J C Montet

Université de Nice - Sophia Antipolis, Valbonne, Provence-Alpes-Cote d'Azur, France

Are you J C Montet?

Claim your profile

Publications (51)111.9 Total impact

  • Article: Role of fibrates and HMG-CoA reductase inhibitors in gallstone formation: epidemiological study in an unselected population.
    [show abstract] [hide abstract]
    ABSTRACT: Fibrate derivatives and HMG-CoA reductase inhibitors modify homeostasis of cholesterol. The aim of this study was to assess in an unselected population whether these hypolipidemic drugs are risk factors for cholelithiasis or, conversely, are protective agents. Both sexes, all socioeconomic categories, pregnant women, and cholecystectomized subjects were included. Clinical data collection and gallbladder ultrasonography were both carried out in a double-blind fashion. Fibrate derivatives were predominantly fenofibrate, HMG-CoA reductase inhibitors were simvastatin and pravastatin. On univariate analysis, age (>50 years), sex, and use of fibrates were found to be significantly related to the presence of cholelithiasis. Age, sex, and fibrate treatment remained independently correlated with the presence of gallstones on multivariate analysis. With fibrates, the relative risk for lithiasis was 1.7 (P = 0.04). The HMG-CoA reductase inhibitors were not associated with a protective effect on univariate analysis. Of the lipid-lowering drugs, only fibrate derivatives were found to increase the risk of gallstone formation.
    Digestive Diseases and Sciences 03/2001; 46(3):540-4. · 2.12 Impact Factor
  • Article: Effect of endoscopic sphincterotomy on bile lithogenicity in patients with gallbladder in situ.
    [show abstract] [hide abstract]
    ABSTRACT: Endoscopic sphincterotomy results in a continuous flow of bile into the duodenum and consequently leads to an increase in the frequency of enterohepatic bile acid cycling. Because bile acids are the driving force of biliary secretion, sphincterotomy may affect bile genesis. The present study was undertaken to determine the influence of endoscopic sphincterotomy on bile composition. The cholesterol saturation index and the bile acid pattern were determined in the gallbladder bile of lithiasis patients with (group III) or without sphincterotomy (group I), and in the hepatic bile of patients with gallbladder in situ who were checked at 3 months after the endoscopic procedure (group II). Stones from each patient were examined for chemical composition and microstructure. All the patients had cholesterol stones. After endoscopic sphincterotomy the molar percentages of cholesterol in the gallbladder bile of group III and in the hepatic bile of group II were significantly lower (-31% and -46% respectively) than in group I. Similarly, the cholesterol saturation index in the hepatic bile (0.79) and the gallbladder bile (0.86) from patients who had undergone sphincterotomy indicated undersaturation whereas bile from group I was oversaturated (1.25). On the other hand, endoscopic sphincterotomy did not modify the hydrophobicity index of the bile acid pool, even though deoxycholate content increased. Endoscopic sphincterotomy causes a marked decrease in the lithogenicity of bile and thus may prevent the risk of recurrence of cholesterol lithiasis.
    Endoscopy 09/1999; 31(6):437-41. · 5.21 Impact Factor
  • Article: CYP2E1 and CYP3A1/2 gene expression is not associated with the ursodeoxycholate effect on ethanol-induced lipoperoxidation.
    [show abstract] [hide abstract]
    ABSTRACT: Ethanol is a well-known hepatotoxicant inducing steatosis and membrane lipoperoxidation. The aim of the present study was to investigate in rats, whether the protective effect of UDC on ethanol-induced lipid peroxidation may be related with CYP2E1 and CYP3A1/2 gene expression. We showed that UDC treatment in ethanol-fed rats induced a significant decrease in liver triglyceride concentration which was closely correlated with a reduction in malondialdehyde and hydroxyalkenal levels. In chronically ethanol-fed rats, CYP2E1 and CYP3A1/2 gene expressions were increased by a post-transcriptional mechanism. These inductions, mainly of CYP2E1, could take part in alcohol-induced hepatic lipoperoxidation. UDC modified neither the specific activity, nor the protein level, nor the mRNA level of CYP2E1 when compared with control. UDC supplementation to alcohol diet did not prevent the increase in CYP2E1 expression of ethanol-fed rats. Furthermore, CYP3A1/2 protein levels were similarly increased by ethanol and ethanol plus UDC treatment. Therefore, UDC protective effect against ethanol-induced lipoperoxidation was not associated with a modification of CYP2E1 and CYP3A1/2 expression.
    Life Sciences 02/1999; 65(11):1103-13. · 2.53 Impact Factor
  • Article: Ursodeoxycholate alleviates alcoholic fatty liver damage in rats.
    [show abstract] [hide abstract]
    ABSTRACT: The hydrophilic bile salt ursodeoxycholate (UDC) improves cholestasis in several liver diseases and is in vitro an efficient membrane stabilizer. However, its action on chronic ethanol-induced liver damage is not established. We thus sought to determine the effect of UDC on chronic ethanol-induced steatosis and on liver plasma membrane fluidity in rats. Male rats were pair-fed liquid diets containing 36% of calories as ethanol (alcohol diet) or an isocaloric maltose-dextrin mixture (control diet). Four groups of 10 animals received, respectively, during 30 days: the control diet, the control diet + UDC (90 mg/kg/day), the alcohol diet, and the alcohol diet + UDC. Bile was collected for assessment of bile flow, biliary lipids, and individual bile salts. Liver lipid contents and lipid peroxidation were determined. Plasma membrane fluidity was assessed by fluorescence polarization of various probes. Alcohol treatment caused a 4-fold increase in liver triacylglycerol and cholesterol ester levels. UDC supplementation significantly reduced these increases by 50% and 40%, respectively. UDC intake was associated with a marked decrease in alcohol-induced lipid peroxidation. Bile flow, bile salt, and phospholipid secretion were slightly increased by alcohol intake. The addition of UDC-enriched bile with tauroursodeoxycholate (38%) without significantly affecting the biliary parameters. Lastly, UDC treatment almost totally prevented the 20% increase in liver plasma membrane fluidity due to chronic alcohol intake. This study shows that UDC intake, concomitant with alcohol diet, exerts a clear-cut membrane protective effect that might alleviate ethanol-induced lipid disorders.
    Alcoholism Clinical and Experimental Research 11/1998; 22(7):1538-43. · 3.34 Impact Factor
  • Article: Ursodeoxycholate Alleviates Alcoholic Fatty Liver Damage in Rats
    [show abstract] [hide abstract]
    ABSTRACT: The hydrophilic bile salt ursodeoxycholate (UDC) improves cholesta-sis in several liver diseases and is in vitro an efficient membrane stabilizer. However, its action on chronic ethanol-induced liver damage is not established. We thus sought to determine the effect of UDC on chronic ethanol-induced steatosis and on liver plasma membrane fluidity in rats. Male rats were pair-fed liquid diets containing 36% of calories as ethanol (alcohol diet) or an isocaloric maltose-dextrin mixture (control diet). Four groups of 10 animals received, respectively, during 30 days: the control diet, the control diet + UDC (90 mg/kg/day), the alcohol diet, and the alcohol diet + UDC. Bile was collected for assessment of bile flow, biliary lipids, and individual bile salts. Liver lipid contents and lipid peroxidation were determined. Plasma membrane fluidity was assessed by fluorescence polarization of various probes. Alcohol treatment caused a 4-fold increase in liver triacylglycerol and cholesterol ester levels. UDC supplementation significantly reduced these increases by 50% and 40%, respectively. UDC intake was associated with a marked decrease in alcohol-induced lipid peroxidation. Bile flow, bile salt, and phosphor-lipid secretion were slightly increased by alcohol intake. The addition of UDC-enriched bile with tauroursodeoxycholate (38%) without significantly affecting the biliary parameters. Lastly, UDC treatment almost totally prevented the 20% increase in liver plasma membrane fluidity due to chronic alcohol intake. This study shows that UDC intake, concomitant with alcohol diet, exerts a clear-cut membrane protective effect that might alleviate ethanol-induced lipid disorders.
    Alcoholism Clinical and Experimental Research 09/1998; 22(7):1538 - 1543. · 3.34 Impact Factor
  • Article: Ursodeoxycholate protects against ethanol-induced liver mitochondrial injury.
    [show abstract] [hide abstract]
    ABSTRACT: The purpose of this work was to examine whether ursodeoxycholate (UDC), a hydrophilic bile salt, could reduce mitochondrial liver injury from chronic ethanol consumption in rats. Animals were pair-fed liquid diets containing 36% of calories as ethanol or isocaloric carbohydrates. They were randomly assigned into 4 groups of 7 rats each and received a specific treatment for 5 weeks: control diet, ethanol diet, control diet + UDC, and ethanol diet + UDC. Respiratory rates of isolated liver mitochondria were measured using a Clark oxygen electrode with sodium succinate as substrate. Mitochondria from rats chronically fed ethanol demonstrated an impaired ability to produce energy. At the fatty liver stage, the ADP-stimulated respiration (V3) was depressed by 33%, the respiratory control ratio (RC) by 25% and the P/O ratio by 15%. In ethanol-fed rats supplemented with UDC, both the rate and efficiency of ATP synthesis via the oxidative phosphorylation were improved: V3 was increased by 35%, P/O by 8%. All the respiratory parameters were similar in control group and control + UDC group. On the other hand, the number and size of mitochondria were assessed by electron microscopy and computer-assisted quantitative analysis. The number of mitochondria from ethanol-treated rats was decreased by 29%, and they were enlarged by 74%. Both parameters were normalized to control values by UDC treatment. These studies demonstrate that UDC has a protective effect against ethanol-induced mitochondrial injury by improving ATP synthesis and preserving liver mitochondrial morphology. These UDC positive effects may contribute to the observed decrease in fat accumulation and may delay the progression of alcoholic injury to more advanced stages.
    Life Sciences 02/1998; 63(25):2259-70. · 2.53 Impact Factor
  • Source
    Article: Effects of tauroursodeoxycholate solutions on cyclosporin A bioavailability in rats.
    [show abstract] [hide abstract]
    ABSTRACT: Cyclosporin A (CsA) exhibits poor bioavailability after oral administration of Sandimmune, with wide intra- and interindividual variations. Our study sought to determine the effect of the coadministration of CsA standard oily formulation and tauroursodeoxycholate (TUDC) and that of an aqueous micellar solution containing TUDC, monoolein, and CsA in promoting and regulating CsA bioavailability in the rat Pharmacokinetic parameters of CsA were determined in fasted rats after either an intravenous administration (5 mg/kg) or a single oral CsA dose of 10 mg/kg. Compared with oral Sandimmune, the CsA micellar solution significantly improved the CsA bioavailability by 160% and decreased the interindividual variability in bioavailability expressed as percent coefficient of variation from 32% to 15%. The concentration-time profile was modified with a 3.5-fold increase in C(max), a reduction of t(max), and an increased trough concentration. Bioavailability slightly improved in rats receiving standard oily solution plus concomitant TUDC, although not significantly. Data indicate that the structure of the CsA carriers greatly affect drug bioavailability and that aqueous micellar solutions of CsA-TUDC-monoolein constitute efficient vehicles, thus providing for CsA high absorption with low variability.
    Drug Metabolism and Disposition 09/1997; 25(8):912-6. · 3.73 Impact Factor
  • Article: [Contact litholysis of common bile duct calculi. Study of 44 patients].
    [show abstract] [hide abstract]
    ABSTRACT: Endoscopic sphincterotomy has become a generally accepted method for extracting common bile duct stones in high risk or cholecystectomized patients. However, stone extraction is impossible by the usual methods in 5 to 10% of cases. The purpose of this study was to evaluate the effect of a recently developed solvent system in patients with large bile duct stones. Forty four patients (15 men and 29 women, median age of years) underwent contact dissolution after unsuccessful Dormia extraction. Solvents were administered via a nasobiliary catheter in 41 patients following papillotomy and through a T-tube in 3 patients. Solvent mixtures (26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an alkaline aqueous solution; and a 70/30 dimethyl sulfoxide/methyl tert-butyl ether mixture) were infused continuously and alternatively for 2 hours. Bile duct stones disappeared in 13-24 hours of infusion in 11 patients. In 29 patients, a clear reduction in stone volume occurred, allowing complete endoscopic extraction of the fragments. In 4 patients, the size of the stone did not change. Only mild and transient side-effects including abdominal pain (68%), nausea (72%), vomiting (52%), diarrhea and sleepiness (50%) were observed. Direct dissolution therapy could be an effective method for the non-surgical management of large bile duct stones in selected patients when intra- or extracorporeal lithotripsy is unsuccessful.
    Gastroentérologie Clinique et Biologique 02/1997; 21(10):655-9. · 0.80 Impact Factor
  • Article: Ursodeoxycholate improves hepatobiliary dysfunction induced by valproate-carbamazepine treatment in the rat.
    [show abstract] [hide abstract]
    ABSTRACT: Carbamazepine (CBZ) and valproate (VPA) are commonly used antiepileptic drugs. These drugs, either alone or combined, may produce hepatotoxicity. We report results of a biochemical and histological study of the liver in rats treated for eight days with VPA (500 mg/Kg/day), CBZ (200 mg/Kg/day) and VPA plus CBZ. A hepatoprotective bile salt, ursodeoxycholate (UDC, 60 mg/Kg/day) was given as a supplement to rats treated with the VPA+CBZ combination. VPA strongly modified the biliary biochemical parameters inducing hypercholeresis and hyposecretion of phospholipids. Microscopically, hepatocytes showed intense vacuolation of the peripheral cytoplasm and alterations of the mitochondrial matrix. CBZ produced increased choleresis but had no effect on biliary lipid parameters. Ultrastructurally, CBZ induced marked proliferation of the smooth endoplasmic reticulum of hepatocytes. The VPA+CBZ association produced a combination of the alterations induced independently by each drug. In both bile and plasma, increased CBZ-epoxide and decreased VPA levels were observed. The addition of UDC restored the biliary phospholipid secretion, decreased cytoplasmic vacuoles and mitochondrial alterations, and diminished the hypertrophy of smooth endoplasmic reticulum, indicating a clear beneficial effect of UDC on hepatobiliary dysfunction induced by the VPA+CBZ combination. Furthermore, the supplementation with UDC did not significantly change the plasma levels of the antiepileptic drugs.
    Life Sciences 02/1996; 59(13):1069-79. · 2.53 Impact Factor
  • Article: Contact solvents for common bile duct stones. Study in an in vitro system.
    [show abstract] [hide abstract]
    ABSTRACT: Cholesterol and brown pigment stones found in the common bile duct are often radiolucent and therefore indistinguishable. The purpose of this study was to define contact solvent systems able to dissolve both stone types. The influence of mucolytic agents on in vitro pigment stone dissolution was first determined. It was shown that dithioerythritol induced more rapid dissolution than N-acetylcysteine. Alternating treatment with an aqueous alkaline solvent (pH = 9.5), composed of sodium deoxycholate 50 mM, ethylenediaminetetraacetate 26 mM and dithioerythritol 50 mM, for 45 min, and an organic solvent methyl tert-butyl ether/dimethyl sulfoxide (90/10) for 15 min, was more effective for bilirubin, cholesterol, and fatty acid solubilization (p < 0.01) than using these solvents separately. The dissolution of brown stones was nearly completed within 9 h and that of mixed cholesterol stones was obtained within 3 h. We conclude that the alternating treatment described is very effective for the rapid in vitro dissolution of the two major stone types present in the bile ducts, and deserves further assessment in vivo.
    Liver International 10/1995; 15(5):247-52.
  • Article: [Direct dissolution therapy of biliary tract calculi].
    [show abstract] [hide abstract]
    ABSTRACT: The aim of this study was to evaluate the effect of a recently developed biphasic multicomponent solvent in 39 patients with biliary duct stones that are too large (15-35 mm) to be removed after endoscopic sphincterotomy. From November 1991 to October 1993, 37 patients with common bile duct stones were papillotomized during endoscopic retrograde cholangiography and a nasobiliary catheter was positioned above the stone. In 2 patients, the residual stones were dissolved via the T-tube inserted during cholecystectomy. Solvent mixtures (solvent 1:26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an aqueous buffer solution glycine-NaOH, pH: 9.2; solvent 2: a 70: 30 mixture of dimethyl sulfoxide and methyl-tert-butyl-ether) were infused continuously and alternatively for 2 h at a rate of 0.3-0.5 ml/kg b.w./h. In order to diminish the absorption of the solvent from the duodenum, charcoal was given orally periodically. Fluoroscopy indicated that the common bile duct stones disappeared during 13-24 h of infusion in 10 of 39 patients. In 25 patients, the size of the stones diminished sufficiently for them to be removed by basket extraction. In 4 patients, the size of the stone did not change and surgery (1 pt) or endoscopic stenting (3 pts) was required. Only mild toxic side-effects were observed, including laboratory abnormalities and moderate duodenitis (34/39). Transient abdominal pain and/or cramp (21/39), nausea and vomiting (34/39) and diarrhoea (19/39) were the most common complaints during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
    Orvosi Hetilap 01/1995; 135(49):2691-4.
  • Article: Hepatoprotection by hydrophilic bile salts.
    P E Queneau, J C Montet
    Journal of Hepatology 09/1994; 21(2):260-8. · 9.26 Impact Factor
  • Article: Improvement of cyclosporin A-induced cholestasis by tauroursodeoxycholate in a long-term study in the rat.
    [show abstract] [hide abstract]
    ABSTRACT: Cyclosporin A is an essential immunosuppressive drug, but it is potentially toxic to the kidney and liver. Ursodeoxycholic acid, a hydrophilic bile acid, has been reported to improve cholestasis in liver disease in man. The purpose of this work was to examine whether tauroursodeoxycholate could reduce cyclosporin A-induced hepatic or renal injuries in the rat. After randomization into three groups (N = 8), rats received daily for 17 days: cyclosporin A intraperitoneally alone (30 mg/kg) or cyclosporin A intraperitoneally and tauroursodeoxycholate (60 mg/kg) by gavage; control received the cyclosporin A excipient. Under tauroursodeoxycholate, cholestatic parameters (bile flow, bile salt secretion, serum bile salts, serum bilirubin) improved significantly without affecting cyclosporin A blood levels, and excretion of the drug and its metabolites in bile increased by 47%. Serum creatinine levels were better preserved, although not significantly. These results show that tauroursodeoxycholate prevents cyclosporin A-induced cholestasis in long-term treatment in rats, possibly by facilitating the drug elimination in bile.
    Digestive Diseases and Sciences 08/1994; 39(7):1581-5. · 2.12 Impact Factor
  • Article: Diminution of an acute cyclosporin-induced cholestasis by tauroursodeoxycholate in the rat.
    [show abstract] [hide abstract]
    ABSTRACT: CsA is a commonly used immunosuppressive drug known to possibly induce cholestatic side effects. Ursodeoxycholic acid (UDC), a nonhepatotoxic bile acid, has proved to be efficient for several types of cholestasis. The aim of this experiment was to evaluate the ability of tauroursodeoxycholate (TUDC) in preventing CsA-induced cholestasis on bile duct-cannulated rats. After bile flow stabilization, a bolus of 30 mg/kg CsA was given i.v. to one group (n = 7) and was associated with a 2 mumol/kg/min TUDC infusion in another group (n = 7). The control group was injected with CsA-solvent. CsA, as used here, had a rapid and marked cholestatic effect. However, both bile flow and bile salt secretion were significantly enhanced in the TUDC group when compared to the CsA alone-treated group and showed no difference with the solvent control group. In addition, TUDC significantly increased elimination of CsA and its metabolites in bile. In contrast to what was found for endogenous bile salts, TUDC uptake was not affected by CsA. The anticholestatic effect of TUDC probably resulted from preventing CsA-induced hepatocyte membrane damage and from easing biliary excretion of CsA. Such properties could be helpful for CsA-treated liver recipients who are especially exposed to cholestatic problems, and thus, to toxic CsA accumulation in the liver. Moreover, regulation of CsA elimination might prevent, in part, its general toxicity.
    Transplantation 10/1993; 56(3):530-4. · 4.00 Impact Factor
  • Article: [Ursodeoxycholic acid. Physical properties and hepatoprotective activity].
    J C Montet
    [show abstract] [hide abstract]
    ABSTRACT: In patients with cystic fibrosis, obstruction of bile ductules by mucus plugs and hepatocellular retention of hydrophobic bile acids including chenodeoxycholic acid may induce cholestasis and biliary cirrhosis. Ursodeoxycholic acid is a hydrophilic bile acid whose physicochemical characteristics differ markedly from those of chenodeoxycholic acid. Critical micellar concentration is higher and surface activity lower with ursodeoxycholate, whose micelles induce less solubilization of lecithin and cholesterol. In animal models, ursodeoxycholate increases bile excretion and prevents cholestasis and cytolysis induced by hydrophobic bile salts. Taken together, these data suggest that ursodeoxycholate therapy may have a beneficial effect on cystic fibrosis-related hepatobiliary disorders.
    Pathologie Biologie 07/1991; 39(6):621-4. · 1.53 Impact Factor
  • Article: Physicochemical determinants of in vitro shock-wave biliary lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: Human gallstones were studied by visual inspection, computerized tomographic imaging, and chemical analysis to assess physicochemical characteristics that may determine the outcome of in vitro shock-wave fragmentation. Eighty-five stones (mean diameter: 13.2 +/- 5 mm) were each collected from different patients. Fifty-five (65%) calculi were angular and 30 (35%) round or oval-shaped. Three easily obtained measures were derived from each stone's optimal computerized tomographic image including the mean stone density, a measure corresponding to the standard deviation of the mean stone density value which we termed the stone density distribution index and which may reflect the physicochemical heterogeneity of a given gallstone, as well as the density range. After the administration of 2500 shock waves using an electrohydraulic generator, fragmentation was noted in 68 calculi (80%) and was satisfactory in 27 (32%) (where the largest resulting fragment diameters were all less than or equal to 5 mm). Strong determinants of satisfactory fragmentation on multivariate analysis included a stone diameter of less than or equal to 15 mm, the presence of an angular stone shape, and a stone density distribution index of greater than or equal to 60 Hounsfield units. The other parameters did not independently determine satisfactory fragmentation. Prospective clinical trials are needed to assess whether these findings result in a better prediction of the success of extracorporeal biliary lithotripsy and a broadening of its indications.
    Gastroenterology 02/1991; 100(1):222-7. · 11.68 Impact Factor
  • Article: Effects of bile salt supplementation on biliary secretion in estrogen-treated rats.
    X M Zhao, J C Montet
    [show abstract] [hide abstract]
    ABSTRACT: The aim of the present study was to determine whether bile acid feeding to rats can reverse ethinyl estradiol-induced cholestasis. Animals received ethinyl estradiol (2 mg/kg/day) for 6 days or were coinfused with estrogen plus various bile acids (60 mg/kg/day). Cholestasis could be significantly prevented by tauroursodeoxycholic acid, was partly corrected by ursodeoxycholic acid, and was unchanged by chenodeoxycholic acid. Total bile salt secretion was increased in every group. The secretion of the major primary bile acids (cholic acid and beta-muricholic acid) was restored to a large extent in rats supplemented with tauroursodeoxycholate but not in chenodeoxycholate-fed rats. In the former group, the canalicular transport of taurocholate and the bile salt pool size were identical with those of control rats. The hydrophilic-hydrophobic balance of the administered bile salt species appears to be an essential factor in the restoration of bile secretion, the more hydrophilic bile salt having the more hepatoprotective effect.
    The Journal of Nutritional Biochemistry 08/1990; 1(8):420-5. · 3.89 Impact Factor
  • Article: Dissolution of human brown pigment biliary stones.
    [show abstract] [hide abstract]
    ABSTRACT: The chemical dissolution of human brown pigment stones was studied using various monophasic multicomponent solvents. Among the nine solutions tested for stone powder dissolution capacity, the two most active were retained for further analysis. The solvent containing 26 mM ethylenediaminetetraacetate, 40 mM sodium deoxycholate, 10 mM monoolein and 30% dimethylsulfoxide was efficient for calcium and bilirubin solubilization. The other solvent containing dimethylsulfoxide/methyl tert-butyl ether (70:30) had a high capacity for dissolution of cholesterol and bilirubin. From in vitro stone dissolution experiments, we found that alternating treatment every 2 h with these two mixtures was more effective than using these solvents separately. Within 24 h, 90% of cholesterol, 80% of bilirubin, and 70% of calcium were dissolved. In vivo, we studied the dissolution of human stones surgically implanted in the gallbladder of 6 rabbits. Alternating perfusions with the solvents selected led to complete disappearance of stones within 16 h in 5 out of 6 cases. The residual histological toxicity in the gallbladder wall, 15 days after perfusion, was low and blood parameters did not differ from the normal values.
    Journal of Hepatology 12/1989; 9(3):301-11. · 9.26 Impact Factor
  • Article: Effect of hyocholic acid on the prevention and dissolution of biliary cholesterol crystals in mice.
    J P Dusserre, A M Montet, J C Montet
    [show abstract] [hide abstract]
    ABSTRACT: Gallstone prevention and dissolution were studied in a mouse model of cholesterol cholelithiasis using hyocholic acid (3 alpha, 6 alpha, 7 alpha-trihydroxy-5 beta-cholanic acid). Addition of hyocholic acid, 0.1 or 0.3%, in the lithogenic diet (1% cholesterol + 0.5% cholic acid) prevented the formation of cholesterol monohydrate crystals in 70 and 90% of cases, respectively. On the other hand, chow diet supplemented with 0.1 or 0.3% hyocholic acid dissolved cholesterol crystals in lithiasic mice in, respectively, 80 and 100% of cases within 12 days. In both protocols, biles were largely supersaturated with cholesterol; lecithin-cholesterol lamellar liquid crystals were responsible for the transport of the excess cholesterol content. The percentage of hydrophilic bile salts (hyocholic acid, hyodeoxycholic acid, beta-muricholic acid) in bile, although moderate (15-50% of total bile salts), appears to induce such liquid crystalline dispersion. This study demonstrates that the balance between hydrophilic and hydrophobic bile salts plays a major role in the prevention and dissolution of cholesterol crystals. It is also shown that the desaturation of biliary cholesterol is not a prerequisite for gallstone dissolution.
    Canadian Journal of Physiology and Pharmacology 09/1988; 66(8):1028-34. · 1.95 Impact Factor
  • Article: Dissolving agents of human mixed cholesterol stones.
    K Y Dai, J C Montet, X M Zhao, J Amic, R Choux
    [show abstract] [hide abstract]
    ABSTRACT: Methyl tert-butyl ether which is a powerful cholesterol monohydrate solvent does not completely dissolve mixed cholesterol gallstones when directly infused into the biliary tree. In this work, we compared the effect of various solvents containing different proportions of methyl tert-butyl ether and dimethylsulfoxide in anhydrous and aqueous systems on the in vitro solubilization of human cholesterol stones. The dissolution rates of cholesterol obtained in the presence of methyl tert-butyl ether was markedly decreased when 10 p. 100 water was added. In contrast, the addition of dimethylsulfoxide (30 p. 100) to methyl tert-butyl ether-water system enhanced the stone-solvent contact, improved the cholesterol dissolution rates and left less stone debris. A subsequent dissolution with an alkaline, pH = 8.8, aqueous dimethylsulfoxide-ethylenediaminetetraacetic acid solution strongly reduced the non cholesterol residues. In vivo, nearly complete dissolution of human cholesterol stones implanted in the gallbladder of rabbits was obtained within 8 hours when methyl tert-butyl ether/dimethylsulfoxide (70/30) solvent was infused at a rate of 0.6 ml/h/kg. With methyl tert-butyl ether, only 84 p. 100 of the original stone weight was dissolved. The infusion of these solvents leads to morphological changes in the gallbladder wall with some focal ulcerations. These alterations can be almost completely recovered after two weeks. No histologic evidence of hepatic, duodenal or renal damage was found. We conclude that the mixture methyl tert-butyl ether/dimethylsulfoxide (70/30) constitutes a good solvent for mixed cholesterol stones. Compared with pure methyl tert-butyl ether, the mixed system allows for a more rapid and a more complete dissolution of gallstones.
    Gastroentérologie Clinique et Biologique 05/1988; 12(4):312-9. · 0.80 Impact Factor