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Metabolic Products (metabolic + products)
Selected AbstractsInterplay of constitutively released nucleotides, nucleotide metabolism, and activity of P2Y receptorsDRUG DEVELOPMENT RESEARCH, Issue 2-3 2001Eduardo R. Lazarowski Abstract At least six mammalian P2Y receptors exist that are specifically activated by ATP, UTP, ADP or UDP. Although the existence of ectoenzymes that rapidly metabolize extracellular nucleotides is well established, the relative flux of ATP and UTP through their extracellular metabolic products remains undefined. In addition, the existence of basal nucleotide release and the contribution of resting levels of ATP and UTP to P2 receptor activation are poorly understood. In the absence of exogenous agonists, an apyrase-sensitive inositol phosphate accumulation was observed in resting 16HBE14o, human bronchial epithelial cells endogenously expressing P2Y receptors and in 1321N1 human astrocytoma cells expressing a recombinant P2Y2 receptor. To test whether nucleotide release may account for basal P2 receptor activities, the rates of extracellular accumulation and metabolism of endogenous ATP were examined with resting 16HBE14o,, C6 rat glioma, and 1321N1 cell cultures. Although extracellular ATP concentrations (1-5 nM) remained unchanged for up to 12 h, [,32P] ATP included in the medium (as a radiotracer) was completely degraded within 120 min, indicating that ATP release balanced ATP hydrolysis. The calculated basal rates of ATP release ranged from 20 to 200 fmol/min per million cells. HPLC analysis during steady state revealed that the gamma-phosphate of ATP was reversibly transferred to species further identified as UTP and GTP, implicating ecto-nucleoside diphosphokinase (NDPK)-catalyzed phosphorylation of endogenous UDP and GDP. At steady state, the final 32P-products of [,32P]ATP metabolism were 32P-orthophosphoric acid and a species further purified and identified as 32P-pyrophosphate. Constitutive nucleotide release balanced by the concerted activities of ecto-ATPase, ecto-ATP pyrophosphatase, and ecto-NDPK may determine the resting levels of extracellular nucleotides and therefore, the basal activity of P2 receptors. Drug Dev. Res. 53:66,71, 2001. © 2001 Wiley-Liss, Inc. [source] Search of Microorganisms that Degrade PAHs under Alkaline ConditionsENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 4 2004A. Gerbeth Abstract Bacterial strains were enriched from building rubble contaminated with polycyclic aromatic hydrocarbons (PAHs). These strains were studied as an inoculum in bioremediation processes with contaminated building rubble. The selection criteria for the bacteria were broad profiles in PAH degradation, stable expression of the traits and tolerance to alkaline conditions. Various strains of Micrococcus sp., Dietzia sp., Rhodococcus sp. and Pseudomonas sp. met the selection criteria. In general, degradative activity was limited at higher pH values. Strains of Micrococcus were suitable for practical use as complete degradation of various PAHs was observed at pH values exceeding 10. Strains of Dietzia sp. showed broad PAH degradation profile, but in some cases degradation came to a halt leaving some of the PAHs unutilized. With Dietzia sp. this could be due to inhibitory effects from the accumulation of toxic PAH metabolic products and/or growth-limiting media conditions. [source] Stereoselective biosynthesis of chloroarylpropane diols by the basidiomycete Bjerkandera adusta: exploring the roles of amino acids, pyruvate, glycerol and phenyl acetyl carbinolFEMS MICROBIOLOGY LETTERS, Issue 1 2003Peter James Silk Abstract Bjerkandera adusta produces many chlorometabolites including chlorinated anisyl metabolites (CAMs) and 1-arylpropane-1,2-diols (1, 2, 3, 4) as idiophasic metabolic products of l -phenylalanine. These diols are stereoselectively biosynthesized from a C7 -unit (benzylic, from l -phenylalanine) and a C2 -unit, of unknown origin, as predominantly erythro (1R,2S) enantiomers. Of the labeled amino acids tested as possible C2 -units, at the 4,10 mM level, none were found to efficiently label the 2,3-propane carbons of the diols. However, glycine (2- 13C), l -serine (2,3,3-d3) and l -methionine (methyl-d3) entered the biomethylation pathway. Neither pyruvate (2,3- 13C2), acetate (1,2- 13C2), acetaldehyde (d4) nor ethanol (ethyl-d5) labeled the 2,3-propane carbons of the diols at the 4,10 mM level. Pyruvate (2,3- 13C2) and l -serine (2,3,3-d3) (which also entered the biomethylation pathway) did, however, effectively label the 2,3-propane carbons of the ,-ketols and diols at the 40 mM level as evidenced by mass spectrometry. Glycerol (1,1,2,3,3-d5) also appeared to label one of the 2,3-propane carbons (ca. 5% as 2H2 in the C3 side chain) as suggested by mass spectrometric data and also entered the biomethylation pathway, likely via amino acid synthesis. Glycerol (through pyruvate), therefore, likely supplies C2 and C3 of the propane side chain with arylpropane diol biosynthesis. Incubation of B. adusta with synthetic [2- 2H1,2- 18O]-glycerol showed that neither 2H nor 18O were incorporated in the ,-ketols or diols. The oxygen atom on the C2 of the ketols/diols, therefore, does not appear to come from the oxygen atom on the C2 of glycerol. Glycerol, however, can readily form l -serine (which can then form pyruvate via PLP/serine dehydratase and involve transamination washing out the 18O label and providing the oxygen from water), and can then go on to label the C2 -unit. Labeled ,-ketol, phenyl acetyl carbinol (5) (PAC; ring-d5, 2,3- 13C2 propane) cultured with B. adusta leads to stereospecific reduction to the (1R,2S)-diol (6) (ring-d5 and 2,3- 13C2); in all other metabolites produced, the 2,3- 13C2 label is washed out. Incubation of the fungus with 4-fluorobenzaldehyde (13) produces a pooling of predominantly erythro (1R,2S) 1-(4,-fluorophenyl)-1,2-propane diol (18 as diacetate) (through the corresponding ,-ketols 16, 17). Blocking the para-position with fluorine thus appears to prevent ring oxygenation and also chlorination, forcing the conclusion that para-ring oxygenation precedes meta-chlorination. [source] Enhanced bio-hydrogen production from sweet sorghum stalk with alkalization pretreatment by mixed anaerobic culturesINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 8 2010Xiang-Xing Shi Abstract Bio-hydrogen production from sweet sorghum stalk using mixed anaerobic sludge was reported in this paper. Batch tests were carried out to analyze influences of several environmental factors on yield of H2 from sweet sorghum stalk under constant mesophillic temperature (36±1°C). The experimental results showed that, for the raw stalk, the cumulative hydrogen yield was 52.1,ml,g,1·TVS with utilization percentages of sugars, hemi-cellulose and cellulose in the stalk being 89.12, 15.23 and 13.89% respectively; whereas for the stalk pretreated by 0.4% NaOH solution at room temperature for 24,h, the cumulative hydrogen yield was 127.26,ml,g,1·TVS with utilization percentages of sugars, hemi-cellulose and cellulose being 99.17, 53.64, 41.56%, respectively. The hydrogen content in the biogas was about 53% while the methane content was less than 4% throughout the study. Besides hydrogen and methane, the main metabolic products detected were ethanol, propionate and butyrate. The experimental results suggested that the alkalization pretreatment of the substrate plays a crucial role in the conversion of the sweet sorghum stalk wastes into bio-hydrogen by the mixed anaerobic sludge. Copyright © 2009 John Wiley & Sons, Ltd. [source] Relationship Between Interindividual Differences and Physiological Indexes of Acute Stress in RatsJOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 4 2005Mitsuo Nagane We used in vivo microdialysis to examine interindividual differences in the effects of acute immobilization stress and diazepam treatment on monoamine turnover in the hippocampus of male rats as an index of stress. Immobilization significantly increased the concentrations of 3,4-dihydroxyphenyl-aceticacid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). This effect was attenuated by injection of diazepam, Interindividual differences in reactivity to stressors caused differential changes in different metabolic products of monoamines. In our study, stress-induced changes in DOPAC levels were relatively great, and there was a similar change in the concentration of HVA. We conclude that at least 2 indexes of stress should be measured to take into account interindividual differences in the changes in stress indexes. [source] Biotransformation of l -menthol by twelve isolates of soil-borne plant pathogenic fungi (Rhizoctonia solani) and classification of fungiJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 6 2003Mitsuo Miyazawa Abstract The microbial transformation of l -menthol (1) was investigated by using 12 isolates of soil-borne plant pathogenic fungi, Rhizoctonia solani (AG-1-IA Rs24, Joichi-2, RRG97-1; AG-1-IB TR22, R147, 110.4; AG-1-IC F-1, F-4, P-1; AG-1-ID RCP-1, RCP-3, and RCP-7) as a biocatalyst. Rhizoctonia solani F-1, F-4 and P-1 showed 89.7,99.9% yields of converted product from 1, RCP-1, RCP-3, and RCP-7 26.0,26.9% and the other isolates 0.1,12.0%. In the cases of F-1, F-4 and P-1, substrate 1 was converted to (,)-(1S,3R,4S,6S)-6-hydroxymenthol (2), (,)-(1S,3R,4S) -1-hydroxymenthol (3) and (+)-(1S,3R,4R,6S)-6,8-dihydroxymenthol (4), which was a new compound. Substrate 1 was converted to 2 and/or 3 by RRG97-1, 110.4, RCP-1, RCP-3 and RCP-7. The structures of the metabolic products were elucidated on the basis of their spectral data. In addition, metabolic pathways of the biotransformation of 1 by Rhizoctonia solani are discussed. Finally, from the main component analysis and the differences in the yields of converted product from 1, the 12 isolates of Rhizoctonia solani were divided into three groups based on an analysis of the metabolites. Copyright © 2003 Society of Chemical Industry [source] Rock hyraces: a cause of San rock art deterioration?JOURNAL OF RAMAN SPECTROSCOPY, Issue 5 2007Linda C. Prinsloo Abstract San rock art sites are found throughout southern Africa, many showing signs of deterioration. In order to conserve this invaluable heritage, a long-term multidisciplinary project has been launched to monitor the rate of their deterioration and determine the various chemical processes that are possibly contributing to the decay. This study was initiated to establish if Raman spectroscopy could contribute to this project and since rock hyrax colonies live in close proximity to many of these archaeological sites, the possible influence of their metabolic products on the deterioration process was investigated. The precipitates from the urine of rock hyraces were analysed with Raman and Fourier-transform infrared (FTIR) spectroscopy. Where the urine was in contact with the faeces, the precipitates are a mixture of vaterite (a rare polymorph of CaCO3) and the hydrated salt calcium monohydrocalcite (also rarely found in nature). On areas where this contact is at a minimum the common and stable polymorph of CaCO3, calcite, is the main component. SEM micrographs and XRD analysis support the Raman and FTIR results. XRD, FTIR and preliminary GC-MS analyses of hyraceum, the fossilised mixture of faeces and urine, identified an inorganic phase (potassium chloride, with small concentrations of other salts, e.g. vaterite and weddelite) and an organic phase, which is a cocktail of various aromatic compounds, mainly amides, alcohols and acids. These compounds could contribute to the crystallisation of these rare carbonates, as well as other uncommon salts detected on the cave walls, such as syngenite. The presence of phosphates in the urine may further act as a stabilizing agent. Copyright © 2007 John Wiley & Sons, Ltd. [source] In vitro biotransformation of anabolic steroids in caninesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000Williams Forensic drug testing of anabolic steroids in racing animals is required because of the potential for steroid abuse. Often when the metabolic products of an administered compound have not been identified, the analysis and verification of the administered compound is difficult. The objective of this study was to qualitatively identify the in vitro phase I biotransformation products of anabolic steroids that have a high potential for abuse in canines. The investigated steroids included testosterone, methyltestosterone, mibolerone and boldenone. Steroid biotransformation products were generated using beagle liver microsomes and analysed by high performance liquid chromatography (HPLC)/mass spectrometry (MS) with an electrospray ionization source. Characterization of steroid metabolites was based on HPLC retention, UV and mass spectra. The major testosterone metabolites were identified as androstenedione and 6,- and 16,-hydroxytestosterone. 6,-Hydroxymethyltestosterone was identified as a major metabolite in the methyltestosterone microsomal incubations. Several mibolerone metabolites were identified as monohydroxylated mibolerones as well as an oxidized mibolerone metabolite. Boldenone metabolites were identified as monohydroxylated boldenones, oxidized boldenone, and testosterone. This information should assist in the determination of anabolic steroid use in canines through the correlation of the urinary metabolites to the administered drug. [source] Application of subsecond spiral chemical shift imaging to real-time multislice metabolic imaging of the rat in vivo after injection of hyperpolarized 13C1 -pyruvateMAGNETIC RESONANCE IN MEDICINE, Issue 3 2009Dirk Mayer Abstract Dynamic nuclear polarization can create hyperpolarized compounds with MR signal-to-noise ratio enhancements on the order of 10,000-fold. Both exogenous and normally occurring endogenous compounds can be polarized, and their initial concentration and downstream metabolic products can be assessed using MR spectroscopy. Given the transient nature of the hyperpolarized signal enhancement, fast imaging techniques are a critical requirement for real-time metabolic imaging. We report on the development of an ultrafast, multislice, spiral chemical shift imaging sequence, with subsecond acquisition time, achieved on a clinical MR scanner. The technique was used for dynamic metabolic imaging in rats, with measurement of time-resolved spatial distributions of hyperpolarized 13C1 -pyruvate and metabolic products 13C1 -lactate and 13C1 -alanine, with a temporal resolution of as fast as 1 s. Metabolic imaging revealed different signal time courses in liver from kidney. These results demonstrate the feasibility of real-time, hyperpolarized metabolic imaging and highlight its potential in assessing organ-specific kinetic parameters. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Mass spectrometric determination of insulins and their degradation products in sports drug testingMASS SPECTROMETRY REVIEWS, Issue 1 2008Mario Thevis Abstract Insulins' anabolic and anti-catabolic properties have supposedly led to its misuse in sport. Hence, doping control assays were developed to allow the unequivocal identification of synthetic insulin analogs and metabolic products derived from human insulin and its artificial counterparts in urine and plasma specimens. Analyses were based on immunoaffinity purification and subsequent characterization of target analytes by top-down sequencing-based approaches, which were conducted with hybrid tandem mass spectrometers that consisted of either quadrupole-linear ion trap or linear ion trap-orbitrap analyzers. Diagnostic product ions and analytical strategies are presented and discussed in light of the need to unambiguously identify misused drugs in urine and plasma specimens for doping control. © 2007 Wiley Periodicals, Inc., Mass Spec Rev 27:35,50, 2008 [source] Profiling human gut bacterial metabolism and its kinetics using [U- 13C]glucose and NMRNMR IN BIOMEDICINE, Issue 1 2010Albert A. de Graaf Abstract This study introduces a stable-isotope metabolic approach employing [U- 13C]glucose that, as a novelty, allows selective profiling of the human intestinal microbial metabolic products of carbohydrate food components, as well as the measurement of the kinetics of their formation pathways, in a single experiment. A well-established, validated in vitro model of human intestinal fermentation was inoculated with standardized gastrointestinal microbiota from volunteers. After culture stabilization, [U- 13C]glucose was added as an isotopically labeled metabolic precursor. System lumen and dialysate samples were taken at regular intervals. Metabolite concentrations and isotopic labeling were determined by NMR, GC, and enzymatic methods. The main microbial metabolites were lactate, acetate, butyrate, formate, ethanol, and glycerol. They together accounted for a 13C recovery rate as high as 91.2%. Using an NMR chemical shift prediction approach, several minor products that showed 13C incorporation were identified as organic acids, amino acids, and various alcohols. Using computer modeling of the 12C contents and 13C labeling kinetics, the metabolic fluxes in the gut microbial pathways for synthesis of lactate, formate, acetate, and butyrate were determined separately for glucose and unlabeled background substrates. This novel approach enables the study of the modulation of human intestinal function by single nutrients, providing a new rational basis for achieving control of the short-chain fatty acids profile by manipulating substrate and microbiota composition in a purposeful manner. Copyright © 2009 John Wiley & Sons, Ltd. [source] Ketones: Metabolism's Ugly DucklingNUTRITION REVIEWS, Issue 10 2003Theodore B. Vanitallie MD Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, dietinduced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders. [source] Odorous compounds in paperboard as influenced by recycled material and storagePACKAGING TECHNOLOGY AND SCIENCE, Issue 4 2001Gottfried Ziegleder Abstract Many volatile compounds can be identified in unprinted paperboard by means of steam distillation in combination with capillary gas chromatography, mass spectrometry and olfactometry. Paperboards produced with recycled material exhibit additional volatiles which partly contribute to off-odours. Using sniffing techniques, benzaldehyde, acetophenone, 1-octen-3-ol, 1-octen-3-one, 2-nonenal, methylguajacol, butanoic and 3-methyl butanoic acid were identified as the most odorous volatiles. The aromatic substances mainly exude from inks and printing solvents in waste materials used for paperboard manufacturing. During storage under controlled conditions, the microbial load of paperboard decreased slightly, and no odorous metabolic products were generated. Copyright © 2001 John Wiley & Sons, Ltd. [source] Uptake and translocation of carpropamid in rice (Oryza sativa L)PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 3 2001Rashmi Rohilla Abstract Translocation of the antiblast compound, carpropamid, was investigated in rice using [14C]carpropamid. When applied to the seed, carpropamid was not only readily absorbed but was translocated to different parts of the seedlings emerging from treated seeds. A substantial portion of fungicide appeared to be exuded onto the leaf surface. In 21-day-old plants grown from [14C]carpropamid-treated seeds, 27.2% of the radioactivity isolated from leaves was present on the surface of lamina. This exuded fraction is probably responsible for its action as a fungal anti-penetrant compound. Following 30-min root dipping of 14-day-old seedlings, carpropamid was rapidly absorbed and translocated throughout the seedling. Its intra-laminar distribution was uniform as determined by autoradiography. Only a small fraction (<2%) of fungicide applied to the foliage was translocated beyond the site of application within the treated leaf. Translocation was primarily apoplastic. Approximately 54% of the radioactivity recovered from leaves was in the form of carpropamid. At least seven radiolabelled metabolic products were observed by TLC. Only 8.3% of radioactivity applied through the seeds could be recovered from 21-day-old seedlings. © 2001 Society of Chemical Industry [source] Mass spectrometric identification and characterization of a new long-term metabolite of metandienone in human urineRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2006Wilhelm Schänzer Anabolic-androgenic steroids are some of the most frequently detected drugs in amateur and professional sports. Doping control laboratories have developed numerous assays enabling the determination of administered drugs and/or their metabolic products that allow retrospectives with respect to pharmacokinetics and excretion profiles of steroids and their metabolites. A new metabolite generated from metandienone has been identified as 18-nor-17, -hydroxymethyl,17, -methyl-androst-1,4,13-trien-3-one in excretion study urine samples providing a valuable tool for the long-term detection of metandienone abuse by athletes in sports drug testing. The metabolite was characterized using gas chromatography/(tandem) mass spectrometry, liquid chromatography/tandem mass spectrometry and liquid chromatography/high-resolution/high-accuracy (tandem) mass spectrometry by characteristic fragmentation patterns representing the intact 3-keto-1,4-diene structure in combination with typical product ions substantiating the proposed C/D-ring structure of the steroid metabolite. In addition, structure confirmation was obtained by the analysis of excretion study urine specimens obtained after administration of 17-CD3 -labeled metandienone providing the deuterated analogue to the newly identified metabolite. 18-Nor-17, -hydroxymethyl,17, -methyl-androst-1,4,13-trien-3-one was determined in metandienone administration study urine specimens up to 19 days after application of a single dose of 5,mg, hence providing an extended detection period compared with commonly employed strategies. Copyright © 2006 John Wiley & Sons, Ltd. [source] Carbon-nitrogen-phosphorus removal and biofilm growth characteristics in an integrated wastewater treatment system involving a rotating biological contactorASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 5 2009Angelo H. Cabije Abstract A new rotating biological contactor-packed media technology (RBC-PMT) is locally innovated using light polyethylene Amazon screen material as disc media. A single-stage co-current fed of this type, which is connected with a series of equalization tanks as an integrated wastewater treatment system (IWWTS), showed good carbon-nitrogen-phosphorus (C-N-P) removal and unveiled biofilm growth characteristics noteworthy for treating pollutants in wastewater. The equalization tanks approached facultative anaerobic conditions while the RBC-PMT exhibited a completely aerated system, both with a slightly alkaline pH, whose temperatures are ranging from 21 to 24 °C, and both performed as biological nutrient removal systems. The combined nutrient removal efficiency at high organic loading rate (HOLR) and low organic loading rate (LOLR) showed fair chemical oxygen demand (COD) removal at 65.68 and 67.89%, respectively. Nitrate-nitrogen removal demonstrated good removal at 79.17% at HOLR and 83.43% at LOLR. There was excellent phosphate-phosphorus removal determined at 91.64 and 94.35% at high and low OLRs, respectively. This indicates that increasing the organic loading rate decreases the C-N-P removal in the IWWTS. Biofilm growth was characterized by the selection and survival of microorganisms present under aerobic environmental conditions in the RBC-PMT system and their respective metabolism in removing C-N-P substrates. Yeasts, coliform bacteria particularly E. coli, Cyanobacteria, and benthic diatoms were dominant microorganisms found upon oil-immersion microscopy. Protozoans and algae including Chlorococcum, Chlorella, Diatoma, Tribonema, Oscillatoria, Euglena, and other motile rotifiers were also dominantly found in the biofilm samples. Biofilm growth is observed and its average thickness was measured to be 7.71 µm at HOLR and 2.81 µm at LOLR. Thicker biofilm at HOLR has caused the reduced rate of diffusion of the microorganisms and their metabolic products as manifested by the low C-N-P removal during HOLR. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd. [source] Development and validation of a rapid and sensitive HPLC method for the quantification of 5-fluorocytosine and its metabolitesBIOMEDICAL CHROMATOGRAPHY, Issue 5 2010Kinta M. Serve Abstract To study the intracellular metabolism of the prodrug 5-fluorocytosine (5FC), we developed a novel reverse-phase high-performance liquid chromatography method to simultaneously detect 5FC and its four major anabolic metabolites: 5-fluorouracil, 5-fluorouridine, 5-fluorouridine-monophosphate and 5-fluoro-2,deoxyuridine-5,-monophosphate. Separation of each compound was accomplished under isocratic conditions using a C18 column and mobile phase of formic acid,water (1,:,99,v/v). The method was validated for both accuracy and reproducibility in cell culture media. Additionally, metabolites were assessed for stability at ambient temperatures and following freeze,thaw cycles. Calibration curves were linear over a range of 1,200,,g/mL. Limit of quantification for four of the five compounds was 1,,g/mL in cell culture media (RSD < 11%). This method was successfully used to monitor intracellular conversion of 5FC to its metabolic products over a 24h period. Copyright © 2009 John Wiley & Sons, Ltd. [source] The role of arachidonic acid metabolites in DRACTA OPHTHALMOLOGICA, Issue 2008AM ABU EL ASRAR Purpose The inducible enzyme cyclooxygense-2 (COX-2) and its metabolic products are important mediators for angiogenesis. We investigated the expression of COX-2 and its downstream enzymes microsomal prostaglandin-E synthase (mPGES)-1, cytosolic PGES (cPGES) and thromboxane synthase (TXS) and correlated it with vascular endothelial growth factor (VEGF) expression and level of vascularization in proliferative diabetic retinopathy (PDR) epiretinal membranes. Methods Fourteen membranes were studied by immunohistochemistry. Results Vascular endothelial cells expressed COX-2, mPGES-1 and VEGF in 75.6%, 64.3% and 50% of the membranes, respectively. TXS was expressed in stromal cells in 85.7% of the membranes. There was no immunoreactivity for cPGES. There were significant correlations between number of blood vessels expressing CD34 and the numbers of blood vessels expressing COX-2 (rs = 0.858; p<0.001), mPGES-1 (rs = 0.743; p = 0.002) and VEGF (rs = 0.845; p = 0.001) and the number of cells expressing TXS (rs = 0.74; p = 0.002). Number of blood vessels expressing VEGF correlated significantly with the numbers of blood vessels expressing COX-2 (rs = 0.879; p<0.001) and mPGES-1 (rs = 0.942; p<0.001) and the number of cells expressing TXS (rs = 0.702; p = 0.011). Conclusion COX-2 and its metabolic products might contribute to PDR angiogenesis. [source] | |||||||||||||||||||