[Condition of lipid peroxidation and antioxidant system in patients with non-alcoholic fatty liver disease].

The article presents research results which made it possible to reveal processes of lipoperoxidation of neutral lipids featuring oxidative stress in patients with non-alcoholic fatty liver disease and biliary tract pathology. All the patients demonstrated contra-directed changes in the antioxidant system enzymes activity requiring therapeutic correction including pathogenetic preparations with antioxidant properties.

Salivary gamma-glutamyl transferase activity in internal diseases.

Salivary gamma-glutamyl transferase (GGT) activity was measured in 116 patients with several diseases that involved the hepatobiliary tract, pancreas, and miscellaneous disorders and in 20 normal subjects. We have found significantly elevated values of salivary GGT in cirrhosis of the liver (8.3 +/- 0.9 [mean +/- SEM] units/L), hepatic tumors (10.4 +/- 1.3 units/L), acute cholecystitis (18.3 +/- 2 units/L), acute pancreatitis (15.1 +/- 2.4 units/L), diabetic ketoacidosis (11.6 +/- 1 units/L), and Sjögren's syndrome (19.6 +/- 4.8 units/L). Salivary GGT activities were unmodified in fatty liver, infectious hepatitis, silent cholelithiasis, and mumps. Several mechanisms explain high salivary GGT activity. Measurement of salivary GGT activity in internal medicine merits further investigations to determine its potential diagnostic value.

Clinical value of biliary alkaline phosphatase in non-jaundiced cholangiocarcinoma.

PURPOSE: Measurement of the activities of alkaline phosphatase isoenzyme has been used for the identification and monitoring of diseases associated with the isoenzyme. Biliary alkaline phosphatase (BALP), an isoform of liver-ALP, has been found in the serum of patients with biliary obstruction and metastatic liver cancer. This study compared the BALP isoform in the serum of patients with cholangiocarcinoma (CCA) with that of non-jaundiced benign hepatobiliary disease, other cancers, and healthy persons. METHODS: ALP isoforms were separated using cellulose acetate electrophoresis and the activity was demonstrated using indolyl blue reagent. RESULTS: The BALP isoform was demonstrated in 65% of CCA patients independently of jaundice condition or histological grading of the tumor. The level of serum BALP in non-jaundiced CCA was significantly lower than that of jaundiced CCA, and not correlated with serum bilirubin. No BALP was detected in healthy persons. In the patients with high serum ALP (> 147U/l), BALP can differentiate non-jaundiced CCA patients from other non-jaundiced carcinoma patients with 85% sensitivity, 79% specificity, and positive and negative predictive values of 81% and 83%, respectively. CONCLUSION: The demonstration of serum BALP, in particular in non-jaundiced patients with high serum ALP, may indicate the presence of tumor in the bile duct.

An interpretation of the elevation of serum alkaline phosphatase in disease.

Evidence is presented in this paper which supports the hepatogenic theory for the mechanism by which the level of serum alkaline phosphatase is raised in liver disease and provides additional evidence that serum phosphatase is not excreted in the bile. By starch gel and paper electrophoresis the normal serum alkaline phosphatase isoenzyme is shown to be rarely present in hepatic bile. The action of neuraminidase demonstrates that beta-globulin isoenzymes of liver and bone are not identical. From these results a theory which clarifies the rationale of the elevation of alkaline phosphatase in bone and liver disease is postulated. The proposed mechanism may be summarized as follows. The normal serum level is the result of two factors, the rate of release of the enzyme from the tissues, principally liver and bone, and the rate of inactivation of the enzymes in the serum and body protein pool. In osteoblastic bone disease the elevated level is due to the rate of release of the enzyme exceeding the rate of inactivation. The raised level does not indicate an inability of the liver to excrete the enzyme via the biliary tract. In liver disease the increase in serum levels is a result of increased liberation of the enzyme from the sinusoidal surface of the liver cell and of regurgitation of the biliary isoenzyme back into the serum.

Origins of serum alkaline phosphatase.

A very rapid method of agar gel electrophoresis on glass slides, together with a superior visualization technique employing simultaneous coupling of a hydrolysed naphthol substrate, have been developed for the identification of the tissues of origin of serum alkaline phosphatase. Combined with L-phenylalanine inhibition, specific for the intestinal enzyme, and heat inactivation, specific for the placental enzyme, the heterogeneity of serum alkaline phosphatase has been demonstrated. Normal adult serum contains predominantly liver-type alkaline phosphatase with a small but variable quantity of intestinal enzyme, and little or no bone enzyme. In childhood and in infancy there is in addition a bone isoenzyme present, the amount gradually falling to adult levels with age. In pregnancy, the rise in serum alkaline phosphatase is due to the placental enzyme.A study of nearly 2,000 sera has been undertaken and it is found that the bone enzyme is increased in osteoblastic bone diseases while in hepato-biliary disorders there is an increase in liver type enzyme. The main theories explaining the rise in serum alkaline phosphatase are examined.

Activation of serum 5' nucleotidase by magnesium ions and its diagnostic applications.

Magnesium ions increase the hydrolysis of adenosine 5' monophosphate (5' AMP) by human serum at pH 7.9 but not at pH 9.3. The additional hydrolysis at pH 7.9 is predominantly due to increased activity of the specific phosphatase 5' nucleotidase (5Nase). This increase is proportional to enzyme concentration and has been employed as a measure of 5Nase activity in a sensitive micro-estimation. The normal range for serum 5Nase activity by this technique was 0 to 20 mIU/ml. In a series of over 200 patients, raised values were found frequently in hepatobiliary disease and infrequently in bone disease. Assay of 5Nase activity gave a more reliable indication of the source of raised serum alkaline phosphatase than isoenzyme electrophoresis in agar gel. The correlation between activities of the two enzymes was low in bone disease generally, and fairly good in hepatobiliary disease. The closest correlation was found in patients with parenchymal liver disease.

Plasma alkaline phosphatase isoenzymes in hepatobiliary disease.

BY CELLULOSE ACETATE OR ACRYLAMIDE GEL ELECTROPHORESIS IT IS POSSIBLE TO SEPARATE THESE ALKALINE PHOSPHATASE ISOENZYMES FROM SERUM: [anode] fast liver, slow liver, placenta/Regan, bone, intestine, bile [cathode]. Heat or chemical inhibition can confirm the differentiation. Normal adult serum always contains slow-liver isoenzyme, and sometimes bone isoenzyme: the latter is always present in serum of children. In hepatobiliary disease slow-liver isoenzyme was always increased: intestinal isoenzyme appeared in many cases of cirrhosis (of blood groups B and 0) but fast-liver and bile isoenzymes were occasionally seen in miscellaneous cases. The findings in other diseases included Regan isoenzyme in six out of 45 cases of malignant disease.

Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study.

There is evidence that mast cells are involved in a number of pathophysiological processes. The significance of mast cells in hepatic fibrosis was examined in 28 patients with histologically normal livers, 34 with acute liver diseases, 51 with chronic liver diseases, and 59 with cholestatic biliary diseases, using immunostaining of the mast cell-specific proteinase, tryptase. Mast cells that were positive for tryptase and for chymase were significantly increased in frequency in fibrotic portal tracts and fibrous septa, particularly in cholestatic/biliary diseases. Mast cells were also increased in frequency around the fibrotic septal and intrahepatic large bile ducts and peribiliary glands of biliary diseases. However, they were less common or even rare in the sclerotic bile ducts and in scarred portal or septal fibrosis. More than half of these more numerous mast cells were positive for histamine, and some were also positive for basic fibroblast growth factor. These two substances were detectable by immunoelectron microscopic in the cytoplasmic granules of mast cells. In contrast, mast cell numbers were not significantly increased in acute viral or drug-induced hepatitis, or in zones 2 and 3 of the hepatic acinus with respect to pericellular and perivenular fibrosis in chronic liver diseases. These findings suggest that mast cells increase in number in cholestatic/biliary diseases, and to a lesser degree in chronic liver diseases, and are involved in the active fibrous enlargement of portal tract and fibrous septa formation and also in the fibrosis of the intrahepatic bile ducts as they display fibrosis-promoting factors such as tryptase, fibroblast growth factor and histamine.

Chronic pancreatitis: a cause of biliary stricture.

This is a report of our experience with 13 patients who had a distal common duct stricture associated with chronic relapsing pancreatitis. All patients, when first seen, had an elevated alkaline phosphatase level; eight of 13 patients also had an elevated serum bilirubin level. Five of the jaundiced patients had a febrile course; a preoperative diagnosis of acute cholangitis was made in four of these. Eight of the 13 patients have had a choledochoduodenostomy for relief of biliary obstruction; seven of these patients are living and well; one died of continued alcoholism and pancreatitis. One patient had a loop cholecystojejunostomy; decompression was inadequate and death due to septicemia secondary to ascending cholangitis ensued. Four patients have not yet had an operation. Two are symptomatic, but elective operation has been refused. Two have been lost to follow-up. We recommend investigation of the biliary tract in patients known to have chronic relapsing pancreatitis who also have persisting abdominal symptoms and an elevated alkaline phosphatase. If a stricture of the distal common bile duct is identified in the absence of acute pancreatitis, choledochoduodenostomy should be performed.

Glycylprolyl-p-nitroanilidase in hepatobiliary disease.

The serum activity of glycylprolyl-p-nitroanilidase (GPN) has been compared with isocitrate dehydrogenase and with alanine and aspartate aminotransferases in patients with hepatobiliary diseases, myocardial infarction and chronic inflammatory bowel disease. Serum GPN was markedly increased in all hepatobiliary diseases, especially secondary carcinoma and chronic alcoholic hepatitis, but no abnormal values were seen in patients with chronic inflammatory bowel disease. Slightly elevated GPN activities were noticed in a few cases of myocardial infarction. It is suggested that serum GPN would be useful for monitoring hepatic function, especially in the clinical trials of new drug.

A critical examination of the value of combined determinations of lecithin:cholesterol acyltransferase and lipoprotein-X in the differential diagnosis of liver disease.

The suggestion that combined determinations of lecithin: cholesterol acyltransferase activity and lipoprotein-X can be used to distinguish between patients with intrahepatic cholestasis and extrahepatic biliary obstruction has been studied. Of 21 patients who were lipoprotein-X positive and in whom an unequivocal diagnosis was made, 11 had intrahepatic cholestasis and 10 extrahepatic obstruction. The range of plasma lecithin:cholesterol acyltransferase activity was similar in the two groups and did not enable distinction to be made between them.

Bile lysosomal enzymes: characteristics and pathological significance for various hepatobiliary disorders.

The activities of several glycosidases (beta-galactosidase, beta-glucosidase, N-acetyl-beta-glucosaminidase) were demonstrated in human bile. The enzyme activities are increased about 100 times after exclusion of bile salts and other small molecular compounds by Sephadex G-50 gel filtration. The use of 4-methylumbelliferyl derivatives as substrates was useful as measurement of the bile enzyme activities are not altered in the presence of bile pigments. Enzyme characteristics of bile glycosidases were determined: pH optimum and isoelectric point. The bile glycosidase activities were also measured in various hepatobiliary disorders (cholelithiasis, cancer of gallbladder, acute hepatitis, liver cirrhosis and fatty liver). The glycosidase activities in bile from patients with liver diseases, as well as with cholelithiasis, were generally decreased. Isoelectric focusing patterns of biliary glycosidases were similar for specimens from patients with hepatobiliary disorders as compared to normal.

pH and concentration of pancreatic enzymes in aspirates from the human duodenum during digestion of a standard meal in patients with biliary or hepatic disorders.

The material comprises 34 patients with anicteric biliary diseases, 20 with obstructive jaundice, 8 with hepatic cirrhosis, and 3 with haemochromatosis. The intestinal contents were aspirated in four subsequent periods of 20 minutes each after ingestion of a standard meal. The volume, pH, and the concentration of alpha-amylase, trypsin, chymotrypsin and lipase were determined in the collections. The concentration of lipase was more markedly reduced than concentrations of amylase and of trypsin in patients with anicteric biliary diseases and in patients with hepatic cirrhosis. Concentrations of enzymes below the lowest normal value throughout the period of digestion represented an uncommon finding. The exocrine pancreatic function is rarely found to be reduced in patients with biliary or with hepatic disorders.

The amylase profile: a discriminant in biliary and pancreatic disease.

Serial serum amylase determinations were made in 85 consecutive patients who presented with an initially elevated value. In 35 patients (Group A), the clinical findings were consistent with biliary tract disease. All underwent cholecystectomy for documented cholelithiasis within a week of diagnosis, and 23 percent had choledocholithiasis as well. Fifty patients (Group B) presented with a first episode of acute alcoholic pancreatitis. An amylase profile, consisting of initial and final values and the daily rate of change, was significantly different between the two groups. The initial serum amylase value was higher in Group A patients and decreased more rapidly to a lower value than in Group B patients. We conclude that both the initial value and pattern of serum amylase decay distinguish the hyperamylasemia of biliary tract disease from that of alcoholic pancreatitis.

Pancreatic enzyme levels in bile of patients with extrahepatic biliary tract disease.

A total of ninety three patients with biliary tract disease were studied to determine the concentration of the pancreatic enzymes, amylase and lipase, in bile obtained from the gallbladder and/or common bile duct. Of seventy gallbladder bile samples, amylase levels were higher than actual or predicted serum levels in 87 per cent, while bile lipase were higher than serum lipase values in 66 per cent. Bile obtained from the common bile duct had enzyme concentrations which fluctuated from values similar to those in serum to remarkably high levels. This suggests that pancreatic enzymes enter the biliary system through a common terminal ampulla which is known to exist in 60 to 90 per cent of human subjects. The premise is advanced that pancreatic enzymes may initiate inflammatory changes in the gallbladder and could play a role in gallstone formation by altering the constituents which maintain cholesterol in a soluble state. Biliary reflux of pancreatic enzymes could play a role in the pathogenesis of some cases of cholecystitis can cholelithiasis.

Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980-1990).

The diagnostic efficacy of serum alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities was examined, using the records of 270 dogs initially suspected of having hepatobiliary disease on the basis of history, findings on physical examination, results of baseline screening tests, or any combination of these data. Histologic examination of hepatic tissue was performed in each dog. Sixty-three dogs did not have histologic evidence of hepatobiliary disease and served as the control group. On the basis of diagnosis, dogs were assigned to 1 of 8 groups: dogs with cirrhosis (n = 34), steroid hepatopathy (n = 16), hepatic neoplasia (primary and secondary, n = 36), chronic hepatitis (n = 14), chronic passive congestion (n = 5), hepatic necrosis (n = 17), portosystemic vascular anomaly (n = 35), and cholestasis (extrahepatic bile-duct obstruction and intrahepatic cholestasis, n = 50). Of the 207 dogs with hepatobiliary disease, 29 (14%) had normal ALP and GGT activities, 31 (15%) had normal ALP activity, and 112 (54%) had normal GGT activity. Of the 63 control dogs, 29 (46%) had normal serum ALP and GGT activities, 32 had normal ALP activity (ALP specificity, 51%), and 55 had normal GGT activity (GGT specificity, 87%). The specificity of ALP and GGT in parallel (positive result = result of either test abnormal) was 46%, and in series (positive result = results of both tests abnormal) was 91%. The highest median activities of ALP developed in dogs with cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis. The highest median activities of GGT developed in dogs with steroid hepatopathy, cholestasis, and hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey.

OBJECTIVE: The aim of this study is to determine the etiologies of serum gamma glutamyltransferase (GGT) elevation and relations between multiple etiologies prevalent in the Pursaklar region of Ankara in Turkey. PATIENTS AND METHODS: The patients referred to the Family Medicine and Internal Medicine departments with various complaints from the Pursaklar region of Ankara between July 2000 and July 2002 were evaluated, and values for GGT, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) levels were determined. GGT elevation was classified as being associated with hepatic, biliary, and other origins. RESULTS: For GGT elevation, hepatobiliary etiologies were more prevalent. The most prevalent hepatic etiology was nonalcoholic steatohepatitis, followed by biliary etiologies. The most prevalent etiology of biliary origin was cholelithiasis. Other etiologies, in order of prevalence, were drug exposure and urinary infection. There were no gender-related differences for distribution of GGT elevation; however, the GGT values for women were higher than those for men.

[A new tumor marker--novel gamma-GTP isoenzyme].

The authors discussed the clinical significance and some properties of the novel gamma-GTP isoenzyme (novel gamma-GTP) which was reported to be specific for sera of hepatocellular carcinoma (HCC) in our previous publications. One or more of specific bands (novel gamma-GTP) such as bands II, II' and I' were electrophoretically detectable in 109 (55%) of 200 patients with HCC, but only in 3% of 279 patients with other hepatobiliary diseases. Novel gamma-GTP was found in 38% of HCC patients with AFP levels below 400 ng/ml. The incidence of novel gamma-GTP was independent of the clinical stage as classified by liver scanning. Even in stage I, where filling defects were not seen, the incidence was 52%. It is concluded that novel gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage. Some properties of gamma-GTP purified from HCC tissues were investigated and compared with those of the normal kidney enzyme. The enzymes from HCC and kidney were identical in enzymatic and immunological properties, whereas a considerable difference was observed in electrophoresis, Con A affinity, effect of neuraminidase and isoelectric point. Respective bands II, II' and I' could be differentiated in Con A affinity and neuraminidase reaction. These results support the possibility that novel gamma-GTP in sera of HCC patients is largely due to a difference in carbohydrate moiety of gamma-GTPs.

Serum trypsin-like immunoreactivity after endoscopic retrograde cholangiopancreatography.

Serum trypsin-like immunoreactivity (TLI) was studied in 31 patients before and after endoscopic retrograde cholangiopancreatography. None of the patients developed clinical acute pancreatitis. Generally, the serum TLI peak was observed within the first 6 hours after the examination. Most patients (73%) showed a pathologically high TLI but very high values were not frequent (19%). Successful pancreatic opacification was followed by a significant increase in serum TLI which was pathologically high in nearly all cases (18/20). On the contrary, after cholangiography alone abnormal values were less frequent (4/8) and the increase was not significant. In most patients TLI and amylase responses were in agreement. A significant, though poor, linear relation was found between serum TLI and serum amylase 3, 6 and 12 hours after the examination.

[Clinical study on serum 5'-nucleotide phosphodiesterase isoenzyme-V as a predictor of liver metastases in patients with gastric and colorectal cancers].

By separating 5'-nucleotide phosphodiesterase isoenzyme-V (5'-NPD-V) as a fast-moving isoenzyme by polyacrylamide electrophoresis, the determination of serum 5'-NPD-V was performed in 302 preoperative patients with gastric and colorectal cancers to assess the clinical usefulness for suspecting liver metastases. Serum levels of CEA, alpha-fetoprotein and tumor markers were simultaneously measured. Angiography, CT scan and echo were also performed preoperatively. The normal values of serum 5'-NPD-V in 67 healthy subjects except heavy smokers were less than 3.0mm. 5'NPD-V values determined in patients with and without liver metastases were as follows: In gastric cancer 1.5 +/- 2.0mm and 8.6 +/- 9.0mm, and in colorectal cancer 2.2 +/- 3.3mm and 5.8 +/- 5.3mm, respectively, indicating a significant difference (p less than 0.05). The sensitivity of 5'-NPD-V in gastric cancer was 0.682, the specificity was 0.892, the predictability was 0.518, and the accuracy was 0.862. The results in colorectal cancer were 0.600, 0.958, 0.805 and 0.800, respectively. Serum 5'-NPD-V value was elevated progressively in accordance with extent of liver involvement. When assessed by 5'-NPD-V and CEA, 80.9% of patients with liver metastases proved to be correctly diagnosed. The results suggest that 5'-NPD-V is clinically a useful marker in that the isoenzyme provides the rationale for the further detection of tumor localization in the liver.