Probiotics: antistaphylococcal activity of 4-aminocyclohexanecarboxylic acid, aminobenzoic acid, and their derivatives and structure-activity relationships.
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OBJECTIVE: To determine the possible complementary role of the ursodeoxycholic acid-p-aminobenzoic acid (UDCA-PABA) loading test in the diagnosis of intestinal bacterial overgrowth. DESIGN: A prospective clinical study. PATIENTS AND METHODS: The hydrogen breath and UDCA-PABA tests were performed simultaneously in 68 patients with suspected contaminated small bowel syndrome (CSBS), and in 10 healthy control subjects. The hydrogen breath test was performed by oral loading of 25 g of lactose and/or 10 g of lactulose. The UDCA-PABA test was carried out by oral loading of 250 mg of UDCA-PABA conjugate, followed by measurement of the amount of PABA excreted in the urine. The diagnosis of bacterial overgrowth was considered to be established when either the hydrogen breath test or the UDCA-PABA test produced abnormal results. RESULTS: Thirty-five of the 68 patients proved to have CSBS. In 13 of these 35 patients, only the enhanced urinary PABA excretion (11.7 +/- 1.42 mg vs. 3.6 +/- 0.68 mg) indicated bacterial overgrowth, 15 of the 35 patients gave only a positive hydrogen breath test, and in the remaining seven cases the results of both tests were abnormal. In eight CSBS patients, the urinary excretion of PABA was decreased significantly following 10-day tinidazole treatment (5.5 +/- 1.29 mg vs. 13.1 +/- 2.07 mg). CONCLUSION: The UDCA-PABA test is a valuable clinical method for the detection of bacterial overgrowth, especially in cases where hydrogen production alone fails to reveal CSBS. It is also a useful procedure for evaluating the efficacy of antibacterial treatment.
UNLABELLED: Contaminated small bowel syndrome is frequently associated with meteorism due to excessive gas formation, and diarrhoea as a result of bacterial fermentative processes, including splitting of carbohydrates or deconjugating and dehydroxylating bile salts. In addition to gas production, bacteria capable of metabolizing bile salts have been shown to release p-aminobenzoic acid (PABA) from and Ursodeoxycholic-acid-PABA substrate. Our aim was to determine the possible complementary role of the UDCA-PABA test in the diagnosis of bacterial overgrowth. PATIENTS AND METHODS: The H2 breath and UDCA-PABA tests were performed simultaneously on 46 patients with suspected contaminated small bowel syndrome, and on 7 healthy subjects. The H2 breath test was performed by oral loading of 25 g lactose and/or 10 g lactulose. The UDCA-PABA test was carried out by determining urinary excretion of PABA after oral loading with 250 mg UDCA-PABA conjugate. The diagnosis of bacterial overgrowth was established, when either H2 breath, or UDCA-PABA test proved to be pathological. RESULTS: Based upon the pathologic values of either the H2 breath test, or the UDCA-PABA test, 25 out of 46 patients proved to have contaminated small bowel syndrome. In 10 out of 25 patients only pathologic urinary PABA excretion (12.772 +/- 1.707 vs 4.1 +/- 0.58), indicated bacterial overgrowth, and in 9 out of the same group only positive H2 breath test (early rise of > 20 ppm of H2) indicated the same, while in 6 cases both tests proved to be pathological. In 7 CSBS patients the urinary excretion of PABA significantly decreased following a 10 day Tinidazole treatment (5.48 +/- 1.286 vs 13.068 +/- 2.068). CONCLUSION: The UDCA-PABA test proved to be a valuable complementary method to detect bacterial overgrowth, when H2 production failed to reveal bacterial overgrowth.
In various studies during recent years, the use of p-aminobenzoic acid has been described in screening tests for exocrine pancreatic function. A synthetic three-unit compound N-benzoyl-L-tyrosyl-p-aminobenzoic acid has been administered orally and hydrolysed in the small intestine in the presence of chymotrypsin to N-benzoyl-L-tyrosine and p-aminobenzoic acid. This study describes a convenient procedure in which, after a selective extraction and derivatization with diazomethane, capillary gas chromatography is used combined with nitrogen-sensitive detection. With the proposed procedure, p-aminobenzoic acid and its major metabolites, acetyl-p-aminobenzoic acid and p-aminohippuric acid, can be monitored in serum and in urine samples.
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The aim of the present study was to evaluate the transfer of N-acetyl-p-aminobenzoic acid (AcPABA) across the rat term placenta and the rat small intestine and to compare it with that of its parent drug p-aminobenzoic acid (PABA). Umbilical perfusion of the rat term placenta was used to determine the materno-fetal transfer. AcPABA appeared in the fetal compartment significantly more slowly than PABA (k transfer = 0.023 and 0.064 min(-1), respectively). The rate of equilibration between the maternal and fetal compartments was slightly lower for AcPABA than for the parent drug (k eqilibration = 0.0082 and 0.011 min(-1), respectively). Similarly, AcPABA was shown to be absorbed from the small intestine significantly more slowly than PABA (ka = 0.052 and 0.82 min(-); tmax = 37 and 3.1 min, respectively). Our results showed that both investigated compounds which are structurally related and very similar in their physical-chemical characteristics crossed both the placental and small intestinal barrier with a different kinetics. AcPABA was transported across both barriers significantly more slowly than its parent compound, which might indicate a possible equipment of the placenta with a carrier for PABA, a similar one to that previously found in the rat small intestine.
Absorption and metabolic characteristics of p-aminobenzoic acid (PABA) and m-aminobenzoic acid (MABA) from the rat small intestine were examined by means of in situ recirculation and in vitro everted sac experiments. p-Aminobenzoic acid was extremely rapidly absorbed from the rat small intestine, whereas the absorption of MABA, the m-isomer of PABA, was comparably slower. This finding was partly explained by the result that PABA is more lipophilic than MABA. The metabolite percentage of PABA was considerably greater than that of MABA in mucosal fluid, tissue, and serosal fluid. On the other hand, a concentration-dependent and a directional difference in the transfer rate of these drugs were observed in everted and noneverted sacs of rat small intestine. Furthermore, mucosal uptake of PABA or MABA was inhibited by 1 mM 2,4-dinitrophenol, 10 mM sodium azide, and pretreatment with HgCl2 (10 mM). These results indicate that MABA, as well as PABA, is transported through the intestine by a carrier-mediated transport system, and that the molecular structure of these drugs is important for their absorption and metabolic characteristics.
Agaricus bisporus contains the unique aniline derivative, N-(gamma-L-glutamyl)-4-hydroxyaniline. 14C-labelled chorismic acid was quantitatively incorporated into the 4-hydroxyaniline moiety of this aniline derivative, whereas 14C-labelled prephenic acid and anthranilic acid were not incorporated into 4-hydroxyaniline. These observations indicate the branch point of the biosynthetic route of 4-hydroxyaniline in the shikimic acid pathway to be chorismic acid. Moreover, 4-aminobenzoic acid proved to be an effective precursor of 4-hydroxyaniline.
The percutaneous absorption and metabolism of three structurally related compounds, benzoic acid, p-aminobenzoic acid (PABA), and ethyl aminobenzoate (benzocaine), were determined in vitro through hairless guinea pig skin. Benzocaine was also studied in human skin. Absorption of benzocaine was rapid and similar through both viable and nonviable skin. The absorption of the two acidic compounds, benzoic acid and PABA, was greater through nonviable skin. A small portion (6.9%) of absorbed benzoic acid was conjugated with glycine to form hippuric acid. Although N-acetyl-benzocaine had not been observed as a metabolite of benzocaine when studied by other routes of administration, both PABA and benzocaine were extensively N-acetylated during percutaneous absorption. Thus, the metabolism of these compounds should be considered in an accurate assessment of absorption after topical application.
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Nitrosation of the carbamate insecticide propoxur at pH 3 and 37 degrees C was determined colorimetrically and found to be time- and sodium nitrite concentration-dependent. Nitrosated propoxur was mutagenic when exposed to the seeds of the higher plant Arabidopsis thaliana but the formation of nitrosopropoxur, the presumed mutagen, was inhibited by humic acids, para-aminobenzoic acid and ascorbic acid. These agents also reduced the mutagenicity of preformed nitrosopropoxur.
3-Hydroxy-para-aminobenzoic acid (3-HPABA), a biotransformation product of procaine and para-aminobenzoic acid, is capable of binding covalently to proteins by simple incubation at alkaline pH. When administered incorporated in Freund adjuvant to rabbits, 3-HPABA conjugates with normal rabbit serum proteins (3-HPABA-NRS) give rise to both hapten specific antibodies and anti-NRS antibodies. Cross immunological reactions were found between 3-HPABA and ortho-aminophenol (OAP) and 3-hydroxy-sulfanilamide (3-HS) immunological systems, but not between 3-HPABA and para-aminophenol (PAP) and 5-aminosalicyclic acid (5-ASA) immunological systems. The significance of these findings for the explanation of procaine allergy and the possible use of 3-HPABA conjugates for skin testing in procaine hypersensitivity is discussed.
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Para-aminobenzoic acid (PABA) and some of its esters, such as amyl para-dimethylaminobenzoate, ethyl 4-bis(hydroxypropyl)aminobenzoate, 2-ethylhexyl para-dimethylaminobenzoate and glyceryl para-aminobenzoate are used as sunscreen agents. Methods for separating PABA and the 5 mentioned PABA esters by thin layer chromatography and high pressure liquid chromatography (HPLC) are presented. Contamination with PABA and benzocaine were measured quantitatively by the HPLC technique in samples of the 4 PABA esters, using different brands and different batches of the same brand. PABA was detected in all 12 samples examined and benzocaine in 11. The degree of contamination was batch-dependent. Minimal amounts of PABA and benzocaine were found in most batches but in glyceryl para-aminobenzoate both substances were present at a level above 0.1% (w/w). High levels of benzocaine were also detected in batches of ethyl 4-bis(hydroxypropyl)-aminobenzoate.
Hydrolysis of ursodeoxycholyl-p-aminobenzoic acid (PABA-UDCA), a synthetic bile acid conjugate used for the evaluation of the activity of intestinal bacterial growth, was studied with pancreatic enzymes, carboxypeptidase A, carboxypeptidase B, trypsin alpha-chymotrypsin, cholylglycine hydrolase, liver homogenate, small intestinal homogenates, and plasma, in comparison with the hydrolysis of glycocholic acid, ursodeoxycholyl-L-leucine (L-Leu-UDCA), and ursodeoxycholyl-L-lysine (L-Lys-UDCA). PABA-UDCA was specifically cleaved by bacterial cholylglycine hydrolase to ursodeoxycholic acid and para-aminobenzoic acid (PABA), but not by pancreatic enzymes. L-Leu-UDCA was cleaved by pancreatic enzymes, carboxypeptidase A, and cholylglycine hydrolase. L-Lys-UDCA was cleaved by pancreatic enzymes, carboxypeptidase B, and cholylglycine hydrolase. The small amount of glycocholic acid was cleaved by pancreatic enzymes and carboxypeptidase A and B, and cholylglycine hydrolase hydrolyzed glycocholic acid completely. In everted gut sac experiments, PABA-UDCA was absorbed by active transport in the rat terminal ileum, and the same rate of PABA was absorbed by passive diffusion in the four segments of the rat small intestine. These observations indicate that PABA-UDCA test can evaluate the activity of small intestinal bacterial growth.
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Specificity and sensitivity of ALTAB test have been estimated in 40 healthy children and 13 cystic fibrosis patients. The test has been carried out in the modification as 2-hour-serum PABA-test. The found specificity was 90%, the sensitivity 100% respectively. Therefore this test is suitable for evaluation of exocrine pancreas function.
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