Clinical significance of topical instillation technique in Japanese glaucoma patients.

The clinical significance of a proper eye drop application technique was evaluated in Japanese glaucoma patients. Patients diagnosed with primary open-angle glaucoma having intraocular pressure (IOP) greater than 21 mmHg were treated with eye drops at home. In some patients, however, the topical treatment was ineffective. They returned to the hospital to receive surgical treatment. On admission, 56% of these patients had IOP greater than 21 mmHg. Patient instillation technique was evaluated based on the proximity of the eyedropper tip to the eyes, application position, eyelid closure, treatment (removal) of excess fluid, and nasolacrimal occlusion. In addition, pharmacists interviewed patients to determine the level of understanding of glaucoma, knowledge of prescribed drugs, home application technique, and sensation after application. Multivariate analysis revealed that the key factors influencing the control of IOP to less than 21 mmHg with topical medication were: application of drops in the center of the eye and removal of excessive fluid, in addition to gender and age. Proper topical application at home was dependent on the patient's understanding of the disease, knowledge of prescribed drugs, patient education on the use of drugs, the competence of the instructor, and knowledge of correct application technique. This study indicates that easily comprehensible patient education on the use of eye drops, the nature of glaucoma and the proper use of prescribed drugs is vital to improving the clinical efficacy of topical ophthalmic medication of glaucoma in adult patients.

Developmental changes of aldehyde oxidase activity in young Japanese children.

Aldehyde oxidase (AO) plays an important role in metabolizing many drugs, so AO activity in individual patients may be a useful parameter for dose adjustment to avoid severe toxicity. In this study, we investigated the developmental changes of AO activity in 101 children. Urine was collected in the morning, and AO activity was assessed in terms of the ratio of pyridone formation from N(1)-methylnicotinamide, an AO substrate. Significant correlations were found between AO activity and various growth indices (age, body weight, body surface area, and liver volume). Age showed the moderate correlation (r(2)=0.506). AO activity rapidly increased with increase of the subjects' age up to about 1 year. These findings suggest that the AO activity begins to increase soon after birth. Because AO activity is immature in children below 1 year of age, dose adjustment based on individual AO activity should be made for such patients.

Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of Helicobacter pylori infection.

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection. 99 patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole. METHODS: The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended. RESULTS: The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79-97%) and 92% in the RCM group (45 of 49; 95% CI = 84-99%). The incidence of adverse events was 16% and 18% for the two groups, respectively. CONCLUSIONS: No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2-blocker is sufficient to achieve optimal H. pylori eradication.

Identification of new C27 and C24 bile acids in the bile of Alligator mississippiensis.

Biliary bile acids of Alligator mississippiensis were analyzed by gas-liquid chromatography-mass spectrometry after fractionation by silica gel column chromatography. It was shown that the alligator bile contained 12 C27 bile acids and 8 C24 bile acids. In addition to the C27 bile acids, such as 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestanoic acid, 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid, 3 alpha,12 alpha-dihydroxy-5 beta-cholestanoic acid, 7 alpha,12 alpha-dihydroxy-3-oxo-5 beta-cholestanoic acid, and 3 alpha,12 alpha-dihydroxy-7-oxo-5 beta-cholestanoic acid, identified previously in the bile of A. mississippiensis, 3 alpha,7 beta-dihydroxy-5 beta-cholestanoic acid, 3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholestanoic acid, 7 beta,12 alpha-dihydroxy-3-oxo-5 beta-cholestanoic acid, 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholestanoic acid, and 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholestanoic acid were newly identified. And in addition to the C24 bile acids, such as chenodeoxycholic acid, ursodeoxycholic acid, cholic acid, and allocholic acid, identified previously, deoxycholic acid, 3 alpha,7 alpha-dihydroxy-5 beta-chol-22-enoic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-chol-22-enoic acid, and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-chol-22-enoic acid were newly identified.

Stereospecific formation of (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid and (24R,25S)-3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid from either (25R)- or (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid by rat liver homogenate.

Studies of the stereochemistry of the intermediates, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid and 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid, in the biosynthetic sequence between 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid and cholic acid have been undertaken. (25R)- or (25S)-3 alpha,7 alpha, 12 alpha-Trihydroxy-5 beta-cholestan-26-oic acid was incubated with rat liver homogenates. The reaction products were converted to p-bromophenacyl ester derivatives and the esters were analyzed by high-performance liquid chromatography. By comparison with authentic samples of two (24E)- and (24Z)-isomers of the alpha, beta-unsaturated acid and of four isomers at C-24 and C-25 of the beta-hydroxy acid, (24E)-3 alpha,7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid and (24R,25S)-3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid were found to be formed from either (25R)- or (25S)-3 alpha,7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid. No formation of the (24Z)-isomer of the trihydroxycholestenoic acid or the other three isomers of the tetrahydroxycholestanoic acid was detected. The findings are discussed in relation to the assumed pathway for side chain cleavage in cholic acid biosynthesis.

Intestinal absorption of bile alcohols.

The absorption of bile alcohols by rat small intestine was studied using in vivo and in vitro preparations. In bile duct cannulated rats, intraduodenal administered bile alcohols were certainly absorbed and excreted in the bile, although the absorption was not so efficient as for bile acids. The absorption during a 24 h period for free bile alcohol, bile alcohol 3-sulfate, and bile alcohol 3-glucuronide was 60%, 31%, and 30% of the dose, respectively, compared with 98% for taurocholate. In situ recirculation experiments demonstrated the linear relationship between perfusate concentration and intestinal absorption for unconjugated and 3-sulfated bile alcohols. Everted gut sacs of rat ileum actively transported a bile alcohol possessing a sulfuric acid ester group on the side chain. However, free bile alcohol, bile alcohol 3-sulfate, and bile alcohol 3-glucuronide were not transported. These results indicate that bile alcohols having no negative charge on the side chain are absorbed by passive diffusion and not by active transport.

Metabolism of bile alcohols, 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-26,27-dinor-5 beta-cholestan-24-one, in rats.

24-Nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-26,27-dinor-5 beta-cholestan-24-one were administered intraperitoneally to bile fistula rats, and the metabolites excreted in the bile were analyzed. No formation of bile acids from these bile alcohols was observed. 7 alpha,12 alpha,25-Trihydroxy-24-nor-5 beta-cholestane-3 alpha-O-(beta-D-glucopyranosid)uronic acid was identified as the only biliary metabolite of the 24-nor-5 beta-cholestanetetrol. The major metabolite of the trihydroxy-26,27-dinor-5 beta-cholestanone was 7 alpha,12 alpha-dihydroxy-24-oxo-26,27-dinor-5 beta-cholestane-3 alpha-O-(beta-D-glucopyranosid)uronic acid, and the minor metabolite was the glucurono conjugate of 26,27-dinor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 beta-tetrol. The results indicated that in rat liver these C25- and C26-bile alcohols, in contrast to C27-bile alcohols, were not converted into bile acids, and that the glucuronide production became necessary for hepatic elimination of the accumulated bile alcohols.

Determination of the glucurono-conjugated position in bile alcohol glucuronides excreted in urine of a patient with cerebrotendinous xanthomatosis by a nuclear magnetic resonance study.

This paper describes the determination of the glucurono-conjugated position in two bile alcohol glucuronides excreted in urine of a patient with cerebrotendinous xanthomatosis by a nuclear magnetic resonance study. The urine sample was extracted with reversed-phase resin, and chromatographed on a reversed-phase partition column and a silica gel column to isolate glucurono-conjugates of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23,25- pentol. Proton and carbon-13 nuclear magnetic resonance spectra of the natural tetrol glucuronide were identical with those of the chemically synthesized tetrol glucuronide, 7 alpha, 12 alpha, 25-trihydroxy-5 beta-cholestane-3 alpha-O-beta-D- glucopyranosyluronic acid. Hence, the glucurono-conjugated position of the natural tetrol glucuronide was determined to be the C-3 position. By comparison of the 13C chemical shift data with that of the unconjugated pentol, 5 beta-cholestane-3 alpha, 7 alpha, 23,25-pentol, the glucurono-conjugated position of the natural pentol glucuronide was determined to be C-23. Thus the natural pentol glucuronide can be formulated as 3 alpha, 7 alpha, 12 alpha, 25- tetrahydroxy-5 beta-cholestane-23-O-beta-D-glucopyranosyluronic acid. The difference in the glucurono-conjugated position between the 25-tetrol glucuronide and the 23,25-pentol glucuronide indicates that the former is not the biosynthetic precursor of the latter.

Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate in hamsters.

Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate, the sulfonate derivative of chenodeoxycholic acid, was studied in hamsters. In bile fistula hamsters, the sulfonate analogue was efficiently absorbed from the ileum and secreted rapidly into the bile without any modification such as conjugation. However, absorption from the jejunum was smaller than that observed for the ileum. After oral administration, the sulfonate analogue of chenodeoxycholic acid was recovered quantitatively in the feces as the unchanged form in contrast to simultaneously administered chenodeoxycholic acid, which was entirely converted to lithocholic acid during its passage through the intestinal tract. These results demonstrate that the sulfonate analogue is absorbed mainly from the ileum by active transport, enters the enterohepatic circulation like the endogenous conjugated bile acids, and completely resists bacterial degradation.

Bile alcohol profiles in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis.

Bile alcohols in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis have been analyzed by a combination of capillary gas-liquid chromatography and mass spectrometry after fractionation into groups according to mode of conjugation. The presence of at least 18 bile alcohols, which were excreted mainly as glucurono-conjugates in bile and urine, and as unconjugated forms in feces, was demonstrated. The following bile alcohols were identified with certainty by direct comparison with reference compounds: 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol; (23R)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,23-tetrol; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrols; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrols; 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol; (22R)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,22,25-pentol; (23R)- and (23S)-5 beta-cholestane-3 alpha,7 alpha, 12 alpha,23,25-pentols; 3 alpha,12 alpha,25-trihydroxy-5 beta-cholestane-7-one; (24R)- and (24S)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentols; 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol. Although the bile alcohol profile in urine was quite different from those in bile and feces, the determination of urinary bile alcohols as well as of biliary and fecal bile alcohols could be used for diagnosis of cerebrotendinous xanthomatosis.

The value of LYM-1 cells for examining vacuole formation and loss of cell viability induced by culture supernates of Helicobacter pylori.

Some strains of Helicobacter pylori are known to produce an extracellular cytotoxin that causes vacuolation in cultured mammalian cells. Screening for such strains makes use of HeLa cells which may not be sensitive enough to detect minimal changes. The aim of this study was to develop a more sensitive cell line. Vacuole formation was examined in HeLa cells, as well as four other cell lines established in this laboratory by ammonium chloride induction. Among five cell lines tested, LYM-1 cells were most sensitive for the detection of intracellular vacuolation with this agent. Loss of cell viability of LYM-1 and HeLa cells induced by H. pylori culture supernates was also examined: LYM-1 were more sensitive than HeLa cells. Cell death was not always accompanied by vacuole formation. This suggests that the mechanism whereby cell death occurs must be different from that for vacuole formation. LYM-1 cells may be useful when measuring vacuole formation and cell death of the cultured cells induced by culture supernates of clinical isolates of H. pylori.

Amnesic effects of the anticholinergic drugs, trihexyphenidyl and biperiden: differences in binding properties to the brain muscarinic receptor.

An amnesic effect of anticholinergic drugs was previously described from several behavioral studies. We examined this effect induced by trihexyphenidyl and biperiden, clinically used in the parkinsonism and schizophrenic patients, by using passive avoidance tasks. Both of these drugs (0.1-10 mg/kg, s.c.) showed dose-dependent amnesic effects in the acquisition and retrieval phases. However, the effect induced by trihexyphenidyl was transient, whereas that of biperiden was long-lasting. To clarify the reason for the different duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [(3)H]quinuclidinyl benzilate ([(3)H]QNB) on the muscarinic receptor (showed increased K(d) and unchanged B(max) value), while biperiden decreased [(3)H]QNB binding (B(max) value) significantly. Furthermore, in an exchange assay for receptor inactivation, trihexyphenidyl binding to muscarinic receptors was exchanged by [(3)H]QNB completely, but biperiden decreased the exchangeable binding of [(3)H]QNB in a dose dependent manner (0.1-100 nM). These results suggested that the binding of trihexyphenidyl and biperiden to muscarinic receptor might be completely reversible and partially irreversible, respectively, whereas the K(i) values of these two drugs were similar. In conclusion, this difference in binding property may explain the difference in the time-course of the amnesic effect induced by trihexyphenidyl and biperiden.

Efficacy of clarithromycin in eradicating Helicobacter pylori.

We reviewed reports on the efficacy of clarithromycin in eradicating Helicobacter pylori. Reports on dual and 1-week triple therapy that included clarithromycin were analyzed to assess the eradication rates of H. pylori infection. Dual therapy with clarithromycin and a proton pump inhibitor achieved eradication rates of 38%-83%, and 1-week triple therapy with omeprazole, clarithromycin, and other antibiotics achieved eradication rates, of 80%-96%. The incidence of side effects with all regimens was low. Clarithromycin is useful for treatment of H. pylori infection. One-week triple therapy that includes clarithromycin and a proton pump inhibitor effectively eradicates H. pylori.

Some personal comments on the Sydney system for the classification of chronic gastritis.

The Sydney system for the classification of chronic gastritis is a system for describing the histopathological findings of a biopsy specimen. It involves the analysis of two to four biopsies of the gastric mucosa taken from arbitrary sites, which, taken alone, are insufficient for extrapolation to the diagnosis of the whole stomach. The system seems to be useful as a computer-oriented method fo documenting the histopathological analysis of the two to four biopsy specimens obtained from the arbitrary sites in the antrum or corpus. One biopsy specimen is obtained from the anterior wall of the antrum, the other from the posterior wall. They would be better obtained from the lesser and greater curvatures, which areas would provide more accurate data concerning the antrum or body. While this may be invaluable for researchers with particular interests, it is quite valueless for the majority of clinicians who must diagnose and treat their patients. When a classification is made, its purposes should, firstly, be clear and definite. Secondly, the classification should be simple and easy to use. If a classification is effective, it will be widely used. However, in this field, it is almost impossible to achieve a classification that will fully satisfy all practitioners and researchers with different interests. The Sydney system alone is not sufficient for the classification of chronic gastritis. It is merely a system for describing the histopathological findings of biopsy specimens. It does not allow for an integrated diagnosis of chronic gastritis of the entire stomach.

Endoscopic topical therapy for the treatment of Helicobacter pylori infection.

We modified a novel topical therapeutic method for the treatment of Helicobacter pylori infection to increase its effectiveness and tolerability. Sixty-six patients (with nonulcer dyspepsia, inactive ulcer, or active ulcer) were given lansoprazole (30 mg, h.s.) and pronase (18,000 tyrosine units, b.i.d.) orally for 2 days before the topical therapy. One hundred milliliters of 7% sodium bicarbonate solution containing bismuth subnitrate, amoxicillin, metronidazole (at two different regimens), and pronase was instilled into the stomach through an endoscope. A double-lumen tube with a balloon at the tip was inserted into the duodenum along with the endoscope. The balloon was inflated with 25 ml of air and was lodged postbulbarly. The solution was kept in the stomach for 2 h, and the patient's position was changed every 15 min from the sitting to the supine, prone, and right lateral position, each position being maintained twice, to expose the entire gastric mucosa. The solution was aspirated at the end of the procedure. H. pylori infection was cured in 16/22 (72.7%) of patients with nonulcer dyspepsia, in 21/26 (80.7%) of patients with inactive ulcer, and in 1/18 (5.6%) patients with active ulcer. H. pylori eradication was confirmed 4 weeks after the therapeutic procedure by smear, culture, and histology of antral and corpus biopsy specimens. Side effects (loose stools) were observed in two patients only, and one patient had loss of appetite. These effects were transient. This endoscopic topical therapy for H. pylori infection is a safe, effective, and well tolerated procedure. With further modifications of the drug regimens and the method itself, this procedure could be of interest as anti-H. pylori therapy.

Simple 13C-urea breath test with infra-red spectrophotometer.

When mass spectrophotometric analysis is used for the 13C-urea breath test to assess H. pylori infection, it is costly, complicated, and time-consuming. To overcome these disadvantages, we utilized an infra-red spectrophotometer as a substitute for the mass spectrophotometer. A total of 153 patients (181 tests) analyzed with peptic ulcers or non-ulcer dyspepsia were investigated. Breath samples were collected 15 min after ingestion of 13C-urea (100 mg in 30 ml water). An infra-red spectrophotometer was used to determine the concentration of 13CO2 in the expirate. The 13CO2/12CO2 ratio was also measured by mass spectrophotometry to compare results with those of infra-red spectrophotometric analysis. Direct detection of H. pylori was qualified in biopsy specimens. Of the 181 biopsies, 138 were positive for H. pylori infection and 43 were negative. With the urea breath test, the mean value in the positive group was significantly higher than that in the negative group (0.062 +/- 0.044 vs 0.011 +/- 0.014, respectively). The cut-off level, 0.01, was determined as delta 13C atom %. The sensitivity of infra-red spectrophotometry was 97.8% (135/138) and specificity was 74.4% (32/43). There was an extremely high coefficient of correlation (r = 0.996) between mass and infra-red photometric analysis. Infra-red spectrometry appears to have great potential not only for diagnosing H. pylori infection but also for assessing treatment results. Its advantages include technical simplicity, cost-effectiveness, and high accuracy.

Comparison of Gastric Histology Among Swedish and Japanese Patients with Peptic Ulcer and <emph type="2">Helicobacter pylori</emph> Infection.

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

Synthesis of alpha,beta-unsaturated C24 bile acids.

Synthesis of the alpha,beta-unsaturated analogues of cholic acid, deoxycholic acid, chenodeoxycholic acid, and ursodeoxycholic acid is described. Each common bile acid was converted to the corresponding C22 aldehyde which was then converted to the delta 22 bile acid by Wittig reaction with methyl (triphenylphosphoranylidene)acetate. The synthetic unsaturated bile acids were characterized by thin-layer chromatography, gas-liquid chromatography, and mass spectrometry.

Metabolism of (24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and 27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid in guinea pigs.

[7beta-3H]-(24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and [7beta-3H]-27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid (C27 and C26 bile acids having the same nuclear configuration as cheno-deoxycholic acid and its precursor, 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic-acid) were synthesized and administered intraperitoneally to bile fistula guinea pigs. The biliary bile acids formed were hydrolyzed and analyzed by thin layer chromatography, and the metabolites were identified by the inverse isotope dilution method. The results showed that both (24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids were not metabolized by the liver and were excreted unchanged as their taurine and glycine conjugates whereas 27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid was converted to chenodeoxycholic acid.