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[Effect of ammonium succinate on pharmacological effects of acetylsalicylic acid].

Ammonia succinate potentiates the main pharmacological properties and reduces the toxic effects (ulcerogenic action and general toxicity) of acetylsalicylic acid. The new preparation astam, representing a combination of acetylsalicylic acid with ammonia succinate in a 2:1 ratio, is proposed. Astam exhibits antiexudative, capillary-reinforcing, antiproliferative, pain-relieving, antipyretic, antiaggregant, and antioxidant properties. In addition, the drug inhibits the development of structural-metabolic disorders in the case of chronic immune inflammation of joints and various internal organs.

Animals↗

[Role of formic acid in transformation of acetic and succinic acids in animal tissues].

Acetic and succinate acids KoA acyl derivatives interacting with formate were displayed to produce alpha-ketoacids--pyruvate and alpha-ketoglutarate. These acids also interact with formate and make pyruvic and malate acids, while alpha-ketoglutarate, evidently, tricarboxy acids. Interaction of formate with acetic and succinate acids inspite of occurring out of the tricarbone cycle increases the latter metabolic functions.

Acetic Acid↗

Synergistic insulinotropic effects of succinic acid dimethyl ester and exendin-4 in anaesthetized rats.

It was recently proposed that suitable succinic acid esters could be used to potentiate the insulinotropic action of glucagon-like peptide 1 (GLP-1) in the treatment of type-2 diabetes mellitus. In such a perspective, the present study aimed mainly at investigating whether exendin-4 (Ex-4), a peptide structurally related to GLP-1(7-36)amide, and succinic acid dimethyl ester (SAD) also act synergistically upon insulin secretion in anaesthetized rats. Despite a higher plasma insulin concentration in SAD-infused rats (5.5+/-1.1 ng/ml) than in saline-infused animals (1.9+/-0.7 ng/ml), the intravenous injection of Ex-4 augmented to a greater extent the plasma concentration of insulin in the former rats (+7.4+/-2.5 ng/ml) than in the latter animals (+2.8+/-0.6 ng/ml). These findings document that the insulinotropic actions of Ex-4 and GLP-1 display comparable nutrient dependency, being both potentiated by a non-glucidic nutrient secretagogue such as SAD.

Anesthesia↗

Lactic and succinic acid levels and refractive indices in the determinations of the age of eggs.

The increase in the concentration of lactic and succinic acid during storage was measured in an attempt to determine the age of eggs. The increase in succinic acid alone is not sufficient to indicate egg age. Although lactic acid concentrations increase more rapidly, the levels are still very low, the increase is not linear, and concentrations in fresh eggs vary widely. On the other hand, refractive indices showed a nearly linear correlation with age and very little variation between eggs. These measurements are reproducible and easy to perform and, with further study, should provide an alternative to the AOAC method.

Eggs↗

[Succinate dehydrogenase and Na+-K+-ATPase activities in cells of rat kidney tubules during increased excretion of sodium, caused by furosemide].

In the cells of nephron tubules an effect of furosemide on kidney function and on succinate dehydrogenase and Na+-K+-ATPase activities was studied cytochemically. Administration of furosemide (1 mg per 100 g of body weight) increased excretion of sodium and potassium. If the rate of filtration through Malpighian tufts was constant, the increase in Na and K excretion demonstrated the tubular effect of the diuretics. Both administration of furosemide and preincubation of the drug with kidney slices in vitro caused a decrease in succinate dehydrogenase activity in the cells of all the nephron sections. These data suggest that a direct effect of the diuretics on oxidative metabolism in renal cells took place. Alteration in the activity of Na+-K+-ATPase was observed only in vivo and in those nephron sections, where sodium reabsorption was decreased under the effect of furosemide.

Adenosine Triphosphatases↗

Histoenzymological demonstration of glycerol-3-phosphate dehydrogenase and succinate dehydrogenase in the telencephalic nuclei and fibre tracts of hillstream cyprinoid, Barilius bendelisis (Hamilton).

The authors studied the regional localization of two dehydrogenases--glycerol-3-phosphate dehydrogenase and succinate dehydrogenase--in the telencephalic nuclei and fibre tracts of Barilius bendelisis by histoenzymological methods. The activity of these dehydrogenases varied from moderately positive to strongly positive in the nuclear areas and from intensely to strongly positive in the fibre tracts, except those related to the olfactory tubercle. G3PD appears to play an important role in the biosyntheses of phospholipids and to form a link between glycolysis and the pathway of the hexose-monophosphate shunt, in addition to its usual role in the degradation of glucose, along with other dehydrogenases, including succinate dehydrogenase.

Animals↗

Active succinate dehydrogenase (SDH) and lack of SDHD mutations in sporadic paragangliomas.

BACKGROUND: Paragangliomas are benign, slow-growing tumours of the head and neck region. The candidate gene for familial and some sporadic paragangliomas, SDHD (succinate dehydrogenase, subunit D), has been mapped to the PGL1 locus in 11q23.3. MATERIALS AND METHODS: Normal and tumour DNA of 17 patients with sporadic paragangliomas were analysed by sequencing (SDHD, SDHB and SDHC genes), fluorescence in situ hybridisation (FISH). In addition, loss of heterozygosity (LOH) and succinate dehydrogenase (SDH) enzyme activity assays were performed. RESULTS AND CONCLUSION: Only two patients from our collective showed SDH gene mutations, one in SDHD and one in SDHB, respectively. Moreover, SDH activity detected in 5/8 patients confirmed the fact that SDH inactivation is not a major event in sporadic paragangliomas. LOH and FISH analysis demonstrated a frequent loss of regions within chromosome 11, indicating that additional genes in 11q may play a role in tumour genesis of sporadic paragangliomas.

Carotid Body Tumor↗

[Correlation between succinate-dependent Ca2+ accumulation and transamination in the heart and the liver mitochondria of experimental animals].

Glutamate (GLU) and alpha-ketoglutarate (KGL), the substrates involved in transamination, have reciprocal effects on succinate-dependent respiration, NADH reduction, as well as on the accumulation and stable retention of Ca2+ in heart and liver mitochondria and homogenates from experimental animals. The succinate-dependent Ca2+ accumulation was shown to be highly sensitive to changes of the concentration ratios of GLU and KGL within the range 1:10 mM. GLU activated this process by transamination of oxalacetate (OAA) to aspartate. The predomination of KGL blocked the activating effect of GLU. The predomination of GLU eliminated the block produced by KGL or phosphoenolpyruvate (sources of OAA and GTP) but did not eliminate the Ca2+ accumulation-suppressing effect of aminoacetate, inhibitor of transaminases.

Amino Acids↗

[Histochemical characteristics of the activity of succinate dehydrogenase and cytochrome oxidase in certain tissues and organs of patients with thyrotoxicosis and animals with experimental thyroidin toxicosis].

The activity of succinic dehydrogenase and cytochromoxidase was studied histochemically in the peripheral blood leukocytes, the thyroid gland tissue and the skeletal muscles of the patients suffering from thyrotoxicosis. The activity of these enzymes is also determined in the blood leukocytes, the cardiac muscle, the liver and the skeletal muscles of the experimental animals given thyroidin in a dose of 0.1 g per 100 g of body weight in the course of 10 days. A marked elevation of the activity of the oxidative enzymes in the patients with an increase of the severity of thyrotoxicosis and in the animals after the thyroidin administration was noted. The absence of any changes in the succinic dehydrogenase and cytochromoxidase activity in the tissue of the skeletal muscles permitted to suppose that increase of the oxidative processes occurred primarily in the organs bearing a great functional load (the thyroid gland, liver, skeletal muscle, etc.).

Animals↗

Isolation and characterization of a Saccharomyces cerevisiae mutant disrupted for the succinate dehydrogenase flavoprotein subunit.

A partial genomic clone of the flavoprotein subunit of the mitochondrial enzyme, succinate dehydrogenase (EC 1.3.99.1) from Saccharomyces cerevisiae has been isolated. The partial clone was used to construct, by targeted gene disruption, a yeast mutant with a defective flavoprotein subunit gene. Submitochondrial membranes from the mutant are defective in activities requiring a functional succinate dehydrogenase but not in other respiratory chain activities. In addition, the mutant contains significantly lower levels of covalently attached flavin adenine dinucleotide cofactor than does the wild type. Disruption of the flavoprotein subunit gene results in the simultaneous loss of both the iron-sulfur and the flavoprotein subunits from mitochondrial membranes.

Amino Acid Sequence↗

[Kidney function and Na+-K+-ATPase and succinate dehydrogenase activity in the cells of the renal tubules of rats with constriction of the thoracic portion of the vena cava inferior].

Circulatory insufficiency in rats was induced by constriction of the thoracic portion of vena cava inferior. Two-three days after the operation renal function was studied and the activity of succinate dehydrogenase and Na+K+-ATPase in the cells of the renal tubules was determined cytochemically. On infusion of 0.9% NaCl solution into the stomach, the filtration in the "caval" rats did not change whereas the excretion of sodium and its concentration in the urine were much lower than in the sham operated rats. At the same time, the activity of Na+K+-ATPase and succinate dehydrogenase in the "caval" rats increased in the cells of the proximal tubule, diminished in Henle's loop, and remained unchanged in the cells of the distal convoluted tubule. Comparison of the results of functional and cytochemical study of the kidneys in caval rats allows the conclusion that intensified proximal reabsorption may be the main cause of antinatriuresis in these animals. The lesser load experienced by the distal segment promotes fuller reabsorption of sodium in this part of the nephron too.

Animals↗

Cloning and characterization of the iron-sulfur subunit gene of succinate dehydrogenase from Saccharomyces cerevisiae.

We describe the cloning and characterization of the complete gene for the iron-sulfur protein subunit of succinate dehydrogenase (EC 1.3.99.1) from Saccharomyces cerevisiae. The promoter and coding sequence have been cloned into an Escherichia coli-yeast shuttle vector. The cloned gene complements the defect in a succinate dehydrogenase-deficient yeast mutant isolated by us, and gene expression is fully responsive to induction by glucose deprivation, indicating that the promoter is intact.

Amino Acid Sequence↗

The spatial relationships and structure of the binuclear iron-sulfur clusters in succinate dehydrogenase.

Two binuclear iron-sulfur clusters (designated S-1 and S-2) are present in succinate dehydrogenase in approximately equal concentration to that of flavin. The large difference in their midpoint potentials (0 and -400 mV, respectively, in the soluble enzyme) permits the acquisition of individual electron paramagnetic resonance spectra characterized by nearly identical rhombic g tensors (gz = 2.025, gy = 1.93, gx = 1.905). Spin-coupling between the two centers is manifested by broadening and splitting of spectra of reconstitutively active and inactive succinate dehydrogenase, respectively, as the temperature is lowered; relief of power saturation of Center S-1 spectra on reduction of Center S 2; and observation of half-field ("delta ms = 2") signals in the dithionite-reduced enzyme. Saturation behavior of fully reduced dehydrogenase is consistent with the presence of S-1 and S-2 at equivalent concentrations/molecule. Simulation of the spin-coupled spectra, assuming dipolar interaction, provides information on molecular structure. Electron paramagnetic resonance spectra of the enzyme in 80% dimethylsulfoxide are nearly identical to the characteristic binuclear spectra obtained with adrenodoxin. These data provide additional evidence for binuclear structure of both Center S-1 and S-2. The extremely fast relaxation of Center S-2 at low temperatures would imply either an anomalously small value of J or an alternative relaxation mechanism, possibly due to the coupling between S-1 and S-2.

Animals↗

[In vitro thermosensitivity of various human tumors evaluated using the SDI (succinate dehydrogenase inhibition) test].

In vitro thermosensitivity of various human tumors including 90 esophageal, 10 gastric and 40 colo-rectal cancers were evaluated using the succinate dehydrogenase inhibition (SDI) test. Tumor fragments minced with scissors were incubated at 43 degrees C as heat treated cells and at 37 degrees C as controls for 20 hrs, and assayed for the succinate dehydrogenase (SD) activity using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as a hydrogen acceptor. The thermosensitivity was estimated by the percentage of SD activity of heat treated cells compared to that of each control. A variation in the thermosensitivity was noted between patients. The SD activity was 60.1 +/- 20.3% (mean +/- standard deviation) for esophageal cancers, 34.9 +/- 21.7% for gastric cancers, 50.3 +/- 20.6% for colo-rectal cancers. Significant differences were noted between esophageal cancers and gastric cancers, colo-rectal cancers (p less than 0.01 and p less than 0.05, respectively). When the thermosensitivity was arbitrarily defined as reduction in the SD activity to 50% of control or less, the positive rates were 31.1% for esophageal cancer, 70% for gastric cancer and 62.5% for colo-rectal cancer. Our results show that the SDI test is a useful method for determination of the thermosensitivity of clinical samples.

Digestive System Neoplasms↗

[Changes in the lipid composition of mitochondrial membranes during succinate oxidase reaction].

Content of lipids, free cholesterol, cholesterol esters, phospholipids and fatty acid composition were studied in mitochondria incubated in samples containing succinate. Induction of lipid peroxidation, production of malonic dialdehyde and alterations in membranes fluidity were not detected in the preparations of mitochondria within 3 hrs of succinate oxidation. Self-inactivation of mitochondria appears to occur due to an increased uncoupling of oxidative phosphorylation.

Animals↗

[Catabolism of labelled alpha-ketoglutarate, succinate, aspartate and gamma-aminobutyric acid in nerve tissue; the effect of pyridoxal-5'-phosphate in vitro].

Proceeding from estimation of the 14CO2 release from [5-14C]alpha-ketoglutarate, [1-14C] gamma-aminobutyric acid (GABA), [1,4-14C] succinate and [4-14C] aspartate (0.4-1 mM) during their incubation with homogenates of different brain areas with regard for the label position and stereospecificity of decarboxylation of citrate formed due to the metabolism, the relative intensity of their catabolism is determined: [1,4-14C] succinate much greater than [4-14C]aspartate greater than [5-14C] alpha-ketoglutarate much greater than [1-14C]GABA. The label release with catabolism of [1-14C] alpha-ketoglutarate considerably exceeds the intensity of decarboxylation of the above enumerated substrates. In all cases the maximum release of 14CO2 has been registered in the cortex homogenates, the minimum--in the medulla homogenates, and only under long-term incubation with high concentration of GABA (50 mM) maximum catabolism was registered in the medulla. Preincubation of nervous tissue with pyridoxal-5'-phosphate (40 microM) results in significant acceleration of catabolism of [1-14C] alpha-ketoglutarate, [5-14C] alpha-ketoglutarate and [4-14C] aspartate with an inconsiderable increase of catabolism of the rest of labelled substrates.

Animals↗

[The sensitivity of 1,000 human tumors to antitumor drugs using the succinate dehydrogenase inhibition (SDI) test].

The chemosensitivity was evaluated by the in vitro succinate dehydrogenase inhibition (SDI) test in 1,000 human tumors including 237 gastric cancers, 116 colorectal cancers, 113 hepatoma and 534 others. These tumor cells were exposed to 5 kinds of antitumor drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cis-platinum (DDP). After exposure to the antitumor drugs, cell viability was assessed with colorimetric assay, based on the ability of succinate dehydrogenase (SD) in living tumor cells to reduced a tetrazolium (MTT) to a formazan. The chemosensitivity was determined to be positive when the SD activity of drug exposed cells decreased to below 50% of that of control cells, on day 3 of exposure. The chemosensitivity varied in the tumor tissues. The chemosensitivity of metastatic lesions of lymph nodes were higher than that of the primary lesions, while metastatic liver tumors had lower sensitivity than the primary lesions. The intra-tumorous distribution of SD activity in 12 human gastric cancers were compared with normal adjacent tissues using histochemistry. Seventy-five % (9/12) of gastric cancer tissues had higher SD activity than normal adjacent tissues. The SDI test is rapid and simple method to predict the sensitivity test of various human tumors to antitumor drugs.

Antineoplastic Agents↗

[Improvement in the method of determination of succinic dehydrogenase in skin].

The authors improved Hershey's measurement of succinic dehydrogenase in the shin. Liquid paraffin was used to replace nitrogen gas sealing. The values of succinic dehydrogenase of guinea pig skin which was kept at 4 degrees C for 2, 4, 6, 8, 10 days were measured by two methods. There were no significant differences between the values measured by two methods (P greater than 0.05). Our method is simpler, more convenient and have good correlation with Hershey's method (r = 0.929).

Animals↗