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PubMed1975

Thiobacillus acidophilus sp. nov.; isolation and some physiological characteristics.

After a brief exposition to glucose, Thiobacillus acidophilus was isolated from a culture of iron-grown T. ferrooxidans. Physicochemical analysis of its DNA showed a G+C content of 62.9-63.2%. The new isolate grows best at 25-30 degrees C and at pH 3.0. Growth is possible between pH 1.5 and 6.0. Thiobacillus acidophilus is apparently strictly aerobic. Ammonium salts are the only suitable source of nitrogen. The bacterium is a facultative autotroph. In addition to elemental sulfur, it obtains energy from organic compounds such as D-glucose, D-galactose, D-fructose, D-mannitol, D-xylose, D-ribose, D-arabinose, L-arabinose, sucrose, sodium citrate, malic acid,dl-aspartic acid, and dl-glutamic acid. Thiobacillus acidophilus possesses the key enzymes of the tricarboxylic acid (TCA) cycle including NAD-and NADP-linked isocitric dehydrogenase and alpha-ketoglutarate dehydrogenase, and the key enzymes of the hexose monophosphate pathway (glucose-6-phosphate and 6-phosphogluconate dehydrogenase, and fructose 1,6-diphosphate aldolase). NADH oxidase has been found in particulate fraction of extracts. Rhodanese and thiosulfate oxidase have also been detected.

Aerobiosis↗
PubMed1992

Almitrine mimics hypoxic vasoconstriction in isolated rat lungs.

The effect of almitrine bimesylate or the solvent malic acid on pulmonary vascular perfusion pressure was assessed in isolated rat lungs and on the contractile behavior of rat aorta and main pulmonary artery rings. Addition of almitrine to the lung perfusate during normoxia caused a dose-dependent, transient increase in pulmonary artery pressure with no change of the lung microvascular pressure. In systemic or pulmonary conduit arteries, the contractile tension was unaffected by almitrine. This indicates a precapillary locus of drug action. We also examined almitrine's effect on hypoxic pulmonary vasoconstriction (HPVC) in isolated lungs perfused with blood or with physiological salt solution (PSS). Low-dose almitrine potentiated hypoxic vasoconstriction in blood- but not in PSS-perfused lungs. However, a high dose of almitrine reduced hypoxic vasoconstriction dose dependently. When almitrine was added to the lung perfusate during hypoxia- or cyanide-induced (NaCN, 5 x 10(-5) M) pulmonary vasoconstriction, almitrine caused no further vasoconstriction. However, when the pulmonary perfusion pressure was elevated by KCl (20 mM) to the same magnitude as by alveolar hypoxia or cyanide, almitrine elicited a pressor response comparable to that observed during normoxia. Almitrine-induced pulmonary vasoconstriction resembled hypoxic vasoconstriction in that agents known to enhance hypoxic vasoconstriction (phorbol myristate acetate, vanadate, and 4-aminopyridine) enhanced, and known inhibitors of HPVC (the Ca2+ entry blocker nifedipine and hypothermia) inhibited, the almitrine-induced vasoconstriction. These findings lead us to speculate that almitrine also affects the oxygen-sensing limb of the hypoxic pressor response, not simply the effector (contractile apparatus of the vascular muscle cell).

Almitrine↗
PubMed1990

Restored hypoxic pulmonary vasoconstriction by peripheral chemoreceptor agonists in dogs.

Hypoxic stimulation of the peripheral chemoreceptors inhibits hypoxic pulmonary vasoconstriction (HPV). On the other hand, almitrine, a peripheral chemoreceptor agonist, has been reported in some studies to enhance HPV. To further explore this apparent contradiction, we investigated the effects of two different low intravenous doses of almitrine on pulmonary arterial pressure (Ppa) versus cardiac index (Q) plots in 32 pentobarbital-anesthetized dogs ventilated alternatively in hyperoxia (FIO2, 0.4) and in hypoxia (FIO2 0.1). HPV, defined as a hypoxia-induced increase in Ppa over the entire range of Q studied, from 2 to 5 L/min/m2, was elicited in 16 dogs. In the first eight of these "responders," almitrine 2 micrograms/kg/min had no vascular effect, and in the other eight, almitrine 4 micrograms/kg/min inhibited HPV. In 16 other dogs, hypoxia did not affect Ppa over the entire range of Q. In these "nonresponders," almitrine 2 micrograms/kg/min (n = 8) as well as 4 micrograms/kg/min (n = 8) restored HPV. To answer the question whether the ability to restore HPV would be specific to almitrine, we administered intravenously the structurally unrelated chemoreceptor agonist doxapram at the dose of 20 micrograms/kg/min to an additional group of eight "nonresponders," and this treatment also restored HPV. Intravenous infusion of the malic acid solution solvent of almitrine had no effect on Ppa/Q plots in a final group of eight "nonresponders". We conclude that low dose almitrine and doxapram restore HPV in dogs with a naturally absent hypoxic pulmonary pressor response, probably by a direct effect at the pulmonary vessels.

Almitrine↗
PubMed1998

Mechanism of the protective effect of sodium malate on cisplatin-induced toxicity in mice.

We examined the mechanism of the protective effect of sodium malate on cis-diamminedichloroplatinum(II) (cisplatin, CDDP)-induced nephrotoxicity in mice and obtained the following findings: 1: Sodium malate showed a maximum reduction of toxicity when it was administered at the same time as CDDP or at 30 min before the administration of CDDP; the reduction was significantly decreased when sodium malate was given after the administration of CDDP. 2: It is thought that diamminoplatinum(II) malate (DPM) is produced in the body following the administration of a combination of CDDP and sodium malate. DPM showed the same antitumor effect as CDDP and produced little nephrotoxicity. 3: When CDDP was combined with sodium malate, the time necessary for the elimination of platinum from the blood was prolonged, showing a intermediate value between the times for the elimination of CDDP and DPM from the blood. When the drug clearance was calculated based on this result, it was found that about 40% of the CDDP administered is converted to DPM in the blood. 4: In an experiment using L-[14C] malic acid, it was shown that sodium malate is distributed in the liver and the kidney at high concentrations, but in the tumor at only a low concentration. 5: When sodium malate was administered in combination with CDDP, the amount of platinum which accumulated in the kidney after 24 h was decreased by about 55% compared with the uncombined group, but there was no change in the amount of platinum which accumulated in the tumor. These results suggest that the sodium malate administered may be distributed rapidly in the blood and the tissue, and about 40% is bound to CDDP and converted to DPM, thus reducing the nephrotoxicity of CDDP.

Animals↗
PubMed1998

Preparation of alkyl-substituted indoles in the benzene portion. Part 15. Asymmetric synthesis of (+)-duocarmycin SA using novel procedure for preparation of hydroxyindoles.

An asymmetric total synthesis of natural (+)-duocarmycin SA (1) starting from L-malic acid (7) was achieved as shown in Chart 5, establishing firmly the absolute configuration of 1. In order to find suitable reaction conditions for the key step, i.e., the formation of an alkoxyindole derivative, model compounds 9 and 40 were synthesized and two acetalization conditions using i) 2-ethyl-2-methyl-1,3-dioxane and boron trifluoride etherate, and ii) 1,3-bis(trimethylsilyloxy)propane and trimethylsilyl triflate were found to be effective. The former conditions were successfully applied to total synthesis and 49b was prepared from 48 in 54% yield. Further elaborations including i) Curtius rearrangement of 53b to 56, and ii) cleavage of the primary benzyloxy group in the presence of the secondary one in its close vicinity (56-->57) led to the relay compound 62, whose conversion to 1 has already been accomplished.

Alkylation↗
PubMed2001

New phenolic constituents from the fruit juice of Phyllanthus emblica.

Six new phenolic constituents, L-malic acid 2-O- (1), mucic acid 2-O- (5), mucic acid 1,4-lactone 2-O- (6), 5-O- (8), 3-O- (10), and 3,5-di-O- (11) gallates, were isolated from the fruit juice of Phyllanthus emblica together with their methyl esters (2-4, 7, 9), and their structures were determined by spectral and chemical methods. Compounds 5, 6, and 8, the major phenolic constituents of the juice, were present as an equilibrium mixture in aqueous solution.

Antioxidants↗
PubMed2000

[Application of radionuclides in pharmaceutical fields].

Application studies of radionuclides in pharmaceutical fields are described concerning two major categories, such as the use of gamma-emitter in nuclear medicine and beta-emitter in tracer investigation. In the former radionuclide an effort has been made to develop radioactive new diagnostic agents in the nephro-urology field. Of several agents examined two new radiopharmaceuticals, 99mTc-malic acid and 99mTc-dimercaptopropionic acid proved to be sufficient for renal imaging with adequate concentration in experimental animals and humans. Useful information was obtained for diagnosis of renal diseases using both the labeled agents. Identification and purity tests of radiopharmaceuticals also set forth for official compendia such as the Japanese pharmacopoeia and so on. In the latter one the fates of two medicines, thalidomide and norphenylephrine, were studied and the safety evaluation of some xenobiotics including food additives, plasticizers and domestic chemical products, etc. was carried out in animals using synthesized 14C- or 3H-labeled compounds. In addition, the metabolism of n-propyl-N-nitrosourea, a carcinogen, in rats, and chemical modification of high molecular substances such as DNA, RNA and proteins by 1,1'-ethylene-bis(1-nitrosourea) (EBNU), a carcinostatic agent, were studied in vitro by the use of the tracer technique.

Animals↗
PubMed1994

Total syntheses of (2S)-antafumicins A and B.

To clarify the absolute configurations of antafumicins A and B, which are antifungal substances from Aspergillus niger NH-401, the total synthesis of (2S)-antafumicins was accomplished by starting from (S)-malic acid in 12 steps. Based upon the physicochemical data of the synthetic samples, the absolute configurations of naturally occurring antafumicins A and B were determined as (2R,4S)- and (2R,4R)-4-(3-acetyl-2,6-dihydroxyphenyl)-2-methoxy-4-butanolide, respectively.

4-Butyrolactone↗
PubMedDate not supplied

A cytotoxic principle of Tamarindus indica, di-n-butyl malate and the structure-activity relationship of its analogues.

Bioassay-guided fractionation of the methanolic extract of Tamarindus indica fruits led to the isolation of L-(-)-di-n-butyl malate which exhibited a pronounced cytotoxic activity against sea urchin embryo cells. In order to study structure-activity relationships, close-structure relatives of di-n-butyl malate were synthesized using D-(+)- and L-(-)-malic acid as starting materials, and their cytotoxic activities were examined for the sea urchin embryo assay. L-(-)-Di-n-pentyl malate was the most effective inhibitor to the development of the fertilized eggs. Significant inhibitory activity was not seen in the esters of D-(-)-isomer.

Animals↗
PubMed1991

A method for the demonstration of NADPH-diaphorase activity in anuran species using unfixed retinal wholemounts.

The presence of NADPH-diaphorase enzyme has been previously revealed in fixed mammalian retinal tissue (Sagar, 1986). Fixed retinae of Bufo marinus and Xenopus laevis failed to yield selective staining when reacted for NADPH-diaphorase. Satisfactory staining of retinal neurons was attained when the histochemical reaction was carried out in unfixed retinal wholemounts. The applied method included the following steps: 1) Dissection of the fresh retina and the separation of the neural retina from all other coats of the eye ball, including the vitreal tissue; 2) pretreatment with 300 mM sucrose in phosphate buffer; 3) incubation with NADP, malic acid and nitroblue tetrazolium in phosphate buffer (pH 7.6); and 4) fixation of the tissue in 10% buffered formaldehyde overnight followed by whole mounting. For control, fixed and unfixed rabbit and human retinae were also reacted for NADPH-diaphorase according to the above method. In these species specific staining was achieved only with fixed tissues. The possible implications of revealing NADPH-diaphorase enzyme activity in fixed mammalian and non-fixed anuran tissues are discussed.

Animals↗
PubMed1988

[Dry-distillation of experimental animal wastes containing radioisotopes].

Mice were dry-distilled at 800 degrees C for 10 min, after [32P]orthophosphate or L-[4,5-3H]leucine was intraperitoneally administered. Phosphorus-32 was quantitatively recovered in the residual solid, whereas 95% of 3H was found int he distillate (condensed water). When 14C (L-[U-14C]malic acid or L-[U-14C]leucine) was administered to mice and they were dry-distilled, 14C-radioactivity was distributed into two fractions; residual solid and exhaust gas. In these cases, the recovery percentage of 14C in residual solid was not very high but increased as the treating temperature decreased. It reached about 40% of the administered 14C at 400 degrees C for 120 min. By the dry-distillation of animals, their weight was reduced to about 10% in every animal tested (mice, rats and rabbits). The volume was reduced to about 20% in cases of mice and rats, and about 30% in case of rabbits. It was concluded that the dry-distillation can be useful as a pre-treatment for disposal of animal wastes containing radioisotopes.

Animals↗
PubMed1996

Heat resistance of Escherichia coli O157:H7 in apple juice.

The objective was to determine the effect of cider composition on the heat resistance of Escherichia coli O157:H7. The average D52 value in a model Empire apple juice was 18 min with a z value of 4.8 degrees C. Increasing the Brix from 11.8 to 16.5 degrees had no effect on thermal resistance, while increasing L-malic acid from 0.2 to 0.8%, or reducing the pH from 4.4 to 3.6 sensitized the cells to heat. The greatest effect on heat resistance was afforded by the preservatives benzoic and sorbic acids: D50 values in ciders containing 1,000 mg/l were 5.2 min in the presence of sorbic acid and only 0.64 min in the presence of benzoic acid. Commercial apple juice concentrates yielded lower numbers of survivors than single-strength juices even though their higher sugar concentrations of about 46 degrees Brix increased heat resistance.

Benzoic Acid↗
PubMed1999

Development and use of polymerase chain reaction for the specific detection of Salmonella Typhimurium in stool and food samples.

Salmonella Typhimurium is one of the most important Salmonella serovars that may cause foodborne disease and human salmonellosis infection. Detection of this organism in the clinical samples of persons with gastroenteritis and the food samples associated with such persons may allow us to trace the cause of disease. Because malic acid dehydrogenase, an enzyme of the citric acid cycle, is common to organisms, the gene (mdh) coding for this enzyme was selected for the design of Salmonella Typhimurium-specific polymerase chain reaction (PCR) primers. By comparison of the mdh gene sequences of Salmonella Typhimurium and other Salmonella serotypes and of some isolates of other genera, two oligonucleotides were designed and used as PCR primers for the specific detection of Salmonella Typhimurium. The molecular weight of the PCR product was 261 bp as expected. Salmonella serovars other than Salmonella Typhimurium and isolates of other genera in the Enterobacteriaceae that is closely related to Salmonella did not generate any false-positive results. When this primer pair was used for the detection of Salmonella Typhimurium cells artificially inoculated into human stool specimens and food samples, such as milk and raw chicken meat, levels as low as 10(0) CFU per 0.1 g of stool specimen or per ml of milk or food homogenate could be detected if an 8- to 12-h preculture step using combined lactose-tetrathionate broth was performed prior to the PCR.

Animals↗
PubMed1980

Malioxamycin, a new antibiotic with spheroplast-forming activity. I. Producing organism, fermentation, isolation and characterization.

Strain No. 15748, identifies as Streptomyces lydicus, produces a new antibiotic malioxamycin. Malioxamycin is a water-soluble, amphoteric antibiotic with low molecular weight, having a valine and a malic acid moieties in its structure. It gave a positive ninhydrin and ferric chloride reactions. Malioxamycin inhibited the growth of some Gram-negative bacteria by acting on peptidoglycan synthesis in the cell wall and produced spheroplasts from those sensitive bacteria.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Mesophilic rod-like nonsporeforming bacterium reducing sulfates].

A pure culture of a new organism, strain X, reducing sulphates is described. According to its morphological, physiological and biochemical properties, the organism is classed as a new species. Desulfovibrio baculatus nov. sp. The cells have the shape of short rods, 1.3X0.6 mcm, with a polar flagellum 0.021 mcm thick. It is an obligate anaerobic culture growing on media only in the presence of sulphates at the account of sodium salts of lactic, pyruvic and malic acids and also in the presence of yeast autolysate at the account of formate and hydrogen. Sulphate, sulphite and thiosulphate can serve as acceptors of electrons during growth on lactate. The organism grows at 2 to 41 degree C in the presence of up to 6% NaCl in the medium and does not require NaCl for its growth. The cells do not contain desulphoviridine as was proved by fluorescence. Hemes of cytochromes b and c were found in the cells. The content of G+C base pairs in DNA is 56.8+/-0.4 mole %. The culture was isolated from dumps of manganese ore.

Anaerobiosis↗
PubMed1978

[Development of experimental brain tumors in modulated amine metabolism].

There was found a correlation between dynamic changes in the serotonin level and mortality in rats with 9,10-dimethyl-1,2-benzanthracene induced blastomogenesis. An estimation was made of the influence of monoamine oxidase inhibitors, transamine and D, L-malic acid benzyldihydrazide on the type of a tumor produced. Chemical blastomogenesis in the case of cerebellar tumors is shown to be associated with the decreased serotonin content at the site of a tumor. But fluctuations of the serotonin level in the hypothalamus have not been detected. This evidenced that the decreased mortality rate caused by the administration of monoamine oxidase inhibitor is due to a lower production of astrocytomas and genetically related glioblastomas. The role of serotonin in increasing the astrocyte resistance to malignant degeneration has been discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Auxotrophic requirement for sporangiospore--yeast transformation of Dimorphomyces diastaticus strain C 12.

The filamentous microorganism tentatively known as Dimorphomyces diastaticus originally isolated from fermenting soursop extract, in contradistinction grew in the considiogeneous form in glucose-ammonium sulphate-basal salts buffered medium which induced polar budding yeast cells of another dimorphic microorganism, D. pleomorphis (1). Further experiments using this medium showed that a number of growth factors including inositol, thymine and uracil separately incorporated inducted yeast morphology. Carbon substrates gave rise to polar budding yeast cells in the following order: galactose, malic acid, maltose, but mycelial fragments were preponderant in the reverse order. There was no growth with citric acid as substrate. With maltose-substrate and uracil incorporation in buffered basal salts medium, only polar budding yeast cells were induced, while granular particles abound with thymine supplementation. It was concluded that D. diastaticus strain C12 auxotrophically required a dissacharide, maltose, and pyrimidine base, uracil, for sporangiospore-yeast transformation in buffered ammonium sulphate-basal salts medium, pH 3.5.

Ascomycota↗
PubMed1979

A radiometric microbiologic assay for the biologically active forms at niacin.

A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced 14CO2 from L-[U-14C] hr malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 micrograms niacin/ml RBC (mean = 15.27 +/- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays.

Animals↗