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Biomedical subjects

N Carulli

Publications and source records attributed to N Carulli.

At least 55 records · Page 3Linked to original sources
PubMed1986

In vivo evaluation of cholesterol 7 alpha-hydroxylation in humans: effect of disease and drug treatment.

7 alpha-Hydroxylation of cholesterol is a stereospecific reaction consisting of the replacement of the 7 alpha-hydrogen with a hydroxyl group. When cholesterol labeled with tritium at the 7 alpha position is administered, the hydroxylation of the substrate will result in the loss of tritium which in turn will label the body water. The rate of tritium enrichment of the body water could thus give a quantitative estimate of the hydroxylation rate. This study describes the validation of the procedure with some 21 studies performed on 15 subjects in different conditions. [7 alpha-3H]cholesterol was administered intravenously in 50 ml of plasma and thereafter blood was sampled at timed intervals for 4 to 5 days. The rate of the hydroxylation of cholesterol was calculated from the time course of the specific activities of plasma cholesterol and body water after tracer administration and was expressed as 7 alpha-hydroxycholesterol formed/24 hr. Calculated values of hydroxylation in three control subjects (493 +/- 206), five patients with hyperlipoproteinemia (539 +/- 168), and seven cirrhotic patients (153 +/- 136) are in good agreement with figures reported for bile acid synthesis determined with other techniques. Cholesterol 7 alpha-hydroxylation rate is reduced in patients with cirrhosis, the impairment being related to the severity of the disease. Cholestyramine administered to one subject for 4 weeks produced a threefold increase of the hydroxylation. Administration of chenodeoxycholic acid resulted in a 50% decrease, whereas that of ursodeoxycholic did not produce consistent changes of the hydroxylation rate. The results support the current view that 7 alpha-hydroxylation of cholesterol is rate-limiting in the synthesis of bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Cholesterol esterase activity of human intestinal mucosa.

It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats, where the increase of cholesterol absorption, after trihydroxy bile acid feeding, seems to be due to the stimulatory effect of cholic acid on the intestinal cholesterol esterase. In the present study, therefore, we investigated some general properties of human intestinal cholesterol esterase, with particular emphasis to the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids. Thus, the stimulatory effect of cholic acid on cholesterol absorption induced by the administration of this bile acid does not seem to be simply due to changes of cholesterol esterase activity of the small bowel mucosa.

Adult↗
PubMed1985

Effect of acute administration of bile acids on fatty acid composition of biliary phosphatidylcholine in man.

Little is known on variations in fatty acid composition of biliary phosphatidylcholine (PC) during acute administration of particular bile acids (BAs) in man. Bile was collected hourly for 5 h in 6 T-tube patients (prereplacement period). Thereafter particular BAs were infused into the duodenum at a rate of 1 g/h for 5 h and bile collected hourly (replacement period). Each patient received two BAs at an interval of 3 days, following a cross-over design. Three patients received deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) and a second 3 patients cholic acid (CA) and chenodeoxycholic acid (CDCA). Bile acid pool contained mainly the two primary BAs in the prereplacement period and more than 80% administered BAs in the replacement period. Hydrophobic and detergent BAs (DCA and CDCA) increased the secretion rates and the percentage of biliary PC species with arachidonic acid and stearic acid; in contrast less detergent BAs (UDCA and CA) did not significantly alter fatty acid composition of biliary PC. Thus, very hydrophobic and detergent BAs would seem to promote the preferential secretion into the bile of lecithin species present in the liver cell plasma membranes, rich in arachidonic and stearic acid.

Adult↗
PubMed1984

Effects of acute changes of bile acid pool composition on biliary lipid secretion.

To elucidate the mechanism responsible for the bile acid-induced changes of biliary lipid secretion, we evaluated bile flow and biliary output of bile acids, cholesterol, phospholipids, and alkaline phosphatase activity in seven cholecystectomized subjects with a balloon occludable T-tube during two experimental periods: (a) depletion of the endogenous bile acid pool and (b) replacement of the pool by means of duodenal infusion with individual bile acids, such as deoxycholic (DCA), chenodeoxycholic (CDCA), cholic (CA), and ursodeoxycholic (UDCA) acids. Bile flow, cholesterol, and phospholipid output were linearly related to bile acid secretion in all experimental periods. During the replacement periods, the amount of cholesterol and phospholipids coupled to bile acids was significantly different (at 1% level at least) for each individual bile acid secreted; it was the highest during DCA secretion (slope value: 0.209 for cholesterol and 0.434 for phospholipids) followed, in the order, by CDCA (0.078 and 1.794), CA (0.044 and 0.127), and UDCA (0.030 and 0.122). The phospholipid to cholesterol ratio was higher during secretion of CA and UDCA as compared with DCA and CDCA. The secretion of CA seemed to stimulate a greater bile flow than the other bile acids did. The infusion of all bile acids, except UDCA, induced an increase of biliary alkaline phosphatase activity as compared with the values of the depletion period. The mean highest increase (13-fold the pretreatment value) was observed during DCA secretion followed by CDCA (fivefold) and CA (1.5-fold). These results would suggest that the physical chemical properties, namely the lipid-solubilizing capacity, of bile acids could directly contribute to the regulation of biliary lipid secretion. The observed changes in biliary alkaline phosphatase activity lend support to the view that bile acid-induced lipid secretion may be, at least in part, contributed by membrane solubilization.

Aged↗
PubMed1983

Effect of cicloxilic acid on bile lipid composition in patients with gallstones: a multicenter trial.

24 gallstone patients were treated with cicloxilic acid, an agent endowed with choleretic activity, at the dose of 240 mg/day for 1 month. 24 comparable patients on placebo treatment acted as controls. Bile lipid composition was determined and the saturation index calculated before and after treatment, on samples collected by duodenal siphonage after caerulein stimulation, in both groups. In the cicloxilic group there was little or no change in bile salts and phospholipids, whereas biliary cholesterol concentration was significantly reduced (p less than 0.05) and consequently the lithogenic index lowered (from 1.5 to 1.2, p less than 0.01). Cicloxilic acid can have a place in gallstone disease therapy in association with the litholytic bile acids or in the prevention of gallstone formation in high-risk populations.

Adult↗
PubMed1983

The effect of dihydroxydibutylether on bile lipid composition in patients with gallstones.

Dihydroxydibutylether (DHBE, 900 mg/day, in divided doses) was given to 13 patients with radiolucent gallstones. Bile lipid composition and bile saturation were studied before treatment and after 1 and 2 months of therapy. Bile was collected by duodenal intubation (after cerulein-induced gallbladder contraction) in each patient, and biliary lipids were estimated with standard laboratory techniques. The results of this study showed that DHBE treatment was associated with a significant (p less than 0.01) reduction of bile saturation with cholesterol (saturation index: 1.37 +/- 0.39 before treatment, 1.14 +/- 0.35 after 1 month, and 1.08 +/- 0.29 after 2 months). The possible mechanism of this effect and the clinical relevance are discussed.

Adult↗
PubMed1982

Gallstone dissolution after 6 months of ursodeoxycholic acid (UDCA): effectiveness of different doses.

In order to compare the effects on gallstone dissolution of three different doses of UDCA (4, 8 and 12 mg/kg/day), a controlled trial was carried out with seventy-one patients. The dissolution rate was higher in the group treated with the highest dose. Stone size was the major factor affecting the outcome of treatment, with a significantly higher success rate in patients with gallstones less than 10 mm than with stones greater than 10 mm.

Adult↗
PubMed1981

Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial.

A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150-mg capsules day. Total serum cholesterol levels did not show appreciable changes with any of the treatments. HDL cholesterol was significantly increased after CDCA but not after UDCA or placebo. CDCA feeding was associated with a significant decrease in serum triglyceride levels, whereas the other treatments failed to show an effect. It is concluded that UDCA does not affect serum lipid levels, whereas CDCA lowers serum triglycerides and may be useful in the treatment of endogenous hypertriglyceridemia.

Adult↗
PubMed1981

Cholesterol absorption in cirrhosis: the role of total and individual bile acid pool size.

Dietary cholesterol absorption was studied in patients with either "mild" (n = 23) or "severe" (n = 12) liver cirrhosis in relation to both total and individual bile acid pool size. Cholesterol absorption was significantly reduced in both groups of patients, and it was inversely related (r = -0.68; p less than 0.001) to the severity of the disease. Total, cholic acid, and deoxycholic acid p ool sizes were significantly reduced in cirrhosis, and a correlation was found between cholesterol absorption and cholic acid pool size (r = 0.78; p less than 0.001). In 5 patients, cholesterol absorption and bile acid pool size were estimated both before and after treatment with cholic acid (15 mg/kg/day) plus ampicillin (2 g/day). The treatment was followed by a mean threefold increase of cholic acid pool and by a sharp enhancement of cholesterol absorption in each patient. In conclusion, cholesterol absorption is often impaired in cirrhosis and is related to the severity of the disease. The correlation between cholic acid pool and cholesterol absorption and the constant increase of the absorption values after cholic acid pool expansion suggest that the size of cholic acid pool may be considered as an important factor in the regulation of cholesterol absorption.

Adult↗
PubMed1981

Effect of the selective expansion of cholic acid pool on bile lipid composition: possible mechanism of bile acid induced biliary cholesterol desaturation.

The effect of cholic acid pool expansion on biliary lipid composition was investigated in 21 subjects with cholesterol gallstones. All subjects were fed cholic acid (15 mg/kg/day) and ampicillin (2 g/day) in order to depress the intestinal degradation of cholic to deoxycholic acid. Five additional subjects were given ampicillin alone. The treatment lasted 2-3 wk. Parameters investigated included biliary and plasma lipid, biliary bile acid composition, and total and individual bile acid pool size. In 11 of 21 subjects (group I) cholic acid pool expanded two-threefold, whereas deoxycholic acid pool increased only slightly. In this group mean saturation index fell from 1.32 +/- 0.27 (mean +/- SD) to 0.93 +/- 0.25 (p less than 0.001), and plasma cholesterol increased from 185 +/- 45 mg/dl before to 213 +/- 37 after treatment (p less than 0.01). In the remaining 10 subjects (group II) the increase of the deoxycholic acid pool for exceeded that of cholic acid, and in these subjects the saturation index rose from a mean value of 1.07 +/- 0.27 to 1.42 +/- 0.22 after treatment (p less than 0.01). In this group plasma cholesterol tended to decrease (from 213 +/- 57 to 197 +/- 51 after treatment). In the 5 subjects treated with ampicillin alone deoxycholic acid pool was greatly reduced, and the saturation index fell from 1.25 +/- 0.25 to 0.95 +/- 0.35. The results suggest that cholic acid pool expansion reduces bile cholesterol saturation, whereas the increase of deoxycholic acid pool tends to supersaturate the bile. It is concluded that a determinant of bile cholesterol saturation might be the detergent power of the bile acid pool.

Adult↗
PubMed1980

Intestinal solubilization, absorption, pharmacokinetics and bioavailability of chenodeoxycholic acid.

Little is known about the physical state, intestinal solubilization, absorption and bioavailability of chenodeoxycholic acid used in the medical treatment of gallstones. Therefore the concentrations of unconjugated chenodeoxycholic acid were measured in the supernatant and precipitate phases of intestinal contents aspirated from stomach, duodenum and jejunum of nine control subjects who took 500 mg chenodeoxycholic acid (4 X 125 mg gelatin-coated capsules) either fasting or together with a standard liquid meal. Chenodeoxycholic acid solubility was markedly influenced by luminal pH but was little affected by endogenous conjugated bile acids when their concentrations were > 1-2 mmol/l. Systemic bioavailability of 250, 500 and 750 doses of chenodeoxycholic acid was measured in five subjects by comparing areas under 4 h serum concentration-time curves after giving the bile acid first as a bolus intraduodenal aqueous infusion of 3H-labelled chenodeoxycholic acid containing either 14C-polyethylene glycol or bromsulphthalein as non-absorbable markers, and then as gelatin-coated capsules by mouth. Absorption was assessed by measuring the ratio of marker: bile acid in intestinal contents aspirated for 2 h from sites 60 and 120 cm distal to the duodenal infusion port and in three subjects quantitative recovery of marker was measured proximal to an occluding intestinal balloon. Absorption of duodenally-infused chenodeoxycholic acid was 96-99% complete and bioavailability was complete with the 250 and 500 mg doses but fell to 81% with the 750 mg dose.

Adult↗
PubMed1980

Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short erm feeding of chenodeoxycholic and ursodeoxycholic acid.

The activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and 7alpha-hydroxylase, the enzymes controlling the rate of hepatic synthesis, respectively, of cholesterol and bile acids, and the microsomal cholesterol content were evaluated in 25 patients with cholesterol gallstones and 17 subjects without gallstones. The same quantities were estimated in 16 additional patients with gallstones given chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg per day in order to investigate the comparative effect of a short term (7 days) administration of the two bile acids on the hepatic sterol metabolism. As compared to the controls, subjects with gallstones exhibited a 36% decrease of 7alpha-hydroxylase (26.8 +/- 6.2 versus 41.7 +/- 4.2 pmol/min per mg protein) and a 24% increase of the microsomal cholesterol (78.7 +/- 15.3 versus 63.1 +/- 18.1 nmol/mg protein). Although higher in the gallstone patients, the activity of HMG-CoA reductase did not differ significantly in the two groups of subjects. Administration of CDCA and UDCA changed the bile acid pool composition so that the fed bile acid predominated in the bile (mean CDCA 73% and mean UDCA 54%). Bile lipid composition did not appreciably change. In the eight subjects treated with CDCA the activity of HMG-CoA reductase was reduced to 45% of the value of untreated subjects (27.9 +/- 14.5 versus 63.5 +/- 25.3 pmol/min per mg protein) whereas in the eight subjects treated with UDCA the same enzyme showed a twofold increase (123.5 +/- 20.9). In the treated groups 7alpha-hydroxylase activity was somewhat decreased but the values did not differ significantly from those of the untreated subjects. Microsomal cholesterol content decreased with CDCA (64.8 +/- 11.6 nmol/mg protein) as well as with UDCA (59.1 +/- 10.1) treatment; however in the latter the difference attained statistical significance (P < 0.05). Altogether the results would suggest that in the liver of patients with gallstones the conversion of cholesterol to bile acids is somewhat reduced, and that changing the bile acid pool composition, by exogenous bile acid feeding, has disparate effects on hepatic cholesterol synthesis. The findings could represent the acute changes produced by bile acid feeding, however they could imply that the effects of two bile acids in dissolving cholesterol gallstones might not be related only to the changes in hepatic sterol metabolism.-Carulli, N., M. Ponz De Leon, F. Zironi, A. Pinetti, A. Smerieri, R. Iori, and P. Loria. Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short term feeding of chenodeoxycholic and ursodeoxycholic acid.

Adult↗
PubMed1979

The effect of chenodeoxycholic acid (CDCA) on cholesterol absorption.

The effect of administration of chenodeoxycholic acid (CDCA) on cholesterol absorption has been investigated in 11 volunteers. Five hundred milligrams of cholesterol 5 muCi of C14 cholesterol, and 10 muCi of H3 sitosterol (as a nonabsorbable marker) were given with a standard meal. Feces were collected for 6 days and cholesterol absorption was estimated from the recovered C14 radioactivity. The study was repeated after 20 days of treatment with CDCA. Cholesterol saturation of bile and biliary bile acid composition were also studied. Percent CDCA in bile was 40.5 +/- 14.0 SDM before treatment and rose to 75.3 +/- 5.7 after treatment. Saturation index fell from 1.08 +/- 0.31 to 0.71 +/- 0.19. Cholesterol absorption was 33.2 +/- 11.0% of the administered dose in basal conditions and decreased to 14.9 +/- 9.7% after treatment (P less than 0.01). In all but 1 subject, CDCA administration was associated with a decreased intestinal transit time. In conclusion, in doses effective to desaturate bile, CDCA seems to decrease dietary cholesterol absorption. This effect could contribute to the desaturation of bile observed during treatment with this bile acid for dissolving gallstones.

Adult↗