Biomedical subjects

N Carulli

Publications and source records attributed to N Carulli.

At least 73 records · Page 4Linked to original sources

PubMed1978

Bile lipid composition and bile acid pool size in diabetes.

Since the prevalence of gallstones is higher in diabetics than in controls and since cholelithiasis is often associated with supersaturated bile, we measured bile lipid composition and bile acid pool size in 8 patients with juvenile diabetes, 16 with maturity-onset diabetes, and 10 control subjects. Bile lipid composition was expressed as "saturation index." In the maturity-onset diabetics the saturation index (1.60 +/- 0.45 SDM) was significantly higher (P less than 0.005) than that in the controls (0.82 +/- 0.20) and in patients with juvenile diabetes (0.75 +/- 0.24). The absolute values for biliary bile acid concentration were significantly lower (P less than 0.01) in the maturity-onset diabetics than in the other two groups. There were no differences in either the proportion of the individual biliary bile acids or the size of the bile acid pool between the three groups. The results suggest that the incidence of cholelithiasis in diabetes is associated with the secretion of a supersaturated bile only in the maturity-onset subgroup.

Adult↗

PubMed1978

Effect of cicloxilic acid on the bile lipid composition in cholelithiasis.

5 patient with cholesterol gallstones were treated with cis-2-hydroxy-2-penyl-cyclohexanecarboxilic acid (cicloxilic acid) 240 mg daily for one year. Before treatment and after 1 month's, 3 months' and 1 year's treatment gallbladder bile was withdrawn by duodenal tube after i.v. cerulein stimulation. The bile was assayed for lipids and the lithogenic index was determined. The pool of bile acids was also determined and liver function tests performed. The results show a gradual lowering of the mean lithogenic index in the course of treatment. The blood chemistry values remained within strictly normal limits.

Adult↗

PubMed1977

[Cholesterol-7-alpha-hydroxylase activity in cholelithiasis].

The physiopathological mechanism of cholesterol supersaturation in the bile was investigated by determining cholesterol-7-alpha-hydroxylase activity in 5 normal controls and 8 subjects with cholesterol gallstones. Bile lipids were also evaluated. Hydroxylase values were higher (though not significantly) in the controls. A linear correlation (r = 0.797) between the hydroxylase and bile acid concentration was noted in both groups.

Adult↗

PubMed1977

[Interpretations of uptake defects in hepatic scintiscanning].

The absence of precise parameters for the interpretation of defective uptake means that personal experience is of great assistance in the examination of scintiscans. Classification of uptake defects in 208 cases was carried out by two experts in accordance with the following parameters: 1) irregular uptake or distinct defects; 2) central or peripheral defects; 3) increased size of the liver picture; 4) uptake by the spleen. Irregular uptake or central or peripheral uptake defects (with or without spleen uptake in each case) were observed as categories. The series as a whole showed that peripheral defects are associated with a greater frequency of false positives, and diagnosis must therefore be checked, spleen uptake is an accurate pointer to diffuse chronic hepatopathy, and central defects are indicative of substitutive pathology.

Gold Colloid, Radioactive↗

PubMed1976

[Bile composition in patients with high risk of cholelithiasis].

Clinical and epidemiological experience has shown that some subjects, such as diabetics and cirrhotics, are particularly prone to cholelithiasis. The cause of this association was sought, with particular reference to the biliary lipid pattern, since this was considered as a pathogenetic factor in high-risk patients of this kind. It was found that diabetics, like subjects with biliary lithiasis, have a high biliary cholesterol saturation index; this was not the case in cirrhosis. This increase was apparently due both to a fall in bile acids and an increase in bile cholesterol. On the other hand, no significant difference was found between diabetics and controls as far as the pool of bile acids was concerned. No important differences in bile acid pattern were noted. Deoxycolate tended to increase in subjects with cholelithiasis and fall (along with lithocolate) in those with cirrhosis. These findings were, however, devoid of statistical significance. The high incidence of cholelithiasis in diabetics is physiopathologically confirmed by significant "lithogenic" changes in bule lipid composition, whereas the high incidence in cirrhosis is not open to this explanation and probably rests on a different pathogenetic basis. The importance of bile saturation is clear, however, together with its therapeutic and prophylatic implications (chenodeoxycholic acid). The possible influence of unknown factors cannot be ruled out.

Adult↗

PubMed1976

Alteration of drug metabolism in Gilbert's syndrome.

The pathophysiology of Gilbert's syndrome was studied by investigating the metabolism of the drug tolbutamide, which is metabolised by the liver but does not undergo glucuronidation. Using rat liver cell supernatant, tolbutamide was shown to bind to the hepatic cytoplasmic Y protein in a manner similar to other organic anions, but not to Z protein. In 31 patients with Gilbert's syndrome the plasma disappearance (plasma half-life, mean +/- SD: 628+/-84 min) and metabolic clearance (7-9+/-1-8 ml/min) were significantly (P less than 0-0005) altered compared with the 13 controls (mean half-life 393+/-26 and mean clearance 13-4+/-1-5). The eight patients with hyperbilirubinaemia due to haemolytic disease showed no difference from the normal control subjects. In three patients with Gilbert's syndrome the cumulative urinary excretion of tolbutamide metabolites, 24 hours after the administration of the drug, was 30% lower than in the controls. In the five patients with Gilbert's syndrome, phenobarbital administration (100 mg/day) produced a significant increase in clearance of the drug from 8-8+/-0-8 to 13-4+/-1-9 ml/min; this was paralleled by a fall in serum bilirubin concentration. The plasma half-life of tolbutamide was similar in Gunn rats and Wistar rats. The results suggest that the metabolic defect(s) of Gilbert's syndrome affects compounds other than bilirubin and that defective uptake is probably the major factor.

Adult↗

PubMed1975

Alteration of drug metabolism during cholestasis in man.

The morphological and functional alterations of the smooth endoplasmic reticulum of the liver cell related to biliary stasis have brought attention to drug biotransformation during cholestasis. The metabolism of meprobamate, pentobarbital and tolbutamide was assessed in subjects with intrahepatic recurrent cholestasis (3), cholestatic hepatitis (6), extrahepatic biliary obstruction (7) and normal controls (16). In the patients with recurrent intrahepatic cholestasis no differences in drug metabolism were noted as compared to the control group. In cholestatic hepatitis the plasma half-lives of meprobamate (828 +/- 422 min.) and pentobarbital (39+-65) were significantly longer than in in controls (444 +/- 37 and 25.4 +/- 1.1 respectively). Tolbutamide plasma half-life appeared unchanged. The most striking variations were observed in the patients with extrahepatic biliary obstruction. In such cases while meprobamate half-life was unchanged, pentobarbital half-life was significantly prolonged (31.2 +/- 2.5) and the in vitro metabolism of the drug, using liver preparations, was decreased to less than 50% of the control value. In contrast the metabolism of tolbutamide was accelerated as evidenced by a significant decrease of plasma half-life (165 +/- 48 min. versus 384 +/- 76 of the controls) and an enhanced urinary excretion of the drug's metabolites. However the metabolism of tolbutamide in vitro did not show any difference between normal and cholestatic liver. Whatever the mechanism of the peculiar behaviour of tolbutamide in extrahepatic biliary obstruction it seems to be related to the increased bile dalt concentration during cholestasis. In fact the low values of plasma half-life increase significantly either relieving the biliary obstruction or producing a bile salt depletion with cholestyramine. Preliminary results in vitro suggest the bile salt could displace tolbutamide from albumin binding thus increasing the amount of free drug available for biotransformation by the liver. In conclusion cholestasis may affect drug metabolism depending on the degree of biliary stasis, liver cell injury and the type of drug tested. The mechanism could be that of an impaired biotransformation in the smooth endoplasmic reticulum or could involve extrahepatic factors.

Adolescent↗

PubMed1973