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C M Rodrigues

Publications and source records attributed to C M Rodrigues.

5 recordsLinked to original sources
PubMed1995

delta 22-Ursodeoxycholic acid, a unique metabolite of administered ursodeoxycholic acid in rats, indicating partial beta-oxidation as a major pathway for bile acid metabolism.

We describe for the first time the identification of 3 alpha, 7 beta-dihydroxy-5 beta-chol-22-en-24-oic acid (delta 22-UDCA) in the plasma, bile, intestinal contents, and liver tissue of Sprague-Dawley rats after intravenous and oral administration of ursodeoxycholic acid (UDCA). Infusion of [2,2,4,4-2H4]UDCA confirmed delta 22-UDCA to be a specific metabolite of UDCA. Definitive confirmation of this unique and major metabolite was established by liquid secondary ionization mass spectrometry and gas chromatography-mass spectrometry by comparison of the retention index and mass spectrum with an authentic standard of delta 22-UDCA. When rats were fed a diet containing 1.0% UDCA, high concentrations of delta 22-UDCA were found in the plasma (40.3 +/- 11.8 mumol/L) and liver tissue (300.9 +/- 64.2 nmol/g of tissue), and these represented 36% and 57%, respectively, of the UDCA concentration. In animals fed 0.4% and 1.0% UDCA, the mass of delta 22-UDCA in the jejunum was high (7.5 +/- 0.9 and 6.6 +/- 0.6 mg, respectively), accounting for 50-60% of the total UDCA, but diminished markedly along the intestine, accounting for < 3% of the total UDCA in the colon. Although delta 22-UDCA was not found in biological samples from control rats, delta 22-beta-muricholic and delta 22-omega-muricholic acids were normal constituents of plasma and intestinal contents and were major muricholate isomers in liver tissue and bile. Synthesis of delta 22-bile acids appears to be highly specific toward bile acids possessing a functional 7 beta-hydroxyl group. We presume that, in common with pathways for endogenous bile acid synthesis, partial side-chain oxidation of UDCA occurs in the peroxisome with formation of alpha/beta unsaturation; since UDCA has only a 5-carbon side chain, release of propionic or acetic acid is not possible, beta-oxidation proceeds no further, and delta 22-UDCA is formed. While the mechanism of formation and physiological significance of delta 22-bile acids remain to be established, our data indicate that partial beta-oxidation is a quantitatively important pathway for endogenous bile acid synthesis and for UDCA metabolism in this species.

Animals↗
PubMed1995

Tauroursodeoxycholate increases rat liver ursodeoxycholate levels and limits lithocholate formation better than ursodeoxycholate.

BACKGROUND & AIMS: To explain the greater hepatoprotective effect of tauroursodeoxycholic acid vs. ursodeoxycholic acid, the absorption, hepatic enrichment, and biotransformation of these bile acids (250 mg/day) were compared in rats. METHODS: Bile acids were determined in intestinal contents, feces, urine, plasma, and liver by gas chromatography-mass spectrometry. RESULTS: The concentration of ursodeoxycholate in the liver of animals administered tauroursodeoxycholic acid (175 +/- 29 nmol/g) was greater (P < 0.05) than in animals administered ursodeoxycholic acid (79 +/- 19 nmol/g). Hepatic lithocholate was substantially higher after ursodeoxycholic acid administration (21 +/- 10 nmol/g) than after tauroursodeoxycholic acid administration (12 +/- 1 nmol/g). A concomitant reduction in the proportion of hydrophobic bile acids occurred that was greatest during tauroursodeoxycholic acid administration. In the intestinal tract, the mass of ursodeoxycholate and its specific metabolites was greater in rats administered tauroursodeoxycholic acid (27.2 mg) than those administered ursodeoxycholic acid (13.2 mg). In feces, the proportion of lithocholate was 21.9% +/- 4.9% and 5.4% +/- 4.0% after ursodeoxycholic acid and tauroursodeoxycholic acid administration, respectively. CONCLUSIONS: Compared with ursodeoxycholic acid, tauroursodeoxycholic acid induces a greater decrease in the percent composition of more hydrophobic bile acids within the pool, limits lithocholate formation, and increases hepatic ursodeoxycholate concentration. These differences are explained by increased hepatic extraction and reduced intestinal biotransformation and not by enhanced absorption of the amidated species.

Absorption↗
PubMed1995

The site-specific delivery of ursodeoxycholic acid to the rat colon by sulfate conjugation.

BACKGROUND & AIMS: Because ursodeoxycholate has been shown to act as a tumor-suppressive agent in the colon, the absorption and metabolism of its sulfate conjugates were examined in rats to show that sulfation would facilitate the site-specific delivery of ursodeoxycholate to the colon. METHODS: Bile acids were measured in intestinal contents, feces, urine, plasma, and liver tissue after oral administration of ursodeoxycholate and its C-3, C-7, and C-3,7 sulfate derivatives. RESULTS: Ursodeoxycholate was found in the jejunum after administration of all bile acids, but the mass was greatest for ursodeoxycholic acid administration. In the colon, lithocholic acid, normally found in negligible amounts, became the major bile acid after ursodeoxycholate administration. In contrast, reductions in mass and proportions of lithocholate and deoxycholate occurred after administering the C-7 sulfates. The fecal lithocholate/deoxycholate ratio, a risk marker for colon cancer, increased markedly after administration of ursodeoxycholate and its C-3 sulfate, but did not change after administering the C-7 sulfates. Unlike ursodeoxycholate or its C-3 sulfate, which increased liver concentrations of lithocholate and ursodeoxycholate, the C-7 sulfates had the opposite effect, which was consistent with poor absorption. CONCLUSIONS: Sulfation of ursodeoxycholate, specifically at the C-7 position, protects the molecule from bacterial degradation and inhibits its intestinal absorption, thereby facilitating delivery to the colon.

Animals↗
PubMedDate not supplied

Sterilization approval and follow-through in Brazil.

The purpose of this study was to examine the factors that affect approval for and completion of sterilization in Rio de Janeiro. Of 2,186 new female family planning clients, 1,256 requested sterilization and 925 were approved for surgery. Among the approved women, 639 scheduled surgery and, of these, 595 were sterilized within three months of approval. While approval is dependent mainly on demographic variables, especially age and parity, follow-through by a woman is related to her education and income. The steps that a woman must complete to obtain a sterilization also affect whether she ultimately undergoes surgery. Almost no women were scheduled for sterilization during their initial clinic visit. Women who were not scheduled because they lacked certain documentation were more likely to follow through than women who, in addition to lacking documentation, were asked to switch from an inefficient contraceptive method (or no method) to a more modern one. The lessons to be learned from this study provide useful information to programs in other countries that are concerned about maintaining high standards but do not want to discourage women in their efforts to be sterilized.

Adult↗