Kinetic analysis of glycogen synthase and PDC in cirrhotic rat liver and skeletal muscle.

Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDC) were kinetically analyzed in the liver and skeletal muscle of fasted and refed rats with thioacetamide-induced cirrhosis of the liver. In control rats, refeeding induced a 54% decrease in the A0.5 for glucose 6-phosphate (G-6-P) of hepatic GS (P < 0.001), reflecting allosteric activation of the enzyme. In skeletal muscle the A0.5 for G-6-P did not change after refeeding, whereas the activity ratio increased by 56% (P < 0.01), indicating a greater percentage of the active G-6-P-independent form of the enzyme. In cirrhotic rats, neither the A0.5 for G-6-P of liver GS nor the activity ratio of muscle GS was influenced by refeeding. Consequently, glycogen replenishment was significantly impaired both in the liver (2.56 +/- 0.2 vs. 5.11 +/- 0.4 g/100 g; P < 0.001) and skeletal muscle (0.45 +/- 0.01 vs. 0.52 +/- 0.02 g/100 g; P < 0.01). Refeeding increased the percentage of the active form of hepatic PDC both in control (+88%; P < 0.01) and cirrhotic rats (+91%; P < 0.001). In the latter, however, the rates of total and active PDC were significantly lower than in controls [-44% and -40% in fasted (P < 0.005) and refed (P < 0.005) rats, respectively]. Muscle PDC kinetics (both maximal velocity and Michaelis constant) and the percent active form were identical in cirrhotic and control rats, regardless of the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum alpha-L-fucosidase. A useful marker in the diagnosis of hepatocellular carcinoma.

BACKGROUND AND METHODS: The value of serum alpha-L-fucosidase activity in the diagnosis of hepatocellular carcinoma (HCC) was investigated by determining the enzyme activity levels in 21 patients with HCC, 76 patients with cirrhosis, 22 patients with other malignant neoplasms, and 23 healthy subjects. RESULTS: The serum alpha-L-fucosidase activity level in patients with HCC (575.76 +/- 212.86 nmol/ml/h) was significantly higher than that found in patients with cirrhosis (274.55 +/- 138.97 nmol/ml/h; P less than 0.001) or other neoplasms (257.91 +/- 128.12 nmol/ml/h; P less than 0.001) and in controls (221.23 +/- 114.45 nmol/ml/h; P less than 0.001). No significant differences were found between controls and patients with cirrhosis and between controls and patients with other malignant neoplasms. When 443 nmol/ml/h is taken as the cutoff value (mean value of controls plus 2 standard deviations), alpha-L-fucosidase sensitivity and specificity were 76% and 90.9%, respectively. CONCLUSIONS: These results suggest that alpha-L-fucosidase is a useful marker for detecting HCC, in conjunction with alpha-fetoprotein and ultrasonography.

[Plasma amino acids in patients with liver cirrhosis treated with lactulose]. / Gli aminoacidi plasmatici in pazienti con cirrosi epatica trattati con lactulosio.

The altered plasma amino acid pattern (i.e. increased levels of aromatic amino acids and decreased levels of branched chain amino acids) is a characteristic feature of cirrhotic patients. Recently it has been proved that an increased net degradation of BCAA is positively correlated to the plasma NH3 level, strongly suggesting that these amino acids are molecularly involved in glutamine synthesis to detoxify ammonia in skeletal muscle. Lactulose, a synthetic, nonabsorbable disaccharide, is believed to actively promote excretion of ammonia from the body by causing it to be trapped in the acidified fecal stream and making it unavailable for absorption. Therefore therapy with lactulose could determine an increase of BCAA. The present study was undertaken to examine plasma amino acid pattern of ten patients with liver cirrhosis before and after lactulose therapy. No statistically significant changes of amino acids were observed.

Longer-term regulation of pyruvate dehydrogenase kinase in cultured rat hepatocytes.

The activities of pyruvate dehydrogenase (PDH) kinase and of PDH kinase activator protein (KAP) were increased 2-2.4-fold during 25 h of culture of hepatocytes from fed rats with glucagon plus n-octanoate. PDH kinase activity in hepatocytes from starved rats (initially 2.2 x fed control) fell during 25 h of culture in medium 199 (to 1.5 x fed control), but was maintained by glucagon plus octanoate. Dibutyryl or 8-bromo cyclic AMP increased PDH kinase activity 2-2.2-fold in hepatocytes from fed rats, but phenylephrine and isoproterenol (isoprenaline) were without effect. Insulin blocked the action of glucagon to increase PDH kinase activity and decreased the effect of octanoate and octanoate plus glucagon. It is suggested that the effects of starvation to increase activities of PDH kinase and of KAP in liver are mediated by alterations in circulating concentrations of glucagon, fatty acids and insulin and in hepatic cyclic AMP.

Serum alpha-L-fucosidase activity and early detection of hepatocellular carcinoma: a prospective study of patients with cirrhosis.

BACKGROUND: Serum alpha-L-fucosidase activity is considered a marker of hepatocellular carcinoma. To the authors' knowledge, its clinical usefulness in the early detection of hepatocellular carcinoma in the follow-up of cirrhotic patients has not been reported previously. METHODS: The authors prospectively studied serum alpha-L-fucosidase activity, in addition to alpha-fetoprotein and ultrasonography, in a regular screening of 132 cirrhotic patients during an 8-year follow-up. RESULTS: At enrollment, 120 patients had low alpha-L-fucosidase activity (below the cutoff value) and 12 had high activity. All patients had serum alpha-fetoprotein levels below the cutoff value. During the follow-up, hepatocellular carcinoma was detected in 19 patients, 16 with alpha-L-fucosidase activity below the cutoff value at enrollment and 3 with activity above it. In 7 of those 16 patients with carcinoma and low enzyme activity, the enzyme activity showed a significant increase 6-9 months before there was ultrasonographic evidence of a focal lesion, and by the time of diagnosis it had risen above the cutoff value in all of them; in only 3 of the 7 patients was the increase in alpha-L-fucosidase activity associated with an increase in alpha-fetoprotein. In another 4 of the 19 patients with carcinoma, only alpha-fetoprotein increased. CONCLUSIONS: Serum alpha-L-fucosidase activity is useful in the early detection of hepatocellular carcinoma. The data from this study suggest that cirrhotic patients who have a marked increase in serum alpha-L-fucosidase levels during follow-up should be closely monitored for signs of hepatocellular carcinoma development.

[Plasma insulin and glucagon during experimental MHV-3 virus hepatitis in mice]. / Insulina e glucagone plasmatici nella epatite sperimentale del topo da virus MHV-3.

Insulin and glucagon values were determined in the plasma of mice during MHV-3 experimental viral infection. The results showed a different behaviour of the two hormones. The insulin values remained normal until the 12th hour of infection, with a statistically significant increase as from the 12th hour up to their maximum peak at the 24th hour, remaining constant at that level until the 72nd hour. As for the glucagon values there was a statistically significant decrease until the 24th hour of infection when they suddenly began to increase up to their maximum peak at the 48th hour remaining constant at that level until the 72nd hour. Increased of the insulin values may be attributed to liver cell damage because of the decreased metabolization of the hormone. As for glucagon the results of the decreased values during the initial phase of the infection may be the concentration decrease of free plasma amino acids, whereas the increased values during the subsequent phases is probably caused by the concentration increase of free plasma amino acids, of hypogycemia and of stress.

Abnormalities of glucose metabolism induced by liver cirrhosis and glycosylated hemoglobin levels in chronic liver disease.

UNLABELLED: The prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) such as defined by National Diabetes Data Group criteria, and glycosylated hemoglobin levels were assessed in a series of consecutive patients who had chronic active hepatitis (CAH) or cirrhosis in the absence of any known diabetogenic risk factors and who had normal fasting glycemic levels. Based on oral glucose tolerance test, the prevalence of IGT (15%) and DM (27%) in cirrhosis was significantly higher (p less than 0.005) than that observed in CAH (0%) and controls (0%). In contrast, HbA1 levels were not statistically different in cirrhotic patients (with normal or altered glucose tolerance) as compared with CAH and control subjects. IN CONCLUSION: (a) HbA1 is an unsatisfactory test in the diagnosis of altered glucose tolerance in patients with cirrhosis, and (b) Cirrhosis (but not CAH) represents itself a risk factor for the development of glucose metabolism alterations. Therefore, routine oral glucose tolerance testing is warranted in these patients.

Plasma free aminoacids pattern in progressive systemic sclerosis.

20 free aminoacids levels have been measured with a chromatographic method (Beckman 118 BL Aminoacid analyzer) in 9 patients affected by progressive systemic sclerosis and in 15 healthy subjects (control group). Both patients and control group were females, mean daily protein intake was between 1,2-1,5 gr/Kg in the two groups. No other pathological condition was found in each patient, none of them was receiving drug therapy at least from 2 months. No significant age different existed between the patients and the control group. Analysis of variance of the results showed significant decreases of proline, histidine, valine and methionine levels and significant increase of aspartic acid concentration in the plasma of PSS patients.