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PubMed1997

Quantitative evaluation of renal parenchymal mass with 99mtechnetium dimercapto-succinic acid scintigraphy after nephrolithotomy.

PURPOSE: We detected renal parenchymal damage after nephrolithotomy. MATERIALS AND METHODS: We studied 12 patients with renal stones treated with nephrolithotomy. Renal function was determined with serum blood urea nitrogen (BUN) and creatinine values, and 99mtechnetium dimercapto-succinic acid scintigraphy of renal parenchymal tissue was performed before, and 7 days and 3 months after nephrolithotomy. Qualitative and quantitative analyses were done with the Wilcoxon signed rank test. RESULTS: There was no visual difference in size and appearance of the nephrotomy site between preoperative and postoperative visual scintigraphic evaluations. Quantitative data did not reveal any significant difference between kidneys with and without a nephrotomy incision (p > 0.05), as well as between nephrotomy regions and intact parenchyma within the same kidney (p > 0.05) 3 months after nephrolithotomy. There was no significant difference in serum BUN and creatinine levels between values preoperatively and 3 months postoperatively (p > 0.05). CONCLUSIONS: There was no significant change in renal cortical function and functioning renal parenchymal mass after nephrolithotomy as shown by serum BUN and creatinine levels, and 99mtechnetium dimercapto-succinic acid scintigraphy.

Adolescent↗
PubMed2004

Local and global chirality at surfaces: succinic acid versus tartaric acid on Cu110.

A detailed comparison of tartaric acid (HOOC-CHOH-CHOH-COOH) and succinic acid (HOOC-CH(2)-CH(2)-COOH) molecules on a Cu(110) surface is presented with a view to elucidate how the two-dimensional chirality exhibited by such robust, chemisorbed systems is affected when both OH groups of the former molecule are replaced with H groups, a stereochemical change that leaves the metal-bonding functionalities of the molecule untouched but destroys both chiral centers. It is found that this change does not significantly affect the thermodynamically preferred chemical forms that are adopted, namely the doubly deprotonated bicarboxylate at low coverages (theta </= (1)/(6) ML) and the singly deprotonated monocarboxylate at higher coverage. However, the kinetics of phase formation are significantly affected so that the conditions required for self-assembling pertinent two-dimensional chiral phases alter substantially. For both molecules, two-dimensional assembly is found to depend strongly on the nature of the local adsorption motif created, with each motif essentially acting as a "synthon" for the supramolecular assembly. In this respect, it seems that molecule-metal bonding interactions define the general self-assembly structure. The presence/absence of the OH groups, instead, cause a subtler, second-order effect on the finer details of the self-assembled structure. Finally, the creation of chirality in the achiral succinate system is shown to arise from adsorption-induced asymmetrization, inducing point chirality via molecular distortion and/or metal reconstruction of the local adsorption unit. This chiral adsorption unit is then responsible for creating chiral supramolecular through-space and through-metal interactions that propagate a chiral organization. However, the achirality of the succinate ensures that nucleation points of either chirality are equally created, producing a racemic conglomerate of coexisting mirror domains. It is in this aspect that the uniquely aligned OH groups of the rigid bitartrate system wield the greatest effect, by favoring one distortion/reconstruction for the (R,R)-bitartrate and its mirror image distortion/reconstruction for the (S,S)-enantiomer, creating surfaces that are globally chiral on the macroscopic scale. So overall, the OH groups do not dictate the general nature of the assembly but are critical as chiral propagators, breaking the degeneracy and thus promoting asymmetry to chirality.

Journal Article↗
PubMed1971

Autoradiographic Studies On The Uptake Of (14)C-Succinic Acid By Clonorchis Sinensis.

The distribution of exogenous C(14)-succinic acid by Clonorchis sinensis incubated in Tyrode medium was studied by using autoradiographic techniques. A comparison was made between macro and microautoradiographs of this worm showed that black grains derived from labeled substance were distinctly observed in parenchymal tissue, oral sucker, ventral sucker, ovary, testes, and uterine tubules with eggs. In pharynx and intestine, a low density was monitored while negligible activity was found in seminal receptacle and vitelline follicles. In studying the further details, microautoradiography was utilized. The most radioactive regions were the reticular tissue and subcuticular musculature of this fluke, closely compatible with the finding of macroautoradiography. Apparent black grains of radioactivity were also found in oral sucker, ventral sucker, pharynx, uterine tubules, eggs in uterus, and intestinal ceca. Structures showing the least radioactivity included ovary, seminal receptacle and vitelline folliciles.

Journal Article↗
PubMed2001

Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase.

IMP-1 metallo-beta-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes beta-lactam antibiotics, including carbapenems, rendering them ineffective. Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility. We have identified a series of 2,3-(S,S)-disubstituted succinic acids that are potent inhibitors of IMP-1. Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors.

Crystallography, X-Ray↗
PubMed2006

Fascination with the conformational analysis of succinic acid, as evaluated by NMR spectroscopy, and why.

A serendipitous effort to use NMR spectroscopy to determine the conformational preferences of succinate monoanion opened a Pandora's box of unexpected uncertainties as to what influences such preferences of succinic acid in its various ionization states, not only in water but also in other less polar protic solvents, as well as a range of aprotic solvents. The dianion in aprotic solvents shows substantial gauche preferences, which give the appearance of violating Coulomb's law.

Magnetic Resonance Spectroscopy↗
PubMed1999

Simultaneous determination of oxalic, fumaric, maleic and succinic acids in tartaric and malic acids for pharmaceutical use by ion-suppression reversed-phase high performance liquid chromatography.

A reliable method for the simultaneous determination of oxalic, fumaric, maleic, and succinic acids in tartaric and malic acids for pharmaceutical use by reversed-phase ion-suppression high performance liquid chromatography is presented. HPLC was achieved on a Nova-Pak C18 column by isocratic elution using water adjusted to pH 2.10-2.15 with perchloric acid, and detection was by UV adsorption at a wavelength of 210 nm. This method was found to be superior to previous liquid chromatography as well as other classical assay, and to be an attractive choice for the analysis of these compounds.

Chromatography, High Pressure Liquid↗
PubMed1997

Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia.

In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia, and hyperketonemia, as well as depletion of both liver and muscle glycogen content. In the liver, LPS severely lowers the ATP and total adenine nucleotide content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected rats, the oxidation of D-glucose is first increased 2 h after administration of the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes prepared from rats killed 24 h after injection of LPS, the phosphorylation of D-glucose, its incorporation into glycogen, and its oxidation are all severely impaired. This sequence of changes, which coincides with a decreased ratio between pyruvate and lactate production from exogenous D-glucose, is comparable to that found with agents that uncouple oxidative phosphorylation. The injection of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of succinic acid (SAD), in terms, for instance, of the sparing action of the ester upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C] glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and futile cycling in the reactions catalyzed by glucokinase and glucose-6-phosphatase. Nevertheless, the infusion of SAD protects the rats against the deleterious effect of LPS upon such variables as the plasma concentration of free fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in the LPS-injected animals. It is proposed, therefore, that the infusion of succinic acid esters may represent a novel therapeutic approach in endotoxemia and multiple-organ failure.

Adenine Nucleotides↗
PubMed1999

Effects of starvation and diabetes on the metabolism of [2,3-13C]succinic acid dimethyl ester in rat hepatocytes.

The metabolism of [2,3-13C]succinic acid dimethyl ester ([2,3-13C]-SAD) 10 mmol/L was examined in hepatocytes from overnight-fasted normal rats, 3-day starved rats, and overnight-fasted hereditarily diabetic Goto-Kakizaki (GK) rats. The amount of 13C-labeled succinate, fumarate, malate, lactate, alanine, and aspartate released by the hepatocytes was much higher in fasted normal rats than in starved or diabetic animals. Although the integrated areas of the 13C2 and 13C3 signals assigned to double-labeled malate, lactate, or alanine were not significantly different, the amount of single-labeled malate, lactate, alanine, and aspartate was higher in C3- versus C2-labeled isotopomers. The release of 13C-labeled glucose by the hepatocytes was lower in fasted versus starved or diabetic rats. Virtually all hexose molecules double-labeled in the C1-C2-C3 and/or C6-C5-C4 moieties corresponded to the [1,2-13C] and/or [5,6-13C] isotopomers. However, in the case of the single-labeled species, 13C-labeling of C1 (or C6) exceeded that of C2 (or C5). Both the single- and double-labeled molecules enriched with 13C in the C1-C2-C3 moiety were less abundant than those labeled in the C6-C5-C4 moiety, with such asymmetry being most marked in overnight-fasted normal rats, less pronounced in diabetic animals, and virtually absent in starved rats. These findings document that SAD is efficiently metabolized in hepatocytes, with its use as a gluconeogenic precursor being influenced by the nutritional and hormonal status of the animals. The present experiments also reinforce the view that asymmetrical labeling of glucose by 13C-labeled precursors is modulated by the relative contribution of exogenous and endogenous nutrients to the production of triose phosphates incorporated into the hexose.

Animals↗
PubMed2006

Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats.

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.

Animals↗
PubMedDate not supplied

Efficient succinic acid production from glucose through overexpression of pyruvate carboxylase in an Escherichia coli alcohol dehydrogenase and lactate dehydrogenase mutant.

An adhE, ldhA double mutant Escherichia coli strain, SBS110MG, has been constructed to produce succinic acid in the presence of heterologous pyruvate carboxylase (PYC). The strategic design aims at diverting maximum quantities of NADH for succinate synthesis by inactivation of NADH competing pathways to increase succinate yield and productivity. Additionally an operational PFL enzyme allows formation of acetyl-CoA for biosynthesis and formate as a potential source of reducing equivalents. Furthermore, PYC diverts pyruvate toward OAA to favor succinate generation. SBS110MG harboring plasmid pHL413, which encodes the heterologous pyruvate carboxylase from Lactococcus lactis, produced 15.6 g/L (132 mM) of succinate from 18.7 g/L (104 mM) of glucose after 24 h of culture in an atmosphere of CO(2) yielding 1.3 mol of succinate per mole of glucose. This molar yield exceeded the maximum theoretical yield of succinate that can be achieved from glucose (1 mol/mol) under anaerobic conditions in terms of NADH balance. The current work further explores the importance of the presence of formate as a source of reducing equivalents in SBS110MG(pHL413). Inactivation of the native formate dehydrogenase pathway (FDH) in this strain significantly reduced succinate yield, suggesting that reducing power was lost in the form of formate. Additionally we investigated the effect of ptsG inactivation in SBS110MG(pHL413) to evaluate the possibility of a further increase in succinate yield. Elimination of the ptsG system increased the succinate yield to 1.4 mol/mol at the expense of a reduction in glucose consumption of 33%. In the presence of PYC and an efficient conversion of glucose to products, the ptsG mutation is not indispensable since PEP converted to pyruvate as a result of glucose phosphorylation by the glucose specific PTS permease EIICB(glu) can be rediverted toward OAA favoring succinate production.

Alcohol Dehydrogenase↗
PubMed2004

N,N,N',N'-Tetramethylethylenediammonium-succinate-succinic acid (1/1/1).

In the title compound, C(6)H(18)N(2)(2+).C(4)H(4)O(4)(2-).C(4)H(6)O(4), the components lie on centres of symmetry in space group P-1, such that the asymmetric unit contains three half-molecules. Despite the different mode (with respect to other dicarboxylic acids) adopted by the intermolecular self-interaction of succinic acid derivatives, the overall structure of the title compound consists of anionic layers that are typical of the packing structures exhibited by other dicarboxylic acid analogues.

Journal Article↗
PubMed1990

High resolution single photon emission computerized tomography (SPECT) 99mtechnetium-dimercapto-succinic acid renal imaging: a state of the art technique.

The 99mtechnetium-dimercapto-succinic acid renal scan has become the gold standard for evaluating renal parenchymal pathology. The traditional pinhole technique provides 2-dimensional imaging. Recent application of high resolution single photon emission computerized tomography (SPECT) has provided the means to obtain even greater cortical detail. With 360-degree imaging and computer reconstruction, SPECT provides coronal, sagittal and transaxial imaging. We prospectively compared the SPECT and pinhole techniques in 33 patients (65 renal units) ranging in age from 2.5 months to 18 years. Both scans were obtained in all patients. All scans were reviewed by an independent interpreter. Using SPECT imaging, diagnostic information was enhanced in 46 of the 65 kidneys (71%). Of the 24 kidneys that appeared "normal" by pinhole imaging 15 (63%) had defects on SPECT imaging. High resolution SPECT imaging improves the ability to identify cortical defects and visualize asymmetry of cortical thickness compared to standard pinhole imaging.

Adolescent↗
PubMedDate not supplied

[Hypoglycemic activity of derivatives of succinic acid amides and hydrazides].

A series of 20 substituted amides and hydrazides of succinic acid were synthesized and studied with respect to their action upon the blood glucose level in intact rats. The structure-activity relationship is considered. Substances exhibiting maximum hypoglycemic activity were additionally characterized by the acute toxicity and the hypoglycemic effect on the model of alloxan diabetes in rats. It was found that 4-aminobenzoyl hydrazide is more effective and less toxic than the reference compounds metformin and glyclazide.

Amides↗
PubMedDate not supplied

Effects of succinic acid dimethyl ester infusion on metabolic, hormonal, and enzymatic variables in starved rats.

BACKGROUND: Succinic acid dimethyl ester (SAD) is efficiently metabolized in several cell types as pancreatic islet cells, hepatocytes, and colonocytes. The purpose of this study was to assess the overall nutritional value of SAD in the whole organism. METHODS: SAD was infused at a rate of 80 micromol/g body weight per day in rats starved for either 2 or 4 days. For comparison, similar experiments were conducted in starved rats receiving an equimolar infusion of D-glucose. RESULTS: The ester failed to prevent the starvation-induced fall in body weight, paraovarian fat mass, and liver or muscle protein content. The infusion of SAD minimized, however, the decrease in plasma glucose and insulin concentrations, liver glycogen content, hepatic glucokinase activity, and islet secretory responsiveness to glucose, otherwise caused by starvation. Likewise, the infusion of SAD delayed the rise in free fatty acid and beta-hydroxybutyrate plasma concentration occurring during starvation. Nevertheless, SAD was less efficient than glucose, infused in an equimolar amount, in preventing the starvation-induced fall in liver glycogen content, decrease in the pancreatic B-cell secretory responsiveness to glucose, and stimulation of lipolysis and ketogenesis. CONCLUSIONS: SAD displays a significant nutritional value when infused in starved rats. It could thus be used as a tool to prevent the imbalance between ATP generation and use in selected metabolic situations.

Animals↗
PubMed1999

Effect of gene disruptions of the TCA cycle on production of succinic acid in Saccharomyces cerevisiae.

Succinate is the main taste component produced by yeasts during sake (Japanese rice wine) fermentation. The pathway leading to accumulation of succinate was examined in liquid culture in the presence of a high concentration (15%) of glucose under aerobic and anaerobic conditions using a series of Saccharomyces cerevisiae strains in which various genes that encode the expression of enzymes required in TCA cycle were disrupted. When cultured in YPD medium containing 15% glucose under aerobic conditions, the KGD1 (alpha-ketoglutarate dehydrogenase) gene disrupted mutant produced a lower level of succinate than the wild-type strain, while the SDH1 (succinate dehydrogenase) gene-disrupted mutant produced an increased level of succinate. On the other hand, the FUM1 (fumarase) gene disrupted mutant produced significantly higher levels of fumarate but did not form malate at all. These results indicate that succinate, fumarate and malate are mainly synthesized through the TCA cycle (oxidative direction) even in the presence of glucose at a concentration as high as 15%. When the growth condition was shifted from aerobic to anaerobic, the increased level of succinate in SDH1 disruptants was no longer observed, whereas the decreased level of succinate in the KGD1 diruptant was still observed. A double mutant of the two fumarate reductase isozyme genes (OSM1 and FRDS) showed a succinate productivity of 50% as compared to the parent when cells were incubated in glucose-buffered solution. These results indicate that succinate could be synthesized through two pathways, namely, alpha-ketoglutarate oxidation via the TCA cycle and fumarate reduction under anaerobic conditions.

Journal Article↗