Abnormal dimercapto-succinic acid scans predict an increased risk of breakthrough infection in children with vesicoureteral reflux.
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The purpose of this study was to evaluate and compare the diagnostic efficacy of (99m)Tc(V) dimercaptosuccinic acid ((99m)Tc(V)DMSA) with the (67)Ga-citrare ((67)Ga-C) scintigraphy in patients with suspected bone and joint infection. Thirty one patients, 19 men and 12 women, aged 18-78 y with median age 56 y, with suspected acute bone infection, were enrolled in this study. Besides (67)Ga-C and (99m)Tc(V)DMSA scintigraphy, all patients underwent X-ray radiography and technetium-99m methylene disphosphonate ((99m)Tc-MDP) bone scan for supporting the initial diagnosis. The (99m)Tc-MDP bone scan was considered positive for acute bone and joint infection when all its four scintigraphic phases were positive. Final diagnosis was based on needle aspiration and/or biopsy findings. Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) were calculated. Our results have shown the following: Seventeen patients (17/31) had histologically confirmed acute bone and joint infections, while the remaining patients had no infection. (99m)Tc(V)DMSA diagnosed bone and joint infections in all positive (17/31) patients while (67)Ga-C in 16/31 patients. Discordant scintigraphic results were observed by (67)Ga-C in 2/31 cases: in one positive case of femur postoperative infection (false negative for (67)Ga-C) and in one case of clinicaly suspected infection in the femur while the patient had a preexisting fracture (false positive with (67)Ga-C). No false negative results were observed with (99m)Tc(V)DMSA. Sensitivity, specificity, PPV, NPV and accuracy were maximum for (99m)Tc(V)DMSA, while for (67)Ga-C were: 94.1%, 93%, 94.1%, 93%, and 93.5% respectively. It is concluded that considering the high sensitivity and specificity of (99m)Tc(V)DMSA in the detection of acute bone and joint infections, the lower radiation dose, the cost and the shorter time spent for the imaging procedure, as compared to (67)Ga-C, (99m)Tc(V)DMSA should be preferred to (67)Ga-C as a bone scan agent for the detection of acute bone and joint infections.
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Effects of TPH-3 on various experimental gastric ulcers in rats and guinea-pigs were studied and the following results were obtained. In the preventive experiments, such as the Shay's ulcer, pylorus-ligated aspirin ulcer and restraint and water immersion stress ulcer, TPH-3 (200 mg/kg i.d. or p.o.) showed a statistically significant inhibition. TPH-3 markedly inhibited the histamine-induced gastric ulcer in guinea-pigs and a dose-response relationship was obtained for doses of 12.5, 25 and 50 mg/kg p.o. TPH-3 showed the weak inhibition regarding therapy for serosa-seared gastric ulcer and the recovery process of restraint and water immersion stress ulcer in rats. TPH-3, dosing 100 mg/kg intraduodenally, significantly inhibited the gastric secretion in the pylorus-ligated rats. TPH-3 significantly inhibited the histamine, pentagastrin and carbachol-induced acid secretion in the stomach-perfused rats. In particular, TPH-3 showed strong sensitivity to the action of histamine. TPH-3 had no anti-ACh or anti-H1-receptor effects.
Methylmalonic acid, succinic acid, and other dicarboxylic acids have been extracted and partially purified from serum and urine using ether extraction and high-performance liquid chromatography. The t-butyldimethylsilyl derivatives were prepared and analyzed using capillary gas chromatography-mass spectrometry with selected ion monitoring. The addition of [methyl-2H3]methylmalonic acid and [1,4-13C2]succinic acid to the starting samples made it possible to quantitate these two dicarboxylic acids. Normal ranges for methylmalonic acid and succinic acid were determined in human and rat serum and in human urine. The utilization of other internal standards would make it possible to quantitate malonic, dimethylmalonic, ethylmalonic, methylsuccinic, glutaric, and other dicarboxylic acids.
A homologous series of four oligomers of acetic acid (namely acetic acid, succinic acid, tricarballylic acid, and tetracarboxylic acid) is characterized using isocratic and linear salt gradient anion-exchange chromatography. The double logarithmic plot of the isocratic retention factors versus the salt concentration gives straight lines for all samples. These straight lines (with the exception of the line for the strongly retained succinate peak) have a common intersection point--something which is proved to be a direct consequence of the stoichiometric mass-action ion-exchange model. The characteristic charge and the equilibrium ion-exchange constant (and the corresponding Gibbs free energy of ion exchange, or deltaG(exchange)) are determined from the isocratic experiments. The characteristic charge agrees satisfactorily with the number of carboxylic acid groups in the samples, and the deltaG(exchange) value decreases linearly with the characteristic charge. Succinic acid always gives two chromatographic peaks despite the proven chemical purity of the sample. The characteristic charge that is calculated for both of the succinic acid peaks is approximately two. The deltaG(exchange) value calculated for the weakly retained succinic acid peak falls in the free energy versus characteristic charge straight line defined by the other homologues. The deltaG(exchange) value of the strongly retained peak is lower than that of the weakly retained peak by 1.85 kJ/mol. The two succinic acid peaks are explained in terms of an equilibrium between two conformers in solution--one binding the solution counterions tightly and the other loosely. An analysis of all samples under a linear salt gradient provides retention times that increase linearly with the number of functional groups. Using an appropriate model (along with the isocratically determined characteristic charge and ion-exchange constant), we predict theoretically the linear gradient retention times, which agree reasonably well with the experimental ones.
Urinary organic acid and acylcarnitine profiles from a 2-month-old boy were studied by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. The patient excreted large amounts of glutaric acid and significant amounts of 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine, and his serum glutaric acid level was markedly elevated. Thus he was chemically diagnosed as having glutaric aciduria type I (GAI). In addition to the above metabolites previously described in GAI, significantly increased excretion of 2-ketoglutaric acid, succinic acid, adipic acid, adipylcarnitine, suberic acid and azelaic acid was found. 2-Ketoadipic acid methylsuccinic acid and ethylmalonic acid were also detectable, suberylcarnitine was not increased, and dehydroadipylcarnitine was decreased in his urine. These results suggest that excess glutaryl-CoA causes the competitive inhibition of the dehydrogenation of adipyl-CoA to dehydroadipyl-CoA and results in an increase of adipic acid and adipylcarnitine and a decrease of dehydroadipylcarnitine. It is also suggested that oxidative decarboxylation of 2-ketoglutaric acid to succinyl-CoA is inhibited by high levels of glutaryl-CoA, and that the dehydrogenation of succinic acid to fumaric acid is inhibited owing to the increased glutaric acid derived from excess glutaryl-CoA. These results indicate that gas chromatography-mass spectrometry is the most appropriate and accurate method for the differential chemical diagnosis of GAI and glutaric aciduria type II.
A homologous series of anionic gas-phase clusters of dicarboxylic acids (oxalic acid, malonic acid, succinic acid, glutaric acid, and adipic acid) generated via electrospray ionization (ESI) are investigated using collision-induced dissociation (CID). Sodiated clusters with the composition (Na(+))(2)(n+1)(dicarboxylate(2-)(n+1) for singly charged anionic clusters, where n = 1-4, are observed as major gas-phase species. Isolation of the clusters followed by CID results mainly in sequential loss of disodium dicarboxylate moieties for the clusters of succinic acid, glutaric acid, and adipic acid (C4-C6). However, all oxalate (C2) and malonate (C3) clusters and dimers (n = 1) of succinate (C4) and glutarate (C5) exhibit more complex chemistry initiated by collision of the activated cluster with water molecules. For example, with water addition, malonate clusters dissociate to yield sodium acetate, carbon dioxide, and sodium hydroxide. More generally, water molecules serve as proton donors for reacting dicarboxylate anions in the cluster and introduce energetically favorable dissociation pathways not otherwise available. Density functional theory (DFT) calculations of the binding energy of the cluster correlate well with the cluster phase reactions of oxalate and malonate clusters. Clusters of larger dicarboxylate ions (C4-C6) are more weakly bound, facilitating the sequential loss of disodium dicarboxylate moieties. The more strongly bound small dicarboxylate anions (oxalate and malonate) preferentially react with water molecules rather than dissociate to lose disodium dicarboxylate monomers when collisionally activated. Implications of these results for the atmospheric aerosol chemistry of dicarboxylic acids are discussed.
Red soil samples collected from southern Hubei province and northern Jiangxi province were tested to analyze their inorganic phosphorus fractions, pH and active aluminum after incubated with added various organic acids. The results indicated that application of organic acids increased the content of Ca2-P in both red soils, in the order of citric acid > malic acid > succinic acid > acetic acid, did not affect the contents of Ca8-P and Ca10-P, but usually reduced Fe-P, Al-P and O-P. The pH values of the soils treated by organic acids, except for acetic acid, were reduced by 0.65-1.96, compared with the control. Soil active Al extracted with 0.02 mol.L-1 CaCl2 in treatments with citric, malic and succinic acid was 5.7-51.3 times as the control, and Al extracted with 1 mol.L-1 KCl also increased 4.0-67.3 times. However, acetic acid had little influence on active soil Al. It was concluded that in red soils, organic acid could improve phosphorus availability, but enhance the soil toxicity caused by active Al.
Indirect UV detection of fourteen short-chain organic acids (e.g., oxalic acid, citric acid, malonic acid, tartaric acid, methylmalonic acid, alpha-ketoglutaric acid, succinic acid, ethylmalonic acid, methylsuccinic acid, glutaric acid, apidic acid, methylglutaric acid, lactic acid and pyruvic acid) by capillary electrophoresis is described. The method used phthalate as the UV-absorbing additive in carbonate buffer and the non-absorbing analytes were detected indirectly at 230 nm. The influences of buffer pH, ionic strength, concentration of phthalate and organic modifier on indirect signal response and migration behavior of the organic acids were investigated. Comparisons of reproducibility on migration time, limit of detection and separation efficiency among three types of capillary (e.g., polyacrylamide-coated, myristyltrimethylammonium bromide-coated and uncoated capillaries) were conducted. The method developed was applied to detect succinic acid, methylmalonic acid, citric acid, glutaric acid and lactic acid in human body fluids, and preliminary results were provided.
Four acidic constituents have been isolated from the spikes of Schizonepeta mulifida. They were identified as docosanoic acid, tetracosanic acid, succinic acid and deoxyoleanolic acid by physico-chemical constants and spectroscopic analysis. They were isolated for the first time from Schizonepeta.
A method for isolating organic acids from acidified urine on an equivolume mixture of Porapak Q and Porapak T is described, and results are compared with extraction with ethyl acetate and ion exchange on DEAE-Sephadex. Average recoveries of 14C-labeled oxalic acid, lactic acid, succinic acid, alpha-ketoglutaric acid, citric acid, and cinnamic acid were equal to or better than those obtained with the solvent-extraction method. The ion-exchange method gave higher recoveries for oxalic acid, lactic acid, and citric acid. The quantification of separated acids from reconstructed mass spectrometric ion traces is compared with quantification from the simultaneously recorded flame ionization detector response signals. A good correlation was obtained. With the present routine metabolic screening method we have detected several patients with inborn errors of metabolism.
The rate of the aerobic metabolism of pyruvic acid by bakers' yeast cells is determined mainly by the amount of undissociated acid present. As a consequence, the greatest rate of oxidation was observed at pH 2.8. Oxidation, at a slow rate, started at pH 1.08; at pH 9.4 there was no oxidation at all. The anaerobic metabolism, only a fraction of the aerobic, was observed only in acid solutions. There was none at pH values higher than 3. Pyruvic acid in the presence of oxygen was oxidized directly to acetic acid; in the absence of oxygen it was metabolized mainly by dismutation to lactic and acetic acids, and CO(2). Acetic acid formation was demonstrated on oxidation of pyruvic acid at pH 1.91, and on addition of fluoroacetic acid. Succinic acid formation was shown by addition of malonic acid. These metabolic pathways in a cell so rich in carboxylase may be explained by the arrangement of enzymes within the cell, so that carboxylase is at the center, while pyruvic acid oxidase is located at the periphery. Succinic and citric acids were oxidized only in acid solutions up to pH 4. Malic and alpha-ketoglutaric acids were not oxidized, undoubtedly because of lack of penetration.