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Biomedical subjects

E Roda

Publications and source records attributed to E Roda.

At least 91 records · Page 5Linked to original sources
PubMed1992

Pathophysiology and pharmacotherapy of cholelithiasis.

Several factors are involved in the development of gallstone formation: formation of supersaturated bile; nucleation; formation, retention and adhesion of cholesterol crystals and eventually stone growth. The dynamics of the gallbladder may play a key role in the overall process. The pathophysiologic theory of cholesterol gallstone formation and the knowledge of their physico-chemical properties support the modern concept of gallstone therapy. Chenodeoxycholic and ursodeoxycholic have been widely used as cholesterol gallstone dissolving agents and evaluated in terms of efficacy and safety.

Bile Acids and Salts↗
PubMed1992

Hepatic uptake and biliary secretion of bile acids in the perfused rat liver.

Hepatic uptake and biliary secretion have been evaluated in the isolated perfused rat liver for cholic, chenodeoxycholic, ursodeoxycholic acid, both free and taurine-conjugated; the physicochemical properties of the bile acids have also been calculated and related to these experimental parameters. Cholic acid disappearance rate from the perfusate was the fastest, followed by that of ursodeoxycholic and chenodeoxycholic; it was also faster for taurine-conjugated bile acids than for their respective unconjugated forms. The recovery in bile was higher for conjugated than for unconjugated bile acids, and among each class, was higher for cholic than for chenodeoxycholic and ursodeoxycholic. The hepatic uptake correlated negatively (r = -0.99) with the bile acid lipophilicity, while the biliary secretion correlated with the solubility of the molecules. These results show the effect of the physicochemical properties of BA on their hepatic handling, at the physiological concentration of BA in the portal blood.

Animals↗
PubMed1992

[Effects of therapy with bis-hemisuccinate of ursodeoxycholic acid bisodium salt in patients with chronic hepatitis].

It has recently been shown that ursodeoxycholic acid administration improves liver function tests in patients with chronic liver diseases. Aim of the present study was to evaluate an ursodeoxycholic acid derivative (bis-hemisuccinate bisodic salt Ursodamor, Farmaceutici Damor, Napoli) in patients with chronic hepatitis. Forty patients (15 M, 25 F) with biopsy proven chronic liver disease participated to the study. Patients were randomly allocated to two treatment groups. Twenty patients (4 PBC, 11 CAH/CPH, 5 cirrhosis) received the ursodeoxycholic acid derivate at the dose of 600 mg/day, while 20 patients (1 PBC, 11 CAH/CPH, 8 cirrhosis) received a placebo. For both groups the treatment period was six months. ALT serum levels were significantly reduced in the treated group (from 84 +/- 14 to 62 +/- 14 p less than 0.0005) while no significant change was observed in the placebo group. In the treated group but not in the placebo group alkaline phosphatases and gamma-GT were also significantly reduced (from 268 +/- 56 to 160 +/- 23 p less than 0.0005 and from 79 +/- 21 to 45 +/- 10 p less than 0.0005). In conclusion, our results suggest that the administration of the ursodeoxycholic acid derivate, bis-hemisuccinate, bisodic salt, improves liver function tests in patients with chronic liver hepatitis. Similarly to ursodeoxycholic acid this new derivate probably interferes with bile acid pool composition by replacing the more detergent and probably more toxic endogenous bile acid.

Alkaline Phosphatase↗
PubMed1991

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↗
PubMed1991

Bile and biliary lipid secretion in rats with hexachlorobenzene-induced porphyria. Effect of S-adenosyl-L-methionine administration.

We investigated liver morphology and biliary function in vivo in rats made porphyric by hexachlorobenzene (HCB). In one group of HCB rats we also evaluated whether S-adenosyl-L-methionine (SAMe), administered during the last 15 days of HCB treatment, attenuated liver injury and the accumulation of porphyrins (HCB + SAMe group). In HCB rats we found: (a) a 100% increase in liver weight; (b) a 500-fold increase in total liver porphyrins (TLP); (c) significantly increased serum bilirubin and cholesterol levels; (d) unchanged total bile flow (TBF) but enhanced levels of the bile acid independent fraction (BAIF); and (e) decreased excretion in bile of bile acids (BA), phospholipids (PL) and cholesterol (CHO) (58, 65 and 47%, respectively, expressed as mmol/min per kg liver). SAMe was found to partially reverse HCB-related effects. TLP levels were about 65% lower in HCB + SAMe treated rats than in HCB rats. However, while SAMe restored bile CHO excretion to control values, it did not influence bile excretion of BA, PL, or BAIF. In conclusion, HCB-induced porphyria was characterized by a complex derangement of liver morphology and biliary function that was unrelated to the extent of porphyrin accumulation in the liver.

Animals↗
PubMed1990

In vivo kinetics of radiolucent gallstone dissolution by oral dihydroxy bile acids.

The rate of decrease of gallstone diameter appeared to be linear with oral bile acid treatment time, as estimated by inspection of graphic data of individual patient serial oral cholecystograms. A theoretical basis for this model was derived. The hypothesis of diameter decrease proportional to treatment time was tested with data from 223 patients with radiolucent gallbladder stones up to 20 mm in diameter treated with 7-8 or 14-15 mg.kg-1.day-1 of either ursodiol or chenodiol for 1 year, followed up after 3, 6, and 12 months of treatment. Linearity of individual sets of data points was tested by mathematical and statistical methods, including polynomial curve fitting, linear regression analysis, quadratic vs. linear analyses of covariance, and prediction of 12-month stone size by linear extrapolation from diameters at 0 and 6 months. Most patients (greater than 70%) had rates of gallstone diameter decrease that were almost linear with treatment time, independently of different dissolution rates on a given regimen. Additional treatment time needed may be estimated from cholecystograms or ultrasonograms performed before treatment and after several months.

Chenodeoxycholic Acid↗
PubMed1990

Evaluation of the ileal absorption capacity for bile acids in the rabbit.

The intestinal absorption of bile acids has so far been studied from the measurement of the biliary secretion after their intestinal infusion. In the present investigation, the ileal absorption capacity for two different bile acids has been evaluated by means of an intestinal perfusion technique and the simultaneous blood drainage from the mesenteric vein corresponding to the isolated loop. Taurocholic acid and unconjugated cholic acid were infused at different concentrations (0.5-10.0 mM), at a flow rate of 4 ml/min/cm intest. Taurocholic acid absorption increased to a maximum with dose, then reaching a plateau, suggesting that a saturable process had taken place. Cholic acid uptake showed a saturable, possibly active, process, together with a nonsaturable one. These results are consistent with the physicochemical properties of the two bile acids. The technique seems so far suitable for the study of the intestinal absorption of substances undergoing the enterohepatic circulation, since it provides a direct measure of the absorbed fraction, without any distortion arising from the hepatic uptake and biliary secretion.

Animals↗
PubMed1990

Effect of gemfibrozil administration on biliary lipid secretion in hyperlipidemic patients. A crossover study with clofibrate.

Gemfibrozil, like clofibrate, is effective in lowering both serum cholesterol and triglycerides and in increasing high-density lipoproteins. The information available about its effects on biliary lipids is still limited, and conflicting results have been reported. In this study we evaluated the effect of gemfibrozil (1.2 g/day) and clofibrate (2.0 g/day), in a single-blind crossover design for 6 weeks with a 4-week washout period, on the biliary cholesterol saturation index (SI) in stimulated hepatic bile and on the hepatic secretion rate of biliary lipids in patients with hyperlipidemia. Clofibrate increased cholesterol SI (from 1.70 +/- 0.14 to 2.05 +/- 0.24), whereas gemfibrozil decreased it (from 1.70 +/- 0.14 to 1.54 +/- 0.16). The results were not statistically significant. The hepatic secretion rate of cholesterol was significantly (p less than 0.04) increased by clofibrate therapy, whereas it was significantly (p less than 0.04) decreased after gemfibrozil; a significant (p less than 0.04) decrease in the hepatic secretion rate of bile acids, bile acid pool size, and bile acid fecal excretion (p less than 0.04) was also found after gemfibrozil administration. Gemfibrozil interferes extensively with bile acid metabolism, but it does not increase biliary cholesterol secretion, as clofibrate does. These results suggest that gemfibrozil does not seem to increase the risk of gallstone formation in patients with hyperlipidemia.

Adult↗
PubMed1989

Uptake of bile acids by perfused rat liver: evidence of a structure-activity relationship.

The hepatic extraction of unconjugated and taurine-conjugated bile acids, provided with different hydrophilicity values, has been measured in the perfused rat liver, in order to evaluate the role of the bile acid structure and bile acid hydrophilicity on their uptake by the liver. Ursocholic, cholic, ursodeoxycholic and chenodeoxycholic acids, free and taurine-conjugated, were injected into the portal vein in dose response studies, using a nonrecirculating perfusion system. For all of the bile acids, the uptake process showed saturation. In addition, a nonsaturable component was apparent in bile acids provided with the lowest hydrophilicity values, as expressed by the lowest values of the water to octanol partition coefficient. The maximum uptake velocity increased with increasing values of the partition coefficient, which in turn were associated with 7-OH alpha to beta epimerization, the presence of 12-OH in alpha position and taurine conjugation. The ratio of maximum uptake velocity to Km (Km being the half-saturation constant) appeared to be markedly increased by taurine conjugation and by 7-OH alpha to beta epimerization, whereas it was reduced by the presence of 12-OH in alpha position.

Animals↗
PubMed1989

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↗
PubMed1989

Gallstone recurrence after successful oral bile acid treatment. A 12-year follow-up study and evaluation of long-term postdissolution treatment.

Recurrence is a major problem in the medical treatment of gallstones but its extent is still uncertain. The aim of this study was to determine the magnitude of this event and to assess the effectiveness of a postdissolution treatment in preventing it. We evaluated the long-term recurrence rate after 96 confirmed dissolutions observed in 86 subjects (71 women, 15 men) over a 12-yr follow-up period. A low-dose postdissolution treatment (ursodeoxycholic acid, 300 mg/day) was administered to 36 subjects, whereas in the remaining 60 cases no postdissolution treatment was given. By actuarial life-table analysis, the cumulative proportion of gallstone recurrence was 12.5% at the first year, rising to 61% at the 11th year. Postdissolution treatment was effective in reducing the frequency of gallstone recurrence (p = 0.0067), but this was mainly related to its effect on younger subjects (less than or equal to 50 yr old). In older subjects the recurrence rate was unaffected by treatment. The probability of gallstone recurrence was significantly higher in subjects with multiple stones before dissolution treatment than in those who had had solitary stones (p = 0.0091). No other factor predictive of gallstone recurrence could be identified.

Actuarial Analysis↗
PubMed1988

Human lymphoblastoid interferon for the treatment of chronic hepatitis B. A randomized controlled trial.

The aim of this study was to demonstrate whether interferon alone could affect the course of chronic hepatitis B. A total of 66 patients have so far been randomly assigned to receive six months of interferon therapy or no therapy; three patients in the interferon group and two in the control group have withdrawn from the study. Loss of hepatitis B virus-DNA and hepatitis B e antigen was significantly higher in the patients receiving interferon than in the control group; a significant loss of hepatitis B surface antigen was observed only in patients who received interferon. The time to alanine aminotransferase normalization was significantly shorter in patients receiving interferon than in the control group. These data encourage the use of interferon in treatment of chronic hepatitis B.

Adult↗
PubMed1988

Quantitative relationship between bile acid structure and biliary lipid secretion in rats.

A series of unconjugated and taurine conjugated bile acids (BAs) differing in water solubility (SWo), critical micellar concentration (CMC), and hydrophilicity (K') were infused iv to rats at a tracer dose and a dose of 6 mumol/min/kg over a 1-h period. Bile was collected for 3 h to evaluate the role of BA structure on cholesterol, phospholipids secretions, and bile flow. The BAs studied differ in the number (2-3), position (-3, -6, -7, -12), and orientation of the hydroxyls (alpha/beta); the side chain structure was modified by shortening (C-23, nor-BA) and by lengthening (C-25, homo-BA), while maintaining the same structure of nuclear hydroxyls (3 alpha 7 beta). At a "tracer" dose, all C-24 natural BAs are efficiently recovered in bile when administered in both unconjugated and taurine conjugated forms. At a "high dose", all taurine conjugated BAs are efficiently recovered in bile (80-100%). However, a variable recovery was observed among unconjugated BAs: trihydroxy BAs are efficiently recovered (85-100%), while dihydroxy BAs are only partially recovered (25-40%). The side chain-modified BAs [i.e., C-23 nor and C-25 homo analogs of ursodeoxycholic acid (UDCA)] are partially recovered at a tracer dose (20-30%), but less at a high dose (10-20%) when administered in the unconjugated form. In contrast, the corresponding taurine conjugates are more efficiently recovered in bile (60-80%). Conjugation with taurine increases total recovery of unconjugated BAs in bile by not more than 30-40%. Highly hydrophilic and water-soluble BAs, such as ursocholic acid (SWo = 1.67 mM) and cholic acid (SWo = 0.27 mM), can also be secreted as unconjugates, and this accounts for their complete recovery. The conjugation step is rate limiting for poorly soluble BAs such as ursodeoxycholic acid (SWo = 0.009 mM) when administered at a high dose, and critical for nor and homo analogs which are poorly soluble and whose side chain modification partially suppresses their conjugation with taurine or glycine and thereby induces alternative pathways such as glucuronidation or sulfation. The induced bile flow is directly related to the hydrophilicity of the natural C-24 bile acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Treatment of chronic hepatitis B with human lymphoblastoid interferon: results of a controlled trial.

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon (Wellferon) in the treatment of chronic hepatitis B virus (HBV) infection. To date 70 patients have entered the study, 33 randomized to receive interferon at doses of 5 MU/m2 i.m. daily for the first 4 weeks and three times weekly for 5 months thereafter and 31 acted as controls. Seventy-nine per cent of the treated group permanently cleared HBV DNA compared with 48% of the control group (p = 0.01): 69% of the treated patients and 38% of the controls who eliminated HBV DNA cleared HBeAg, HBeAb (p = 0.02). Twenty-four per cent of the treated patients and 3% (p = 0.01) of the control group had clearance of HBsAg and seroconversion to HBsAb. From these results it was concluded that interferon had a therapeutic effect on Italian heterosexual patients with chronic hepatitis B viral replication.

Clinical Trials as Topic↗
PubMed1987

Effect of albumin on taurocholate uptake kinetics in rat liver.

Isolated rat livers were perfused in a single pass with increasing doses of taurocholate with and without albumin in the perfusion media. The kinetics of taurocholate uptake were thus evaluated. In all the experiments, taurocholate uptake showed Michaelis-Menten kinetics. Increasing the albumin concentration in the medium resulted in an increase in the Km, without effect on the Vmax.. When taurocholate and albumin were kept constant (20:1 molar ratio), the Vmax. was significantly lower than in the other experiments. These data suggest that taurocholate uptake shows saturation in the absence of albumin and that albumin reduces taurocholate uptake.

Animals↗