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PubMed1997

Determination of the exocrine pancreatic function with the NBT-PABA test using a novel dual isotope technique and gas chromatography-mass spectrometry.

We describe a tubeless test of exocrine pancreatic function based on a new dual isotope technique, using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA) as a substrate for intestinal chymotrypsin activity and the stable isotope, 13C-PABA as marker. Gas chromatography-mass spectrometry (GC-MS) was used for the quantification of PABA and 13C-PABA in blood. The method involves hydrolysis, extractions, separation by HPLC, and methyl ester formation of the test substances before GC-MS analysis. The test is precise and shows good separation of healthy volunteers from patients with pancreatic insufficiency. The PABA/13C-PABA ratios in serum after 1.5 h were 2.64 +/- 0.14 (mean +/- SEM) in 10 healthy volunteers and 1.26 +/- 0.22 in 10 patients with exocrine pancreatic insufficiency. We present a sensitive and specific assay, which is free of analytical interference and radiation hazards and, additionally, it illuminates extrapancreatic pharmacokinetic conditions. This test can eliminate the need for duodenal intubation, which makes it very acceptable to the patients.

4-Aminobenzoic Acid↗
PubMed1997

Evaluating exocrine function tests for diagnosing chronic pancreatitis.

To evaluate the effectiveness of exocrine function tests in diagnosing chronic pancreatitis (CP), we compared the sensitivity and specificity of duodenal intubation with tubeless tests. While the secretin test (ST) was necessary to diagnose CP, especially in noncalcified CP, and tubeless tests demonstrated insufficient sensitivity to diagnose CP, the combination assay of tubeless tests was specific enough to diagnose severe exocrine dysfunction. Our studies found the sensitivity of secretin testing to diagnose definite CP to be 87%. In patients with probable CP, 60% had mild exocrine insufficiency and 40% had normal function. The false-positive rate of the ST results in nonpancreatic diseases, except diabetes mellitus, was 5%. The correlation between morphological changes in endoscopic retrograde pancreatography (ERP) and exocrine function evaluated by ST was 74%. In patients with calcified CP, 81% had parallel results between ERP and the ST, but in noncalcified CP, 47% had parallel results. In patients with severe or moderate exocrine insufficiency demonstrated by ST, abnormally low levels were observed in 63% by N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test, 61% by fecal chymotrypsin test (FCT), and 44% by pancreatic amylase (PA). In patients with normal exocrine function demonstrated by ST, abnormally low levels were observed in 28% by BT-PABA test, 28% by FCT, and 10% by PA. A combination assay of BT-PABA test, FCT, and PA improved the specificity for diagnosing CP but not the sensitivity.

4-Aminobenzoic Acid↗
PubMed1998

Comparative study of bentiromide test and endoscopic retrograde pancreatography in patients with chronic pancreatitis.

We performed a bentiromide test in 25 patients with chronic pancreatitis and 7 normal controls to evaluate pancreatic exocrine function, and compared the test results of patients with their endoscopic retrograde pancreatography(ERP) findings. The cumulative 6-hour recovery rate of para-aminobenzoic acid(PABA) in the urine was significantly lower in patients with chronic pancreatitis(55.8 +/- 24.2%) than in controls(82.0 +/- 10.0%). Among 25 patients with chronic pancreatitis, however, 7 patients showed normal recovery rates of PABA. Pancreatograms of the patients represented 4 mild changes, 5 moderate changes, and 16 marked changes. The average 6-hour recovery rates of PABA of the groups were 56.9 +/- 21.6%, 78.4 +/- 10.5%, and 47.2 +/- 23.7%, respectively. Urinary PABA recovery rates were found subnormal as follows: 3(75%) in the mild changes group; 1(20%) in the moderate changes group; and 14(87.5%) in the marked changes group. We found hardly any correlation between the degree of functional impairment and the changes noted by ERP. These findings suggest that both the pancreatic function test and morphologic study are required to evaluate the degree of functional impairment in patients with chronic pancreatitis.

4-Aminobenzoic Acid↗
PubMed1991

Development of assays for the detection of photomutagenicity of chemicals during exposure to UV light--I. Assay development.

Two complementary assay systems have been adapted for the detection of compounds which may form mutagenic photoproducts during exposure to UV light from an Osram Ultra-Vitalux sunlamp as used in the evaluation of the effectiveness of sun filters. The effects of UVA and of UVB were evaluated. A bacterial plate test using Escherichia coli strain WP2 allowed the bacteria, co-plated with test chemical in soft agar, to be irradiated with various doses of UV light. Mutagenesis was assessed by scoring numbers of tryptophan-independent colonies. The chosen reference compound was 8-methoxypsoralen (8-MOP) which was non-mutagenic alone at the highest dose tested (1000 micrograms/plate). Following simultaneous exposure of bacteria to 8-MOP and doses of UV light which alone had little effect, large numbers of revertants were scored. Numbers of mutants were dependent upon the doses of both 8-MOP and of UV light. The second test system involved the exposure of Chinese hamster ovary cells to UV light in the presence of test chemical to determine the clastogenic effects of photoproducts. Treatment with 8-MOP alone up to 50 micrograms/ml was not clastogenic but concomitant exposure to non-damaging doses of UV light caused large increases in the incidence of chromosome aberrations of all types. Damage was again dependent on the doses of both components. Two additional photoactive compounds, para-aminobenzoic acid and chlorpromazine both show photoclastogenic but not photomutagenic properties. These two complementary assay systems take advantage of using no-effect levels of UV light as a baseline against which photomutagenicity readily can be compared.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobenzoic Acid↗
PubMed1991

Study on brain uptake of local anesthetics in rats.

Brain uptake of local anesthetics under steady-state plasma condition and/or following intravenous bolus administration was investigated in rats. All ester-type anesthetics examined such as ethyl (Et), propyl (Pr), butyl (Bu) esters of p-aminobenzoic acid (PABA), and procaine disappeared rapidly from plasma in a dose-dependent manner. Plasma profiles of these compounds were well explained by a 2-compartment model with a Michaelis-Menten type elimination process from a central compartment. On the other hand, lidocaine, amide-type anesthetic, showed a linear pharmacokinetic characteristic and its half life in the elimination phase was far longer than those of ester type agents. Extents of brain uptake (brain-to-plasma partition coefficient, Kp value) of these drugs were determined at 3 different steady-state plasma concentrations (1-15 microM). The Kp value of each drug was similar under the three different steady-state plasma concentrations. The Kp value increased in the following order; procaine (1.1) less than PABA-Et (1.9) less than lidocaine (2.2) less than PABA-Pr (2.7) less than PABA-Bu (3.6). A linear relationship was observed between the Kp value and the logarithmic value of the partition coefficient obtained in n-heptane/water or n-octanol/water partition system. The value of PABA-Et and PABA-Bu following intravenous bolus administration were varied with time elapsed but the mean values were almost same with those obtained under steady-state plasma conditions.

4-Aminobenzoic Acid↗
PubMed1996

Biosynthesis of methanopterin.

This paper establishes the pathway for the biosynthesis of methanopterin in Methanosarcina thermophila to proceed by the following series of reactions. First, 5-phospho-alpha-D-ribosyl diphosphate (PRPP) and 4-aminobenzoic acid condense together to produce 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate, which then reacts with 6-hydroxymethyl-7,8-H2pterin pyrophosphate to produce 7,8-H2pterin-6-ylmethyl-4-(beta-D-ribofuranosyl)aminobenz ene 5'-phosphate (3'). Compound 3' is then reduced to 7,8-H2pterin-6-ylmethyl-l-(4-aminophenyl)-1-deoxy-D-ribitol 5'-phosphate (4') in a reaction stimulated by the addition of FMN or factor F(420). Dephosphorylation of compound 4' leads to 7,8-H2pterin-6-ylmethyl-1-(4-aminophenyl)-1-deoxy-D-ribitol (5'). Compound 5' then condenses with another molecule of PRPP to form 7,8-H2pterin-6-ylmethyl-1-(4-aminophenyl)-1-deoxy-5-[1-alpha -D- ribofuranosyl 5-phosphate]-D-ribitol (9'). Compound 9', in the presence of ATP, then condenses with (S)-2-hydroxyglutaric acid to form demethylated H2methanopterin, a known precursor to methanopterin. The occurrence of this pathway was confirmed by (a) the chemical and/or biochemical synthesis of most of the proposed intermediates, (b) the detection of these intermediates in cell-free extracts, and (c) by the measurement of their conversion to demethylated methanopterin and/or other intermediates in the pathway.

4-Aminobenzoic Acid↗
PubMed1992

Simultaneous determination of some antibacterial drugs in isosensitest broth using high-performance liquid chromatography with solid-phase extraction.

A method is described for the simultaneous determination of combinations of some antibacterial drugs in a matrix of isosensitest broth. A double solid-phase extraction procedure is described in which trimethoprim and dibromopropamidine isethionate together with 4-chlorophenylbiguanide as internal standard are freed from endogenous components by a cation-exchange extraction cartridge and subsequently removed and individually separated by reversed-phase ion-pair chromatography. Sulfadiazine, sulfamerazine and p-aminobenzoic acid, unretained by ion exchange, are similarly isolated for chromatography by adsorption on a CH-bonded phase cartridge and individually assayed using the same chromatographic system. The rationale of the pre-treatment and chromatography is described and the quantitative aspects of the analyses of selected combinations of these drugs are reported.

4-Aminobenzoic Acid↗
PubMed2004

Proteasomal degradation of N-acetyltransferase 1 is prevented by acetylation of the active site cysteine: a mechanism for the slow acetylator phenotype and substrate-dependent down-regulation.

Many drugs and chemicals found in the environment are either detoxified by N-acetyltransferase 1 (NAT1, EC 2.3.1.5) and eliminated from the body or bioactivated to metabolites that have the potential to cause toxicity and/or cancer. NAT1 activity in the body is regulated by genetic polymorphisms as well as environmental factors such as substrate-dependent down-regulation and oxidative stress. Here we report the molecular mechanism for the low protein expression from mutant NAT1 alleles that gives rise to the slow acetylator phenotype and show that a similar process accounts for enzyme down-regulation by NAT1 substrates. NAT1 allozymes NAT1 14, NAT1 15, NAT1 17, and NAT1 22 are devoid of enzyme activity and have short intracellular half-lives ( approximately 4 h) compared with wild-type NAT1 4 and the active allozyme NAT1 24. The inactive allozymes are unable to be acetylated by cofactor, resulting in ubiquitination and rapid degradation by the 26 S proteasome. This was confirmed by site-directed mutagenesis of the active site cysteine 68. The NAT1 substrate p-aminobenzoic acid induced ubiquitination of the usually stable NAT1 4, leading to its rapid degradation. From this study, we conclude that NAT1 exists in the cell in either a stable acetylated state or an unstable non-acetylated state and that mutations in the NAT1 gene that prevent protein acetylation produce a slow acetylator phenotype.

4-Aminobenzoic Acid↗
PubMed1993

Biochemical tests in the diagnosis of chronic pancreatitis and in the evaluation of pancreatic insufficiency.

Chronic pancreatitis (adults) and cystic fibrosis (children) are the most common diseases leading to exocrine pancreatic insufficiency that, when reduced to < 5% of normal function, is characterised by steatorrhoea. The pathogenesis of the former condition is outlined, and recent concepts are emphasized. Biochemical tests to detect pancreatic insufficiency and to identify pancreatic disease as the cause of steatorrhoea include: serum enzyme tests (lipase, amylase, trypsin); stool chymotrypsin; isotopic tests based upon the assimilation of [14C] lipids and starch or excretion of the isotope as breath CO2, as well as the dual-labelled Schilling test; oral function tests utilising substrates hydrolysed by pancreatic enzymes such as benzoyl tyrosyl-p-aminobenzoic acid and fluorescein dilaurate; and duodenal intubation studies following meal-induced or hormonal stimulation of the pancreas. The rationale for these tests and the cumulative clinical experience of their utility are reviewed. A recommended diagnostic strategy is briefly presented. The role of various biochemical procedures to evaluate the efficacy of pancreatic enzyme replacement therapy is also described.

4-Aminobenzoic Acid↗
PubMed1993

[Quantitative and qualitative criteria for assessing the efficacy of antimutagens in an experiment].

The antimutagenic effect of para-aminobenzoic acid, tocopherol, adenosine and caffeine has been studied in experiments with microorganisms, Crepis capillaris seed cells, human lymphocytes, murine bone marrow cells in vivo. The activity, of antimutagens, their nature and action range, effective concentrations have been assessed. The type and severity of removable damages have been identified. Quantitative criteria for evaluating the effects of antimutagens have been defined.

4-Aminobenzoic Acid↗
PubMed1981

Pancreatic exocrine function testing.

It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

4-Aminobenzoic Acid↗
PubMed1996

Exocrine pancreatic function in the early period after pancreatoduodenectomy and effects of preoperative pancreatic duct obstruction.

Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700 +/- 4300 IU/day), and recovered on days 9-15 (48,000 +/- 8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440 +/- 260 IU/day) and BT-PABA test results were low (45 +/- 17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient, rs = 0.715, P < 0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.

4-Aminobenzoic Acid↗
PubMed1990

[High lactose content of the Lundh test meal adversely affects the reliability of the ALTAB test].

UNLABELLED: The exocrine pancreatic function was examined in 20 patient without any detectable gastrointestinal disorder. We used 1 g 4(N-acetyl-L-thyrosil) aminobenzoic acid (ALTAB) an Lundh's test meal containing 25 g lactose, and the test was repeated with 3 g lactase (Galantase). The urine was collected for 6 hours to check PABA excretion in urine. Lactose intolerance was diagnosed in 10 patients on the basis of an increase of H2 in the breath at least 15 ppm after Lundh's test meal and/or diarrhoea after test in two hours if this diarrhoea could be prevented by giving Galantase orally. We measured PABA excretion in patients with and without lactose intolerance after Lundh's test meal: 17.8% (SD = 6.7) and 47% (SD = 13) respectively (p less than 0.001), and after Lundh's test meal with Galantase: 34.3% (SD = 12.7) and 43.6% (SD = 10.9) respectively. The increase after Galantase in the group with lactose intolerance was significant (p less than 0.01). CONCLUSIONS: 1. Lactose content of Lundh's test meal causes a considerable lactose load in patients with lactose intolerance. 2. Oral lactase enzyme usually normalises the result of ALTAB test. 3. It is necessary to detect lactose intolerance before use of Lundh's test meal.

4-Aminobenzoic Acid↗
PubMed1995

Pancreatic involvement in patients with Sjögren's syndrome and primary biliary cirrhosis.

Serum pancreatic enzyme activities, exocrine pancreatic function, and pancreatic ductal morphology were evaluated in patients with one or both of Sjögren's syndrome and primary biliary cirrhosis. Ten of 20 patients with Sjögren's syndrome (50%), 6 of 17 patients with primary biliary cirrhosis (35%), and 4 of 11 patients with both diseases (36%) had an elevated level of at least one pancreatic enzyme, including elastase-1, lipase, and trypsin. Diminished excretion of N-benzoyl-L-tyrosyl-para-aminobenzoic acid was observed in 3 of 17 patients with Sjögren's syndrome (18%), 4 of 16 with primary biliary cirrhosis (25%), and none of 7 with both diseases. Endoscopic retrograde pancreatograms demonstrated an abnormal pancreatic ductal configuration in 3 of 11 patients with Sjögren's syndrome (27%), 2 of 9 with primary biliary cirrhosis (22%), and 3 of 4 with both diseases (75%). Only minimal changes in branches of the pancreatic duct were observed in the pancreatogram. Finally, 9-30% of patients with Sjögren's syndrome and/or primary biliary cirrhosis had a mild and intermittent abdominal pain. These findings support the concept of a disease complex, "autoimmune exocrinopathy," in patients with Sjögren's syndrome, primary biliary cirrhosis, and chronic pancreatitis.

4-Aminobenzoic Acid↗
PubMed1992

Pancreatic morphology and function in adult patients with cystic fibrosis.

To determine the relation between pancreatic morphology and pancreatic exocrine and endocrine function, we have studied 8 adult cystic fibrosis patients and 14 normal control subjects by ultrasonography and pancreatic function testing. In the patients with cystic fibrosis the maximum anteroposterior diameter of the pancreatic head was significantly increased over that in control subjects (p less than 0.01), whereas the maximum diameter of the body was significantly decreased (p = 0.05). Increased echogenicity of the pancreatic body was observed in most patients. In the cystic fibrosis patients postprandial insulin secretion was reduced in the 1st h (p less than 0.005 versus control), whereas pancreatic polypeptide secretion was virtually abolished for at least 3 h (p less than 0.01 versus control). All cystic fibrosis patients had evidence of exocrine pancreatic dysfunction as reflected by a diminished urinary para-aminobenzoic acid excretion. Intraduodenal enzyme and bicarbonate output in response to secretin-cholecystokinin was reduced in all of three patients studied. It is concluded that loss of endocrine and exocrine pancreatic function in adult cystic fibrosis patients is accompanied by a small and echo-dense pancreatic body relative to a large pancreatic head.

4-Aminobenzoic Acid↗
PubMed1983

Pancreolauryl test for pancreatic exocrine insufficiency.

Pancreolauryl test (PLT), a tubeless pancreatic function test, was performed in 40 consecutive patients suffering from chronic pancreatitis, in 21 patients with miscellaneous digestive diseases, and in 18 control subjects to assess its diagnostic sensitivity and specificity. N-benzoyl-L-tyrosyl-p-aminobenzoic acid test (PABA test) and secretin-cerulein test were also carried out to compare the diagnostic value of PLT with that of these two pancreatic function tests. PLT was abnormal in 22 of 40 patients with chronic pancreatitis (55%). In particular, pathological results were found in all patients with severe pancreatic insufficiency and only in four of 14 patients with mild to moderate insufficiency. PABA test showed a slightly lower sensitivity in severe insufficiency, and the same sensitivity in mild-moderate insufficiency. PLT was normal in all control subjects and in 17 of 21 patients with nonpancreatic digestive diseases. Its specificity (90%) was slightly higher than that of PABA test (82%). The results indicate that PLT may be used to support a diagnosis of severe pancreatic exocrine insufficiency, while in mild or moderate insufficiency its diagnostic value is limited.

4-Aminobenzoic Acid↗
PubMed1980

Evaluation of sunscreen protection by measurement of epidermal DNA synthesis.

Different sunscreens were tested to determine their protection of epidermis from ultraviolet light effects. Ultraviolet light-induced changes in hairless mouse epidermal DNA synthesis were used for measurement of sunscreen protection. Visual assessment of erythema and edema was also performed. This initial study has evaluated sunscreens containing para-aminobenzoic acid (PABA) as the principle sunscreen chemical. These experiments were conducted using fluorescent sunlamp tubes and hydroxylapatite extraction of epidermal DNA. The ultraviolet light exposure was measured using a recording radiometer. The results showed that the sunscreens tested were able to partially prevent ultraviolet light induced changes in epidermal DNA synthesis. It may be possible to use this assay as one of the initial evaluations of potential ultraviolet light protectants.

4-Aminobenzoic Acid↗
PubMed1998

Preoperative exocrine pancreatic function predicts risk of leakage of pancreaticojejunostomy.

BACKGROUND: The objective of this study was to clarify the relationship between preoperative exocrine pancreatic function and pancreatic anastomotic leakage after pancreatectomy. METHODS: Fifty-five patients who underwent proximal pancreatectomy with pancreaticojejunostomy were reviewed with regard to preoperative exocrine pancreatic function, size of the main pancreatic duct, postoperative pancreatic juice output, and pancreaticojejunostomy leakage. RESULTS: There were 32 patients with a normal value at the preoperative N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion test (> 70%) and 23 with a low BT-PABA value (< or = 70%). The greatest diameter of the main pancreatic duct in the group with normal BT-PABA results was significantly smaller than that in the group with low BT-PABA results (4.6 +/- 2.7 mm vs 7.1 +/- 4.2 mm; P < .05). The output of pancreatic juice during a 10-day period (from postoperative days 5 through 14) in the group with normal BT-PABA results was significantly higher than that in the group with low BT-PABA results (1738 +/- 898 mL vs 1072 +/- 1174 mL; P < .05). Pancreatic leakage occurred in 8 (25%) of the 32 patients in the group with normal BT-PABA results and in none of the 23 patients in the group with low BT-PABA results (P < .01). CONCLUSIONS: Patients with normal exocrine pancreatic function produce a larger amount of pancreatic juice than those with low exocrine pancreatic function and have a potential risk of anastomotic leakage after pancreatectomy.

4-Aminobenzoic Acid↗