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Biomedical subjects

R Tritapepe

Publications and source records attributed to R Tritapepe.

At least 55 records · Page 3Linked to original sources

Double-blind placebo-controlled clinical trial of microporous cholestyramine in the treatment of intra- and extra-hepatic cholestasis: relationship between itching and serum bile acids.

In order to investigate the effectiveness of microporous cholestyramine in the pharmacological management of intra- and extrahepatic cholestasis, a double-blind placebo-controlled study was carried out in 10 patients. Microporous cholestyramine or placebo 3 g t.i.d. were given orally over a four-week period. The active drug resulted statistically superior to the placebo in reducing itching intensity (p less than 0.01) and serum bile acids (p less than 0.01). A positive linear relationship between itching and serum bile acids (p less than 0.01) was also demonstrated.

Adult↗

The treatment of retained biliary stones with monooctanoin: report of 16 patients.

The aim of this study was to estimate efficacy, safety, and tolerance of monooctanoin in 16 patients with retained radiolucent biliary stones and indwelling biliary drainage. Monooctanoin was infused continuously at a rate of 3-4 ml/h. Monitoring of pressure with a manometer broken off at 20 cm prevented the development of excessive pressure in the common bile duct. The mean volume of the compound instilled (+/- SD) was 848 +/- 393 ml (range 80-1450) and the mean duration of treatment was 13 +/- 6 days (range 2-23). Monooctanoin induced disappearance of stones in 11 of 16 patients giving a success rate of 69%. Three patients exhibited a partial dissolution of stones which were then successfully removed through the postoperative T-tube. The two failures can be attributed to the type of stones mainly composed of bile pigments. Side effects from the infusion of monooctanoin were only minor and easily controlled by reducing the infusion rate of the solution. Laboratory tests, including hepatic and pancreatic enzymes, remained stable. In one subject endoscopic and histological evidence of mild duodenitis was found when pre- and posttreatment features were compared. On the basis of these data, we recommend monooctanoin to treat biliary-retained cholesterol stones.

Adult↗

Effect of cicloxilic acid on bile flow and biliary lipid secretion in humans.

Previous investigations have shown that cicloxilic acid, a hydrocholeretic drug, lowers bile cholesterol saturation without interfering with the intestinal absorption of cholesterol as well as with the hepatic synthesis of both cholesterol and bile acids. The mechanism whereby cicloxilic acid antagonizes lithogenic bile secretion is still unknown. However, most evidence favors the view of a relationship between choleretic and antilithogenic effects of the drug. To test this hypothesis the effects of a single oral dose (240 mg) of cicloxilic acid on bile flow and biliary lipid excretion rates have been examined in four nonobese cholecystectomized patients with balloon-occludable, reinfusion T-tubes. The results indicate that cicloxilic acid exerts a marked choleretic effect combined with a reduced output of bile cholesterol and an increase in bile acid excretion. Bile cholesterol saturation significantly decreases 90 min after cicloxilic acid in respect to control value. These data provide evidence of a link between choleretic and antilithogenic effects of cicloxilic acid and suggest its usefulness in the treatment of bile cholesterol supersaturation.

Adult↗

Bile secretion and liver microsomal mixed function oxidase system in mice with griseofulvin-induced hepatic protoporphyria.

Administration of 2.5% griseofulvin in the diet to male CD1 mice produced protoporphyria and cholestasis. Protoporphyria became evident as early as after 10 days of treatment, whereas cholestasis, expressed in terms of total bile flow reduction, developed only after 45 days of griseofulvin. Bile flow impairment was due both to the length of treatment and to the severity of liver protoporphyria. Griseofulvin administration was also associated with a significant modification of the relative amounts of hepatic microsomal cytochromes P-450 and b5, a loss in concentration/mg of protein of cytochrome P-450 and a concomitant increase of b5. Despite these changes, the activity of aniline hydroxylase expressed per mg of microsomal protein, assessed in vitro, was not modified.

Aniline Hydroxylase↗

3-Hydroxy-3-methylglutaric acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster.

3-Hydroxy-3-methylglutaric acid (HMGA) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) and strongly reduces cholesterol biosynthesis both in vitro and in vivo. Since the effects of this compound on biliary lipid composition are hitherto unknown, we have investigated whether it prevents dietary cholesterol induction of saturated bile in the hamster. Female Golden Syrian hamsters have been divided into four groups and treated for 10 weeks as follows: I) Standard diet, containing 0.8 mg cholesterol/g food; II) Standard diet plus HMGA (100 mg/kg b.w./day per os); III) Lithogenic diet containing 2.4 mg cholesterol/g food; IV) Lithogenic diet plus HMGA as above. The results indicate that HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia. Inhibition of hepatic cholesterogenesis at the level of mevalonate synthesis by HMGCoAR and reduction of intestinal cholesterol absorption may be responsible for these effects.

Animals↗

Effect of ethanol on biliary unconjugated bilirubin and its implication in pigment gallstone pathogenesis in humans.

Though some epidemiological investigations support the association between pigment gallstone formation and chronic alcoholism with cirrhosis, little attention has been paid to the influence of alcohol itself on biliary bilirubin secretion, so that the pathogenesis of pigment cholelithiasis in alcoholics is hitherto unknown. On different days we intravenously administered ethanol (0.7 g/kg body weight), diluted with 500 ml of saline, or saline alone to 6 non-obese patients with an indwelling T tube and reestablished enterohepatic bile circulation. At the time of the investigation bile cultures were negative for aerobic and anaerobic bacteria. Ethanol significantly increased biliary unconjugated bilirubin in respect to control values. The phenomenon reached a maximum 2 h after alcohol infusion when the value of unconjugated bilirubin averaged 2.37 +/- 0.30% of total bilirubin in contrast to 0.65 +/- 0.14% in control conditions (p less than 0.01), and subsided 6 h after the end of ethanol infusion. Since increased amounts of biliary unconjugated bilirubin predispose to pigment stone formation, it can be speculated that alcohol contributes to pigment cholelithiasis pathogenesis by enhancing the biliary concentrations of this form of pigment.

Adult↗

S-adenosyl-L-methionine antagonizes ethynylestradiol-induced bile cholesterol supersaturation in humans without modifying the estrogen plasma kinetics.

Previous investigations have shown that S-adenosyl-L-methionine antagonizes both cholestasis and bile lipid alterations induced by ethynylestradiol in the rat. Since it is still unknown whether S-adenosyl-L-methionine prevents ethynylestradiol-induced cholesterol supersaturation of bile in humans also and how methynation interferes with plasma ethynylestradiol disappearance, the present study has been carried out. On different days, 5 nonobese subjects with indwelling biliary drainage and reestablished enterohepatic bile circulation received 200 micrograms of intravenous ethynylestradiol or ethynylestradiol plus 200 mg of S-adenosyl-L-methionine intramuscularly. S-adenosyl-L-methionine administration prevented any ethynylestradiol-induced changes in hepatic bile saturation index. Moreover, S-adenosyl-L-methionine did not affect ethylnylestradiol pharmacokinetics which was evaluated in a group of 6 nonobese women receiving 100 micrograms of intravenous ethynylestradiol or ethynylestradiol plus 100 mg of S-adenosyl-L-methionine intramuscularly. These findings indicate that S-adenosyl-L-methionine prevents ethynylestradiol-induced bile lipid changes without interfering with ethynylestradiol kinetics in humans.

Adult↗

Effect of a concomitant treatment with ethynylestradiol and ascorbic acid on bile secretion in female hamsters.

The administration of large doses (5 mg/kg b.wt./day) of ethynylestradiol to adult female hamsters did not induce cholestasis or modifications of bile lipid composition. These findings are in contrast with the data of other authors who in different experimental conditions described the sensitivity of hamsters to the estrogen-induced hepatobiliary toxicity. Ascorbic acid alone or added to ethynylestradiol did not impair bile secretion. However, it significantly increased the plasma levels of radioactivity tested 24 hours after the oral administration of a tracer dose of radiolabelled ethynylestradiol. These results confirm previous data showing in humans the capability of ascorbic acid to favour the rise of plasma concentrations of ethynylestradiol.

Animals↗

Acute ethanol administration increases biliary concentrations of total and unconjugated bilirubin in rabbits.

Epidemiological investigations have revealed that alcoholic cirrhosis is associated with a high frequency of pigment gallstones, but only scanty information is available on the effects of ethanol on biliary secretion of bilirubin. We have injected intravenously 1.0 and 1.5 g/kg body wt of ethanol into six cholecystectomized rabbits and a common bile duct fistula. Experiments were performed ten days after surgery and a stream-splitting apparatus was interposed in the circuit in order to withdraw continuously biliary samples without interruption of enterohepatic bile circulation. Analysis of hourly data showed that both ethanol doses significantly increase the biliary concentration of total bilirubin, without affecting bile flow and lipid composition. Alcohol also promoted the efflux of unconjugated bilirubin into bile. The maximum effect occurred within the first 5 hr following alcohol administration. Thereafter the bile returned to normal. Since excessive concentrations of biliary unconjugated bilirubin favor pigment gallstone development, it can be speculated that alcohol acts as a risk factor for pigment lithiasis by enhancing the biliary levels of this form of pigment.

Animals↗

Spontaneous reversal of ethinyl estradiol-induced cholestasis in the rat.

The spontaneous reversal ethinyl estradiol-induced cholestasis has been documented 7 days after the last estrogen administration in the rat. This finding supports the hypothesis that estrogens produce only a transient functional failure of the hepatocytic structures responsible for bile secretion.

Animals↗

Infusional therapy for post-surgical biliary stones.

A variety of effective non-surgical forms are used for dealing with retained and recurrent biliary stones. These are endoscopic papillotomy, infusional therapy, intraductal laser or electrohydraulic lithotripsy and extracorporeal shock waves. Saline washout or chemical stone dissolution is currently used in high-risk subjects or in cases in which endoscopic papillotomy fails. For many years now drugs that should dissolve stones topically have been tested by direct infusion into the biliary tract. This approach has given better results over the last ten years with the adoption of Monooctanoin (Mo) and more recently Methyl tertbutyl ether (MTBE). Both preparations have their pros and cons, which are weighed.

Caprylates↗

[Pros and cons of chemical litholysis in bile duct calculi].

Chemical litholysis of biliary stones is currently performed using monooctanoin (Mo) and methyl tert-butyl ether (MTBE). These two solvents dissolve cholesterol gallstones at different speeds due to their viscosity, high for Mo (47 cps) and low for MTBE (0.2 cps). A third compound was recently used which was produced by combining the previous two agents, Mo and MTBE, at a ratio of 2:1 v/v. The mixture has an intermediate viscosity (2.8 cps) and has shown good tolerability, management and efficacy with a 90% success rate in the treatment of post-surgical gallstones in 28 patients.

Adult↗