference range. In acute hepatitis and metastatic carcinoma of the liver, the activities were especially high. Validity (sensitivity + specificity) of guanase, which in all tests was above 1.66, was compared to that of AST and ALT in liver diseases. With guanase, the highest validity (1.98) was found in acute hepatitis and metastatic carcinoma. Specificity of guanase was 0.98, whereas sensitivity of AST was 1.00 in all diseases. Sensitivity and specificity of ALT were 0.85 to 0.97 in all diseases. As guanase was specific, including this enzyme with other liver function tests, such as AST and ALT, may decrease false-positive results and may be effective for prediction of liver disease.

Enzymological aspects of disorders in purine metabolism

Congenital enzyme defects of purine synthesis de novo and the salvage pathway are responsible for excessive uric acid production and are often associated with hyperuricemia and gout. On the other hand, defects of enzymes essential for the purine nucleotide cycles are the biochemical basis of dysfunction of the immune system. The influence of several congenital enzyme deficiencies on the regulation of biosynthesis de novo, on the regulation of purine nucleotide concentrations, and on adenosine concentration, as well as the effect on purine transport through cell membranes are discussed. The determination of enzymes involved in purine metabolism in noncongenital diseases seems to be of diagnostic importance. As examples, enzyme activities in lymphocytes of leukemic patients, and the determination of serum guanase activity in patients with liver dysfunction are described.

Clinical Value of the Determination of Serum Guanase Activity

Serum guanase activity was measured by a new method and compared with serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase levels in 150 patients with various disorders, 21 dogs with experimental myocardial infarction, and 2 CCl4-treated dogs. Additionally, studies of the effect of CCl4 on enzyme release were undertaken using cultured rat hepatocytes. Glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and guanase activities were found to be significantly elevated in patients with various liver disorders, those with acute myocardial infarction with prominent congestion of the liver, and also in CCl4-treated dogs. However, serum guanase activity was normal in patients with a variety of non-liver-related diseases including acute myocardial infarction, and in dogs with experimental myocardial infarction without liver damage, even when the serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase activities were increased. The glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and guanase activities in the culture medium of rat hepatocytes indicated in the presence of 0.5 mM CCl4 were elevated. These findings indicate that serum guanase activity is a more specific indicator of liver damage than serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase.

Clinical evaluation of measurement of serum guanase activity as a screening test of liver damage

A new method was developed for assay of guanase activity by direct colorimetric determination of ammonia. In this method, dotite bicine buffer is used for preparation of a stable substrate solution and with a fixed concentration of substrate of sufficient strength serum guanase can be measured sensitively and reproducibly. This assay system could be used as a routine clinical laboratory test in the diagnosis of liver damage. GOT, GPT and guanase activities were found to be significantly elevated in patients with various liver disorders, and those with acute myocardial infarction with prominent congestion of the liver and also in CCl4- treated dogs. However, serum guanase activity was normal in patients with various other diseases, in those with acute myocardial infarction and in dogs with experimental myocardial infarction without liver damage, even when the serum GOT and GPT activities were increased. The GOT, GPT and guanase in the medium of rat hepato cytes culture with 5.0 mM CCl4 were elevated. These findings suggest that serum guanase activity is a more specific indicator of liver damage than serum GOT and GPT. The determination of serum guanase activity in patients without liver damage, even when their serum GOT and GPT levels elevated, might be useful as a screening test of liver damage.

A sensitive new method for measurement of guanase with 8-azaguanine in bicine bis-hydroxy ethyl glycine buffer as substrate

Serum guanase activity has been considered as a possible specific indicator of hepatocellular diseases. However, no suitable method is available for routine clinical determination of serum guanase activity. Conventional assay methods are troublesome and inaccurate, since guanine and 8-azaguanine, the substrates of the enzyme, are scarcely soluble in water so that it is not possible to prepare a stable substrate solution of sufficient concentration for use in assays. A new method was developed for assay of guanase activity by direct colorimetric determination of ammonia. In this method, bicine bis-hydroxy ethyl glycine (dotite bicine) buffer is used for preparation of a stable substrate solution and with a fixed concentration of substrate of sufficient strength serum guanase can be measured sensitively and reproducibly. This assay system could be used as a routine clinical laboratory test in the diagnosis of liver damage.

Clinical and experimental studies of the determination of serum guanase activity in acute myocardial infarction.

Serum guanase activity was measured by a new method using direct colorimetric determination of ammonia in 25 patients with acute myocardial infarction, 21 dogs with experimental myocardial infarction and 6 CCl4-treated dogs, and compared with serum GOT and GPT activity. We found normal serum guanase activity in patients with acute myocardial infarction and in dogs with experimental myocardial infarction without liver damage, even when the serum GOT and GPT activities increased. On the other hand, serum guanase and transaminase activities were elevated significantly in the patients with acute myocardial infarction who had prominent symptoms of cardiac failure and congestion of the liver and CCl4-treated dogs. These findings suggested that the serum guanase activity was more specific than serum GOT and GPT activity as an indicator of liver damage and determination of serum guanase activity in the patients with acute myocardial infarction might be useful in assessing the presence of liver impairment.

Serum guanase activities after myocardial infarction

Serum guanase, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase and hydroxybutyrate dehydrogenase activities were measured in 290 blood samples from 96 consecutive patients admitted to a Coronary Care Unit. Elevated serum guanase activities (greater than 2 U/1) were found in 19 patients (20%). The magnitude and frequency of these elevations did not negate the value of guanase as a “liver function test”, since all cases with raised guanase also had abnormal serum alanine aminotransferase activities. This fact, together with other information in the literature, indicated that elevated serum guanase activity following myocardial infarction was consequent upon some degree of sub-clinical hepatic necrosis. Caution must be exercised when serum aspartate aminotransferase is used as an index of heart muscle necrosis unless guanase or some other “liver specific” enzyme is known to be normal, or unless creatine phosphokinase or hydroxybutyrate dehydrogenase activities are elevated.

Assay of human serum and liver guanase activity with 8-aza-guanine as substrate

Guanase activity of human serum and liver supernatant was measured using 8-azaguanine as substrate. The ammonia liberated was assayed by the phenol-hypo-chlorite reaction of Berthelot. The method does not require protein precipitation. Because of this, and the superiority of 8-azaguanine compared with guanine as a substrate, the method is the most sensitive colorimetric technique for guanase yet presented; test and control each require only 50 μl of serum. A sharp optimum at pH 6.3 was shared by serum and liver guanase with this substrate and the K m values for the two enzymes were similar, being 0.174 and 0.144 mM respectively. Inhibition of the Berthelot reaction by serum is small and consistent and can be compensated by a correction factor. The normal range for human serum guanase activity by the new method is 0.6–2.0 IU/litre.

Guanase activity in endemic balkan nephropathy

Serum guanase activity was studied in 71 patients with renal diseases and in 30 normal individuals. A significant increase of serum guanase activity was recorded in 73.3 per cent of patients with endemic nephropathy. Only in isolated cases of chronic glomerulonephritis and chronic pyelonephritis, guanase activity was shown to be slightly increased. It is admitted that increased guanase activity in patients with endemic nephropathy is due to destructive lesions and cytolysis in the epithelial cells of the renal tubuli and, possibly, in the liver parenchyma as well. No correlation was found between increased serum guanase activity, on the one hand, and the degree of nitrogen retention, glomerular filtration and flocculation tests, on the other.

Clinical evaluations of indocyanine grean test (ICG) and serum guanase activity (G) in liver diseases

Clinical evaluations of indocyanine grean test (ICG) and serum guanase activity (G) in liver diseases

Colorimetric Determination of Serum Guanase Activity

Abstract A colorimetric method for the determination of serum guanase has been developed whereby ammonia, formed by the deteramination of guanine, is measured by the phenatehypochlorite reaction. Variations in substrate concentration, time of incubation, pH, temperature, and concentration of enzyme have been investigated with respect to enzyme activity. The determination of serum guanase appears to be useful in the differential diagnosis of jaundice.