Search PubMed⌕ Search

Biomedical subjects

N Carulli

Publications and source records attributed to N Carulli.

At least 19 recordsLinked to original sources
PubMed1999

Herpesvirus DNA is frequently detected in liver tissue from hepatitis C patients.

BACKGROUND AND AIMS: Herpesviruses infect the liver and cause minor hepatitis. Our aim is to verify the presence of herpesviruses in the liver from hepatitis C patients and the possible influence of these viruses in the liver disease. METHODS: We searched for herpesvirus DNA in liver biopsies from patients with hepatitis C and from a control group without hepatitis by means of nested polymerase chain reaction. Serological investigations were carried out as well. RESULTS: Thirty-four liver specimens from hepatitis C patients were examined, 12 of which (35.3%) were positive for at least one herpesvirus DNA, whereas among the 19 control specimens only two were positive (10.5%; P = 0.049). Liver biopsies from seven patients, three with acute hepatitis of unknown origin, three with non-alcoholic steatohepatitis and one with autoimmune hepatitis were also investigated and three positive samples were found. CONCLUSIONS: The prevalence of herpesvirus DNA was found higher in patients with hepatitis C than in individuals without hepatitis. The influence of herpesviruses on the clinical course of hepatitis C is considered.

Adult↗
PubMed1998

Influence of age and sex on serum concentrations of total dimeric activin A.

Several studies have shown that activin A is secreted in substantial amounts into the systemic circulation. The changes that occur during menstrual cycle and pregnancy suggest a correlation with reproductive function. At present, however, no definitive evidence has confirmed this pattern throughout adult life; moreover, neither the origin nor the physiological implications of this circulating growth factor have been clearly defined. The aim of the present study was to evaluate whether circulating concentrations of activin A change in adult men and women according to age and sex, and to examine the possible correlation with serum concentrations of FSH. Total dimeric activin A was measured using a specific two-site enzyme immunoassay in serum specimens collected from a cohort of normal individuals enrolled in an epidemiological survey. A group of men (n = 106) and one of women (n=151) were subdivided into six age groups (20-30, 30-40, 40-50, 50-60, 60-70 and 70-90 years). In a small group of 8 men and 11 women, serum concentrations of activin A were evaluated twice, in specimens collected at an interval of 10 years. Serum FSH concentrations were also measured in all specimens. Serum concentrations of activin A were not significantly different in men and women and showed an age-related progressive increase between 20 and 50 years of age (P<0.01, those aged 40-50 compared with those aged 20-30 years). After the age of 50 years, activin A concentrations remained in the same range of values in women, whereas they increased significantly in men, reaching peak values between 70 and 90 years (P<0.01 compared with the group aged between 20 and 50 years). From the age of 50 years, activin A concentrations were significantly greater in men compared with those in women in the corresponding age groups (P<0.001). Activin A concentrations correlated with age in men, but not in women. No significant correlation between concentrations of activin A and FSH was found in either sex. Activin A concentrations in specimens collected 10 years apart showed an increase in seven of eight men, but not in women. Finally, no significant variations of activin A concentrations were observed when fertile and postmenopausal women were compared. The present data indicate that circulating concentrations of activin A vary according to age; furthermore, men older than 50 years have greater concentrations than women. These changes, which occur irrespectively of FSH concentrations, indicate that circulating activin A is not a hormone of the reproductive axis.

Activins↗
PubMed1997

Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans.

This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061 micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.

Aged↗
PubMed1997

Factors associated with gallstone disease in the MICOL experience. Multicenter Italian Study on Epidemiology of Cholelithiasis.

The epidemiological associations of gallstone disease were evaluated in a general population sample of 29,584 individuals (15,910 men and 13,674 women; age range, 30-39 years) belonging to 14 cohorts examined between December 1984 and April 1987. Subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire, and underwent a physical examination and blood chemistry tests. Participants were considered to have gallstone disease if they had already had cholecystectomy or gallstones. Statistical associations were established by univariate analysis of the age-standardized data and by stepwise multiple logistic regression. Increasing age and body mass index and a maternal family history of gallstone disease were the most consistent associations (both at univariate and multivariate analysis and in both sexes) found in this study. Personal history of dieting was associated with gallstone disease in men, and at univariate analysis, in women. Decreasing serum total cholesterol levels and increasing serum triglycerides were associated with gallstone disease in both sexes in the multivariate analysis. In women, associations were also found with a number of pregnancies and paternal family history of gallstone disease. A slight but negative association with contraceptive pill use was identified only at multivariate analysis. Associations (investigated at univariate analysis) were also found with diabetes, cirrhosis, angina or myocardial infarction, and peptic ulcer. There was no association with smoking habits and use of aspirin or antirheumatic drugs.

Adult↗
PubMed1997

Effect of liver cirrhosis on the systemic availability of naltrexone in humans.

BACKGROUND/AIMS: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It is used for detoxification treatment for heroin addicts and has been proposed as a possible treatment of pruritus in cholestasis. Such patients are likely to have impaired liver function, underscoring the need to understand the pharmacokinetic behavior of naltrexone in liver disease. These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone. METHODS: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). A bolus of 100 mg of naltrexone was administered orally in the morning, after an overnight fast. Blood samples were taken in basal conditions and at fixed intervals, up to 24 h after administration. Serum levels of naltrexone and of its major active metabolite, 6 beta-naltrexol, were assayed by reversed-phase HPLC analysis. RESULTS: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6 beta-naltrexol (area under the curve: naltrexone, 200 +/- 97 ng/ml x 24 h; 6 beta-naltrexol, 2467 +/- 730 ng/ml x 24 h, p < 0.01). In severe cirrhosis serum levels of 6 beta-naltrexol increased more slowly, so that circulating levels of naltrexone during the first 2-4 h after drug intake were higher than those of 6 beta-naltrexol (6 beta-naltrexol/naltrexone ratio at 2 h: controls, 10.91 +/- 4.80; cirrhosis, 0.39 +/- 0.18, p < 0.01). The area under the curve for naltrexone (1610 +/- 629 ng/ml x 24 h) was significantly greater than in controls, whereas that for 6 beta-naltrexol (2021 +/- 955 ng/ml x 24 h) was not significantly different. Patients with compensated cirrhosis showed an intermediate pattern. No differences in elimination half-life of the two drugs were detected among the groups. CONCLUSIONS: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6 beta-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6 beta-naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.

Adult↗
PubMed1996

Alpha but not beta interferon is useful in chronic active hepatitis due to hepatitis C virus. A prospective, double-blind, randomized study.

Interferon-alpha has been widely used in chronic hepatitis C, but controlled studies with intramuscular interferon-beta are lacking. We therefore performed a prospective, double-blind, randomized study comparing intramuscular IFN-alpha and -beta in patients with chronic hepatitis C. Sixty patients were randomly assigned to receive 3 MU thrice weekly intramuscularly of either recombinant IFN-alpha or leukocyte IFN-alpha or fibroblast IFN-beta for six months. Nine of 20 patients (45.0%) in the recombinant IFN, 5/19 (26.3%) in the leukocyte IFN, and none in the IFN-beta group had a complete response during therapy (recombinant IFN vs IFN-beta: P < 0.01). Only in IFN-alpha-treated patients, was infection with a single HCV genotype (type 2a or 2b) associated with significantly better long-term outcome. IFN-alpha is useful in chronic hepatitis C while intramuscular IFN-beta interferon does not exert any beneficial effect. This is probably due to an insufficient bioavailability of IFN-beta when given intramuscularly.

Adolescent↗
PubMed1996

Growth of human herpesvirus 6 in HEPG2 cells.

HepG2 cells, a well differentiated liver cell line, were shown to be permissive for both human herpesvirus 6 (HHV-6) A and B strains by three independent methods of analysis: detection of viral antigens, viral DNA sequences and infectious virus. HepG2 cell infection with HHV-6 resulted in functional damage as shown by the increased release in the culture medium of some hepatocyte markers. Cells surviving the acute infection were serially passaged without showing cytopathic effect, but, some months later, HHV-6 DNA was still present in the cells and virus induction with a phorbol ester was successful. A possible pathogenetic role of HHV-6 in liver diseases is discussed. Experiments of HepG2 infection with human herpesvirus 7 (HHV-7) were also carried out. The lack of an efficient virus replication suggested a difficulty for HHV-7 to infect hepatic cells.

Cells, Cultured↗
PubMed1996

Bile acid structure and regulation of biliary protein secretion and composition in man.

To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation. Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid. Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid. A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). Quantitative and qualitative changes in biliary proteins, associated with the administration of bile acids that have different physico-chemical structures, may be relevant to the process of cholesterol crystal nucleation and the pathogenesis of gallstone formation.

Bile↗
PubMed1996

Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group.

OBJECTIVE: Because large-scale reports of PSC in the Mediterranean area we are still lacking, in this study we evaluated by Kaplan-Meyer analysis the natural history of primary sclerosing cholangitis (PSC) in Italy and by means of other statistical methods we identified the variables most useful in predicting survival of such patients. DESIGN: Retrospective multicentre study of unselected patients with PSC. Several variables involving sex, age, associated diseases, clinical features, laboratory, cholangiographic and histological findings at presentation and clinical outcome at data recording were collected by means of a detailed questionnaire. SETTING: 16 Italian university and regional hospitals all over the country, thus giving a geographically representative population. PATIENTS: A total of 117 PSC patients (73 men and 44 women); median age 35 years. METHODS: Survival analysis was performed by the Kaplan-Meyer method; the prognostic influence on survival of collected data was evaluated by univariate chi(2) analysis with Wilcoxon and log-rank tests. The same prognostic variables were also evaluated by multivariate analysis (Cox model), using a stepwise regression procedure. All statistical analyses were performed using the SAS statistical software. RESULTS: At presentation 70% of patients were symptomatic; symptoms did not relate to liver histology. Both intra- and extrahepatic bile duct lesions were detected in 46% of patients at cholangiography. Inflammatory bowel disease was found in 54% of symptomatic patients, ulcerative colitis was 36% of total. Clinical outcome (91/117): 15 underwent liver transplantation or died from liver disease (cholangiocarcinoma). Survival at 10 years was 74%. Features of poor prognosis were cholesterol, aspartate aminotransferase (AST), haemoglobin and albumin. CONCLUSION: PSC in Italy mainly follows a benign course and among clinical features recorded at presentation, serum cholesterol, AST, haemoglobin and albumin may provide some objective criteria to assess disease severity.

Adult↗
PubMed1996

Effect of taurohyodeoxycholic acid on biliary lipid secretion in man: preliminary report.

Taurohyodeoxycholic acid and tauroursodeoxycholic acid were infused intraduodenally at a rate of 0.8 g/h for three hours in 3 cholecystectomized T-tube patients. Biliary lipid secretion and bile acid composition were evaluated before and after replacement of the endogenous bile acid pool with the two bile acids. As compared to basal values (2.78 +/- 1.67 mM/l), taurohyodeoxycholic acid induced a greater increase in the biliary concentration of phospholipids (4.12 +/- 1.23 mM/l) as compared to tauroursodeoxycholic acid (3.14 +/- 0.98 mM/l). Biliary cholesterol concentration after taurohyodeoxycholic acid (1.89 +/- 0.63 mM/l) was unchanged as compared to the pretreatment period (1.98 +/- 0.58 mM/l), while it decreased significantly after tauroursodeoxycholic acid (0.85 +/- 0.08 mM/I). Biliary cholesterol secreted per unit of bile acid was greater during taurohyodeoxycholic acid than during tauroursodeoxycholic acid, while the opposite was observed for the secretion of phospholipids.

Bile↗
PubMed1995

Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study on Cholelithiasis (M.I.COL.)

This study was designed to obtain a general overview of gallstone disease in Italy. A total of 18 cohorts in 10 Italian regions were enrolled in this survey. Four cohorts were excluded from analysis because of a participation rate of less than 50 percent. Field activities started in December 1984 and terminated in April 1987. A precoded questionnaire was administered to each subject by a trained member of the medical staff. Participants underwent an ultrasonographic examination of the upper abdomen and blood sampling. Each research group was provided with an identical ultrasonographic machine. Standardized criteria were established for both the examination and diagnosis. The inter- and intraobserver variation in the ultrasonographic procedure was assessed using a reliability study. The overall kappa score for interobserver agreement was good (0.649), while intraobserver agreement was good or excellent (kappa scores > 0.60) in 75 percent of the observers. A total of 29,739 of the 46,139 (64.4 percent) enrolled subjects were examined. Among those with a clear-cut definition of the gallbladder status, 6.5 percent of the males and 10.5 percent of the females had gallstones. Additional 3.0 and 8.4 percents, respectively, had already undergone cholecystectomy. Prevalence of gallstone disease (gallstones plus cholecystectomy) increased linearly with age in both sexes. Among subjects with gallstones, 76.7 percent of men and 72 percent of women were not aware of having gallstones; 87.0 percent of men and 84.9 percent of women were asymptomatic. This study confirms that gallstone disease is a highly prevalent condition. Gallstones rarely cause symptoms, and subjects are mostly unaware of their presence.

Adult↗
PubMed1995

Effects of different phenotypes of hyperlipoproteinemia and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation in humans.

Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of [7 alpha-3H]cholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined hyperlipidemia group (P < .05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P = NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Short-term effects of simvastatin on bile acid synthesis and bile lipid secretion in human subjects.

To test whether de novo synthesis of cholesterol is a limiting factor for bile acid synthesis, we studied the acute effect of simvastatin, an inhibitor of HMG-coenzyme A reductase (the limiting step of cholesterol synthesis) on bile acid synthesis and biliary lipid secretion in subjects with interrupted enterohepatic circulation. In these conditions bile acid synthesis is derepressed and is assumed to equal biliary bile acid secretion. Five cholecystectomized patients fitted with T-tubes were studied. All subjects were administered simvastatin (80 mg as a single dose) 5 days after surgery. Bile was collected in 3-hr intervals for 15 hr before and 30 hr after the administration of the drug. During the experiment we kept the enterohepatic circulation of bile acid interrupted by inflating an occludable balloon inserted, during cholecystectomy, in the common bile duct. Simvastatin induced significant decreases of plasma total and low density lipoprotein cholesterol concentrations, from 163 +/- 29 mg/dl and 97 +/- 24 mg/dl of the pretreatment value to 144 +/- 30 mg/dl and 82 +/- 22 mg/dl 18 hr after simvastatin administration, respectively. Bile flow tended to increase after simvastatin, and the mean values from the third to the 15th hour after simvastatin administration (22.1 +/- 1.9 ml/hr) were significantly greater than the mean values of the pretreatment period (19.9 +/- 2.8 ml/hr). Concomitantly biliary bile acid, cholesterol and phospholipid concentrations fell from basal values of 15.9 +/- 5.1, 2.3 +/- 0.3 and 5.5 +/- 0.3 mmol/L to mean values, after treatment, of 9.0 +/- 3.5, 1.9 +/- 0.5 and 3.0 +/- 0.9 mmol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Effect of aging on cholesterol 7 alpha-hydroxylation in humans.

In order to investigate the alterations of bile acid synthesis in aging, we studied the rates of cholesterol 7 alpha-hydroxylation, the rate-limiting step, in 28 patients of different ages (34-83 years old, 14 below and 14 above the age of 65) of both sexes. Hydroxylation rates were determined by tritium release assay after an intravenous bolus of [7 alpha-3H]cholesterol. Cholesterol 7 alpha-hydroxylation was significantly decreased in the older age group, compared to middle-aged subjects, both in males and females; moreover, a significant inverse correlation between hydroxylation rates and age was found in the whole sample (r = -0.56; P < 0.01) and in females, but not in males. The percent concentration of deoxycholic acid in plasma (determined by gas-liquid chromatography) was increased in older subjects. Plasma cholesterol and triglyceride levels were not related with age even though triglyceride concentrations tended to be lower in the older age group. Triglyceride, but not cholesterol levels, were directly correlated with hydroxylation rates (r = 0.45, P < 0.05). After cholestyramine treatment (8-12 g/day for 4 weeks) a sharp increase in 7 alpha-hydroxylation rates was observed in three elderly patients, accompanied by reduced levels of dihydroxylated bile acids. Our data are consistent with a reduced rate of conversion of cholesterol to bile acids with aging, particularly in females, and suggest a coordinate reduction of triglyceride production. Alterations of the quantitative and/or qualitative pattern of the bile acid pool recirculating to the liver may be responsible, at least in part, for the changes observed.

Adult↗
PubMed1991

Effect of fish oil and coconut oil diet on the LDL receptor activity of rat liver plasma membranes.

The influence of 4 weeks treatment with fish oil and coconut oil enriched diets on the chemical composition of rat liver plasma membranes and LDL and on the binding of LDL to liver membranes was investigated. Rats fed fish oil diet showed a total, LDL and HDL plasma cholesterol concentration lower than the values observed in rats fed coconut oil and to a lesser extent lower than those of rats fed standard laboratory diet. LDL of rats on fish oil diet had a relative percentage of cholesterol and phospholipid lower, while that of triacylglycerol was greater. Furthermore, fish oil feeding was associated with a greater concentration of n - 3 fatty acids and a lower arachidonic and linoleic acid content in LDL. Liver plasma membranes isolated from fish oil rats showed a higher percentage of n - 3 fatty acids, while only a trace amount of these fatty acids was found in control and coconut oil fed animals. In binding experiments performed with LDL and liver membranes from fish oil fed rats and control rats, binding affinity (Kd = 3.47 +/- 0.93 and 4.56 +/- 1.27, respectively) was significantly higher (P less than 0.05) as compared to that found using membranes and lipoprotein from coconut oil fed rats (Kd = 6.82 +/- 2.69). In cross-binding experiments performed with fish oil LDL and coconut oil liver plasma membranes or coconut oil LDL and fish oil liver plasma membranes, the LDL binding affinity was comparable and similar to that found in fish oil fed animals. No difference was found in the Bmax among all the groups of binding experiments. Our data seem to indicate that during fish oil diet the higher binding affinity of LDL to liver plasma membranes might be partly responsible of the hypocholesterolemic action of marine oil rich diet as compared to saturated diet. Furthermore, the modifications of binding affinity induced by changes of LDL and membrane source, suggest that lipoprotein and liver plasma membrane composition may be an important variable in binding studies.

Animals↗
PubMed1991

Regulation of bile acid synthesis in humans: effect of treatment with bile acids, cholestyramine or simvastatin on cholesterol 7 alpha-hydroxylation rates in vivo.

The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid synthesis from cholesterol) were evaluated in vivo in patients administered bile acids with different structural properties, cholestyramine or simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Twenty-three subjects, with normal hepatic and intestinal functions, were studied in basal conditions and after one of the following treatment schedules, lasting 4 to 6 weeks: cholestyramine, 4 and 12 gm/day (four patients); ursodeoxycholic acid, 9 to 11 mg/kg/day (four patients); chenodeoxycholic acid, 12 to 15 mg/kg/day (five patients); deoxycholic acid, 8 to 10 mg/kg/day (four patients); and simvastatin, 40 mg/day (six patients). 7 alpha-Hydroxylation of cholesterol was assayed by measuring the increase in body water tritium after intravenous bolus of cholesterol tritiated at the 7 alpha position. Plasma bile acid composition, evaluated by gas-liquid chromatography, revealed a substantial enrichment of the recirculating pool by the administered bile acid, whereas treatment with cholestyramine decreased the content of dihydroxylated bile acids. Cholesterol 7 alpha-hydroxylation increased in a dose-related manner after cholestyramine, in parallel with a decrease of cholesterol in total plasma and low-density lipoproteins (1.006 to 1.063 gm/ml). Hydroxylation rates decreased by an average of 47% with chenodeoxycholic acid and by an average of 78% with deoxycholic acid; ursodeoxycholic acid treatment did not affect 7 alpha-hydroxylation significantly. Simvastatin markedly reduced plasma total and low-density lipoprotein-cholesterol but exerted no change on 7 alpha-hydroxylation rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of bile acid pool composition on hepatic metabolism of cholesterol in man.

This work reviews the evidence concerning the role of the bile acid pool composition in the regulation of the overall hepatic metabolism of cholesterol in man. It has been known that bile acids regulate bile secretion, biliary lipid transport and hepatic cholesterol metabolism. However, the intimate mechanisms of these regulatory functions are not well understood. Current thinking attributes most of this regulation to the size of the bile acid pool. A typical example is represented by the negative feed-back mechanism by which bile acids returning to the liver control their own synthesis. Recent evidence however tend to suggest that not only the size but also the composition contributes to the regulatory activity of the bile acid pool. Specifically the hydrophobic-hydrophilic balance of the pool, as resulting from the characteristics and the proportions of the individual bile acids present within the pool, seems to dictate most of the effects of bile acids on hepatic cholesterol metabolism. Thus abundance within the pool of hydrophobic bile acids, such as deoxycholic or chenodeoxycholic acid, seems to induce a greater biliary lipid secretion and to exert inhibition of cholesterol and bile acid synthesis whereas hydrophilic bile acids such as ursodeoxycholic acid seem to be uneffective. It follows that by changing the composition of the bile acid pool it is possible to influence the hepatic metabolism of cholesterol.

Animals↗