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Biomedical subjects

A K Batta

Publications and source records attributed to A K Batta.

At least 37 records · Page 2Linked to original sources
PubMed1999

Gas chromatography of bile acids.

Bile acids, the end products of cholesterol metabolism in the liver, are of vital importance in the tissue distribution of cholesterol. Abnormalities in cholesterol biosynthesis or metabolism are often reflected in the proportions, concentrations and conjugation of bile acids in various tissues and determination of bile acids in these tissues is important in the diagnosis of hepatobiliary diseases. Several methods for quantitative determination of bile acids in biological fluids are known and have been reviewed. In this review, we have discussed the gas-chromatographic method for determination of bile acids with special reference to bile acid quantitation in plasma, bile, urine and stool.

Animals↗
PubMed1999

Campestanol (24-methyl-5alpha-cholestan-3beta-ol) absorption and distribution in New Zealand White rabbits: effect of dietary sitostanol.

Campestanol (24-methyl-5alpha-cholestan-3beta-ol) is a naturally occurring plant stanol, structurally similar to cholesterol (5-cholesten-3beta-ol) and widely distributed in vegetable oils consumed in human diets. We measured the absorption and turnover of campestanol by the plasma dual-isotope ratio method and mathematical analysis of specific activity versus time decay curves after simultaneous oral and intravenous pulse-labeling with [3alpha-3H]- and [23-14C]-labeled campestanol, respectively, in New Zealand White (NZW) rabbits: six fed chow and six fed chow with 125 mg/d campestanol and 175 mg/d sitostanol (24-ethyl-5alpha-cholestan-3beta-ol). Plasma concentrations increased insignificantly from 0.08+/-0.01 to 0.09+/-0.01 mg/dL with dietary stanols. The percent campestanol absorption measured by the plasma dual-isotope ratio method after the rabbits were fasted for 6 hours yielded the percent absorption in the absence of competing intestinal sterols and stanols and declined insignificantly from 11.6%+/-3.5% in controls to 8.1%+/-3.7% in the treated rabbit groups. In contrast, the turnover, which measured actual absorption averaged over 24 hours, increased from 0.12+/-0.05 to 0.37+/-0.05 mg/d (P < .05) with campestanol and sitostanol added to the diet. However, the actual percent absorption declined from 3% to 0.3% of dietary intake with the campestanol and sitostanol-enriched diet. Campestanol pool sizes, although remaining small, increased slightly from 1.1+/-0.4 to 2.5+/-1.5 mg. The removal constant (KA) from pool A (MA) did not change significantly with added dietary campestanol and sitostanol (KA= -0.040+/-0.005 v -0.037+/-0.007 d(-1)). The results demonstrate small campestanol plasma concentrations and body pools even when the rabbits consumed substantial amounts because (1) intestinal absorption was limited and (2) was further reduced by competing dietary sitostanol, and (3) campestanol was removed rapidly from the body. Thus, campestanol, which shares the same basic structure and intestinal absorption pathway with cholesterol, does not accumulate when fed, and may be incorporated into the diet to block cholesterol absorption.

Administration, Oral↗
PubMed1999

A convenient synthesis of dinorbile acids: oxidative hydrolysis of norbile acid nitriles.

We report a convenient method for the synthesis of dinorbile acids (23,24-dinor-5beta-cholan-22-oic acids, pregnane-20-carboxylic acids) in fair to good yields from norbile acid nitriles in one step by oxidative hydrolysis with oxygen in the presence of potassium-t-butoxide. The method results in stepwise overall removal of two carbon atoms in bile acid side chains in two steps. Dinorbile acids corresponding to several common bile acids have been prepared and their structures confirmed by spectroscopic methods. This simple method for synthesis of dinorbile acids may facilitate their study metabolically.

Bile Acids and Salts↗
PubMed1999

Bile acid abnormalities in cholestatic liver diseases.

There is ample reason to believe that UDCA is the drug of choice in cholestatic liver diseases. It is possible that UDCA has to be administered for prolonged periods to see appreciable reversal in liver damage. Nevertheless, the amelioration of symptoms and improvement in nutrition of patients are equally important. Disabling symptoms such as pruritus are often brought under control, and quality of life improves. Clearly the goal for UDCA therapy is to slow the rate of disease progression, lessen the mortality risk, and improve the quality of life in patients. It is possible that a combination therapy would be more beneficial than UDCA alone. Initial results of administering UDCA with colchicine have shown no improvement in liver histology; however, administration of UDCA together with a strong anti-inflammatory drugs may be helpful to halt immune destruction of liver cells.

Bile Acids and Salts↗
PubMed1999

Highly simplified method for gas-liquid chromatographic quantitation of bile acids and sterols in human stool.

A simple method for the gas-liquid chromatographic quantitation of human fecal bile acids and sterols is described where bile acids are subjected to n-butyl ester derivatization, without prior isolation from the stool, followed by trimethylsilylation of the sterols and bile acids. Under these conditions, bile acid derivatives are well resolved from each other and from the trimethylsilyl ether derivatives of fecal sterols and no overlap occurs. The method was shown to be highly reproducible and recoveries were similar to those obtained with other methods used for fecal bile acid analysis. Application of the method for bile acid and sterol analysis in human stool is described.

Bile Acids and Salts↗
PubMed1999

Bile acid synthesis in the Smith-Lemli-Opitz syndrome: effects of dehydrocholesterols on cholesterol 7alpha-hydroxylase and 27-hydroxylase activities in rat liver.

The Smith-Lemli-Opitz syndrome (SLOS) is a congenital birth defect syndrome caused by a deficiency of 3beta-hydroxysterol Delta(7)-reductase, the final enzyme in the cholesterol biosynthetic pathway. The patients have reduced plasma and tissue cholesterol concentrations with the accumulation of 7-dehydrocholesterol and 8-dehydrocholesterol. Bile acid synthesis is reduced and unnatural cholenoic and cholestenoic acids have been identified in some SLOS patients. To explore the mechanism of the abnormal bile acid production, the activities of key enzymes in classic and alternative bile acid biosynthetic pathways (microsomal cholesterol 7alpha-hydroxylase and mitochondrial sterol 27-hydroxylase) were measured in liver biopsy specimens from two mildly affected SLOS patients. The effects of 7- and 8-dehydrocholesterols on these two enzyme activities were studied by using liver from SLOS model rats that were treated with the Delta(7)-reductase inhibitor (BM15.766) for 4 months and were comparable with more severe SLOS phenotype in plasma and hepatic sterol compositions. In the SLOS patients, cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase were not defective. In BM15.766-treated rats, both enzyme activities were lower than those in control rats and they were competitively inhibited by 7- and 8-dehydrocholesterols. Rat microsomal cholesterol 7alpha-hydroxylase did not transform 7-dehydrocholesterol or 8-dehydrocholesterol into 7alpha-hydroxylated sterols. In contrast, rat mitochondrial sterol 27-hydroxylase catalyzed 27-hydroxylation of 7- and 8-dehydrocholesterols, which were partially converted to 3beta-hydroxycholestadienoic acids. Addition of microsomes to the mitochondrial 27-hydroxylase assay mixture reduced 27-hydroxydehydrocholesterol concentrations, which suggested that 27-hydroxydehydrocholesterols were further metabolized by microsomal enzymes. These results suggest that reduced normal bile acid production is characteristic of severe SLOS phenotype and is caused not only by depletion of hepatic cholesterol but also by competitive inhibition of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by accumulated 7- and 8-dehydrocholesterols. Unnatural bile acids are synthesized mainly by the alternative pathway via mitochondrial sterol 27-hydroxylase in SLOS.

Animals↗
PubMed1998

Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption.

The regulation of dietary cholesterol absorption was examined in C57BL/6 and transgenic mice with liver overexpression of the scavenger receptor BI (SR-BI Tg). In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) dietary cholesterol resulted in a dose-dependent decrease in the percentage of dietary cholesterol absorbed. A plot of total daily mass of dietary cholesterol absorbed versus the percentage by weight of cholesterol in the diet yielded a curve suggesting a saturable process with a Km of 0.4% (wt/wt) and a Vmax of 0.65 mg cholesterol/g body weight per day. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity, stimulated cholesterol 7alpha-hydroxylase activity, and enhanced fecal excretion of bile acids, but none of these changes correlated with the percentage of dietary cholesterol absorption. Dietary cholesterol also caused an increase in biliary cholesterol concentration, and in this case the concentration of biliary cholesterol was strongly and inversely correlated with the percentage dietary cholesterol absorption (r = -0.63, P < 0.0001). Biliary cholesterol concentration was also directly correlated with daily cholesterol intake, dietary cholesterol mass absorption, and liver cholesterol ester content. Transgene-induced overexpression of SR-BI resulted in a stimulation of excretion of cholesterol into the bile and suppressed percentage dietary cholesterol absorption. Furthermore, biliary cholesterol levels in SR-BI Tg mice were strongly and inversely correlated with the percentage of dietary cholesterol absorbed (r = -0.99, P < 0.0008). In summary, these results suggest that the excretion of cholesterol into the bile plays an important role in regulating the percentage absorption of dietary cholesterol.

Animals↗
PubMed1998

Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal water-soluble fraction after feeding to rats with colon polyps.

We recently showed that feeding the cytoprotective bile acid ursodeoxycholic acid (UDCA) to rats resulted in significant reduction in polyps and especially cancers, both in number and size (D. L. Earnest et al., Cancer Res., 54: 5071-5074, 1994). Because fecal secondary bile acids [particularly deoxycholic acid (DCA)] are considered to promote formation of colon adenomas and cancer, we have now attempted to find a relationship between polyp reduction and fecal secondary bile acids after feeding UDCA to these rats. We examined the fecal bile acids in rats with polyps and compared them with fecal bile acids in control rats and also determined the bile acid composition in fecal aqueous phase, which is in direct contact with the colon epithelium and may be physiologically more active. Treatment with azoxymethane did not significantly alter fecal bile acid composition in the rats. Cholic acid feeding resulted in greatly increased proportions of DCA (82% of total bile acids versus 18% in control rats). On the other hand, UDCA feeding significantly reduced the proportion of fecal DCA (2% in control rats fed UDCA and 3% in rats also treated with azoxymethane). In control rats, 96% of the bile acids were present in the water-insoluble fraction and 4% in the water-soluble fraction. The major insoluble bile acids included DCA and hyodeoxycholic acid (73% of total bile acids). In contrast, the muricholic acids were concentrated in the soluble fraction (37%). When 0.4% UDCA was added to the diet, lithocholic acid increased in the insoluble fraction (40 versus 1%), but the hydrophilic UDCA and muricholic acids were enriched in the water-soluble fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were distributed predominantly in the water-insoluble fraction, whereas the hydrophilic bile acids were distributed preferentially in the water-soluble fraction. These data suggest that UDCA may prevent colon tumors and polyps by countering the toxic effect of DCA and enhancing the possible cytoprotective effects of UDCA and muricholic acids in the water-soluble fraction in the feces of rat.

Animals↗
PubMed1998

Capillary gas chromatographic analysis of serum bile acids as the n-butyl ester-trimethylsilyl ether derivatives.

Gas chromatographic separations of n-butyl ester-trimethylsilyl ether derivatives of several common bile acids were compared with those of the corresponding methyl ester-trimethylsilyl ether derivatives on a CP-Sil-5 CB capillary column. Both types of derivatives were similarly resolved from each other. However, the n-butyl ester-trimethylsilyl ether derivatives of the bile acids showed longer retention times than the corresponding methyl ester-trimethylsilyl ethers and unlike the methyl ester-trimethylsilyl ether derivatives, were completely resolved from and eluted later than the trimethylsilyl ethers of common plasma sterols including sitosterol. A simplified method of plasma work-up for quantitation of bile acids and application of the above method in quantification of plasma bile acids in humans is described.

Bile Acids and Salts↗
PubMed1998

Regulation of early cholesterol biosynthesis in rat liver: effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities.

Cytosolic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase catalyzes the formation of HMG-CoA, the substrate for the rate-controlling enzyme in the cholesterol biosynthetic pathway. To explore the regulation in liver, we developed a new, accurate, and reliable reversed-phase ion-pair chromatographic assay that uses nonradioactive substrates and n-propionyl coenzyme A as an internal recovery standard. The hepatic activities were measured in rats treated with cholesterol, sitosterol, cholic acid, deoxycholic acid, ursodeoxycholic acid, cholestyramine, bile fistula, lovastatin, and BM 15.766, an inhibitor of 7-dehydrocholesterol delta7-reductase, and were compared with microsomal HMG-CoA reductase and cytosolic acetoacetyl coenzyme A (AcAc-CoA) thiolase activities. HMG-CoA synthase activity was effectively suppressed in synchrony with HMG-CoA reductase activity by treatments with cholesterol (-41%, P < .05), cholic acid (-72%, P < .005), and deoxycholic acid (-62%, P < .05). However, ursodeoxycholic acid increased activity 84% (P < .05) and intravenous sitosterol did not change activity. AcAc-CoA thiolase activities also paralleled HMG-CoA reductase and HMG-CoA synthase activities, but differences were not statistically significant. In contrast to inhibition, up-regulation of hepatic HMG-CoA synthase activities by cholestyramine, bile fistula, and lovastatin was much less than HMG-CoA reductase activities. In addition, BM 15.766 did not stimulate synthase activity, whereas lovastatin increased activity 2.4-fold. Thus, hepatic HMG-CoA synthase activity was regulated coordinately with HMG-CoA reductase, and responded more forcefully to regulatory stimuli than acetoacetyl-CoA thiolase activity but usually less than HMG-CoA reductase.

Acetyl-CoA C-Acetyltransferase↗
PubMed1998

Relationship between abnormal cholesterol synthesis and retarded learning in rats.

We examined the relationship between brain sterol composition and associative learning (classical conditioning of the eyeblink response) in newly weaned rats fed BM 15.766 (BM) for 4 months. This compound inhibits 7-dehydrocholesterol-delta7-reductase, which catalyzes the conversion of 7-dehydrocholesterol to cholesterol, the last step in the synthetic pathway. As countertreatment, half of the BM-treated rats were fed 2% cholesterol during the last 2 months. With BM, cholesterol concentrations declined 91% in plasma, but with cholesterol feeding, the levels increased 50% compared with baseline values. 7-Dehydrocholesterol, which was not detected at baseline, increased to 55% of plasma sterols with BM but decreased to 5% of total plasma sterols when cholesterol was added. With BM, brain cholesterol levels decreased 60% and did not increase after cholesterol was added. However, 7-dehydrocholesterol, which comprised 39% of brain sterols with BM, decreased to 31% (P < .05) when cholesterol was fed. Hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase activity in the liver increased 2.2-fold with BM and declined 95% after adding cholesterol, but did not change in the brain. BM treatment for 4 months prevented learning of the conditioned eyeblink response as compared with controls. In contrast, BM-treated rats supplemented with cholesterol acquired the conditioned eyeblink response. Chronic inhibition of 7-dehydrocholesterol-delta7-reductase reduced cholesterol and increased 7-dehydrocholesterol levels in plasma and brain, and was associated with impaired learning. Cholesterol feeding corrected plasma and hepatic sterol levels and reduced brain 7-dehydrocholesterol concentrations to reestablish normal learning.

Administration, Oral↗
PubMed1998

Accurate detection of Smith-Lemli-Opitz syndrome carriers by measurement of the rate of reduction of the ergosterol C-7 double bond in cultured skin fibroblasts.

The activity of ergosterol delta 7-reductase (3 beta-hydroxysteroid delta 7-reductase) was measured in cultured skin fibroblasts from 7 controls, 10 Smith-Lemli-Opitz syndrome (SLOS) patients, and 10 parents (obligate carriers). The fibroblasts were exposed to delipidated medium supplemented with lovastatin for 24 h and the enzyme activity was determined by incubating cell-free homogenate with ergosterol (ergosta-5,7,22-trien-3 beta-ol) and measuring the mass of brassicasterol (ergosta-5,22-dien-3 beta-ol) formed by gas chromatography-mass spectrometry with selected-ion monitoring. In carriers, the activity was significantly lower than in controls (22 +/- 2 vs 65 +/- 10 pmol/min per mg protein, p < 0.0005), and no overlap was observed. The mean activity in carriers' fibroblasts was more than 100 times higher than in patients' cells (0.2 pmol/min per mg protein). The use of ergosterol avoids the many problems caused by the instability and lack of availability of radiolabelled 7-dehydrocholesterol. The present method makes it possible to discriminate SLOS carriers from both controls and patients using a commercially available substrate and common analytical equipment.

Cells, Cultured↗
PubMed1998

Cholesterol and oxygenated cholesterol concentrations are markedly elevated in peripheral tissue but not in brain from mice with the Niemann-Pick type C phenotype.

Niemann-Pick disease type C (NP-C) is a rare genetic disorder characterized by progressive neurodegeneration, frequent developmental delay and early death. Tissues of affected individuals accumulate large quantities of free cholesterol in lysosomes. Because cytotoxic oxygenated derivatives of cholesterol are known to form readily when cholesterol concentrations are elevated, we searched for these compounds in liver, kidney, spleen and brain from mice with the NP-C phenotype. In order of abundance, we identified 7 alpha- and 7 beta-hydroxycholesterol, 5 alpha, 6 alpha-epoxycholestan-3 beta-ol, 4 beta-hydroxycholesterol, cholest-4-en-3 beta, 7 alpha-diol and cholest-4-en-3 beta, 6 beta-diol in most tissue samples. Cholesterol concentrations in affected mice were increased 3-fold in kidney and 7- to 8-fold in spleen and liver compared to controls (all p < 0.001) but were unchanged in brain. Although oxysterol levels were markedly elevated in nonbrain tissue, the oxysterol and cholesterol concentrations increased proportionally so that oxysterols expressed as percentage of total sterols were the same for all animals (0.34 +/- 0.19% averaged over all organs in affected animals vs 0.40 +/- 0.42% in control mice). In contrast to peripheral tissue, we could not detect any increase in either absolute or relative oxysterol levels in the brains of affected and control mice (49 +/- 61 vs 53 +/- 43 micrograms/g wet weight and 0.45 +/- 0.52 vs 0.47 +/- 0.37%, respectively). Thus, brain sterols are normal in NP-C mice and it is unlikely that an accumulation of cytotoxic oxygenated derivatives of cholesterol could account for the progressive neuropathology seen in the disease.

Animals↗
PubMed1998

Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis.

OBJECTIVE: Ursodeoxycholic acid (UDCA) improves liver biochemistries and enriches the bile with UDCA in patients with primary biliary cirrhosis. The aim of this study was to determine whether the degree of enrichment of bile correlated with that of serum and whether either of these measures correlated with improvement in measures of liver disease. METHODS: In a randomized study, biliary and serum bile acid analyses were performed at entry and after 2 yr of UDCA or placebo. RESULTS: The percentage of ursodeoxycholic acid in bile increased by 42% in the UDCA group (n = 61) compared with 8% in the placebo group (n = 57) (p < 0.0001). Measurement of serum bile acids in 32 patients (18 ursodeoxycholic acid, 14 placebo) indicated that at 2 yr, ursodeoxycholic acid comprised 65% of serum bile acids in the treated group and 7% in the placebo group. Agreement between bile and serum was fair (r = 0.75, p < or = 0.00002) because in some patients, plasma but not biliary bile acids were enriched with UDCA. Changes in biliary ursodeoxycholic acid correlated significantly but weakly with the changes in serum alkaline phosphatase, AST, bilirubin, and in Mayo risk score. Correlations between changes in serum bile acid composition and biochemical measures of disease activity were even weaker. CONCLUSION: The measurement of biliary bile acids is superior to that of serum bile acids for assessing the compliance and changes in the circulating bile acids in patients receiving ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Furthermore, measures to further increase the proportion of ursodeoxycholic acid in circulating bile acids should be explored.

Bile↗
PubMed1998

Down-regulation of cholesterol biosynthesis in sitosterolemia: diminished activities of acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase, reductase, squalene synthase, and 7-dehydrocholesterol delta7-reductase in liver and mononuclear leukocytes.

Sitosterolemia is a recessively inherited disorder characterized by abnormally increased plasma and tissue plant sterol concentrations. Patients have markedly reduced whole body cholesterol biosynthesis associated with suppressed hepatic, ileal, and mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-controlling enzyme in cholesterol biosynthetic pathway, coupled with significantly increased low density lipoprotein (LDL) receptor expression. To investigate the mechanism of down-regulated cholesterol biosynthesis, we assayed several other key enzymes in the cholesterol biosynthetic pathway including acetoacetyl-CoA thiolase, HMG-CoA synthase, squalene synthase, and 7-dehydrocholesterol delta7-reductase activities in liver and freshly isolated mononuclear leukocytes from four sitosterolemic patients and 19 controls. Hepatic acetoacetyl-CoA thiolase, HMG-CoA synthase, reductase, and squalene synthase activities were significantly decreased (P < 0.05) -39%, -54%, -76%, and -57%, respectively, and 7-dehydrocholesterol delta7-reductase activity tended to be lower (-35%) in the sitosterolemic compared with control subjects. The reduced HMG-CoA synthase, reductase, and squalene synthase activities were also found in mononuclear leukocytes from a sitosterolemic patient. Thus, reduced cholesterol synthesis is caused not only by decreased HMG-CoA reductase but also by the coordinate down-regulation of entire pathway of cholesterol biosynthesis. These results suggest that inadequate cholesterol production in sitosterolemia is due to abnormal down-regulation of early, intermediate, and late enzymes in the cholesterol biosynthetic pathway rather than a single inherited defect in the HMG-CoA reductase gene.

Acetyl-CoA C-Acetyltransferase↗
PubMed1998

Fetal Smith-Lemli-Opitz syndrome can be detected accurately and reliably by measuring amniotic fluid dehydrocholesterols.

The Smith-Lemli-Opitz syndrome, characterized by limb, face and organ abnormalities, and mental retardation, is caused by an inherited block in the step of cholesterol biosynthesis in which the delta 7 double bond of 7-dehydrocholesterol is reduced. It is diagnosed by the presence of markedly elevated levels of 7-dehydrocholesterol and 8-dehydrocholesterol in plasma and tissue. We measured amniotic fluid sterols in 15 pregnancies in 13 women who had previously carried an affected fetus. Cholesterol, 7-dehydrocholesterol and 8-dehydrocholesterol concentrations averaged 18 +/- 3, 9.8 +/- 2.9 and 5.0 +/- 1.7 micrograms/ml, respectively, in seven pregnancies with an affected fetus or child. In contrast, these levels were 19 +/- 3, 0.05 +/- 0.01 and < 0.005 micrograms/ml, respectively, in eight increased-risk pregnancies with normal outcomes and 16 +/- 2, 0.07 +/- 0.01 and < 0.005 micrograms/ml in normal controls. 7-dehydrocholesterol concentrations, 2.2-26 and 0.05-0.10 micrograms/ml in pregnancies with an affected and unaffected fetus, respectively, did not overlap. Thus, abnormally elevated amniotic fluid dehydrocholesterol concentrations are an accurate predictor of fetal Smith-Lemli-Opitz syndrome. A false-positive or a false-negative result is highly unlikely.

Adult↗
PubMed1998

Synthesis and intestinal metabolism of ursodeoxycholic acid conjugate with an antiinflammatory agent, 5-aminosalicylic acid.

5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesized in above 90% yield by adding a basic solution of 5-aminosalicylic acid into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with cholylglycine hydrolase and Clostridium perfringens, that deconjugate naturally occurring glycine and taurine conjugates of bile acids. However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was partially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid and 5-aminosalicylic acid. We believe that this unique conjugation of ursodeoxycholic acid with 5-aminosalicylic acid may facilitate the transport of both 5-aminosalicylic acid and ursodeoxycholic acid to the colon and may be useful for the treatment of colonic inflammatory bowel diseases, ulcerative colitis and Crohn's disease.

Amidohydrolases↗