Biomedical subjects

A Roda

Publications and source records attributed to A Roda.

At least 91 records · Page 5Linked to original sources

PubMed1992

Bile acid active and passive ileal transport in the rabbit: effect of luminal stirring.

The intestinal absorption of bile acids (BA) with different chemical structure has been evaluated in the rabbit, after intestinal infusion of different concentrations (0.25-30 mM) of BA, by mesenteric blood sampling. Cholic (CA), chenodeoxycholic (CDCA), ursodeoxycholic (UDCA) acid, free and taurine (T-) conjugated, together with glycocholic (GCA) acid and deoxycholic acid (DCA) were studied. The apparent uptake parameters were calculated. All conjugated BA showed active transport (T max, nmol min-1 cm-1 int.), with Tmax values in the following order: TCA > TUDCA > TCDCA; unconjugated BA showed passive uptake, with values in the following order: DCA > CDCA > UDCA > CA. GCA and CA showed both passive uptake and active transport. For all BA studied the % uptake in the ileal segment considered was less than 10%, BA uptake being thus limited by transport and/or diffusion kinetics, rather than by flow velocity. The liquid resistance to BA radial diffusion inside the lumen was evaluated, and the infusate-to-blood uptake parameters corrected for it, in order to get the uptake parameters from the epithelium-to-liquid interface to mesenteric blood: the apparent Km decreased, passive uptake coefficient increased, while Tmax was unchanged. The passive component of the uptake, corrected for the luminal resistance, correlated with the BA hydrophobicity (r = 0.963; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Immunoperoxidase localization of ursodeoxycholic acid in rat biliary epithelial cells. Evidence for a cholehepatic circulation.

To explain the hypercholeretic effect of ursodeoxycholic acid, a cholehepatic shunt circulation has been postulated. This pathway includes secretion by the hepatocyte into bile and absorption by the biliary epithelial cells. To test this possibility, we have attempted to localize ursodeoxycholic acid in hepatocytes and portal bile duct cells by an indirect immunoperoxidase technique using specific polyclonal antibodies against ursodeoxycholic acid and cholic acid conjugates. Rat livers were fixed with paraformaldehyde, incubated with antibodies directed against bile acids and examined by electron microscopy. After infusion of ursodeoxycholic acid and incubation with antibodies against this bile acid, an electron-dense staining was observed on the apical (luminal) membrane of the portal bile ductal cells. In contrast, no staining was observed when no ursodeoxycholic acid was infused, or after infusion with taurocholate and incubation with antibodies against cholic acid conjugates. These observations are consistent with absorption of ursodeoxycholic acid by the portal bile ducts and a cholehepatic circulation of this bile acid.

Animals↗

PubMed1992

Determination of free and amidated bile acids by high-performance liquid chromatography with evaporative light-scattering mass detection.

A simple reverse phase high-performance liquid chromatographic method for a simultaneous analysis of free, glycine- and taurine-amidated bile acids is described. The resolution of ursodeoxycholic, cholic, chenodeocycholic, deoxycholic, and lithocholic acids, either free or amidated with glycine and taurine, is achieved using a C-18 octadecylsilane column (30 cm length, 4 micron particle size) with a gradient elution of aqueous methanol (65----75%) containing 15 mM ammonium acetate, pH 5.40, at 37 degrees C. The separated bile acids are detected with a new evaporative light-scattering mass detector and by absorbance at 200 nm. A complete resolution of the 16 bile acids, including the internal standard nor-deoxycholic acid, is obtained within 55 min. Using the light-scattering mass detector, amidated bile acids and, for the first time, free bile acids can be detected with similar detection limits in the order of 2-7 nmol. The new detector improves the baseline and the signal-to-noise ratio over the UV detection as it is not affected by impurities present in the samples with higher molar absorptivity than bile acids or by the change in the mobile phase composition during the gradient. The method fulfills all the standard requirements of precision and accuracy and the linearity of the mass detector is over 5 decade the detection limit. The new method has been used for the direct analysis of bile acid in stools and bile with only a preliminary clean-up procedure using a C-18 reverse phase extraction.

Bile↗

PubMed1992

Chemical properties of bile acids. V. Interaction with concentrated sulfuric acid.

The reaction between concentrated sulfuric acid and steroid hydroxy compounds, previously studied for a series of sterols, was used to develop an analytical method for bile acids. The reaction generates species absorbing in the wavelength ranges 300-320 and 370-390 nm, corresponding to isomeric allylic and dienylic carbocations. Eleven bile acids were examined and influence of time, temperature and sulfuric acid concentration on the chromogenic reaction was studied. The linear dependence of absorbance on concentration of individual bile acids demonstrates that the method can be used to measure spectrophotometrically micromolar concentrations of bile acids.

Adsorption↗

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

Microdialysis and luminescent probe: analytical and clinical aspects.

Immobilized enzymes are widely used in the clinical laboratory to assay several analytes and enzymes. The use of immobilized enzymes makes these reagents recoverable, disposable and in most cases increases their stability and catalytic activity. In conjunction with bioluminescent enzymes (firefly and bacterial luciferases) and chemiluminescent catalyst (peroxidase) we set up high-sensitive flow sensors based on the use of nylon tube coil or epoxy methacrylate column as solid support. For in-vivo determination a suitable microdialysis probe inserted directly into brain or blood allows continuous measurement of extracellular lactate levels by means of a bioluminescent flow detector system. This procedure performs more measurements in the same time interval than other systems (HPLC), e.g. to give a detailed description of the effects of ischemia, or other pathological events, on lactate concentration in the brain.

Animals↗

PubMed1991

Pharmacokinetics of ursodeoxycholic acid in rat.

The pharmacokinetic behaviour and metabolism of ursodeoxycholic acid (UDCA) have been studied in the rat. After oral administration of both 3H-labelled (4 muCi/kg body wt) and unlabelled (20 mg) UDCA, UDCA appeared in serum almost entirely in conjugated form (taurine conjugated); UDCA was present in bile mostly as taurine conjugated; the more relevant metabolite is 3 alpha,6 alpha, 7 beta-trihydroxycholanoic acid which represents 10% of the total bile acid pool. UDCA increased bile flow and selectively decreased biliary cholesterol secretion, while phospholipid secretion was unaffected. Faecal UDCA excretion was 15-20% while the urinary extraction was 1.5% during 24 h. The data show that UDCA, when administered in high dose, is promptly secreted into bile almost entirely metabolized to tauroursodeoxycholic acid, where it (1) desaturates the cholesterol in bile, (2) exerts choleretic properties.

Administration, Oral↗

PubMed1991

Effects of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis: a dose-response study.

The effect of ursodeoxycholic acid administration on liver function tests and on bile acid metabolism was investigated in 18 patients with chronic active hepatitis. Three different doses of ursodeoxycholic acid--250 mg, 500 mg and 750 mg--were administered daily to each patient for consecutive 2-mo periods. The order of doses was randomly assigned according to a replicated Latin-square design. A significant decrease in serum transaminases and gamma-glutamyl transpeptidase occurred with the lowest dose of ursodeoxycholic acid, which corresponded to 4 mg/kg body wt/day, and no further significant decrease with the higher doses was seen. Biliary bile acid composition was determined by high-performance liquid chromatography and gas chromatography-mass spectrometry. At entry the relative proportions of major bile acids were similar to those observed in normal individuals. During treatment the mean percentage of ursodeoxycholic acid in bile (22% with the 250 mg dose, 32% with the 500 mg dose and 34% with the 750 mg dose) was lower than values previously reported for patients with gallstones and normal liver function. The major bile acids were cholic, chenodeoxycholic and deoxycholic acids. A number of unusual bile acids were identified by gas chromatography-mass spectrometry, but these accounted for only 3% to 5% of the total and did not change during ursodeoxycholic acid therapy. No correlation between the improvement in liver function tests and the percentage of ursodeoxycholic acid in bile existed. These data suggest that even a slight enrichment of bile with ursodeoxycholic acid, as is attained with 250 mg/day, is effective in improving biochemical markers of liver function in patients with chronic active hepatitis.

Adult↗

PubMed1990

Quantitative structure-antimicrobial activity relationship in 5 beta-cholanyl-24-benzylamine derivatives.

Some representative physicochemical properties of benzylamido and amino derivatives of common bile acids have been determined and correlated with their antimicrobial activity against gram-positive bacterial strains. Steroid hydroxyls do not affect the basicity of amino derivatives; they promote solubility in a parallel way to unconjugated bile acids and mainly control hydrophobicity of this class of compounds as measured by log P values. Activity was correlated to hydrophobicity; that is, the nature of the side chain modulated activity, affected basicity, and facilitated changes in partition ability. Benzylamino derivatives proved to be even more active than the corresponding amides when ionization is taken into account. Trihydroxy derivatives possess the lowest log P values and were practically inactive. Decreased activity was also observed in those cases where, due to the orientation of the hydroxy group in the 6 or 7 position, the back beta face of the molecule had a reduced hydrophobic surface area. Antimicrobial activity, in terms of -log MIC (minimal inhibitory concentration), was found to correlate linearly with log P values of uncharged species. This linear relationship is discussed with respect to the structure of the steroid moiety and the ability of these molecules to cross cellular membranes.

Anti-Bacterial Agents↗

PubMed1990

Effects of ursodeoxycholic acid and taurine on serum liver enzymes and bile acids in chronic hepatitis.

Hydrophobic bile acids have been shown to be hepatotoxic, whereas treatment with ursodeoxycholic acid, a hydrophilic bile acid, has improved liver function indices in patients with chronic liver disease. Taurine administration has also been suggested to be useful for chronic hepatitis, taurine-conjugated bile acids being more hydrophilic than glycine-conjugated bile acids. To determine if taurine and ursodeoxycholic acid are beneficial and if their effects are additive, a double-blind, randomized trial was designed comparing the effects of ursodeoxycholic acid, taurine, and a combination of the two on indices of liver injury in 24 patients with chronic hepatitis. They were assigned at random to two of the four following treatments: ursodeoxycholic acid (600 mg/day), taurine (1.5 g/day), ursodeoxycholic acid plus taurine (600 mg + 1.5 g/day) or placebo, given in two successive cycles of 2 mo each, according to a balanced incomplete-block design. Ursodeoxycholic acid became the predominant biliary bile acid when administered alone or in combination with taurine, and taurine conjugate levels increased during taurine administration. Ursodeoxycholic acid reduced aspartate aminotransferase (35%), alanine aminotransferase (33%), and gamma-glutamyl transpeptidase (41%), whereas taurine alone did not. The addition of taurine to ursodeoxycholic acid produced only minor changes in the effects of ursodeoxycholic acid alone. Results were confirmed by the administration of ursodeoxycholic acid, in a successive open phase of the study, to the entire patient population, which was large enough for different subsets of patients to be compared. Serum bile acids were measured at entry and during the open phase: primary bile acids did not change, whereas ursodeoxycholic acid levels increased from trace amounts to very high levels, especially in patients with more severe histological disease. It is concluded that ursodeoxycholic acid, but not taurine, improves enzymatic indices of liver injury in chronic hepatitis.

Adult↗

PubMed1990

Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis.

The hydrophilic bile acid ursodeoxycholic acid (UDCA) has recently been shown to improve indexes of liver function in adult patients with various liver diseases. The clinical and biochemical responses to UDCA administration (10 to 15 mg/kg body weight per day) were therefore investigated in nine patients with cystic fibrosis and evidence of liver disease. All patients were receiving pancreatic enzymes and taurine supplementation. Liver function tests were done and serum bile acid concentrations and biliary bile acid composition were determined before and during UDCA therapy; fat balance studies and fecal bile acid excretion were carried out before and 6 months after UDCA treatment. After 2 months of bile acid therapy, biliary bile acid composition was enriched in UDCA from approximately 5% before treatment to 25%, at the expense of cholic and chenodeoxycholic acids, thus making the pool more hydrophilic. This enrichment is lower than that reported for adults with chronic liver diseases. Serum concentrations of UDCA increased significantly but variably. UDCA became the predominant fecal bile acid excreted (12% to 67%), indicating a variable absorption of the administered bile acid. Liver function improved in all patients after 2 to 6 months of therapy, although the degree of improvement (aspartate aminotransferase, -34%; alanine aminotransferase, -41%; gamma-glutamyltranspeptidase, -41% alkaline phosphatase, -19%) was lower than that observed in adults with chronic liver diseases. Mean coefficient of fat absorption and growth rate were, on average, unaffected by UDCA therapy, although an improvement was noted for three patients with greater severity of steatorrhea. The study indicates that UDCA can be used safely in this patient population but that higher doses of UDCA may be of greater benefit in the treatment of the liver disease associated with cystic fibrosis.

Adolescent↗

PubMed1990

Bioluminescent flow sensor for the determination of L-(+)-lactate.

The amount of L-lactate in biological fluids (serum, plasma and cerebrospinal fluid) was determined by monitoring the reduced form of nicotinamide adenine dinucleotide (NADH) produced by immobilised lactate dehydrogenase (LDH), with bacterial bioluminescent enzymes immobilised on a separate nylon coil. The LDH catalysed the reaction of L-lactate with NAD; this reaction took place in a nylon coil that preceded the coil for the bioluminescent detection. The co-immobilisation of alanine aminotransferase (ALT) with LDH improved the lactate transformation by 117-183%. The response was linear from 0.1 to 50 micron mol l(-1) at 25 degrees C for the LDH - ALT reactor. The intra- and inter-assay coefficients of variation were less than 5% and the recoveries ranged from 93 to 106%. The results agreed well with those obtained with a spectrophotometric method and with the normal reference values.

Alanine Transaminase↗

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↗

PubMed1990

Bile acid structure-activity relationship: evaluation of bile acid lipophilicity using 1-octanol/water partition coefficient and reverse phase HPLC.

Two independent methods have been developed and compared to determine the lipophilicity of a representative series of naturally occurring bile acids (BA) in relation to their structure. The BA included cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursocholic acid (UCA), hyocholic acid (HCA), as well as their glycine and taurine amidates. Lipophilicity was determined using a 1-octanol/water shake-flask procedure and the experiments were performed at different pH and ionic strengths and at initial BA concentrations below their critical micellar concentrations (CMC) and the water solubility of the protonated form. The experimental data show that both the protonated (HA) and ionized (A-) forms of BA can distribute in 1-octanol, and consequently a partition coefficient for HA (logP' HA) and for A- (logP' A-) must be defined. An equation to predict a weighted apparent distribution coefficient (D) value as a function of pH and pKa has been developed and fits well with the experimental data. Differences between logP for protonated and ionized species for unconjugated BA were in the order of 1 log unit, which increased to 2 for glycine-amidate BA. The partition coefficient of the A- form increased with Na+ concentration and total ionic strength, suggesting an ion-pair mechanism for its partition into 1-octanol. Lipophilicity was also assessed using reverse phase chromatography (C-18-HPLC), and a capacity factor (K') for ionized species was determined. Despite a broad correlation with the logP data, some BA behaved differently. The logP values showed that the order of lipophilicity was DCA greater than CDCA greater than UDCA greater than HDCA greater than HCA greater than CA greater than UCA for both the protonated and ionized unconjugated and glycine-amidate BA, while the K' data showed an inversion for some BA, i.e., DCA greater than CDCA greater than CA greater than HCA greater than UDCA greater than HDCA greater than UCA. The logP data fitted well with other indirect measurements of BA monomeric lipophilicity such as albumin binding or accessible total hydrophobic surface area data calculated by energy minimization and molecular computer graphics. Differences between unconjugated and amidated BA are consistent with the presence of an amide bond and a lower pKa when pH dependence was studied. Capacity factors, on the other hand, were related to properties of BA micelles such as cholesterol-solubilizing capacity and membrane disruption, reflecting the BA detergency.(ABSTRACT TRUNCATED AT 400 WORDS)

Bile Acids and Salts↗

PubMed1990

Physicochemical and biological properties of natural and synthetic C-22 and C-23 hydroxylated bile acids.

In order to define the effect of a side chain hydroxy group on bile acid (BA) physicochemical and biological properties, 23-hydroxylated bile acids were synthesized following a new efficient route involving the alpha-oxygenation of silylalkenes. 22-Hydroxylated bile acids were also studied. The synthesized bile acids included R and S epimers of 3 alpha,7 alpha,23-trihydroxy-5 beta-cholan-24-oic acid (23R epimer: phocaecholic acid), 3 alpha,12 alpha,23-trihydroxy-5 beta-cholan-24-oic (23R epimer: bitocholic acid), and 3 alpha,7 beta,23-trihydroxy-5 beta-cholan-24-oic acid. A 3 alpha,7 alpha,22-trihydroxy-5 beta-cholan-24-oic acid (haemulcholic acid) was also studied. The presence of a hydroxy group on the side chain slightly modified the physicochemical behavior in aqueous solution with respect to common BA: the critical micellar concentration (CMC) and the hydrophilicity were similar to naturally occurring trihydroxy BA such as cholic acid. The pKa value was lowered by 1.5 units with respect to common BA, being 3.8 for all the C-23 hydroxy BA. C-22 had a higher pKa (4.2) as a result of the increased distance of the hydroxy group from the carboxy group. When the C-23 hydroxylated BA were intravenously administered to bile fistula rats, they were efficiently recovered in bile (more than 80% unmodified) while the corresponding analogs, lacking the 23- hydroxy group, were almost completely glycine- or taurine-conjugated. On the other hand, the C-22 hydroxylated BA were extensively conjugated with taurine and less than 40% of the administered dose was secreted without being conjugated. In the presence of intestinal bacteria, they were mostly metabolized to the corresponding 7-dehydroxylated compound similar to common BA with the exception of bitocholic acid which was relatively stable. The presence of a hydroxy group at the C-23 position increased the acidity of the BA and this accounted for poor absorption within the biliary tree and efficient biliary secretion without the need for conjugation. 3 alpha,7 beta-23 R/S trihydroxy-5 beta-cholan-24-oic acids could improve the efficiency of ursodeoxycholic acid (UDCA) for gallstone dissolution or cholestatic syndrome therapy, as it is relatively hydrophilic and efficiently secreted into bile without altering the glycine and taurine hepatic pool.

Animals↗

PubMed1989

Coupled reactions for the determination of analytes and enzymes based on the use of luminescence.

Immobilized enzymes are widely used in the clinical laboratory in the assay of several analytes and enzymes. The use of immobilized enzymes makes these reagents recoverable and re-usable, and in most cases increases their stability and catalytic activity. In conjunction with bioluminescent enzymes (firefly and bacterial luciferases) and chemiluminescent catalyst (peroxidase) we set up high-sensitive flow methods based on the use of nylon tube coil or epoxy methacrylate column as solid support. All the NAD(P)/NAD(P)H-dependent dehydrogenases (bacterial luciferase), ATP-dependent enzymes (firefly luciferase) and oxidases producing H2O2 (peroxidase) can be immobilized and a large variety of analytes have been sensitively measured. As an alternative format we also reported a dry chemistry method in which all the enzymes, substrates and cofactors are ready to use, supported on dry cellulose disks. Methodological problems such as flow conditions, stability, pH, ionic strength and analytical performances are also reported.

Animals↗

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↗