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M Frezza

Publications and source records attributed to M Frezza.

At least 37 records · Page 2Linked to original sources

Abnormal serum gamma-glutamyltranspeptidase in alcoholics. Clues to its explanation.

In order to investigate the reason for the elevation of serum gamma-glutamyltranspeptidase (GGT) after chronic alcohol consumption, the activity of this enzyme, together with the activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in serum (parameters of liver cell damage) and the excretion of D-glucaric acid (D-GA) in urine (parameter of microsomal enzymatic induction) were determined in 72 chronic alcoholics. Of these, 32 had no significant liver disease (1st group) and 40 had an overt liver disease varying from fatty liver to liver cirrhosis (2nd group). The GGT was elevated in only 62% of the patients of the first group, but in 95% of the second group. Of the latter group, patients with cirrhosis had significantly higher GGT mean levels than the patients with fatty liver. On the other hand, increased D-GA excretion was only found in 23% of the group 1 patients and in 44% of the group 2 patients. Moreover, in all patients there was a significant correlation between the values of GGT and aspartate aminotransferase, but not between GGT and D-GA. From these results, the GGT increase in chronic alcoholics, would seem to be better related to cellular damage than to enzymatic induction assessed on the basis of D-GA urinary excretion.

Adult↗

Prevention of S-adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women.

Women with past histories of intrahepatic cholestasis of pregnancy (ICP) exhibit a congenital exaggerated sensitivity to estrogens, which may express as abnormal hepatic reactivity to oral contraceptive intake and increased risk of developing gallbladder disease. Since previous investigations have shown that S-adenosylmethionine (SAMe) is effective in antagonizing ICP, we wondered whether its administration to subjects with previous ICP could 1) protect them from a challenge with ethynylestradiol (EE) or 2) normalize the cholesterol saturation index (CSI). To test the first hypothesis, six women volunteered to receive EE (0.1 mg/day orally for 1 wk) and, after 3 months, the same EE dose plus oral SAMe (800 mg/day for 1 wk). EE significantly increased serum values of transaminases, conjugated bilirubin, and total bile acids with respect to basal values. In the rechallenge with EE plus SAMe, liver function tests did not differ from basal levels and were significantly lower than the values obtained after EE. In the second experiment, we gave oral SAMe (800 mg/day for 2 wk) to seven women with previous ICP who exhibited cholesterol supersaturation of duodenal bile. Both subjects were nonpregnant and nonobese and had cholecystograms negative for gallstones. Bile CSI decreased from a basal value of 1.35 +/- 0.07 to 0.98 +/- 0.08 after SAMe (p less than 0.01). These findings indicate that SAMe protects women with previous ICP from EE-induced liver toxicity and normalizes bile CSI in the same subjects who secrete lithogenic bile. The data support the belief that SAMe acts as a physiological antidote against estrogen hepatobiliary toxicity in susceptible women.

Adult↗

Unconjugated hyperbilirubinaemia in HBV carriers. Discriminant value of nicotinic acid (NA) test.

Recently an unconjugated hyperbilirubinaemia, without any other abnormalities in liver function test, in 14.3% of HBV Japanese carriers has been noticed. Therefore, it would be possible to argue that the persistent infection of HBV in hepatocytes might play a role in an hypothetical metabolic derangement of bilirubin clearance. Twenty-five subjects in a group of 468 HBsAg+ patients (equal to 5.33%) presented an hyperbilirubinaemia. This percentage was not different from the 5.83% found in 3083 HBsAg- controls coming from the same institution. Therefore we could exclude that in our population the presence of HBV surface antigen itself would determine a statistically higher level of total bilirubin (TB) than in controls. The nicotinic acid (NA) loading test may reveal some bilirubin metabolic defects (i.e. Gilbert syndrome), even in subjects with normal basal values of TB. According to this background, we performed in 11 HBsAg+ males with basal TB higher than 17.1 mumol/l (1 mg%) (group A/1), 13 HBsAg+ males with basal TB lower or equal to 17.1 mumol/l (group A/2) and 14 HBsAg- normal controls matched for sex and age (group B) the NA test according to Röllinghoff et al. All the parameters calculated by the NA test resulted significantly different in the A/1 group compared with the B group, but not different from those found by several authors in the Gilbert's syndrome. On the contrary, no significant differences have been noticed between the latter group and the A/2 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Alteration in sulfobromphthalein hepatic storage capacity (S) in non-pregnant women previously affected with intrahepatic cholestasis of pregnancy (ICP).

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is still unknown, although it is currently accepted that the disease represents an abnormal reaction of genetically predisposed maternal liver, to estrogen hormones. To gain a better insight into the hepatic handling of cholephilic anions outside of pregnancy itself, we determined, using the perfusion technique of Wheeler et al. (1960), the hepatic maximum excretory rate (Tm) and the storage capacity (S) of sulfobromphthalein (BSP) in 6 women with a past history of ICP and in 6 controls, matched for age and parity, but with no history of ICP or other liver disease. The BSP Tm in the group with previous ICP did not differ significantly from that measured in the control group (9.22 +/- 2.37 vs 7.92 +/- 1.20). By contrast, BSP S values in the 'previous ICP' group was critically higher than that of the controls (120.43 +/- 55.89 vs 39.15 +/- 16.17: t-test p less than 0.005, U-test p less than 0.001). A possible explanation for this result could be the existence of a metabolic defect responsible for an increased intrahepatic concentration of the cholephilic substances inside the liver cells.

Adult↗

S-adenosyl-L-methionine antagonizes oral contraceptive-induced bile cholesterol supersaturation in healthy women: preliminary report of a controlled randomized trial.

Recent experimental investigations have shown that S-adenosyl-L-methionine (SAMe) reverses estrogen-induced bile secretion impairment. The mechanism of this action seems to be related to the capability of SAMe both to inactivate catecholestrogens by methylation reaction and to methylate membrane phospholipids increasing the liver plasma membrane fluidity reduced by the estrogens. Aim of this investigation was to know whether SAMe also prevents oral contraceptive-induced cholesterol supersaturation of gallbladder bile in humans. To six healthy nonobese women whose bile cholesterol saturation index increased from a mean basal value of 0.77 (SD 0.22) to 1.20 (SD 0.38) (p less than 0.01) after two cycles of treatment with oral contraceptives containing 50 micrograms ethynylestradiol, plus 250 micrograms d-norgestrel, 200 mg SAMe per os tid was administered in addition to the oral contraceptive for other two cycles. The bile cholesterol saturation index decreased to 0.88 (SD 0.26) (p less than 0.05 versus oral contraceptive value). These results indicate that SAMe antagonizes biliary lipid changes induced by estrogen-progestin containing oral contraceptive and suggest its potential usefulness in women on oral contraceptive treatment to prevent lithogenic bile secretion.

Adult↗

[Endotoxins in the plasma and ascitic fluid of the cirrhotic patient. Their clinical significance].

The endotoxin presence was tested by Limulus Lysate Test (LLT) in plasma and ascites of 29 patients with cirrhosis, all having demonstrable portal hypertension and ascite. It was positive in plasma in 7 cases (24.1%) and in ascite in 12 cases (73.12%). All the cases with endotoxin in the plasma were positive in ascite too. 21 patients presented porto-sistemic encephalopathy from 1 to 4 grade, 1 case only had the clinical features of hepatorenal syndrome. The CHE and protrombin test values were significantly different in LLT positive patients in plasma and ascite respect to the values of negative ones.

Ascitic Fluid↗

[S-adenosylmethionine as a regulator of protein synthesis. Influence on plasmatic fibrinogen].

S-adenosyl-L-methionine (SAMe) is a physiological compound which plays an important role in numerous biological processes, such as transmethylations, transulphurations and aminopropylations. Starting from a study about the usefulness of the SAMe to normalize protein synthesis in old age, the drug was found to have an interesting action with respect to fibrinogen. Later research regarding a large number of patients, led us to discover after treatment for 40 days with 60 mg/die of SAMe, highly significant variations in fibrinogen values with constant normalization of this parameter, in both hypo- and hyper-fibrinogenemia. So far we don't know anything about the action of the drug on various metabolic stages of the fibrinogen; interestingly however our data exclude a rise in fibrinolysis.

Adult↗