PubMed Health⌕ Search

Biomedical subjects

M Ronchi

Publications and source records attributed to M Ronchi.

At least 19 recordsLinked to original sources

Synthesis of glutathione in response to methionine load in control subjects and in patients with cirrhosis.

The fasting plasma level of reduced glutathione (GSH), a methionine-derived tripeptide, is reduced in cirrhosis. There is evidence that a reduced activity of S-adenosyl-L-methionine synthetase limiting the flux of methionine along the transmethylation/transsulfuration pathway may contribute to decrease GSH levels. No studies have analyzed plasma GSH in response to a methionine load. In 6 control subjects and in 10 patients with cirrhosis, plasma sulfur amino acid and plasma and erythrocyte GSH levels were measured in response to a L-methionine load (0.1 g/kg). Blood samples were obtained throughout the day after the oral load. Urine was collected for measurement of sulfur excretion. During the study period, all subjects consumed a standard diet of 1,683 kcal containing 2% protein and virtually no methionine. Plasma methionine increased in both groups to a peak level exceeding 20 times the basal value 90 minutes after the load, and declined thereafter. Methionine clearance, calculated on the descending part of the methionine-time curve, was reduced by 50% in cirrhosis (P = .0001). Fasting GSH was higher in controls (mean +/- SD, 3.9 +/- 1.3 v 1.6 +/- 0.7 micromol/L, P = .0004). In response to a methionine load, it peaked at 10.2 +/- 7.2 and 3.2 +/- 1.3 micromol/L, respectively (P = .009). Thereafter, plasma GSH progressively declined, and after 24 hours, it returned to the fasting preinfusion values in both groups. Plasma cysteine and taurine concentrations, as well as the erythrocyte GSH time course, paralleled plasma GSH levels, with less significant differences between groups. Sulfate excretion was delayed. GSH synthesis is stimulated by a methionine load. The reduced flux of methionine along the transmethylation/transsulfuration pathway reduces GSH synthesis in cirrhosis. Defective methionine metabolism also may be responsible for reduced fasting GSH.

Aged↗

Cardiovascular disease in cirrhosis--a point-prevalence study in relation to glucose tolerance.

OBJECTIVE: Impaired glucose tolerance or diabetes are frequently observed in cirrhosis. Overt diabetes was reported to affect long term survival of cirrhotic patients by increasing the risk of hepatocellular failure, without increasing the risk of diabetes-associated cardiovascular events. METHODS: We evaluated the prevalence of cardiovascular disease in 122 patients with cirrhosis, subdivided according to their glucose tolerance. The following parameters were considered: arterial pressure, peripheral vascular disease (ankle to brachial pressure ratio), ischemic heart disease, microalbuminuria, retinopathy. The prevalence of abnormal findings was compared with that observed in 60 randomly selected patients with noninsulin-dependent diabetes and in 40 controls. RESULTS: Noninsulin-dependent diabetic patients and patients with cirrhosis and diabetes were comparable for age, metabolic control, and smoking habits; the duration of diabetes was 5 yr longer for noninsulin-dependent diabetes. In cirrhosis, the prevalence of micro- and peripheral macroangiopathy, as well as coronary heart disease, was not different in relation to glucose tolerance, it was comparable to that of controls, and significantly lower than that observed in non-insulin-dependent diabetes. CONCLUSIONS: Cirrhotic patients, even in the presence of overt diabetes, are at low risk of cardiovascular disease. The low prevalence may be related to shorter duration of diabetic disease, also in relation to reduced life expectancy, as well as to liver disease-induced abnormalities protecting the cardiovascular system from atherosclerosis.

Adolescent↗

Zinc supplementation improves glucose disposal in patients with cirrhosis.

Zinc deficiency is common in cirrhosis, and was proved to affect nitrogen metabolism. In experimental animals, zinc status may also affect glucose disposal, and acute zinc supplementation improves glucose tolerance in healthy subjects. This study was aimed at measuring the effects of long-term oral zinc supplements on glucose tolerance in cirrhosis. The time courses of glucose, insulin, and C-peptide in response to an intravenous (i.v.) glucose load were analyzed by the minimal-model technique before and after long-term oral zinc supplements (200 mg three times per day for 60 days) in 10 subjects with advanced cirrhosis and impaired glucose tolerance or diabetes. The test was performed using a simplified procedure, based on 20 blood samples collected within 4 hours from the glucose load. Normal values were obtained in 25 age-matched healthy subjects. Zinc levels were low to normal or reduced before treatment, and were normalized by oral zinc. Glucose disappearance improved by greater than 30% in response to treatment. There were no changes in pancreatic insulin secretion and systemic delivery, or in the hepatic extraction of insulin. Insulin sensitivity (SI), which was reduced by 80% before treatment, did not change. Glucose effectiveness (SG) was nearly halved in cirrhosis before treatment (0.013 [SD 0.007] min(-1) v. 0.028 [SD 0.009] in controls; P < .001), and increased to 0.017 (SD 0.009) after zinc (P < .05 v. baseline). The return to normal of plasma zinc levels after long-term zinc treatment in advanced cirrhosis improves glucose tolerance via an increase of the effects of glucose per se on glucose metabolism. Poor zinc status may contribute to the impaired glucose tolerance and diabetes of cirrhosis.

Administration, Oral↗

Echo-guided SWL of vesical stones with Dornier MPL 9000 lithotripter in obstructed and unobstructed patients.

Sixty-one patients with vesical stones (38 with underlying obstructive conditions and 23 unobstructed) underwent SWL using ultrasound targeting under no regional or general anesthesia. A foley catheter was not routinely employed, and the bladder was filled in a physiologic way. Complete resolution was obtained in 47 patients (78%); in particular, 66% of the obstructed patients and 96% of the unobstructed patients became stone free in one to four SWL sessions. The average number of sessions for all patients was 1.28+/-0.63. Fragments were completely evacuated also in some patients with severe obstruction and in all three patients with neurogenic bladder dysfunction. The size and number of stones did not seem to play a limiting role in SWL effectiveness: the principal limiting factor was the hardness of the stone. No severe complications occurred. However, in six patients (10%), some fragments stopped in the urethra, causing acute urine retention, and endoscopic extraction was necessary. Echo-guided SWL of bladder stones is safe and highly effective in nonobstructed patients and can be considered the elective monotherapy method. In obstructed patients, SWL efficacy is lower, but the method may be suggested for patients who refuse or delay other, more invasive techniques.

Adolescent↗

Glutathione kinetics in normal man and in patients with liver cirrhosis.

BACKGROUND/AIMS: The dynamics of glutathione in plasma has always been studied by bolus injections. Data are available suggesting that the low plasma levels of cirrhosis are due to decreased production in glutathione-producing tissues, mainly the liver. We aimed to measure the kinetics of glutathione during controlled steady-state conditions, and to determine the reasons for its reduced plasma levels in advanced cirrhosis. METHODS: The plasma clearance of glutathione was measured in six control subjects and in ten patients with cirrhosis during a 2-step infusion study, producing steady-state levels approximately 5 and 10 times basal values. The plasma disappearance curve after infusion stop was used to determine the apparent volume of distribution and half-life of glutathione, and the estimated basal appearance rate. RESULTS: The clearance of glutathione did not reject 1st-order kinetics, i.e., it was concentration-independent, and was nearly doubled in cirrhosis. The half-life of exogenous glutathione was not different, whereas the volume of distribution was larger in cirrhosis, in the same range as extracellular water. The endogenous basal appearance rate of glutathione was reduced by 50%, and correlated with liver function, measured by routine and dynamic tests. CONCLUSIONS: The data confirm that the primary defect responsible for reduced glutathione in liver disease is a reduced production, possibly related to hepatocyte dysfunction and a block along the pathway of methionine metabolism.

Adult↗

Effect of lactulose on carbohydrate metabolism and diabetes mellitus.

BACKGROUND: Unabsorbable disaccharides, by reducing transit time and possibly glucose absorption, are expected to affect carbohydrate metabolism. AIM: To test the effects of a preparation containing fibre and lactulose in the form of biscuits on glucose and insulin levels in obesity. METHODS: In 10 obese patients glucose and insulin were measured in the fasting state and in response to a meal during two consecutive days on a strictly controlled diet; on one day a total of 11 biscuits (10 g dietary fibre, 2 g raw fibre +8.2 g lactulose) were randomly substituted for an equicaloric part of a diet. RESULTS: Glucose and insulin in response to breakfast and to lunch were blunted by dietary fibre and lactulose, without any trend towards post-meal hypoglycaemia. Average day-time glucose decreased by 0.53 +/- SD 0.28 mmol/L, and insulin by 74.6 +/- 45.2 pmol/L. Plasma amino acids were higher during supplementation, ruling out malabsorption as a cause of glucose flattening. CONCLUSION: Because of the rationale of the preparation, good compliance of patients, and significant results in short-term experiments, the association of fibre and lactulose deserves more careful evaluation in long-term clinical studies.

Blood Glucose↗

Transamination of methionine after loading in patients with cirrhosis.

BACKGROUND/AIMS: An impaired methionine degradation along the transsulfuration pathway has been widely described in cirrhosis. Evidence has been provided that methionine can also be degraded via a transamination pathway, leading to formation of methanethiol and its metabolites, protein-S-SCH3 (a mixed disulphide of blood proteins and methanethiol), alpha-ketomethylthiobutyrate and X-S-SCH3 (a mixed disulphide of a thiol with an unknown component X and methanethiol). This pathway seems to be of little importance in normal subjects, even after methionine loading, but its role in the presence of an acquired transsulfuration defect has never been tested. METHODS: We measured the plasma concentration of methanethiol metabolites in six normal subjects and 11 patients with cirrhosis receiving a primed-continuous infusion of L-methionine, at rates able to increase plasma methionine to levels approximately 20 times basal concentrations. RESULTS: Before methionine infusion, the sum of transamination metabolites was similar in the two groups (0.29 +/- SD 0.07 mumol/l in controls and 0.45 +/- SD 0.22 in patients with cirrhosis). During methionine infusion and after the end of infusion, there was a progressive increase of transamination metabolites, which reached values approximately 10 times basal concentrations, with no difference between groups. CONCLUSIONS: We conclude that transamination cannot represent a quantitatively important exit for excess methionine in subjects with cirrhosis, in the presence of an acquired block along the transsulfuration pathway.

Galactose↗

In situ echoguided extracorporeal shock wave lithotripsy of ureteric stones with the Dornier MPL 9000: a multicentric study group.

OBJECTIVE: To study the efficacy of the Dornier MPL 9000 lithotripter with a real time ultrasound transducer in the localization and treatment of upper and prevesical ureteric stones. PATIENTS AND METHODS: Two-hundred and eighty-five patients with pre-vesical ureteric stones and 247 patients with upper ureteric stones underwent extracorporeal shock wave lithotripsy (ESWL) using ultrasound targeting, under no regional or general anaesthesia. RESULTS: At follow-up after 3 months 97% of patients with pre-vesical stones and 96% with upper ureteric stones were stone free. Ninety-nine patients were treated more than once. The average number of sessions of ESWL for all patients was 1.19 (1.17 for patients with prevesical stones and 1.22 for those with upper ureteric stones). Ureteric stenting was employed in 6% of cases. The infrequent use of ureteric stenting did not reduce ESWL efficacy, nor increase either the complication or the retreatment rates. In many cases upper urinary tract dilatation was provoked by administering intravenous fluid and a diuretic. CONCLUSION: In situ echoguided ESWL is a simple, safe and effective technique for treating ureteric stones which can be detected on ultrasound.

Adolescent↗

Comparative evaluation of chenodeoxycholic and ursodeoxycholic acids in obese patients. Effects on biliary lipid metabolism during weight maintenance and weight reduction.

Obesity is a condition associated with an increased frequency of gallstone disease. This study attempted to evaluate the comparative effects of two gallstone-dissolving agents, chenodeoxycholic acid and ursodeoxycholic acid, on bile acid metabolism and biliary lipid secretion in obese subjects in order to identify the bile acid of choice in preventing and treating gallstone disease in obesity. Twenty obese subjects (greater than 120% ideal body wt) were randomly treated with ursodeoxycholic acid (10 mg.kg-1.day-1.1 mo-1) and then with chenodeoxycholic acid (15 mg.kg-1.day-1.1 mo-1) or with chenodeoxycholic acid first and then with ursodeoxycholic acid. Patients 1-10 were studied while eating an unrestricted weight-maintenance diet, whereas patients 11-20 were eating a 1080-kcal/d hypocaloric diet. Biliary lipid composition, cholesterol saturation index, and biliary bile acid pattern were evaluated in all subjects before and after each treatment period; in subjects 6-10 and 16-20, biliary lipid secretion rates and bile acid pool size were also evaluated. Both ursodeoxycholic acid and chenodeoxycholic acid decreased cholesterol outputs and cholesterol saturation index. However, during the weight-maintenance period the decrease induced by chenodeoxycholic acid was not significant. Biliary cholesterol outputs and cholesterol saturation index were always lower during ursodeoxycholic acid administration than during chenodeoxycholic acid therapy. Ursodeoxycholic acid levels during ursodeoxycholic acid administration and chenodeoxycholic acid levels during chenodeoxycholic acid administration increased in bile to 50% and 77%, respectively, of total bile acid levels. Bile acid pool size remained unchanged during chenodeoxycholic acid administration and was significantly reduced by ursodeoxycholic acid administration during the weight-reduction period. In conclusion, ursodeoxycholic acid in obese subjects seems more effective than chenodeoxycholic acid, at least during weight maintenance, in reducing cholesterol saturation of bile. This effect is related to a significant decrease of biliary cholesterol output.

Adolescent↗

Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution.

Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function.

Adolescent↗

Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis.

The hydrophilic bile acid ursodeoxycholic acid (UDCA) has recently been shown to improve indexes of liver function in adult patients with various liver diseases. The clinical and biochemical responses to UDCA administration (10 to 15 mg/kg body weight per day) were therefore investigated in nine patients with cystic fibrosis and evidence of liver disease. All patients were receiving pancreatic enzymes and taurine supplementation. Liver function tests were done and serum bile acid concentrations and biliary bile acid composition were determined before and during UDCA therapy; fat balance studies and fecal bile acid excretion were carried out before and 6 months after UDCA treatment. After 2 months of bile acid therapy, biliary bile acid composition was enriched in UDCA from approximately 5% before treatment to 25%, at the expense of cholic and chenodeoxycholic acids, thus making the pool more hydrophilic. This enrichment is lower than that reported for adults with chronic liver diseases. Serum concentrations of UDCA increased significantly but variably. UDCA became the predominant fecal bile acid excreted (12% to 67%), indicating a variable absorption of the administered bile acid. Liver function improved in all patients after 2 to 6 months of therapy, although the degree of improvement (aspartate aminotransferase, -34%; alanine aminotransferase, -41%; gamma-glutamyltranspeptidase, -41% alkaline phosphatase, -19%) was lower than that observed in adults with chronic liver diseases. Mean coefficient of fat absorption and growth rate were, on average, unaffected by UDCA therapy, although an improvement was noted for three patients with greater severity of steatorrhea. The study indicates that UDCA can be used safely in this patient population but that higher doses of UDCA may be of greater benefit in the treatment of the liver disease associated with cystic fibrosis.

Adolescent↗

Effects of taurine and ursodeoxycholic acid on liver function tests in patients with cystic fibrosis.

In 9 CF patients with clinical and biochemical evidence of liver disease, taurine (30 mg/kg/day) was administered one month before and during the successive treatment with ursodeoxycholic acid (10-15 mg/kg/day). Standard liver function tests were determined before and after each period of treatment. Taurine administration produced only inconsistent changes of liver function tests from baseline, whereas after the addition of ursodeoxycholic acid a substantial improvement in all abnormal indices was observed. The effects of longer period of treatment are currently investigated, with purpose of establishing their clinical impact and their relationship with changes in bile acid metabolism.

Bile Acids and Salts↗

Effect of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis.

Ursodeoxycholic acid (UDCA) has been reported to improve liver function tests when administered to patients with cholestatic liver diseases, such as primary biliary cirrhosis (PBC). However, its effects on biliary lipid metabolism in patients with PBC are still unknown. In this study we report the effect that UDCA (600 mg/day, for four weeks) had on biliary cholesterol saturation index, biliary bile acid pattern and pool size, and biliary lipid output in seven female patients (ages 34-58 years) with PBC, stages I to III. A significant improvement of liver function tests was observed after four weeks of treatment. Saturation index was significantly decreased from 1.23 +/- 0.1 to 0.7 +/- 0.08 (P less than 0.02); this effect was due to the significant decrease of biliary cholesterol concentration from 6.7 +/- 0.36 to 3.6 +/- 0.37 percent molar (P less than 0.02). A significant decrease of cholesterol output (from 88 +/- 9 to 55 +/- 10 mumol/hr, P less than 0.02) was also observed. The amount of cholic acid, the predominant bile acid in bile, significantly decreased (from 47.3 +/- 3.5 to 35.4 +/- 2.6 percent molar, P less than 0.02), as did amounts of chenodeoxycholic and deoxycholic acids, while the amount of UDCA rose from 1.6 +/- 1.0 to 34.0 +/- 1.3 percent molar (P less than 0.02). Total bile acid pool size was not affected by UDCA, but the evaluation of individual bile acid pool sizes showed an increased proportion of UDCA relative to the endogenous bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serum levels of immunoreactive trypsin during development: comparison with levels of lipase and amylase.

In order to obtain additional information on serum pancreatic enzyme levels during development, we have measured immunoreactive trypsin (IRT), immunoreactive lipase (IRL), and total amylase in paired fetal and maternal sera. Samples were obtained during early gestation (14-21 week of gestation) and at the time of normal delivery. IRT levels were lower in maternal sera as compared to paired fetal and neonatal (p less than 0.005); conversely, IRL and amylase, although present in measurable concentrations, were significantly lower in fetal and neonatal sera than in the maternal (p less than 0.001). We also serially monitored serum pancreatic enzyme levels in a group of premature infants during the first 10 days of life. Concentrations of IRT showed a significant increase over time (p less than 0.05) and those of IRL remained stable while amylase levels decreased sharply, suggesting possible maternal origin of this enzyme. Serum concentrations of the three pancreatic enzymes in newborns at term (second day of life) were higher than in infants aged 0.5-6 months; however, only IRT levels were above the normal range for adults. Beyond the neonatal period, IRT levels were stable and comparable to adults, whereas amylase and IRL levels were very low in infants younger than 6 months and increased significantly with age (p less than 0.001). These data seem to indicate that "physiologic hypertrypsinemia" occurs early during development and may be accentuated by postnatal events. They provide an indirect indication of both early fetal production of trypsinogen and possible placental transfer of pancreatic enzymes from the maternal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

Rheological properties and diffusion dissolution behaviour of hydrophilic polymers.

In a mathematical model that has been recently proposed to predict drug release from polyvinyl alcohol matrices, polymer dissolution is described as a chain disentanglement process and characterized by a threshold polymer concentration. In present work viscosity measurements were employed for defining the characteristic entanglement concentration of polymer solutions. The viscosity of aqueous polymer solutions of differing concentrations was measured over a wide range of shear rate using a rotational viscometer. The flow curves were fitted according to an asymptotic model and from the best fit equation the relevant viscosity parameters were obtained. The relationships between polymer concentration and viscosity parameters were also examined. The critical concentration at which an abrupt change of viscosity properties occurred was identified and related to the molecular chain disentanglement conditions.

Chemical Phenomena↗

Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile.

A detailed study of the qualitative and quantitative composition of bile acids in human fetal gallbladder bile is described. Bile was collected during early gestation (weeks 16-19) and analyzed by gas chromatography and mass spectrometry, fast atom bombardment ionization mass spectrometry, and high performance liquid chromatography. Bile acids were separated into different conjugate groups by chromatography on the lipophilic anion exchange gel, diethylaminohydroxypropyl Sephadex LH-20. Quantitatively more than 80% of the bile acids were secreted into bile conjugated to taurine. Unconjugated bile acids and glycine conjugates accounted for 5-10% of the total biliary bile acids. Bile acid sulfates were present only in trace amounts indicating that quantitatively sulfation is not an important pathway in bile acid metabolism during development. Total biliary bile acid concentrations were low (0.1-0.4 mM) when compared to reported values for adult bile (greater than 10 mM). Chenodeoxycholic acid was the major biliary bile acid and exceeded cholic acid concentrations by 1.43-fold indicating either a relative immaturity in 12 alpha-hydroxylase activity during early life or a dominance of alternative pathways for chenodeoxycholic acid synthesis. A relatively large proportion of the biliary bile acids comprised metabolites not found in adult bile. The presence of relatively high proportions of hyocholic acid (often greater than cholic acid) and several 1 beta-hydroxycholanoic acid isomers indicates that C-1 and C-6 hydroxylation are important pathways in bile acid synthesis during development. We describe, for the first time, evidence for the existence of a C-4 hydroxylation pathway in the metabolism of bile acids, which may be unique to early human development. Mass spectrometry was used to confirm the identification of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic and 3 alpha,4 beta-dihydroxy-5 beta-cholanoic acids. Quantitatively, these C-4 hydroxylated bile acids accounted for 5-15% of the total biliary bile acids of the fetus, suggesting that C-4 hydroxylation is quantitatively an important pathway in the bile acid metabolism during early life.

Bile↗

Effect of taurine supplementation on fat and bile acid absorption in patients with cystic fibrosis.

Eleven children with cystic fibrosis (CF) and pancreatic insufficiency were given supplementation with taurine (30-40 mg/kg/day) for 2 months, while taking their usual dosage of enzymatic therapy. One patient dropped out of the study because she developed severe constipation. In the other 10 patients, urinary taurine excretion (88 +/- 30.1 mg/m2s.a./24 h) was similar to that of controls (86.2 +/- 6 mg/m2s.a./24 h) before taurine and increased markedly after supplementation (618.2 +/- 79.97 mg/m2s.a./24 h), indicating efficient intestinal absorption. Their coefficient of fat absorption was 81.2 +/- 2.3% and increased significantly after taurine (91.3 +/- 1.13%; p less than 0.01); the area under the curve of plasma triglyceride postprandial levels (1 +/- 0.1 mg X min/ml) also increased significantly after taurine (1.4 +/- 0.3 mg X min/ml; p less than 0.05), showing values very similar to those of controls. Conversely, no change was observed in the serum postprandial levels of glycocholic acid: the maximum postprandial peak before (1.2 +/- 0.3 mumol/l) and after taurine (1 +/- 0.1 mumol/l) remained significantly lower than in controls (2.4 +/- 0.3 mumol/l); p less than 0.01 and p less than 0.001, respectively. Mean total fecal bile acid (BA) excretion was 10.24 +/- 2.15 mg/kg/day before taurine and 12.8 +/- 4.27 mg/kg/day after taurine (normal pediatric values, 2.91 +/- 1.1 mg/kg/day); however, in the individual patients we found a variable trend, four of them showing a net increase in fecal BA excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗

Biliary bile acid composition of the human fetus in early gestation.

Using analytical techniques, which included capillary column gas-liquid chromatography and mass spectrometry, detailed bile acid profiles were obtained for 24 fetal bile samples collected after legal abortions were performed between the 14th and 20th wk of gestation. Qualitatively, the bile acid profiles of all fetal bile samples were similar. The predominant bile acids identified were chenodeoxycholic and cholic acid. The presence of small but variable amounts of deoxycholic acid and traces of lithocholic acid suggested placental transfer of these bile acids from the maternal circulation. 3 beta-Hydroxy-5-cholenoic acid was detected at higher levels than lithocholic acid. A conspicuous feature of the profiles was the presence of bile acids with hydroxyl groups at positions C-1 and C-6, and one other nuclear position of unknown origin, indicating fetal hepatic synthesis via pathways different from those normally seen in the adult. Quantitatively total biliary bile acid concentrations were extremely low (less than 0.05 mM) before wk 17 of gestation, but thereafter concentrations markedly increased reflecting a possible surge in bile acid synthesis; however, the ratio of cholic:chenodeoxycholic acids remained relatively constant over this period (mean +/- SD = 0.85 +/- 0.36) and different from that reported for the healthy newborn (ca. 2.5) and adult (ca. 1.6). These data indicate an immaturity in hepatic 12 alpha-hydroxylation of bile acids during early development and may explain why other pathways, in particular 1 beta and 6 alpha-hydroxylation, are activated at this stage of life.

Bile Acids and Salts↗