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Biomedical subjects

M Angelico

Publications and source records attributed to M Angelico.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of isosorbide-5-mononitrate compared with propranolol on first bleeding and long-term survival in cirrhosis.

BACKGROUND & AIMS: Isosorbide-5-mononitrate (Is-5-Mn) exerts beneficial hemodynamic effects in portal hypertension, yet the long-term clinical value is uncertain. The aim of this study was to determine the long-term effects of Is-5-Mn vs. propranolol (Pro) on first bleeding, complications, and death in cirrhosis. METHODS: One hundred eighteen patients included in a previously published randomized trial comparing Is-5-Mn (20 mg three times daily) with Pro were followed up for up to 7 years (range, 2-91 months). Fifty-seven patients received Is-5-Mn and 61 received Pro. RESULTS: Thirty episodes of first upper bleeding occurred; 16 were in the Is-5-Mn group. Actuarial probability of bleeding did not differ between the two groups. Endoscopic variceal red signs were the only independent predictors of early bleeding. Of the 52 patients who died, 28 were in the Is-5-Mn group. The likelihood of death was greater among patients assigned to Is-5-Mn than to Pro, but only in patients older than 50 years (72% vs. 48% at 6 years; P = 0.006). Child-Pugh score, bleeding, age, and assignment to Is-5-Mn were independent predictors of death. The likelihood of death without bleeding was also higher (P = 0.05) in the Is-5-Mn group. CONCLUSIONS: Is-5-Mn is as effective as Pro in preventing early bleeding but is associated with higher long-term mortality.

Adrenergic beta-Antagonists↗
PubMed1997

Hepatitis C virus infection in Italian kidney graft recipients. Changing risk factors and hepatitis C virus genotypes.

BACKGROUND/AIMS: The risk for hepatitis C virus infection in kidney transplant recipients has been reduced by the introduction of accurate diagnostic tests. Little is known, however, of the current risk factors and the molecular genetics of hepatitis C virus infection in Italy. METHODS: We studied 101 Italian kidney allograft recipients, transplanted between 1975 and 1995, in Italy or abroad. Sera were assayed for biochemistry, presence of HBsAg, anti-hepatitis C virus antibodies, hepatitis C virus-RNA (by reverse transcription nested PCR) and hepatitis C virus genotyping. RESULTS: HBsAg was found in 4 sera and anti-Hepatitis C Virus antibodies in 33 (33%). The duration of pre-transplant dialysis was longer in anti-hepatitis C virus positive than in anti-hepatitis C virus negative patients (5.9 +/- 4.3 vs 2.8 +/- 1.9 years, p = 0.0004). Anti-hepatitis C virus seropositivity was more frequent among patients grafted before than after 1990 (50% vs 27%, p = 0.04) and varied depending on the country of transplantation (25% in Italy; 56% in other European countries; and 40% in non-European developing countries). Twenty-seven sera were hepatitis C virus-RNA positive, including 5 without anti-hepatitis C virus antibodies. Hepatitis C virus genotype 1b was found in 13 (48%) patients, the remainder being infected with genotypes 1a (6 cases), 2a, 2c, 3a and 4. Genotype 1b was largely predominant among patients grafted in Europe but never found in those transplanted in developing countries. All but one patient without a sustained antibody response were infected by non-1b genotypes. Hepatitis C virus-RNA seropositivity was associated (p = 0.03) with a higher dose of prednisone (p = 0.03) and a lower dose of cyclosporine (p = 0.05) used as immunosuppressants. CONCLUSIONS: Current risk factors for hepatitis C virus infection in Italian kidney graft recipients include the duration of haemodialysis, transplantation in developing countries and the level of post-transplant immunosuppression. The pattern of hepatitis C virus genotypes is changing from predominantly 1b to non-1b genotypes and the latter infection often occurs without a sustained antibody response. Few patients develop clinical liver disease.

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

Lamellar bodies coexist with vesicles and micelles in human gallbladder bile. Ursodeoxycholic acid prevents cholesterol crystal nucleation by increasing biliary lamellae.

The aggregative forms of lipids in human gallbladder bile and their relation to cholesterol crystallization are controversial. Using combined chemical, gel-chromatographic, optical/electron microscopic and quasielastic light-scattering methods, we investigated this issue in native gallbladder bile obtained from nine untreated cholesterol gallstone patients and eight cholesterol gallstone patients treated for 1 week with 600 mg/day of ursodeoxycholic acid. Bile obtained at cholecystectomy was ultracentrifuged for 2 h at 150,000 g to obtain isotropic samples. The conventional cholesterol crystal observation time was 3.1 +/- 4.1 (SD) days in controls and 19.0 +/- 1.9 days in the ursodeoxycholic acid-treated group (p < 0.001). Bile was analyzed by high-resolution gel-chromatography using 7 mM sodium taurocholate in the elution buffer. Biliary lipids eluted in four chromatographic zones: zone #I, corresponding to the column void volume, contained only minimal amounts of lipids; zone #II (apparent m.w. 100-220 kDa) comprised 29.1 +/- 12.4% of biliary cholesterol in the untreated group and 8.3 +/- 4.3% in the ursodeoxycholic acid-group (p < 0.001). At negative staining electron microscopy, this region was composed of roundish vesicles ranging from 7 to 20 nm in diameter. Zone #III (apparent m.w. 50-100 kDa) carried 59.1 +/- 2.1% of cholesterol in untreated patients and 81.2 +/- 9.5% in ursodeoxycholic acid-rich biles, respectively (p < 0.001). At negative staining electron microscopy, this region was composed of lamellar stacks of variable length, usually with 5 nm interspaces and up to 30 nm in width. In ursodeoxycholic acid-rich biles, lamellae often appeared in the form of concentric fingerprint-like images. Quasielastic light-scattering measurements in this region were compatible with the size estimates obtained at electron microscopy. Zone #IV (apparent m.w. 6-50 kDa) carried 11.8 +/- 9.4% and 11.6 +/- 9.0% of cholesterol, respectively (not significant). Since this region comprised a considerable fraction of endogenous bile salts and had no distinct morphological structures, it was interpreted as mixed micelles. The cholesterol crystal observation time showed a significant inverse correlation (r = -0.85, p < 0.001) with percent cholesterol carried by vesicles (zone #II) and a direct correlation (r = 0.86, p < 0.001) with percent cholesterol carried by lamellar bodies (zone #III). Vesicles and lamellae identical to those observed in isolated gel-chromatographic fractions were observed also on direct electron microscopic examination of unfractionated isotropic native biles. Similar findings were observed also in matched model biles.(ABSTRACT TRUNCATED AT 400 WORDS)

Bile↗
PubMed1995

Dissolution of human cholesterol gallstones in bile salt/lecithin mixtures: effect of bile salt hydrophobicity and various pHs.

BACKGROUND: Unconjugated bile salts currently available for gallstone dissolution are poorly effective. We evaluated in vitro the litholytic potency of taurine-amidated bile salts against human cholesterol gallstones. METHODS: Seventy radiolucent gallstones with similar size and composition (cholesterol content, 70.1 +/- 0.9%) from a single patient were incubated in model biles composed of 100 mM of either taurochenodeoxycholate (TCDC), taurocholate (TC), taurohyodeoxycholate (THDC) or tauroursodeoxycholate (TUDC) and of 45 mM egg yolk lecithin in saline buffered with tris/HCl (at pHs 7 and 8) or phosphate (at pHs 4 and 6). Biles (total lipids, 10 g/dl; cholesterol saturation, 99%) were incubated at 37 degrees C for 40 days. Gallstones were periodically weighed and returned to the dissolution vials, and the biliary cholesterol concentration was monitored. RESULTS: Model biles remained optically clear during the initial 48 h of incubation. Then, biles containing THDC and TUDC, but not those with TC and TCDC, became progressively turbid until, after several days, a white precipitate surrounded the residual stone. Abundant liquid crytalline droplets were observed at polarizing microscopy in biles containing TUDC and THDC. Gallstone dissolution was closely related to cholesterol solubilization and decreased in the order TCDC > THDC > or = TC > TUDC, being highest at pH 8. At the physiologic pH of 7 THDC was more litholythic than TC. CONCLUSIONS: In vitro, the litholytic potency of bile salts on cholesterol gallstones primarily depends on their hydrophobicity. THDC is a new potential gallstone-dissolving agent, deserving in vivo studies.

Cholagogues and Choleretics↗
PubMed1995

N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: effects of acute feeding in the rat.

The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Recombinant interferon-alpha and ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up.

OBJECTIVES: The purpose of this study was to compare, within a randomized controlled trial, the efficacy of recombinant interferon-alpha in combination with ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic HCV hepatitis. METHODS: Forty anti-HCV positive chronic hepatitis patients with ALT levels persistently greater than 3 times the upper normal level were randomized to receive either interferon-alpha (6 million units three times/wk for 6 months) plus ursodeoxycholic acid (10 mg/kg/day for 9 months) (n = 20) or interferon-alpha (6 million units three times/wk for 6 months) alone (n = 20). Disease activity was monitored monthly by ALT measurement until 18 months after interferon-alpha cessation. Serum HCV-RNA was measured at baseline and after 6, 9, and 24 months. Liver biopsies (basal and at the 9th month) were evaluated blindly and scored by Knodell's criteria. RESULTS: The probability of full or partial response during interferon-alpha treatment was similar in the two groups. The probability of biochemical relapse (i.e, any persistent return of ALT above normal) after 18-month of posttreatment follow-up was 75% in both the combination and the monotherapy group. Relapse, however, occurred significantly later in the combination than in the monotherapy group (6.6 +/- 5.4 [SD] months and 1.8 +/- 1.6 months after IFN-alpha cessation, respectively, p < 0.02). Severe biochemical relapse (i.e., a persistent ALT elevation greater than 3 times normal) occurred more frequently and earlier (p = 0.05) in patients treated with interferon-alpha (58.3%) than in those receiving the combination therapy (27.3%). The cumulative duration of normalized ALT periods during and after treatment was significantly greater (p = 0.005, chi 2) in patients treated with IFN-alpha + UDCA than with monotherapy (189/354 months vs 136/323 months. Lobular necrosis improved in both groups (p = 0.056 and p = 0.001, respectively), whereas portal inflammation improved (p = 0.009) only in the combination therapy group. Among the 30 patients who were viremic at entry, plasma HCV-RNA was no longer detectable after 6 months in four from the combination group and in five from the monotherapy group, yet all patients but one returned HCV-RNA positive 3 months after interferon-alpha cessation and were still viremic after 18 months. Cox's multiple regression identified the histological degree of posttreatment portal inflammation as the sole positive indicator of relapse. CONCLUSIONS: The combination of interferon-alpha and ursodeoxycholic acid prolongs the efficacy of interferon-alpha alone in chronic hepatitic C by delaying the probability of biochemical relapse and/or by reducing its severity, without affecting HCV viremia.

Adult↗
PubMed1994

Development and validation of a quantitative assay for cholesterol crystal growth in human gallbladder bile.

Crystal observation time is a rough estimate of the first microscopic appearance of cholesterol monohydrate crystals in an isotropic bile, and does not provide information on crystal growth kinetics. We have developed a method for quantitating cholesterol crystal growth in gallbladder bile. Crystals were separated from other biliary particles by ultracentrifugation on a discontinuous NaBr gradient, after bile density adjustment to d = 1.060 g/ml. More than 95% of crystals, both of native or synthetic source, floated in the density range 1.045-1.055. This density fraction was collected and crystal mass was measured by photometric turbidity, after calibration with suspensions of different-sized cholesterol crystals. The recovery of crystals added to original bile samples averaged 96.0 +/- 2.8%. Contamination with vesicles, which may potentially interfere with the turbidimetric assay, was excluded by gel-chromatography. The method was sequentially applied, until the 20th day of incubation, to biles obtained at surgery from patients with (A, n = 6) or without cholesterol gallstone (B, n = 4), and from gallstone patients pretreated for 1 week with oral ursodeoxycholic acid (C, n = 5). Crystal growth curves greatly differed, being much steeper in group A and almost flat in patients receiving ursodeoxycholic acid. The mean percent mass of biliary cholesterol in crystalline form at the 20th day was 19.2 +/- 13.5%, 1.2 +/- 0.8% and 2.7 +/- 1.1% in A, B and C, respectively (A vs. B: P = 0.014; A vs. C: P = 0.008). We conclude that the method allows a precise estimate of cholesterol crystal growth and can be usefully applied to human gallbladder biles.

Bile↗
PubMed1994

Effect of taurohyodeoxycholic acid, a hydrophilic bile salt, on bile salt and biliary lipid secretion in the rat.

Taurohyodeoxycholic acid is a natural 6 alpha-hydroxylated bile acid with an apparent hydrophilicity intermediate between those of tauroursodeoxycholic and taurocholic acids. We investigated in the rat the hepatobiliary metabolism, choleretic properties, and biliary maximum secretory rate (SRmax) of taurohyodeoxycholic in comparison with these two bile salts. Each compound was infused intravenously, at a rate increased in a stepwise manner from 100 to 300 nmol/min/100 g body wt, in bile salt-depleted bile fistula rats. The three bile salts appeared rapidly starting with the infusion and increased to represent more than 95% of the total bile salts. No apparent biliary metabolites were formed. All the bile salts caused a dose-dependent increase in bile flow and biliary lipid output. The absolute increase in bile flow was lower in rats infused with taurohyodeoxycholic acid, yet the volume of bile formed per nanomole of secreted bile salt was 13.8 nl for taurohyodeoxycholic, 6.4 nl for tauroursodeoxycholic acid, and 10.9 nl for taurocholic. The SRmax values were 1080, 3240, and 960 nmol/min/100 g, respectively. At all infusion rates, taurohyodeoxycholic acid caused a greater (P < 0.001) secretion of biliary lecithin compared to the other bile salts. There were no significant differences in the biliary secretion of cholesterol and proteins. Electron microscopy showed the recruitment of vesicles and lamellar bodies around and within bile canaliculi. In conclusion, taurohyodeoxycholic promotes a biliary lecithin secretion greater than expected from physicochemical predictions, representing a novel secretory property with potential pharmacological relevance.

Animals↗
PubMed1994

Taurine-induced diuresis and natriuresis in cirrhotic patients with ascites.

Taurine is a non-protein sulfur amino acid widely distributed in mammalian tissues, with poorly understood functions. Taurine administration has a variety of hemodynamic effects, including improvement of cardiac function and suppression of sympathetic activity. Increased urinary volume and sodium excretion have been reported in taurine-fed hamsters. Since patients with ascitic liver cirrhosis have severe hemodynamic and renal abnormalities potentially sensitive to taurine feeding, we evaluated the effects of the i.v. infusion of taurine on urinary flow and sodium excretion and on the hormones involved in the control of hydrosaline homeostasis. Eight cirrhotic patients with tense ascites were given an i.v. bolus of taurine (16 mumoles in 40 ml of saline). The next day patients were given saline only, as a control. Diuresis, urinary sodium and plasma renin activity, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured for the following 6 hrs. Plasma taurine increased ten fold after infusion, then decreased exponentially. No side effects were recorded. After taurine, but not after saline, there was a prompt and significant increase in both urinary volume and sodium excretion. Diuresis increased from 340 +/- 43 to 817 +/- 116 microliters/min (p < 0.01); urinary sodium from 13.8 +/- 3 to 26.3 +/- 4 mumoles/min (p < 0.05). Both values returned to normal after 2-3 hrs. Taurine infusion caused a concomitant significant decrease in plasma renin activity (from 7.7 +/- 2.2 to 4.3 +/- 1.9 ng/ml/hr, p < 0.05) and aldosterone (from 588 +/- 47 to 348 +/- 89 pg/ml, p < 0.05), but no changes in atrial natriuretic peptide and arginine vasopressin. We conclude that i.v. taurine infusion in ascitic cirrhosis promotes a transient diuresis and natriuresis, apparently through the inhibition of the renin-aldosterone axis.

Adult↗
PubMed1994

Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.

Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating.

Absorption↗
PubMed1994

Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis.

We investigated whether the oral administration of SAMe influences the hepatic availability of sulphur amino acids and the extent of bile salt amidation with taurine in liver cirrhosis. Ten patients with cirrhosis (eight Child-Pugh A and 2 B, aged 48-65 years), were studied before and 2 months after oral SAMe administration (800 mg per day). Bile was obtained using a string-test device (Entero-test), after gall-bladder contraction with caerulein. No significant changes were found in the per cent composition of biliary amino acids, except for an increase in glutamic acid (from 3.7 +/- 0.6% before to 6.1 +/- 1.1% after SAMe, p = 0.003) and taurine from 2.2 +/- 2.3% (range 0.4-6.8) to 7.2 +/- 9.2% (range 0.5-28.1), (NS). HPLC analysis showed a trend towards increased per cent tauroconjugation of all individual bile salts, with a significant rise in taurochenodeoxycholic acid (from 15.0 +/- 9.4% to 25.3 +/- 9.7%, p = 0.05) and a drop in glycocholic acid (from 39.1 +/- 15.3% to 25.3 +/- 9.8%, p = 0.05). These data suggest that in the cirrhotic liver exogenous SAMe is partially metabolized to taurine, which is used for bile salt amidation.

Administration, Oral↗