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[A pharmacokinetic study of para-aminobenzoic acid administered into the rabbit eye by phonophoresis].

The pharmacokinetics of para-aminobenzoic acid (PABA) was studied after introduction of 3H-PABA in the rabbit eye by phonophoresis (1.8 ml 3H-PABA per eye, calculated from 10 muCi in 1 ml 0.9% sodium chloride). The label was found by liquid scintillation in all studied eye tissues, including the retina. Within 1 h the label content in the tissues was higher than within 3 after the isotope introduction. Thus, in addition to subcutaneous injection (Stroeva et al., 1992), another method of PABA introduction in the eye was used in order to further study its activity as a medicinal drug during treatment of degenerative processes in the retina.

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Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II) nephrotoxicity.

Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.

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Synthesis, characterization and biological activity of some transition metals with Schiff base derived from 2-thiophene carboxaldehyde and aminobenzoic acid.

Metal complexes of Schiff base derived from 2-thiophene carboxaldehyde and 2-aminobenzoic acid (HL) are reported and characterized based on elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance and thermal analysis (TGA). The ligand dissociation as well as the metal-ligand stability constants were calculated pH metrically at 25 degrees C and ionic strength mu=0.1 (1M NaCl). The complexes are found to have the formulae [M(HL)2](X)n.yH2O (where M=Fe(III) (X=Cl, n=3, y=3), Co(II) (X=Cl, n=2, y=1.5), Ni(II) (X=Cl, n=2, y=1) and UO2(II) (X=NO3, n=2, y=0)) and [M(L)2] (where M=Cu(II) (X=Cl) and Zn(II) (X=AcO)). The molar conductance data reveal that Fe(III) and Co(II), Ni(II) and UO2(II) chelates are ionic in nature and are of the type 3:1 and 2:1 electrolytes, respectively, while Cu(II) and Zn(II) complexes are non-electrolytes. IR spectra show that HL is coordinated to the metal ions in a terdentate manner with ONS donor sites of the carboxylate O, azomethine N and thiophene S. From the magnetic and solid reflectance spectra, it is found that the geometrical structure of these complexes are octahedral. The thermal behaviour of these chelates shows that the hydrated complexes losses water molecules of hydration in the first step followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. The activation thermodynamic parameters, such as, E*, DeltaH*, DeltaS* and DeltaG* are calculated from the DrTG curves using Coats-Redfern method. The synthesized ligands, in comparison to their metal complexes also were screened for their antibacterial activity against bacterial species, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus pyogones and Fungi (Candida). The activity data show that the metal complexes to be more potent/antibacterial than the parent Schiff base ligand against one or more bacterial species.

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The use of gamma-glutamyl-p-aminobenzoic acid as the substrate for determination of gamma-glutamyltranspeptidase activity in blood serum.

By the phthaloyl method less toxic and readily soluble gamma-L-glutamyl-p-aminobenzoic acid was synthesized. This substance was used as a substrate for gamma-glutamyltranspeptidase activity assay in blood serum and urine. Close correlation was shown between the results obtained with the new method and with the old one which used gamma-L-glutamyl-p-nitroanilide.

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High yield formation of o-aminobenzoic acid-7-O-beta-D-(beta-1,6-O-d-glucopyranosyl)-glucopyranosyl ester in cell suspension cultures of Solanum mammosum.

Cell suspension cultures of Solanum mammosum cultivated in modified Murashige & Skoog media could synthesize o-aminobenzoic acid-7-O-beta-D-(beta-1,6-O-D-glucopyranosyl)-glucopyranosyl ester from o-amino benzoic acid with a yield of about 20% dry weight in 7 days. The maximum production of o-aminobenzoic acid-7-O-beta-D-(beta-1,6-O-D-glucopyranosyl)-glucopyranosyl ester was 31.8% on dry weight basis.

Aminobenzoates↗

Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function.

OBJECTIVE: To evaluate glycine conjugation of para-aminobenzoic acid (PABA) to the hippurated metabolites, para-aminohippuric acid (PAHA), and para-acetamidohippuric acid (PAAHA) as a quantitative liver function test in patients with liver disease. DESIGN AND METHODS: Serum concentrations of PABA and metabolites were measured by high pressure liquid chromatography in 24 controls and 50 patients with hepatobiliary disease. RESULTS: Hippurate formation was significantly decreased in all patient groups with chronic liver disease versus controls. The hippurate ratio (% hippurated metabolites formed) correlated with severity of disease, serum albumin, and factor VII concentrations. PAHA concentration was a better prognostic indicator than factor VII concentrations in patients with acute liver disease; concentrations of zero correctly predicted a poor outcome in patients with fulminant liver failure. CONCLUSIONS: Glycine conjugation of PABA may be useful as a quantitative liver function test in patients with hepatobiliary disease and as a prognostic index in patients with fulminant liver failure.

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Non-pancreatic hydrolysis of N-benzoyl-l-tyrosyl-p-aminobenzoic acid (PABA-peptide) in the human small intestine.

1. Hydrolysis of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (PABA-peptide) has been measured in soluble and particulate fractions of human small intestinal mucosa. 2. Both soluble and particulate fractions contained enzymic activity capable of splitting the PABA-peptide. In the particulate fractions this activity increased threefold towards the distal small intestine. 3. Neither soluble nor particulate activity was inhibited by the chymotrypsin inhibitor 1-chloro-4-phenyl-3-L-toluene-p-sulphonamidobutan-2-one (TPCK). 4. Column chromatography on Sephacryl S-300 resolved a peak of PABA-peptide hydrolase activity that was clearly distinct from other known brush-border peptide hydrolases and from added chymotrypsin standard. 5. This PABA-peptide hydrolase thus represents a distinct intestinal enzyme, possibly bound to the brush-border membrane, which could account for the residual urinary PABA recovery observed in patients and animal models with exocrine pancreatic insufficiency.

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A model for p-aminobenzoic acid ester narcosis in goldfish.

A three-parameter equation which successfully quantifies the turnover time in goldfish exposed to variable concentrations of eight alkyl esters of p-aminobenzoic acid is described. One parameter characterizes the target concentration necessary to induce narcosis, and the other two parameters represent the resistances encountered by the drug when it migrates through aqueous and lipid phases from source to target. The octanol-water partition coefficients, or aqueous solubilities, and melting points of the esters are included to account for variation in drug hydrophobicity, the relationship between these properties being quantified. The inactivity of high-melting-point esters is explained by the constraint imposed by melting point on the maximum aqueous concentration which can be achieved by solid solutes.

4-Aminobenzoic Acid↗

Evaluation of the mutagenicity of an N-nitroso contaminant of the sunscreen Padimate O: N-nitroso-N-methyl-p-aminobenzoic acid, 2-ethylhexyl ester (NPABAO).

The nitrosamine contaminant, N-nitroso-N-methyl-p-aminobenzoic acid, 2-ethylhexyl ester (NPABAO), of the major sunscreen ingredient Padimate O (4-N,N'-dimethylamino-benzoic acid, 2-ethylhexyl ester) was synthesized and tested for mutagenicity in the Salmonella typhimurium and mouse lymphoma L5178Y TK +/- assays. In contrast to the previously reported positive responses in S. typhimurium tester strains TA100 and TA1535 [Loeppky et al., 1991], there were no increases in the number of revertants with strains TA98, TA100, TA1535, and TA1538 in either the Salmonella plate incorporation [Ames et al., 1975] or preincubation [Yahagi et al., 1977] assays. Additional testing with Salmonella, following the modified preincubation procedure [Rogan, 1990] that gave the initial positive response, was also negative. Data from the mouse lymphoma assays were also uniformly negative. During synthesis of NPABAO, small amounts of 4-N,N'-dimethylamino-3-nitrobenzoic acid, 2-ethylhexyl ester (DMANBAO) can be formed. To determine whether the reported positive mutagenicity response of NPABAO could be the result of trace amounts of DMANBAO in the NPABAO, that compound was also synthesized and tested for mutagenicity with Salmonella. Positive responses were obtained with tester strains TA98 and TA 1538 but not with TA100 and TA1535, indicating that DMANBAO was not responsible for the increase in revertants originally reported.

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Standard photopatch testing with Waxtar, para-aminobenzoic acid, potassium dichromate and balsam of Peru.

194 patients were standard photopatch tested with Waxtar as is (coal tar 5%) and 161 patients were photopatch tested with para-aminobenzoic acid (PABA) 5% in alcohol, potassium dichromate 0.5% in petrolatum, and a mixture of balsams of Peru as is. The photopatches were irradiated with UVA. 40 patients (25%) had phototoxic reactions to Waxtar and 4 of them showed pigmentation after 7 days. Only a few patients had photocontact urticaria. 1 patient had a late-reaction to PABA and showed a cross-reaction to glyceryl PABA but a negative reaction to paraphenylenediamine (PPD) and benzocaine 5% in the standard test. No patients had positive photopatch reactions to potassium dichromate when irradiated with UVA. 2 patients had phototoxic reactions to balsam of Peru. None had photoallergic reactions. Standard photopatch testing is a time consuming procedure which creates problems both for the staff and for the patients. The yield of unexpected, relevant positive reactions is insignificant. From a cost-benefit view, photopatch testing is only warranted in cases giving rise to a clinical suspicion of photodermatitis.

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[Regulation of the mitotic activity in the rat cornea in response to protective and therapeutic effects of para-aminobenzoic acid in experiments with roentgen radiation].

The protective and therapeutic action of p-aminobenzoic acid (PABA), at doses effective in interferon induction (Akberova et al., 1999), was studied on the rat cornea in the experiments with X-irradiation (5 Gy). PABA at 10 mg/kg preserved the postradiation mitotic activity at the level of irradiated control, while at 1.4 and 100 mg/kg it increased the mitotic activity above the control level. In all experiments, PABA at all three doses decreased the rate of pathological mitoses in equal proportions to the total number of mitoses.

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Free and total para-aminobenzoic acid analysis in plants with high-performance liquid chromatography/tandem mass spectrometry.

para-Aminobenzoic acid (PABA), a precursor in the synthesis of folates in plants, is determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS). In plants PABA can be converted into its beta-D-glucopyranosyl ester (PABA-Glc) and can also exist in its free form. In this work, we developed and validated a quantitative method to study free and total PABA in plants. The total PABA (free PABA plus PABA-Glc) can be evaluated after acid hydrolysis at 80 degrees C for 2 hours. The plant material is homogenized and the PABA content is quantified using the standard addition procedure. The validated method is selective, sensitive, simple, accurate, has a recovery between 99.6 to 102.5%, is reproducible (RSD between 1.4 and 4.4%), and is linear between 2.5 and 1538 ng/mL. Free and total PABA determinations in five vegetables showed that different plant species had different amounts of free and total PABA, and that the ratios of total versus free PABA were also variable. This new method could be valuable for studies of folate synthesis in plants.

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Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection.

Plasmodia species, unlike humans, can utilize p-aminobenzoic acid (PABA) for the de novo generation of folate. Plasmodial enzymes for the synthesis of PABA via the shikimate pathway are being investigated as novel targets for malaria chemotherapy. We show that, despite the presence of biosynthetic machinery to synthesize PABA, Plasmodium yoelii, a rodent malaria species, requires exogenous dietary PABA for survival. Mice fed low-PABA diets do not die from lethal doses of P. yoelii. The initiation of a PABA-deficient diet after P. yoelii infection is established leads to the clearance of parasites and subsequent resistance to infection by P. yoelii. An intact immune system is not necessary for protection, given that mice with severe combined immunodeficiency were also protected by PABA-deficient diet. Our studies suggest that the PABA content in the diet will affect the host clearance of malaria parasites and may affect the efficacy of treatments that target the shikimate pathway.

4-Aminobenzoic Acid↗

The chemotherapy of rodent malaria, XXXII. The influence of p-aminobenzoic acid on the transmission of Plasmodium yoelii and P. berghei by Anopheles stephensi.

More oocysts of Plasmodium yoelii developed in Anopheles stephensi if the mosquitoes received a supplement of p-aminobenzoic acid (PABA) in their diet prior to their taking an infective blood meal, than in unsupplemented control insects. The optimum concentration was 0.05% PABA in 10% sucrose. This effect was not observed if the blood meal was taken prior to feeding with PABA. Similarly, PABA administered to gametocyte-carrying mice increased the numbers of oocysts developing in mosquitoes fed on them subsequently, the effect also being dose dependent, and not mediated through an increase in gametocyte numbers. Sulphadoxine (which blocks PABA uptake) had the opposite action, reducing the numbers of oocysts either when fed directly to the mosquitoes or to the donor mice. These results are compared with those reported in other host-parasite systems by earlier workers, and certain paradoxical observations are discussed with reference to a possible relationship between sulphonamides and contaminating microorganisms in the vector mosquitoes.

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[The antithrombotic activity of para-aminobenzoic acid in experimental thrombosis].

It was shown for the first time that p-aminobenzoic acid (PABA), in addition to the previously described fibrinolytic activity, exerts the properties of a direct anticoagulant both in vitro and in vivo. PABA not only displays antithrombin activity, but also inhibits activated factor X and, upon intravenous injection to rats and rabbits, shows the antithrombotic effect. The most pronounced antithrombotic affect was observed at a dose of 1.5 mg/kg. PABA at 0.5 mg/kg has insignificant efficacy and at 3 mg/kg, a high efficacy, but induces hemolysis of erythrocytes in about a half of cases. Equally efficient antithrombotic activity of blood plasma of rats was noted after intravenous injection of low molecular weight heparin "Fraxiparin" at 40 anti-Xa U/kg and PABA at 25 anti-Xa U/kg (1.5 mg/kg). Unlike "Fraxiparin", which exerts an immediate effect, the effect of PABA was expressed within 1.5 to 5 h after injection with a peak of antithrombotic activity at 3 h (which correlates with anti-IIa and anti-Xa activities of plasma) and terminated by 5 h after injection. For PABA, the ratio of anti-Xa to anti-IIa activities (an important parameter, which determines the antithrombotic potential of drugs) equals 2.4. PABA at 0.5 or 1.5 mg/kg did not affect the number of thrombocytes, while at 3 mg/kg, it decreased the number of thrombocytes by 20%. Thus PABA at 1.5 mg/kg, which has a high anticoagulant activity and does not cause side effects, is most interesting for further studies.

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