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Corrosion of dental amalgams in solutions of organic acids.

A conventional and two high copper amalgams were tested in 0.5% aqueous solutions of acetic, formic, lactic and succinic acid. The corrosion behavior of the amalgams in the different solutions was evaluated by analyzing the soluble corrosion products using an atomic absorption spectrophotometer every month during a 6-month experimental period. The high copper amalgams showed a high dissolution rate in formic and lactic acid solutions from the initial stages of immersion when compared to the conventional. Later a marked decrease of the dissolution rate could be observed but it still remained at high levels. In acetic acid the amounts of elements dissolved from high copper amalgams were much less. Conventional amalgam released much smaller amounts of elements in almost all solutions tested except in the case of silver in lactic acid. Finally, in succinic acid solution, the amounts of elements dissolved were unexpectedly small considering the low pH of the solution and the dissolution rates of the amalgams in the other organic acid solutions.

Acetates↗

[Abiogenic synthesis of peptide-like substances induced by UV-irradiation and heat].

Dry mixtures of glycine and succinic acid as well as of glycine, phenylalanine and succinic acid were exposed to UV-irradiation and heating up to 170 degrees in atmospheres of O2 and N2. Under these conditions, synthesis of substances with peptide bonds was observed. Irradiation or heating of the first mixture results in synthesis of a substance which is water soluble and capable of dialysis, exhibiting therefore low degree of polymerization. This substance contains COOH-groups, but lacks free NH2-groups. The latter reveal themselves during hydrolysis which brings about the appearance of the initial compounds. In the second mixture, which contains an aromatic amino acid, several products are synthesized some of them being presented by the insoluble and non-dialysed precipitate (polymer). Among soluble products, peptide-like substances (without free NH2-groups) and dipeptides were found. UV-irradiation causes photolysis of phenylalanine which is mixed with succinic acid; as the result, tyrosine, alanine and asparagic acid are found among the products synthesized. These amino acids are not formed during heat-induced synthesis. Abiogenic synthesis takes place more readily in the presence of O2 than in a N2 atmosphere. Irradiation of aqueous solution of the product synthesized resulted in the photolysis of the latter. The results obtained indicate that during abiogenic period, synthesis of peptides and peptide-like substances from dry mixtures of amino acids and organic acids induced by UV-irradiation and heat might take place on the litosphere.

Amino Acids↗

Studies on the extracellular polysaccharide from Agrobacterium radiobacter biovar I S-1231.

A strain S-1231 isolated from specimen of soil around Beijing area is gram-negative, non-sporing, motile by peritrichous flagella. It produces exopolysaccharide succinoglycan from carbohydrates as its carbon source but not starch and cellulose. Acid is produced during fermentation of glucose. Growing for 12-24 hr, the cells are rods 0.7-0.8 x 1.3-1.5 microns, round ended, single or in pairs. Colonies on nutrient agar plate are unpigmented, circular, raised, smooth and moist-glistening, edge entire. The organism produces 3-ketolactose and is unable to invade sunflower tissue. The G+C content of DNA is 62.8-63.4 mol%. The organism is referred to as Agrobacterium radiobacter. Moreover, the strain is oxidase-positive, catalase-positive, H2S-produce and can grow at 35 degrees C and 2% NaCl also. Litmus milk is alkalified. Thus, the organism was renamed Agrobacterium radiobacter biovar I. Component analyses showed that the exopolysaccharide (Agran-S) from A. radiobacter biovar I S-1231 consisted of D-glucose (69.1%), D-galactose (8.6%), pyruvic acid (9.5%) and succinic acid (10.5%). Methylation analyses revealed that the polysaccharide Agran-S contained following main structural units: (1-->3)-linked D-glucose (21.2%), (1-->3)-linked D-galactose (11.4%), (1-->6)-linked D-glucose (10.5%), (1-->4)-linked D-glucose (30.4%), (1-->4, 1-->6)-linked D-glucose (22.2%) and terminal D-glucose (4.3%). The -1H-NMR spectrum of the polysaccharide indicated that the linkages in the polymer are all beta-glycosidic. The IR spectra of the polysaccharide revealed the presence of ester linkage in polysaccharide Agran-S.

Bacterial Typing Techniques↗

A method for the degradation of radioactive nicotinic acid.

A chemical degradation scheme is reported, which permits the measurement of the radioactivity of each carbon atom of nicotinic acid. Nicotinic acid is decarboxylated by heating with copper chromite to give carbon dioxide (C-7) and pyridine. The pyridine is converted into 4-nitropyridine 1-oxide, which is heated with aqueous calcium hypobromite to give tribromonitromethane. Combustion of the latter gives carbon dioxide derived from C-4 of the nicotinic acid. Nicotinic acid is also reduced to nipecotic acid, which is oxidized to succinic acid by acidic potassium permanganate. Stepwise degradation of the succinic acid by standard procedures gives two samples of carbon dioxide, which correspond to C-3, C-6 and C-4, C-5 of the nicotinic acid. Benzoylation of the nipecotic acid, followed by oxidation with permanganate at pH7, gives 5-amino-4-carboxyvaleric acid; this is converted into 2-methyleneglutaric acid by the action of nitrous acid. Hydrogenation of the 2-methyleneglutaric acid over rhodium in methanol gives 2-methylglutaric acid, which is oxidized with dilute chromic acid to acetic acid. Stepwise degradation of the acetic acid by standard procedures gives two samples of carbon dioxide, which correspond to C-2 and C-3 of the nicotinic acid. Thus the radioactivities of C-2, C-3, C-4 and C-7 are determined directly and those of C-5 and C-6 by difference. The method was shown to be isotopically valid for [2,3,7-(14)C]-, [4,6-(14)C(2)]- and [5-(14)C]-nicotinic acid.

Carbon Dioxide↗

Comparative effects of several chelating agents on the toxicity, distribution and excretion of aluminium.

The relative efficacy of citric, malic, malonic, oxalic and succinic acids, and deferoxamine mesylate (DFOA) on the toxicity, distribution and excretion in mice exposed to aluminum were compared. Chelating agents were administered intraperitoneally at a dose equal to one-fourth of their respective LD50. To determine the effect of the various chelators on the toxicity of aluminum, various doses of aluminum nitrate (938-3188 mg/kg) were administered intraperitoneally, followed by one of the chelators. Survival was recorded at the end of 14 days. Malic and succinic acids were the most effective. Malic acid and DFOA were the most effective in increasing the urinary excretion of aluminum. Citric acid was the most effective in increasing the faecal excretion of aluminum. Malonic, oxalic and succinic acids had no overall beneficial effects. Citric acid would appear to be the most effective agent of those tested in the prevention of acute aluminium intoxication. However, before the use of these compounds in human aluminium intoxication is possible, further investigations including the effects of these chelators after chronic aluminium intoxication are required.

Aluminum↗

Influence of Nutritional Conditions on Production of l-Glutamine by Flavobacterium rigense.

The nutritional conditions for the production of l-glutamine by Flavobacterium rigense strain 703 were investigated. The optimum concentration of ammonia for achieving the highest yield of l-glutamine (25 mg/ml of broth) was relatively broad, from 0.9 to 1.6%, whereas fumaric acid had a narrow optimum range, near 5.5%. High concentration of inorganic ions such as chloride or sulfate ion clearly inhibited cell growth. Therefore, ammonium salts other than (NH(4))(2)-fumarate were unsuitable for the highest production. The optimum concentration of (NH(4))(2)-fumarate was 7%. To reduce the concentration of fumaric acid in the medium, many substances were evaluated as substitutes. The fumaric acid concentration required for highest l-glutamine yield could not be replaced by any one of the compounds tested. However, part of fumaric acid could be replaced with succinic acid and cupric ion; 4% (NH(4))(2)-fumarate plus 2.5% succinic acid or 5% (NH(4))(2)-fumarate plus 1 mM cupric ion produced results similar to 7% (NH(4))(2)-fumarate in the fermentation medium.

Journal Article↗

Selection of hypotoxigenic Vibrio cholerae population by human intestinal bacteria in gnotobiotic mice.

Strains of human intestinal bacteria when cultured with Vibrio cholerae 569B, classical Inaba, exerted either inhibitory or promotive effects on cholera toxin production. An inhibitory strain of Bacteroides fragilis was orally given to germfree mice a week before vibrio administration. In vibrio-monoassociated mice, the toxin production of most vibrios isolated from feces was as high as the inocula, while in Bacteroides-vibrio-diassociated mice toxin production decreased starting on day 3 after vibrio administration and vibrios with 1/250 to 1/1,000 of the toxin production levels of the inocula dominated 1 and 2 wk after administration. The number of vibrios remained basically unchanged in vibrio-monoassociated mice, but was kept low in Bacteroides-vibrio-diassociated mice throughout the experimental period of 4 wk. Fecal concentration of succinic acid was higher in Bacteroides-associated mice than in vibrio-monoassociated mice. An isolate from a vibrio-monoassociated mouse yielded poorer colony formation on a heart infusion agar plate containing 6.25 mM succinic acid than a vibrio from a Bacteroides-vibrio-diassociated mouse. Isolates from agar plates containing succinic acid showed low cholera toxin productivity. Thus, the presence of the Bacteroides in gnotobiotic mice may have resulted in the selection of a less toxigenic vibrio population, and succinic acid produced in abundance in Bacteroides-associated mice may be one of the selecting factors.

Animals↗

Intestinal metabolism after ischemia-reperfusion.

PURPOSE: This study explores the effects of ischemia-reperfusion on various metabolic aspects of the small intestine. METHODS: Intestinal ischemia-reperfusion was obtained by clamping and unclamping the superior mesenteric artery in adult rats. Four groups of animals were studied: (A) sham operation for 150 minutes, (B) 90-minute intestinal ischemia, (C) 150-minute intestinal ischemia, and (D) 90-minute intestinal ischemia followed by 60-minute reperfusion. Body temperature was maintained at normothermia (36.5 to 37.5 degrees C). Concentrations of intestinal glucose, succinate, lactate, amino acids, phosphocholine (PC), glycerophosphocholine (GPC), choline, and phosphoenergetics were measured using magnetic resonance spectroscopy of freeze-clamped small intestine extracts. RESULTS: Intestinal ischemia (groups B and C) alone caused a significant drop in glucose and phosphoenergetics but caused an increase in amino acids, succinate, and lactate. Ischemia and ischemia-reperfusion decreased PC and GPC but increased choline. After intestinal reperfusion (group D), no recovery of phosphoenergetics was observed, but there was partial recovery of glucose, succinate, lactate, and amino acids. CONCLUSIONS: There is no recovery of phosphoenergetics after 90 minutes of intestinal ischemia followed by 60 minutes of reperfusion. Partial recovery of glucose, succinate, lactate, and amino acids may reflect equilibration of these metabolites between damaged cells and extracellular fluid.

Amino Acids↗

[Isolation and identification of growth stimulators of Escherichia coli M-17].

The stimulating activity of E. coli M-17 culture fluid (CF) is determined by the action of low-molecular exometabolites, readily soluble in water. The high-molecular fraction was removed from CF by ultrafiltration, the growth stimulators were adsorbed on anion exchange resin and eluated at pH 3.1. In further purification HPLC and chromatography on TSK gel HW-40 were used. The identification of compounds was carried out by the methods of thin-layer chromatography, amino acid analysis and 1H-NMR spectroscopy. Glutamic acid (glutamine) and succinic acid proved to be the most active growth autostimulators. The data of biological testing made it possible to believe that CF also contained less active stimulators and/or synergic substances which had no their own activity, but stimulated growth, acting jointly with other compounds. In view of the definite specificity of action observed in initial CF, some differences in the spectrum of growth stimulators of other E. coli strains may be supposed.

Biological Factors↗

Simultaneous gas chromatographic determination of carboxylic acids in soft drinks and jams.

A method was developed for simultaneous gas chromatographic determination of sorbic acid, dehydroacetic acid, and benzoic acid used as preservatives, and succinic acid, fumaric acid, malic acid, and tartaric acid used as acidulants in soft drinks and jams. A sample was dissolved in NH4OH-NH4Cl pH 9 buffer solution, and an aliquot of the solution was passed through a QAE-Sephadex A 25 column. The column was washed with water, and the carboxylic acids were eluted with 0.1N HCl. Sorbic acid, dehydroacetic acid, and benzoic acid were extracted with ethyl ether-petroleum ether (1 + 1), and determined on a 5% DEGS + 1% H3PO4 column. Succinic acid, fumaric acid, malic acid, and tartaric acid in the lower layer were derivatized with N,O-bis(trimethylsilyl)acetamide and trimethylchlorosilane, and determined on a 3% SE-30 column. Recoveries from soft drink and jam samples fortified with 0.1% each of 7 carboxylic acids ranged from 92.4 to 102.6% for preservatives, and from 88.1 to 103.2% for acidulants.

Beverages↗

Disruption of the p53-p53r2 DNA repair system in ulcerative colitis contributes to colon tumorigenesis.

With ulcerative colitis (UC)-associated tumorigenesis, p53 gene alteration is considered to be a key event. To clarify whether the p53-checkpoint is operating in foci of inflammation and that its disruption is a feature of UC-associated neoplasms, the present immunohistochemical study was conducted. Since accumulation of butyric acid with active UC is associated with apoptosis, effects of in vitro exposure of newly established UC-cancer derived cell lines to organic acids were also assessed. The regulatory subunit of ribonucleotide reductase, p53R2, was found to be localized with p53 in situ, and levels of p53, phospho-p53, p53R2 and inducible nitric oxide synthase were significantly intercorrelated. However, p53R2 expression was clearly reduced with progression through UC-associated dysplasia to carcinoma, demonstrating an inverse relation with p53 overexpression. In vitro treatment with butyrate or propionic acid, but not succinic acid, elicited a positive response in the p53-p53R2 system. Moreover, p53-dependent DNA repair, investigated by radioactive nucleotide incorporation, was induced by butyric acid and inhibited by short-interfering p53 and p53R2 RNAs. Therefore, it was concluded that the p53-p53R2-dependent DNA repair system is constitutively stimulated by butyric acid, which accumulates in UC inflammatory lesions. Since failure of the p53-G(1) checkpoint may cause dysfunction of repair under the influence of butyrate, gene alterations may increase and spread through the genome, leading to tumorigenesis.

Apoptosis↗

An organic acid-induced sigmoidal release system for oral controlled-release preparations.

To achieve time-controlled or site-specific drug delivery in the gastrointestinal tract, a sigmoidal release system (SRS) was developed, which achieved a prolonged lag time, followed by rapid release. The theophylline beads with a thick Eudragit RS film coating showed very low drug release in water, whereas the release rate increased considerably in organic acid solutions. A hydration study of Eudragit RS films suggested that the increase in drug release was attributable to structural changes of the film induced by polymer-acid interactions. When succinic acid was incorporated into the core of Eudragit RS-coated theophylline beads, the drug release profile showed a typical sigmoidal pattern. SRS beads containing acetaminophen were also prepared by the same technique. Again, a sigmoidal release pattern was observed in which the lag time was prolonged with an increase in the coating level, whereas the drug release rate thereafter was almost constant irrespective of the coating level. Acetaminophen-containing SRS beads with different coating thickness were orally administered to beagle dogs. The drug plasma concentration curves showed lag periods similar to the in vitro lag time.

Acetaminophen↗

Gamma-irradiation stability of saturated and unsaturated aliphatic polyanhydrides--ricinoleic acid based polymers.

The effect of terminal sterilization by gamma-irradiation on several ricinoleic acid based polyanhydrides was investigated. The following polymers were used: poly(ricinoleic acid maleate) [P(RAM)], poly(ricinoleic acid succinate) [P(RAS)], poly(hydroxy stearic acid succinate) [P(HSAS)], poly(hydroxy stearic acid maleate) [P(HSAM)], and their copolymers with sebacic acid. The polymers were irradiated with an absorbed dose of 2.5 or 10 Mrad by means of a 60Co source under dry ice or at room temperature. No differences were found between samples irradiated under dry ice and at room temperature. Polymers prepared from monomers containing maleate residues, which contain double bonds adjusted to the anhydride linkage along the polymer chain, decreased in molecular weight, became insoluble, and showed fast hydrolytic degradation. For example, p(RAM), p(HSAM), and their copolymers with sebacic acid decreased in Mw from about 10,000 to about 2000, and from about 30,000 to about 5000, respectively, while polymers based on RAS and HSAS remained stable. This phenomenon was explained by an anhydride interchange-self-depolymerization process of the unsaturated anhydride bonds induced by gamma-irradiation. This explanation was supported by the depolymerization of another class of polymers having an anhydride bond between two double bonds, fumaric acid anhydride polymers. The anhydride bond that lies between two double bonds was found to be more sensitive to gamma-irradiation. This anhydride bond may be cleaved to form two radicals that further react with aliphatic anhydride bonds along the polymer chain to form inter- and/or intracyclization products.

Anhydrides↗

Insulinotropic response to enterally administered succinic and glutamic acid methyl esters.

Both the monomethyl and dimethyl esters of succinic acid, administered enterally to fasted rats, caused a rapid increase in plasma insulin. Such was not the case, however, after enteral administration of either succinic acid or the dimethyl ester of glutamic acid. The time course for the appearance of radioactive material in plasma was also vastly different after enteral administration of either [1,4-14C]succinic acid or its dimethyl ester. In the latter case, the separation of acidic and nonacidic radioactive metabolites and the measurement of 14C-labelled D-glucose indicated that, after enteral administration of succinic acid dimethyl ester (2 mmol), its initial appearance rate in plasma averaged 45 +/- 9 microM/min resulting, after 120 min, in a plasma concentration of 1.34 +/- 0.14 mM.

Animals↗

Organic acid profiles in feces of pigs with pathogenic or non-pathogenic diarrhea.

A chemical characteristic of the feces of diarrheal piglets permits differentiation among piglets receiving antibiotic treatment and those with colibacillosis or dyspepsia. A high concentration of lactic or succinic acid was observed in the diarrheic feces of piglets receiving antibiotic treatments and those with dyspepsia; however, no lactic or succinic acids were detected in piglets with colibacillosis. There was, however, little difference in the total concentration of organic acids among the three types of diarrheal illnesses. A quantitative analysis of lactic and succinic acids in diarrheic feces might provide a means for rapidly differentiating between colibacillosis and non-pathogenic diarrheas in piglets.

Animals↗

Haloperidol binding to monoclonal antibodies: conformational analysis and relationships to D-2 receptor binding.

A library of 22 monoclonal antibodies to the D-2 dopaminergic receptor antagonist haloperidol has been developed by immunizing BALB/c mice with two conformationally distinct immunogens. The two immunogens were prepared by coupling haloperidol to bovine serum albumin through the tertiary alcohol at the 4-position of the piperidine ring with a succinic acid linkage and by coupling to bovine serum albumin through the ketone group of the butyrophenone with a carboxymethyl oxime linkage. Seventeen monoclonal antibodies displayed specific, saturable, high affinity binding of [3H]haloperidol which could be inhibited by a variety of neuroleptic drugs. Three monoclonal antibodies raised against the succinic acid conjugate and two monoclonal antibodies raised against the oxime conjugate were selected for detailed analysis of the molecular characteristics of binding specificity and for relationships to bovine striatal D-2 dopaminergic receptor binding. The monoclonal antibody with highest affinity for haloperidol, 185(2)-1 (raised against the succinic acid conjugate and herein referred to as mAb A), had a Kd of 3.3 (+/- 0.06) nM and primarily recognized chemical determinants in the butyrophenone ring (ring 1) and side chain. Inhibition of [3H]haloperidol binding to mAb A by 16 unlabeled haloperidol analogs displayed a good correlation [r = 0.82, n = 16, m = 1.06(+/- 0.38)] with D-2 receptor binding affinity, suggesting that the parts of the D-2 receptor combining site which recognize butyrophenone antagonists may have molecular characteristics which are similar to those of the monoclonal antibody. Other dopaminergic ligands such as dopamine and the D-1 antagonist SCH-23390 were not recognized by monoclonal antibodies raised against the succinic acid conjugate. Monoclonal antibodies raised against the oxime conjugate such as 258(2)-1 (herein referred to as mAb D) primarily recognized chemical determinants in ring 2 and the tertiary amino group of the piperidine ring. Although the D-2 receptor and mAb D both prefer electron-withdrawing substituents in the para position of ring 2, the antibody was more sensitive than the receptor to changes and displayed affinities that were much lower for substituents attached to the p-chlorophenyl ring (ring 2), which were electron donating. In addition, dopamine was able to completely displace 4 nM [3H]haloperidol from mAb D at a concentration of 6 mM.

Animals↗

Effects of microgravity on the binding of acetylsalicylic acid by Rhizobium leguminosarum bv. trifolii.

Bacteroids can be induced in vitro by treating growing Rhizobium leguminosarum bv. trifolii with succinic acid or succinic acid structural analogs like acetysalicylic acid. Quantitating bacteroid induction by measuring acetylsalicylic binding under normal (1 g) conditions showed two forms of binding to occur. In one form of binding cells immediately bound comparatively high levels of acetylsalicylic acid, but the binding was quickly reversed. The second form of binding increased with time by first order kinetics and reached saturation in 40 s. Similar experiments performed in the microgravity environment aboard the NASA 930 aircraft showed only one form of binding and total acetylsalicyclic acid bound was 32% higher than at 1 g.

Aspirin↗