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Sample records for acetoacetates

  1. Evidence for the existence of mammalian acetoacetate decarboxylase: with special reference to human blood serum

    NARCIS (Netherlands)

    Stekelenburg, Gerard J. van; Koorevaar, Gerrit

    1972-01-01

    In this article evidence is presented for the existence of mammalian acetoacetate decarboxylase (acetoacetate carboxy-lyase: E.G. 4.1.1.4). From experiments with human blood serum the presence of a non-ultrafiltrable activator, accelerating the decomposition of acetoacetate into acetone and carbon d

  2. [11C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure

    International Nuclear Information System (INIS)

    The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic–reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [11C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure. Methods: A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [14C]-Acetoacetate, a non-positron (β −) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [11C]-acetoacetate (β +) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(−) (n = 15) and treated Dox(+) (n = 6) rats. The uptake rate (K1) and myocardial clearance rate (k2or kmono) were extracted. Results: [14C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p < 0.05). PET kinetic analysis of [11C]-acetoacetate showed that rate constants K1, k2 and kmono were decreased in Dox(+) (p < 0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p < 0.001). Conclusion: Radioactive acetoacetate ex vivo analysis [14C], and in vivo kinetic [11C] studies provided evidence that [11C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest–stress protocol), [11C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [11C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [11C]-acetoacetate in cardiac pathophysiology

  3. Cosolvent Effect on the Tautomerism of Ethyl Acetoacetate in Supercritical CO2

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The effect of cosolvent cyclohexane, chloroform, and acetonitrile on the keto-enol tautomeric equilibrium of ethyl acetoacetate in supercritical CO2 was studied by UV-Vis spectroscopy over the pressure range from 76 to 110 bar at 308.15 K. It was found that the equilibrium constant decreases with increasing polarity of the cosolvents.

  4. Enhanced and suppressed mineralization by acetoacetate and β-hydroxybutyrate in osteoblast cultures.

    Science.gov (United States)

    Saito, Akihiro; Yoshimura, Kentaro; Miyamoto, Yoichi; Kaneko, Kotaro; Chikazu, Daichi; Yamamoto, Matsuo; Kamijo, Ryutaro

    2016-04-29

    It is known that diabetes aggravates alveolar bone loss associated with periodontitis. While insulin depletion increases the blood concentration of ketone bodies, i.e., acetoacetate and β-hydroxybutyrate, their roles in bone metabolism have not been much studied until today. We investigated the effects of acetoacetate and β-hydroxybutyrate on mineralization of extracellular matrix in cultures of mouse osteoblastic MC3T3-E1 cells and primary mouse osteoblasts in the presence and absence of bone morphogenetic protein-2. Acetoacetate potentiated alkaline phosphatase activity in MC3T3-E1 cells in a concentration-dependent manner, ranging from physiological to pathological concentrations (0.05-5 mmol/L). In contrast, β-hydroxybutyrate lowered it in the same experimental settings. Mineralization in cultures of these cells was also up-regulated by acetoacetate and down-regulated by β-hydroxybutyrate. Similar results were obtained in cultures of mouse primary osteoblasts. Neither alkaline phosphatase mRNA nor its protein expression in MC3T3-E1 cells was affected by acetoacetate or β-hydroxybutyrate, indicating that these ketone bodies control the enzyme activity of alkaline phosphatase in osteoblasts and hence their mineralization bi-directionally. Finally, either gene silencing of monocarboxylate transporter-1, a major transmembrate transporter for ketone bodies, nullified the effects of ketone bodies on alkaline phosphatase activity in MC3T3-E1 cells. Collectively, we found that ketone bodies bidirectionally modulates osteoblast functions, which suggests that ketone bodies are important endogenous factors that regulate bone metabolism in both physiological and pathological situations.

  5. Baker's yeast catalyzed asymmetric reduction of methyl acetoacetate in glycerol containing systems

    Directory of Open Access Journals (Sweden)

    Adi Wolfson

    2008-09-01

    Full Text Available The asymmetric hydrogenation of methyl acetoacetate was successfully performed with baker's yeast in pure glycerol and mixtures of glycerol and water. Though yeast viability was very low after exposure to glycerol, the enzymatic activity in pure glycerol was preserved for some days. In addition, a mixture of glycerol and water combined the advantageous of each individual solvent and resulted in high catalytic performance and efficient product extraction yield

  6. Baker's yeast catalyzed asymmetric reduction of methyl acetoacetate in glycerol containing systems

    OpenAIRE

    Adi Wolfson; Nisim Haddad; Chrstina Dlugy; Dorith Tavor; Yoram Shotland

    2008-01-01

    The asymmetric hydrogenation of methyl acetoacetate was successfully performed with baker's yeast in pure glycerol and mixtures of glycerol and water. Though yeast viability was very low after exposure to glycerol, the enzymatic activity in pure glycerol was preserved for some days. In addition, a mixture of glycerol and water combined the advantageous of each individual solvent and resulted in high catalytic performance and efficient product extraction yield

  7. Chlorine Dioxide-Iodide-Methyl Acetoacetate Oscillation Reaction Investigated by UV-Vis and Online FTIR Spectrophotometric Method

    OpenAIRE

    Laishun Shi; Xiaomei Wang; Na Li; Jie Liu; Chunying Yan

    2012-01-01

    In order to study the chemical oscillatory behavior and mechanism of a new chlorine dioxide-iodide ion-methyl acetoacetate reaction system, a series of experiments were done by using UV-Vis and online FTIR spectrophotometric method. The initial concentrations of methyl acetoacetate, chlorine dioxide, potassium iodide, and sulfuric acid and the pH value have great influence on the oscillation observed at wavelength of 289 nm. There is a preoscillatory or induction period, and the amplitude and...

  8. Ethyl acetoacetate ligand distribution in the course of titanium n-butoxide chelation

    Energy Technology Data Exchange (ETDEWEB)

    Kurajica, S., E-mail: stankok@fkit.hr; Škorić, I.; Lozić, I.; Mandić, V.

    2014-10-15

    Sols obtained by chelation of titanium n-butoxide with ethyl acetoacetate, Eaa, in various ratios have been subjected to FTIR, {sup 1}H and {sup 13}C NMR, HSQC and UV–Vis spectroscopy in order to provide insight in the compounds obtained, their structure and quantitative relationships. Three compounds, the bis-chelated monomer, Ti(O{sup n}Bu){sub 2}(Eaa){sub 2}, bis-chelated dimer, (Ti(O{sup n}Bu){sub 3}Eaa){sub 2} and monochelated dimer, Ti{sub 2}(O{sup n}Bu){sub 7}Eaa have been established. As the molar ratio Eaa/Ti(O{sup n}Bu){sub 4} increases, the coordination changes from the monochelated and bis-chelated dimer to the bis-chelated monomer. Additionally, the transesterification reaction, influencing the chemical composition of the compounds was noted. The hydrolysis of the prepared sols was partial, leaving some residual butoxy and ethyl acetoacetate groups attached to titanium. Thermal treatment of the prepared amorphous gels at 350 °C yielded with the formation of nanocrystalline anatase. It was noted that high Eaa/Tnb ratio slightly retards the anatase formation. - Highlights: • Titanium n-butoxide was modified with ethyl acetoacetate in various ratios. • Among other chelate phases, previously undescribed Ti{sub 2}(O{sup n}Bu){sub 7}Eaa was obtained. • NMR-based mass balance procedure was introduced to obtain quantitative relationships. • The transesterification reaction has been noted. • Nanocrystalline anatase has been obtained by thermal treatment at 350 °C.

  9. Sbi00515, a Protein of Unknown Function from Streptomyces bingchenggensis, Highlights the Functional Versatility of the Acetoacetate Decarboxylase Scaffold.

    Science.gov (United States)

    Mueller, Lisa S; Hoppe, Robert W; Ochsenwald, Jenna M; Berndt, Robert T; Severin, Geoffrey B; Schwabacher, Alan W; Silvaggi, Nicholas R

    2015-06-30

    The acetoacetate decarboxylase-like superfamily (ADCSF) is a group of ~4000 enzymes that, until recently, was thought to be homogeneous in terms of the reaction catalyzed. Bioinformatic analysis shows that the ADCSF consists of up to seven families that differ primarily in their active site architectures. The soil-dwelling bacterium Streptomyces bingchenggensis BCW-1 produces an ADCSF enzyme of unknown function that shares a low level of sequence identity (~20%) with known acetoacetate decarboxylases (ADCs). This enzyme, Sbi00515, belongs to the MppR-like family of the ADCSF because of its similarity to the mannopeptimycin biosynthetic protein MppR from Streptomyces hygroscopicus. Herein, we present steady state kinetic data that show Sbi00515 does not catalyze the decarboxylation of any α- or β-keto acid tested. Rather, we show that Sbi00515 catalyzes the condensation of pyruvate with a number of aldehydes, followed by dehydration of the presumed aldol intermediate. Thus, Sbi00515 is a pyruvate aldolase-dehydratase and not an acetoacetate decarboxylase. We have also determined the X-ray crystal structures of Sbi00515 in complexes with formate and pyruvate. The structures show that the overall fold of Sbi00515 is nearly identical to those of both ADC and MppR. The pyruvate complex is trapped as the Schiff base, providing evidence that the Schiff base chemistry that drives the acetoacetate decarboxylases has been co-opted to perform a new function, and that this core chemistry may be conserved across the superfamily. The structures also suggest possible catalytic roles for several active site residues. PMID:26039798

  10. New liner and reticular polyelectrolytes based an acetoacetic ehter and acrylic acid: synthesis, structure and stimulating sensitivity characteristics

    International Nuclear Information System (INIS)

    Novel linear and crosslinked poly-carbolytes based on acetoacetic ester and acrylic acid were synthesized for the first time via Michael addition reaction followed by the radical poly-mineralization. The structure and properties of polyelectrolytes were characterized by FTIR, Raman and NMR spectroscopy, TGA, DSC, GPC, viscosimetry, and potentiometric titration. Considerable influence of water content on the swelling rate of hydrogel was established. The swelling-deswelling properties of hydrogels were studied in water-organic solvent mixtures, electric and magnetic fields. (author)

  11. Chlorine Dioxide-Iodide-Methyl Acetoacetate Oscillation Reaction Investigated by UV-Vis and Online FTIR Spectrophotometric Method

    Directory of Open Access Journals (Sweden)

    Laishun Shi

    2012-01-01

    Full Text Available In order to study the chemical oscillatory behavior and mechanism of a new chlorine dioxide-iodide ion-methyl acetoacetate reaction system, a series of experiments were done by using UV-Vis and online FTIR spectrophotometric method. The initial concentrations of methyl acetoacetate, chlorine dioxide, potassium iodide, and sulfuric acid and the pH value have great influence on the oscillation observed at wavelength of 289 nm. There is a preoscillatory or induction period, and the amplitude and the number of oscillations are associated with the initial concentration of reactants. The equations for the triiodide ion reaction rate changing with reaction time and the initial concentrations in the oscillation stage were obtained. Oscillation reaction can be accelerated by increasing temperature. The apparent activation energies in terms of the induction period and the oscillation period were 26.02 KJ/mol and 17.65 KJ/mol, respectively. The intermediates were detected by the online FTIR analysis. Based upon the experimental data in this work and in the literature, a plausible reaction mechanism was proposed for the oscillation reaction.

  12. Succinyl-CoA:acetoacetate transferase deficiency : identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K E; Wanders, R J; Ruiter, J P; Ijlst, L; Visser, G; Reitsma-Bierens, W C; Heijmans, Hugo; Reijngoud, D J; Smit, G P

    1997-01-01

    UNLABELLED: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis,

  13. Succinyl-CoA : acetoacetate transferase deficiency: identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    NiezenKoning, KE; Ijlst, L; Visser, G; ReitsmaBierens, WCC; Heymans, HSA; Reijngoud, DJ; Smit, GPA; Ruiter, Jos P. N.

    1997-01-01

    We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis, and subsequ

  14. Hyperketonemia (Acetoacetate Upregulates NADPH Oxidase 4 and Elevates Oxidative Stress, ICAM-1, and Monocyte Adhesivity in Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Preeti Kanikarla-Marie

    2015-01-01

    Full Text Available Background/Aims: The incidence of developing microvascular dysfunction is significantly higher in type 1 diabetic (T1D patients. Hyperketonemia (acetoacetate, β-hydroxybutyrate is frequently found along with hyperglycemia in T1D. Whether hyperketonemia per se contributes to the excess oxidative stress and cellular injury observed in T1D is not known. Methods: HUVEC were treated with ketones in the presence or absence of high glucose for 24 h. NOX4 siRNA was used to specifically knockdown NOX4 expression in HUVEC. Results: Ketones alone or in combination with high glucose treatment cause a significant increase in oxidative stress, ICAM-1, and monocyte adhesivity to HUVEC. Using an antisense approach, we show that ketone induced increases in ROS, ICAM-1 expression, and monocyte adhesion in endothelial cells were prevented in NOX4 knockdown cells. Conclusion: This study reports that elevated levels of ketones upregulate NOX, contributing to increased oxidative stress, ICAM-1 levels, and cellular dysfunction. This provides a novel biochemical mechanism that elucidates the role of hyperketonemia in the excess cellular injury in T1D. New drugs targeting inhibition of NOX seems promising in preventing higher risk of complications associated with T1D.

  15. Hyperpolarized [1,3-13C2 ]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer.

    Science.gov (United States)

    Jensen, Pernille R; Serra, Sonia Colombo; Miragoli, Luigi; Karlsson, Magnus; Cabella, Claudia; Poggi, Luisa; Venturi, Luca; Tedoldi, Fabio; Lerche, Mathilde H

    2015-02-15

    An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses 13C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized 13C-MR. This work led to the identification of a class of substrates, low molecular weight ethyl-esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3-13C2 ]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an ∼4 times higher metabolic substrate-to-product ratio than in the surrounding healthy tissue, (p=0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13C-MR marker. This could be appreciated by the signal-to-noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state-of-the-art hyperpolarized substrate, [1-13C]pyruvate. Also, the contrast-to-noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1-13C]pyruvate.

  16. Preparation and Catalytic Activity of PW12/PAn Material in Synthesis of 2 -Methyl-2-Ethyl Acetoacetate-1,3 -Dioxolane

    Institute of Scientific and Technical Information of China (English)

    YANG Shui-jin; YU Xie-qing; LU Bao-lan; SUN Ju-tang

    2004-01-01

    Acetals and ketals are among the most important perfume materials and industrial materials of organic synthesis. Up to now, there are many methods to synthesize them.Conventionally H2SO4 is used as catalyst in factories, but it causes many problems, such as the erosion of equipment, difficulty for after-treatment, low quality of the products, etc. Heteropolyacids (HPA) and their salts have been extensively studied because of their interesting catalytic properties.Significant research effort has been directed towards the entrapment of heteropolyanions in suitable polymeric matrices with the main goal of preparing a new type of polymer-supported catalyst for various applications in heterogeneous and electrocatalysis. It showed that the main catalysis of HPA occurs through Brφnsted acid. The reports pointed that the rate of dehydration and etherification is directly in proportion to total acidity of heteropolyacids, HPA and its salts showed excellent catalytic activity to the esterification and have recently attracted much attention as catalysts for various industrial processes, because that their acidic and redox properties can be controlled at atomic/molecular levels. Mizuno and Misono, Pope, Kozhevnikov and Wang Enbo have reviewed the homogeneous catalysis and fine organic synthesis catalyzed by heteropoly compounds.Polyaniline (PAn) is another example of a polymer host which can accommodate anions originating from 12-tungstophosphoric acid (PW12). The polyemeraldine base was prepared by condensation-polymerization of aniline in aqueous HCl using (NH4)2S2O8 as the oxidant.PW12/PAn can be achieved by doping the protonation of the polyemeraldine base with H3PW12O40 in a two-step procedure. However, there is no report on the synthesis of 2-methyl-2-ethyl acetoacetate-1,3-dioxolane catalyzed by PW12/PAn.In this paper, 2-methyl-2-ethyl acetoacetate-1,3-dioxolane was synthesis from ethyl acetoacetate and ethylene glycol in the presence of PW12/PAn. The factors

  17. 乙酰乙酰基丙烯酸酯聚合物乳液的合成及室温交联改性%Synthesis and Ambient Crosslinking of Acetoacetate Acrylate Polymer Emulsion

    Institute of Scientific and Technical Information of China (English)

    雷亮; 夏正斌; 邢俊恒; 钟理

    2014-01-01

    A core-shell acrylate polymer emulsion containing acetoacetate group was synthesized via semi-continuous seeded emulsion polymerization, and the resulted polymer was crosslinked with 1,6-hexamethylenediamine at ambient temperature. The effects of polymerization condition and acetoacetoxyethyl methacrylate (AAEM) contents on the property of the emulsion and the latex films were discussed. The results indicate that the monomer conversion rate is high and the gel content is low when the content of the emulsifier (dodecyl diphenyl ether disulfonic acid sodium, DSB) and the initiator (potassium persulfate, KPS) was 1.5%(wt) and 0.5%(wt), respectively. TEM analysis indicates that the latex particle has an obvious core-shell structure and the particle size is about 130 nm. DSC, TGA and mechanical property tests indicate that crosslinking enhances the glass-transition temperature, thermostability and mechanical properties of the latex films. These properties of the latex films are improved by increasing AAEM. When 7%(wt) of AAEM was used, the emulsion had good storage stability even 1,6-hexamethylenediamine was added into the emulsion. Therefore, the crosslinking process improves the performance of the obtained latex films.%采用半连续种子乳液聚合法合成了核壳型乙酰乙酰基丙烯酸酯聚合物乳液,并采用1,6-己二胺对其进行了室温交联改性。探讨了乳液聚合反应条件和交联单体甲基丙烯酸乙酰乙酰氧基乙酯(AAEM)用量对乳液及乳胶膜性能的影响。结果表明:当乳化剂十二烷基联苯醚二磺酸钠(DSB)、引发剂过硫酸钾(KPS)用量分别为单体总量的1.5%(wt)和0.5%(wt)时,单体转化率高,凝胶率低。透射电镜(TEM)分析显示乳胶粒呈明显的核壳结构,粒径约为130 nm。DSC、TGA 和力学性能测试表明交联提高了乳胶膜的玻璃化转变温度、热稳定性及力学性能。随着 AAEM 用量的增加,乳胶膜的性能逐渐得到提高

  18. 附子乙酸乙酯提取物对虚寒模型大鼠肝LA、LDH、PA、Gn含量及ATP酶活力的影响%Effects of Acetoacetate Extract of Radix Aconite on Hepatic Contents of LA, LDH, PA, Gn, and ATPase Activities in Deficient Cold Model Rats

    Institute of Scientific and Technical Information of China (English)

    刘一洋; 王世军; 韩冰冰; 刘珊; 杨富梅

    2011-01-01

    目的 观察中药附子乙酸乙酯提取物与附子水煎液相比对虚寒模型大鼠能量代谢的影响.方法 将Wistar大鼠随机分为空白对照组(空白组,10只)及虚寒模型组(30只).采用生石膏、龙胆草、黄柏和知母水煎液灌胃大鼠15天复制虚寒模型,之后将虚寒模型组大鼠再随机分为附子乙酸乙酯提取物组(治疗组,10只)、附子水煎液组(对照组,10只)及模型组(10只),两个用药组分别用附子乙酸乙酯提取物和附子水煎液分别灌胃治疗5天,模型组继续予模型药灌胃,空白对照组继续予生理盐水灌胃.检测大鼠肝组织乳酸(LA)、乳酸脱氢酶(LDH)、丙酮酸(PA)、糖原(Gn)含量以及Na+ -K+ -ATP酶、Ca2+ -Mg2+ -ATP酶的活力.结果 与空白组比较,模型组PA含量、Na+ -K+ -ATP酶、Ca2+ -Mg2+ -ATP酶活力降低;与模型组比较,两个给药组PA含量升高;与对照组比较,治疗组LDH含量、PA含量、Na+ -K+ -ATP酶活力升高,差异均有统计学意义(P<0.05).结论 附子乙酸乙酯提取物比附子水煎液热性略大,似乎能产生更多的能量,但是最终结论及具体作用机制有待进一步研究.%Objective To observe different effects of acetoacetate extract of Radix Aconite and Radix Aconite Decoction on the energy metabolism in deficient cold model rats. Methods Wistar rats were randomly divided into the blank control group (n = 10) and the deficient cold model group (n = 30). The deficient cold rat model was established using decoction consisting of gypsum, Radix Gentianae, Cortex Phellodendri, and Rhizoma Anemarrhenae. The decoction was given to rats of the deficient cold model group by gastrogavage for 5 days. Then these rats were randomly divided into the acetoacetate extract of Radix Aconite group (n = 10), the Radix Aconite Decoction group (n = 10), and the model group (n = 10). Rats in the model model group were administered with the decoction by gastrogavage. Rats in the other two groups were

  19. Relationship between plasma concentration of β-hydroxybutyrate,acetoacetate, lactate and pyruvate and alcohol after oral or intravenous administration of alcohol to normal human subjects: a population pharmacodynamics (PD) analysis%口服及静注乙醇后血中乙醇与β-羟丁酸,乙酰乙酸,乳酸及丙酮酸浓度关系的探讨:一项群体药效动力学的研究

    Institute of Scientific and Technical Information of China (English)

    万捷; 李建国; HUI C ko; Tom LIONETTI; David T GEORGE; Susan E SHOAF

    2005-01-01

    目的:应用群体药理学方法探讨血浆中乙醇浓度对β-羟丁酸,乙酰乙酸,乳酸,丙酮酸,β-羟丁酸/乙酰乙酸(H/A)比值及乳酸/丙酮酸(L/P)比值变化的效应.方法:给14名健康成人口服剂量相当于1.02 g·L-1总身体水的乙醇.在另一项实验中,给8名健康成人静脉注射剂量相当于0.83 g·L-1总身体水的乙醇.在服用乙醇后380 min采取静脉血测定乙醇,β-羟丁酸,乙酰乙酸,乳酸及丙酮酸的血浆浓度.在静注乙醇后340min采血测定上述5种物质的血浆浓度.结果:在口服乙醇实验中,G0为66.6±8.1 mg·dl-1,显著低于102mg·dl-1,(t检验,P<0.001).清除相斜率β为0.229±0.05 mg·dl-1·min-1.在静注实验中,G0为75.6±10.9 mg·dl-1,与83 mg·dl-1比较无显著性差异,β为0.245±0.05mg·dl-1·min-1.在两项实验中,我们应用群体间接生理反应模型来拟合乙醇浓度对β-羟丁酸,乙酰乙酸,乳酸,丙酮酸,β-羟丁酸/乙酰乙酸比值及乳酸/丙酮酸比值变化的效应,并得出各项参数.同时,我们发现,当乙醇的清除相结束时,H/A比值尚未达最大值,说明在乙醇的零级代谢相时肝脏仍在产生NADH.乳酸和乙醇的关系曲线显示乳酸的变化呈现一种逆时钟方向的滞后.结论:血L/P比值不适合用作实时肝脏氧化状态的指标.本研究提供的参数将有益于将来研究乙醇对肝脏氧化状态的影响.%To investigate the relationship between plasma concentration of β-hydroxybutyrate, acetoacetate, lactate, pyruvate, β-hydroxybutyrate/acetoacetate (H/A ratio) and lactate/pyruvate (L/P ratio) and alcohol by population PD analysis after oral or intravenous administration of alcohol. METHODS: An oral dose of alcohol tered to 14 normal human subjects and an Ⅳ infusion (30 water was administered to 8 normal subjects. Venous blood was sampled for determination of alcohol (BAC),β-hydroxybutyrate, acetoacetate, lactate and pyruvate for 380 min after oral administration and for

  20. Asymmetry Bioreduction of Ethyl Acetoacetate Catalyzed by Baker's Yeast%面包酵母催化乙酰乙酸乙酯的不对称还原反应

    Institute of Scientific and Technical Information of China (English)

    朱文洲; 许建和; 俞俊棠

    2000-01-01

    利用面包酵母催化的乙酰乙酸乙酯立体选择性还原反应,制备了光学活性的手性化合物--(S)-3-羟基丁酸乙酯.分别考察了能源供体、蔗糖浓度、反应温度、底物加量和压榨酵母用量等因素对产物得率和对映体过量值的影响.结果表明,乙酰乙酸乙酯不对称生物还原反应的最适条件为:能源供体200g/L蔗糖,反应温度35℃,压榨酵母170g/L,底物加量0.2mol/L.

  1. 含水有机溶剂体系中固定化Acetobacter sp.CCTCC M209061细胞催化乙酰乙酸乙酯不对称还原反应%Biocatalytic Asymmetric Reduction of Ethyl Acetoacetate with Immobilized Acetobacter sp.CCTCC M209061 Cells in a Micro-water-containing Organic Solvent

    Institute of Scientific and Technical Information of China (English)

    徐玉; 王晓婷; 娄文勇; 宗敏华

    2014-01-01

    本论文报道了含微水有机溶剂体系中固定化Acetobacter sp.CCTCC M209061细胞催化乙酰乙酸乙酯不对称还原为(R)-3-羟基丁酸乙酯.研究表明,Acetobacter sp.CCTCC M209061细胞能遵循反Prelog规则高选择性地催化乙酰乙酸乙酯不对称还原.与单水相反应体系相比,含有机溶剂体系不仅可有效地解决底物和产物的抑制作用,而且可提高反应底物的浓度和产率.在所研究的不同有机溶剂中,正己烷为该反应的最适有机相,其能较好溶解底物且对Acetobacter sp.CCTCC M209061细胞的毒性较小,从而导致反应的初速度较快,产率较高.异丙醇为该反应的最佳辅底物,其最适浓度为60 mmol/L;该反应体系中的最适正己烷体积百分比、反应温度、底物浓度分别为约100.00%(水含量约为0.01 wt%),35℃,40 mmol/L.在此条件下,反应的初速率、产率和产物的e.e.值分别为0.72 μmol/min,85.24%和99.00%以上,明显好于水单相反应体系进行该反应的结果.

  2. Determination of ketone bodies in blood by headspace gas chromatography-mass spectrometry

    DEFF Research Database (Denmark)

    Holm, Karen Marie Dollerup; Linnet, Kristian; Rasmussen, Brian Schou;

    2010-01-01

    A gas chromatography-mass spectrometry (GC-MS) method for determination of ketone bodies (ß-hydroxybutyrate, acetone, and acetoacetate) in blood is presented. The method is based on enzymatic oxidation of D-ß-hydroxybutyrate to acetoacetate, followed by decarboxylation to acetone, which...... was quantified by the use of headspace GC-MS using acetone-(13)C(3) as an internal standard. The developed method was found to have intra- and total interday relative standard deviations acetone+acetoacetate levels (~25 to 8300 µM) and D-ß-hydroxybutyrate levels (~30 to 16500 µM). Recovery values varied...

  3. Synthesis and investigation of solvent effects on the ultraviolet absorption spectra of 5-substituted-4-methyl-3-cyano-6-hydroxy-2-pyridones

    Directory of Open Access Journals (Sweden)

    NATASA V. VALENTIC

    2001-08-01

    Full Text Available A number of 5-substituted-4-methyl-3-cyano-6-hydroxy-2-pyridones from cyanoacetamide and the corresponding alkyl ethyl acetoacetates were synthesized according to modified literature procedures. The alkyl ethyl acetoacetates were obtained by the reaction of C-alkylation of ethyl acetoacetate. An investigation of the reaction conditions for the synthesis of 4-methyl-3-cyano-6-hydroxy-2-pyridone from cyanoacetamide and ethyl acetoacetate in eight different solvents was also performed. The ultraviolet absorption spectra of synthesized pyridones were measured in nine different solvents in the range 200–400 nm. The effects of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of linear solvation energy relationships using a general equation of the form n = n0 + sp* + aa + bb, where p* is a measure of the solvent polarity, a is the scale of the solvent hydrogen bond donor acidities and b is the scale of the solvent hydrogen bond acceptor basicities.

  4. Synthesis of 1, 4-Dihydropyridine Derivatives using FeCl3 as Catalyst under Solvent-free Condition

    Directory of Open Access Journals (Sweden)

    ABDORRAHMAN KEYHANI

    2013-06-01

    Full Text Available A mixture of ethyl acetoacetate, benzaldehyde and ammonium acetate and in the presence of FeCl3 under solvent-free condition were converted to 1, 4-dihydropyridines with good yields.

  5. A New Strategy for the Synthesis of 3-Acyl-coumarin Using Mesoporous Molecular Sieve MCM-41 as a Novel and Efficient Catalyst

    Institute of Scientific and Technical Information of China (English)

    HERAVI,Majid M; POORMOHAMMAD,Nargess; BEHESHTIGA,Yahia Sh; BAGHERNEJAD,Bita; MALAKOOTI,Reihaneh

    2009-01-01

    3-Acyl-coumarins were obtained in high yields from ortho-hydroxybenzaldehydes and ethyl acetoacetate or ethyl benzoylacetate in acetonitrile in the presence of a catalytic amount of mesoporous molecular sieve MCM-41. 3-Acyl-coumarins were obtained in high yields from ortho-hydroxybenzaldehydes and ethyl acetoacetate or ethyl benzoylacetate in acetonitrile in the presence of a catalytic amount of mesoporous molecular sieve MCM-41.

  6. Concentrations of ketone bodies in the blood of the green lizard Ameiva ameiva (Teiidae) in different physiological situations.

    Science.gov (United States)

    Pontes, R de C; Cartaxo, A C; Jonas, R

    1988-01-01

    1. The concentrations of acetoacetate and 3-hydroxybutyrate have been determined in the blood of the green lizard Ameiva ameiva (Teiidae) in fed animals and in animals starved for periods from one week to about four months. 2. The concentrations of acetoacetate are low and unaltered in fed and starved animals, being in the range from 0.014 to 0.018 mM. 3. The concentrations of 3-hydroxybutyrate are high: 2.67 mM, in fed animals, falling during starvation down to 0.26 mM. 4. The 3-hydroxybutyrate/acetoacetate ratio is high, 151, in fed animals, falling down to 17. 5. The possible importance of ketone bodies in the metabolism of Ameiva ameiva is discussed. PMID:2896561

  7. SYNTHESIS AND MICROBIAL EVALUATION OF NOVEL TETRAZOLO-TRIAZOLE DERIVATIVES SYNTHESIS und mikrobielle Evaluierung neuartiger Tetrazolo-triazol DERIVATE

    Directory of Open Access Journals (Sweden)

    Vijay V Dabholkar, Navnath Shinde, Abhishekh Karekar and Prem Naik

    2013-01-01

    Full Text Available 5-(4'-Bromomethyl-1, 1'-biphenyl-2-yl -1H-tetrazole (1 was converted into its azide derivative using sodium azide (2, which on further treatment with malonitrile, diethyl malonate, ethyl acetoacetate and isopropyl acetoacetate to yielded the respective tetrazole-triazole derivatives. The structures of the synthesized compounds were confirmed by Physico-chemical test and spectral techniques, representative samples were screened for their antimicrobial activity against gram positive and gram negative bacteria. Key words: Tetrazoles, Triazoles, Triphenyl phosphine, azides

  8. Nano aluminium nitride as a solid source of ammonia for the preparation of Hantzsch 1,4-dihydropyridines and bis -(1,4-dihydropyridines) in water via one pot multicomponent reaction

    Energy Technology Data Exchange (ETDEWEB)

    Ghorbani-Choghamarani, Arash; Goudarziafshar, Hamid; Nikoorazm, Mohsen; Yousefi, Somaieh; Tahmasbi, Bahman, E-mail: arashghch58@yahoo.co [Ilam Univ., Ilam (Iran, Islamic Republic of). Faculty of Science. Dept. of Chemistry; Zolfigol, Mohammad Ali; Hajjami, Maryam [Bu-Ali Sina University, Hamadan (Iran, Islamic Republic of). Faculty of Chemistry

    2011-07-01

    Nano aluminium nitride in the presence of water acts as solid source of ammonia, which is used for the preparation of 1,4-dihydropyridines and bis-(1,4-dihydropyridines). An efficient and simple procedure for the one-pot synthesis of 1,4-dihydropyridine and bis-(1,4-dihydropyridine) derivatives was achieved by combination of methyl acetoacetate or ethyl acetoacetate with aldehydes or dialdehydes and aluminium nitride at 80 deg C in water in high purity and good yields. (author)

  9. Synthesis of carbon-14 labelled (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone:

    DEFF Research Database (Denmark)

    Persson, T.; Johansen, S.K.; Martiny, L.;

    2004-01-01

    The potent quorum sensing inhibitor (5Z)-4-bromo-5-(bromomethylene)-2(5H)-[2-C-14]furanone has been prepared in five steps in 7.7% overall yield starting from bromo[1-C-14]acetic acid. Condensation of ethyl bromo[1-C-14]acetate with ethyl acetoacetate followed by decarboxylation was accelerated...

  10. L-proline-catalysed synthesis of functionalized unsymmetrical dihydro-1H-indeno[1,2-b]pyridines

    Indian Academy of Sciences (India)

    Farahnaz Kargar Behbahani; Hourieh Sadat Alaei

    2013-05-01

    Aromatic aldehydes have been employed in a one-pot four-component reaction with ethyl acetoacetate, 1,3-indandione and ammonium acetate in the presence of L-proline in water and under reflux condition to afford the corresponding dihydro-1H-indeno[1,2-b]pyridines in very good yields.

  11. A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis

    Directory of Open Access Journals (Sweden)

    Majid M. Heravi

    2016-04-01

    Full Text Available A novel one pot synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-diones, via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate, and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium acetate catalyzed via both of heterogeneous and homogeneous catalysis in water, is reported.

  12. New Condensation Reaction of β-keto-δ-valerolactones, Carbon Disulfide and Alkyl Halides

    Institute of Scientific and Technical Information of China (English)

    You Ming WANG; Yu Xin LI; Su Hua WANG; Zheng Ming LI

    2004-01-01

    β-Keto-δ-valerolactones, which were obtained by reaction of acetoacetate with aldehydes or ketones, reacted with carbon disulfide, alkyl halides and a new condensation reaction was developed. The structures of the products 3 were confirmed by 1HNMR spectra and elemental analysis.

  13. Silica (NPs) supported Fe (III) as a reusable heterogeneous catalyst for the one-pot synthesis of 1, 4-dihydropyridines under mild conditions

    Indian Academy of Sciences (India)

    Javad Safaei-Ghomi; Abolfazl Ziarati; Safura Zahedi

    2012-07-01

    A cheap and recyclable silica (NPs) supported Fe (III) was prepared as heterogeneous catalyst for the synthesis of various substituted 1,4-dihydropyridines via condensation of aldehydes with ethyl acetoacetate and ammonium acetate in ethanol. The products were separated from the catalyst simply by filtration and the catalyst could be recycled and reused for several times without noticeable decrease in the catalytic activity.

  14. Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis

    NARCIS (Netherlands)

    van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

    2015-01-01

    This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene

  15. ZnO Nanoparticles: An Efficient Reagent, Simple and One-Pot Procedure for Synthesis of Highly Functionalized Dihydropyridine Derivatives

    OpenAIRE

    Khazaei, Marziyeh; Anary-Abbasinejad, Mohammad; Hassanabadi, Alireza; Sadeghi, Bahareh

    2012-01-01

    A new and efficient one-pot synthesis of dihydropyridones derivatives by four-component reaction between cyanoacetamide, aryl aldehydes, and ethyl acetoacetate with ammonium acetate using nano ZnO is described. The reaction was performed in ethanol under reflux conditions and afforded good yields of products.

  16. Ferric Perchlorate Catalyzed One-pot Synthesis of 1,2,3,4-Tetrahydro-2-pyrimidinones and -thiones:an Expedient Protocol for the Biginelli Reaction

    Institute of Scientific and Technical Information of China (English)

    HERAVI,Majid Momahed; BEHBAHANI,Farahnaz Kargar OSKOOIE; Hossien Abdi

    2008-01-01

    An efficient synthesis of 1,2,3,4-tetrahydro-2-pyrimidinones and -thiones using ferric perchlorate as the catalyst from an aldehyde, ethyl acetoacetate, and urea or thiourea in acetonitrile was described. Compared to the classical Biginelli reaction conditions, this new method consistently has the advantage of full catalysis, good yields and short reaction time.

  17. Poly(4-vinylpyridine efficiently catalyzed one-pot four-component synthesis of pyrano[2,3-c]pyrazoles

    Directory of Open Access Journals (Sweden)

    Jalal Albadi

    2014-10-01

    Full Text Available An efficient one-pot synthesis of pyrano[2,3-c]pyrazoles via four-component reaction of phenyl hydrazine, ethyl acetoacetate, malononitrile and aromatic aldehydes, catalyzed by poly(4-vinylpyridine is reported. This method provides many advantages such as, atom-economy, easy work up, clean procedure, short reaction times and high yields of products.

  18. Pechmann Reaction Promoted by Boron Trifluoride Dihydrate

    Directory of Open Access Journals (Sweden)

    J. Mezger

    2005-08-01

    Full Text Available The Pechmann reaction of substituted phenols 1a-e with methyl acetoacetate (2 can be activated by boron trifluoride dihydrate (3 to give the corresponding 4-methyl- coumarin derivatives 4a-e in excellent yield (98-99 %.

  19. Methyl 6-Methyl-1-(4-methylphenyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate

    Directory of Open Access Journals (Sweden)

    Haiping Wang

    2012-04-01

    Full Text Available Methyl 6-methyl-1-(4-methylphenyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylate has been synthesized via the modified Biginelli reaction from benzaldehyde, p-tolylurea, and methyl acetoacetate, promoted with microwave irradiation and catalyzed by TsOH under solvent-free conditions in high yield.

  20. Characterization of some Pr(III) complexes in terms of electronic spectral parameters

    International Nuclear Information System (INIS)

    Pr(III) complexes from the ligands derived from methyl acetoacetate, ethyl acetoacetate, veratraldehyde, ethyl vanillin and 2,5 dimethoxy benzaldehyde forming Schiff-bases with ortho, meta and para phenylene diamines have been synthesized. The complexes have been characterized in terms of various Slater-Condon Lande and Judd-Ofelt parameters. The various trends in the parametric values have also been described. The involvement of 4f-orbital in the Pr(III) complexes including deviation in the symmetry have been discussed on the basis of electronic spectral parameters. The validity of the theories used has been established while comparing observed and calculated energies and intensities of the various bands in the present complexes on the basis of r.m.s deviation. The trends of the curves observed in the solution spectra have also been discussed. (author). 21 refs., 5 tabs., 2 figs

  1. 西尼地平的合成工艺研究%Study on the Synthesis Technology of Cilnidipine

    Institute of Scientific and Technical Information of China (English)

    施务务; 李立标

    2014-01-01

    With 2-methoxyethyl acetoacetate and cinnamyl acetoacetate as the starting materials, the cilnidipine can be obtained from 3-Aminocrotonic Cinnamate by Aldol condensation and Hantzsch cyclization. It is a suitable way to produce cilnidipin industrially,which provides the advantage of simplicity and safety.%以乙酰乙酸甲氧基乙基酯、乙酰乙酸肉桂醇酯为起始原料,经中间体3-氨基巴豆酸肉桂醇酯,通过Aldol缩合、Hantzsch环合反应,合成出了钙离子拮抗剂西尼地平。该合成工艺安全可行,操作简单,适合工业化生产。

  2. An efficient three-component domino synthesis of difluoromethyl-containing 1,4-dihydropyridines under solvent and catalyst free conditions

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The difluoromethyl-containing Hantzsch 1,4-dihydropyridines were synthesized in good yields by a one-pot cyclocondensation of ethyl difluoroacetoacetate (EDFAA),a variety of aromatic aldehydes and ammonium acetate under solvent and catalyst free conditions.The comparison of reaction conditions and products was made among the different 1,3-carbonyl substrates (ethyl acetoacetate,ethyl difluoroacetoacetate and ethyl trifluoroacetoacetate) for the Hantzsch reaction.

  3. Cerium(Ⅳ) ammonium nitrate catalysed facile and efficient synthesis of polyhydroquinoline derivatives through Hantzsch multicomponent condensation

    Institute of Scientific and Technical Information of China (English)

    Cherkupally Sanjeeva Reddy; Mekala Raghu

    2008-01-01

    A general and convenient practical approach for the synthesis of polyhydroquinoline derivatives has been achieved via one-pot four-component Hantzsch condensation of aromatic aldehydes,dimedone,ethyl acetoacetate and ammonium acetate in the presence of a catalytic amount of cerium(Ⅳ) ammonium nitrate (CAN),in ethanol solvent at ambient temperature.Simple work-up,mild reaction conditions,inexpensive and non-toxic catalyst,and excellent product yields are the advantageous features of this method.

  4. Efficient Synthesis of β-Acetamido Ketones and Esters Using Aluminum Chloride as an Inexpensive and Green Catalyst%Efficient Synthesis of β-Acetamido Ketones and Esters Using Aluminum Chloride as an Inexpensive and Green Catalyst

    Institute of Scientific and Technical Information of China (English)

    Mohammad Ali, Zolfigol; Ardeshir, Khazaei; Mohammad, Mokhlesi; Abdolkarim, Zare; Maliheh, Safaiee; Fatemeh, Derakhshan-Panah; Hassan, Keypour; Ahmad, Ali Dehghani-Firouzabadi; Maria, Merajoddin

    2012-01-01

    Aluminum chloride (AlCl3) efficiently catalyzes one-pot multicomponent condensation of enolizable ketones or alkyl acetoacetates with aldehydes, acetonitrile and acetyl chloride to afford β-acetamido ketone or ester derivatives in high to excellent yields and in relatively short reaction times. Moreover, by this synthetic method, some novel β-acetamido ketones and esters (i.e. one complex structure) are prepared.

  5. Benzothiazolylazo derivatives of some β-dicarbonyl compounds and their Cu(II), Ni(II) and Zn(II) complexes

    OpenAIRE

    KRISHNANNAIR KRISHNANKUTTY; MUHAMMED BASHEER UMMATHUR; DAMODARAN KAMALAKSHY BABU

    2010-01-01

    The coupling of diazotized 2-aminobenzothiazole with 1,3-dicar-bonyl compounds (benzoylacetone, methyl acetoacetate and acetoacetanilide) yielded a new series of tridentate ligand systems (HL). Analytical, IR, 1H--NMR, 13C-NMR and mass spectral data indicated that the compounds exist in the intramolecularly hydrogen bonded azo-enol tautomeric form in which one of the carbonyl groups of the dicarbonyl moiety had enolised and hydrogen bonded to one of the azo nitrogen atoms. The compounds forme...

  6. Solid-supported sulfonic acid-containing catalysts efficiently promoted one-pot multi-component synthesis of -acetamido carbonyl compounds

    Indian Academy of Sciences (India)

    Mohammad Ali Zolfigol; Ardeshir Khazaei; Abdolkarim Zare; Mohammad Mokhlesi; Tahereh Hekmat-Zadeh; Alireza Hasaninejad; Fatemeh Derakhshan-Panah; Ahmad Reza Moosavi-Zare; Hassan Keypour; Ahmad Ali Dehghani-Firouzabadid; Maria Merajoddin

    2012-03-01

    Silica-functionalized sulfonic acid (SFSA) and sulfuric acid-modified polyethylene glycol-6000 (PEG-OSO3H) efficiently catalysed one-pot multi-component condensation of enolizable ketones or alkyl acetoacetates with arylaldehydes, acetonitrile and acetyl chloride to afford the corresponding -acetamido ketone or ester derivatives in high to excellent yields and in relatively short reaction times. Moreover, in this work, some novel -acetamido carbonyl compounds (i.e., one complex structure) are synthesized.

  7. Synthesis of Polyfunctionalized 4H-Pyrans

    Directory of Open Access Journals (Sweden)

    Manisha Bihani

    2013-01-01

    Full Text Available Amberlyst A21 catalyzed one-pot three-component coupling of aldehyde and malononitrile with active methylene compounds such as acetylacetone and ethyl acetoacetate for the synthesis of pharmaceutically important polyfunctionalized 4H-pyrans has been reported. Simple experimental procedure, no chromatographic purification, no hazardous organic solvents, easy recovery and reusability of the catalyst, and room temperature reaction conditions are some of the highlights of this protocol for the synthesis of pharmaceutically relevant focused libraries.

  8. Ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease

    OpenAIRE

    Youm, Yun-Hee; Nguyen, Kim Y.; Grant, Ryan W.; Goldberg, Emily L.; Bodogai, Monica; Kim, Dongin; D'Agostino, Dominic; Planavsky, Noah; Lupfer, Christopher; Kanneganti, Thirumala D.; Kang, Seokwon; Horvath, Tamas L.; Fahmy, Tarek M.; Crawford, Peter A.; Biragyn, Arya

    2015-01-01

    Ketone bodies , β-hydroxybutyrate (BHB) and acetoacetate support mammalian survival during states of energy deficit by serving as alternative source of ATP 1 . BHB levels are elevated during starvation, high-intensity exercise or by the low carbohydrate ketogenic diet 2 . Prolonged caloric restriction or fasting reduces inflammation as immune system adapts to low glucose supply and energy metabolism switches towards mitochondrial fatty acid oxidation, ketogenesis and ketolysis 2-6 . However, ...

  9. PPA-SiO2 catalyzed efficient synthesis of polyhydroquinoline derivatives through Hantzsch multicomponent condensation under solvent-free conditions

    Institute of Scientific and Technical Information of China (English)

    Amir Khojastehnezhad; Farid Moeinpour; Abolghasem Davoodnia

    2011-01-01

    Silica gel-supported polyphosphoric acid (PPA-SiO2) was found to be an efficient catalyst for the one-pot four-component Hantzsch condensation reaction of aryl aldehydes, dimedone, ethyl acetoacetate and ammonium acetate to afford the corresponding polyhydroquinoline derivatives in high yields. The main advantages of the present approach are short reaction times, clean reaction profiles, simple experimental and workup procedures.

  10. The Homogentisate Pathway: a Central Catabolic Pathway Involved in the Degradation of l-Phenylalanine, l-Tyrosine, and 3-Hydroxyphenylacetate in Pseudomonas putida

    OpenAIRE

    Arias-Barrau, Elsa; Olivera, Elías R.; Luengo, José M.; Fernández, Cristina; Galán, Beatriz; García, José L.; Díaz, Eduardo; Miñambres, Baltasar

    2004-01-01

    Pseudomonas putida metabolizes Phe and Tyr through a peripheral pathway involving hydroxylation of Phe to Tyr (PhhAB), conversion of Tyr into 4-hydroxyphenylpyruvate (TyrB), and formation of homogentisate (Hpd) as the central intermediate. Homogentisate is then catabolized by a central catabolic pathway that involves three enzymes, homogentisate dioxygenase (HmgA), fumarylacetoacetate hydrolase (HmgB), and maleylacetoacetate isomerase (HmgC), finally yielding fumarate and acetoacetate. Wherea...

  11. Screening Study on the antipyretic Fraction from Peristrophe japonica(Thumb)Brem%九头狮子草乙酸乙酯部位的作用研究

    Institute of Scientific and Technical Information of China (English)

    杨洁; 刘香

    2012-01-01

      目的观察九头狮子草醇提乙酸乙酯部位的解热、止咳作用。方法采用系统溶剂法对九头狮子草醇提物进行初步分离。采用用酵母人工发热模型,测量大鼠体温变化;采用氨水引咳法,研究九头狮子草乙酸乙酯部位的解热止咳作用。结果九头狮子草醇提乙酸乙酯萃取部位有明显的解热作用,九头狮子草乙酸乙酯部位中、高剂量组可明显减少浓氨水引起的咳嗽次数。结论九头狮子草乙酸乙酯部位具有较强的解热止咳作用%  Objective: To investigate antipyretic and anti-tussive activities of The ethanol-extracted acetoacetate-abstraction group of Peristrophe japonica(Thumb)Brem.. Methods:Systematic solvent method is used to separate the ethanol extract of Peristrophe japonica(Thumb)Brem. Fever model induced by dry yeast in mice was used to screen the valid target of the antipyretic effect. Anti-tussive activity was evaluated using ammonia-induced mice coughing. Results: The ethanol-extracted acetoacetate-abstraction group showed marked antipyretic effect on the yeast-induced fever. The acetoacetate-abstraction group could significantly inhibit mice's frequency of cough induced by ammonia and inhibit frequency of cough. Conclusion: The ethanol-extracted acetoacetate-abstraction group of Peristrophe japonica(Thumb)Brem. is most propably the valid target of antipyretic and anti-tussive activities.

  12. Synthesis of Some New 1,4-Dihydropyridine Derivatives through a Facile One-pot Hantzsch Condensation Catalyzed by Triethylamine

    Institute of Scientific and Technical Information of China (English)

    Ghalem, Wassima; Boulcina, Raouf; Debache, Abdelmadjid

    2012-01-01

    A facile and efficient synthesis of new 1,4-dihydropyridine derivatives was reported via Hantzsch three-com- ponent condensation reaction of aldehydes or formylphenylboronic acids, ethyl acetoacetate, and ammonium acetate in the presence of a catalytic amount of triethylamine under solvent-free conditions. The method described here of- fers several advantages including high yields, short reaction times, and simple work-up procedure.

  13. Reactions of CH-acids with α,β-unsaturated aldehydes in ionic liquids

    DEFF Research Database (Denmark)

    Kryshtal, G. V.; Zhdankina, G. M.; Astakhova, Irina Kira;

    2004-01-01

    Metal carbonate-catalyzed reactions of CH-acids (diethyl malonate, ethyl acetoacetate, ethyl cyanoacetate, and ethyl 2-acetyl- and 2-ethoxycarbonyl-5,9- dimethyldeca-4,8-dienoates) with α,β-unsaturated aldehydes (acrolein, crotonaldehyde, citral) were studied in an ionic liquid, 1-butyl-3...... of the Michael adducts. The ionic liquid [bmim][PF 6] can be recovered and repeatedly used in the reactions....

  14. Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

    OpenAIRE

    de Reggi Max; Nieoullon André; Khrestchatisky Michel; Abou-Hamdan Mhamad; Cornille Emilie; Gharib Bouchra

    2010-01-01

    Abstract Background The administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasi...

  15. Roles and Regulation of Ketogenesis in Cultured Astroglia and Neurons Under Hypoxia and Hypoglycemia

    OpenAIRE

    Takahashi, Shinichi; Iizumi, Takuya; Mashima, Kyoko; Abe, Takato; Suzuki, Norihiro

    2014-01-01

    Exogenous ketone bodies (KBs), acetoacetate (AA), and β-hydroxybutyrate (BHB) act as alternative energy substrates in neural cells under starvation. The present study examined the endogenous ketogenic capacity of astroglia under hypoxia with/without glucose and the possible roles of KBs in neuronal energy metabolism. Cultured neurons and astroglia were prepared from Sprague-Dawley rats. Palmitic acid (PAL) and l-carnitine (LC) were added to the assay medium. The 4- to 24-hr production of AA a...

  16. Synthesis and Spectroscopic Studies of Mixed Ligand Complexes of Pt(II) and Pd(II) with Ethyl-α-Isonitrosoacetoacetate and Dienes

    OpenAIRE

    Anita Krishankant Taksande; Ravishankar D. Raut; Mahendra D. Choudhary

    2015-01-01

    The mixed ligand complexes of the kind [M(L1) (L2)] where M= Pt(II), Pd(II).L1 = primary ligand ethyl-α-isonitrosoacetoacetate derived from reaction between ethyl acetoacetate, acetic acid and sodium nitrite and L2=secondary ligand para-phenyldiamine (PPD) are synthesized. All the prepared complexes were identified and confirmed by elemental analysis, molar conductance measurements, and infrared electronic absorption. Their complexes has been made based on elemental analysis, molar conductivi...

  17. NMR Studies on the Subacute Biochemical Effects of Aristolochic Acid on Rat Serum

    Institute of Scientific and Technical Information of China (English)

    Xiao Yu ZHANG; Hui Feng WU; Xiao Jing LI; Feng Kui PEI; Jia Zuan NI

    2005-01-01

    The subacute effect of aristolochic acid (AA) on rat serum was studied by NMR method.The biochemical effects induced by AA were characterized by an increase in the amounts of creatinine, trimethylamine N-oxide, acetoacetate, acetate and 3-D-hydroxybutyrate and lactate in serum from 1H NMR spectra. Principal component analysis was used for further comparing the similarities of 1H NMR spectral profiles of serum from rats treated with AA and model toxins.

  18. Mesostructured SBA-15-Pr-SO3H: An efficient solid acid catalyst for one-pot and solvent-free synthesis of 3,4-dihydro-2-pyridone derivatives

    Indian Academy of Sciences (India)

    Ghodsi Mohammadi Ziarani; Somayeh Mousavi; Negar Lashgari; Alireza Badiei

    2013-11-01

    3,4-Dihydro-2-pyridone derivatives have been prepared efficiently via a one-pot four-component reaction of benzaldehyde derivatives, Meldrum’s acid, methyl acetoacetate and ammonium acetate in the presence of sulphonic acid-functionalized ordered nanoporous SBA-15 as a nano heterogeneous catalyst under solvent-free conditions. This process is a simple, environmentally friendly, rapid and high yielding reaction.

  19. Influence of Electronic Factors on “Solvent-Free and Catalyst-Free Biginelli Reaction

    Directory of Open Access Journals (Sweden)

    Tanay Pramanik

    2013-12-01

    Full Text Available A series of Biginelli condensation were carried out employing urea, ethyl acetoacetate with a series of different derivatives of benzaldehyde. A green synthetic procedure was followed for performing the Biginelli reactions. The reaction conditions were found to be different for electron rich and electron deficient benzaldehydes. So the electronic effect has shown a significant impact on the reaction condition of the Biginelli condensation.

  20. Purification and characterization of a novel carbonyl reductase with high stereo-selectivity

    Institute of Scientific and Technical Information of China (English)

    YANG Ming; XU Yan; MU Xiaoqing; XIAO Rong

    2007-01-01

    A novel NADPH-dependent carbonyl reductase was separated from Candida parapsilosis CCTCC 203011.The enzyme gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE),which was purified through ammonium sulfate,Diethylamino Ethanol (DEAE) sepharose Fast flow (FF),phenyl-sepharose FF and blue sepharose FF chromatography from cell-free extract.The molecular mass of the enzyme was about 30 kDa.The optimum pH and temperature for reduction were 4.5℃ and 35℃,respectively.The Cu2+ had strong restrictive effect on enzyme activity.In addition,the carbonyl reductase was an enzyme with high substrate specificity and stereo-selectivity,and showed high asymmetric reduction activity towards α-hydroxyacetophenone and ethyl 4-chloro acetoacetate.For the asymmetric reduction of α-hydroxyacetophenone and ethyl 4-chloro acetoacetate,(S)-1-phenyl-1,2-ethanediol and (R)-ethyl 4-chloro-3-hydroxybutanoate were produced by the purified enzyme,with the 100% and 94.3% e.e.value,respectively.Therefore,the enzyme could be one of the effective biocatalysts for asymmetric synthesis of chiral alcohols.The amino acid sequences of one peptide from the purified enzyme were analyzed by LC-MASS-MASS,and the carbonyl reductase showed some identity to the hypothetical protein CaO 19.10414 reported.

  1. Fatty acid oxidation and ketogenesis in astrocytes

    International Nuclear Information System (INIS)

    Astrocytes were derived from cortex of two-day-old rat brain and grown in primary culture to confluence. The metabolism of the fatty acids, octanoate and palmitate, to CO2 in oxidative respiration and to the formation of ketone bodies was examined by radiolabeled tracer methodology. The net production of acetoacetate was also determined by measurement of its mass. The enzymes in the ketogenic pathway were examined by measuring enzymic activity and/or by immunoblot analyses. Labeled CO2 and labeled ketone bodies were produced from the oxidation of fatty acids labeled at carboxy- and ω-terminal carbons, indicating that fatty acids were oxidized by β-oxidation. The results from the radiolabeled tracer studies also indicated that a substantial proportion of the ω-terminal 4-carbon unit of the fatty acids bypassed the β-ketothiolase step of the β-oxidation pathway. The [14C]acetoacetate formed from the [1-14C]labeled fatty acids, obligated to pass through the acetyl-CoA pool, contained 50% of the label at carbon 3 and 50% at carbon 1. In contrast, the [14C]acetoacetate formed from the (ω-1)labeled fatty acids contained 90% of the label at carbon 3 and 10% at carbon 1

  2. Study of ketone body kinetics in children by a combined perfusion of /sup 13/C and /sup 2/H3 tracers

    Energy Technology Data Exchange (ETDEWEB)

    Bougneres, P.F.; Ferre, P.

    1987-11-01

    Ketone body kinetics were quantified in six children (3-5 yr old), who were fasted for 13-22 h, by a combined perfusion of (3-/sup 13/C)acetoacetate ((/sup 13/C)AcAc) and D-(-)-beta-(4,4,4-/sup 2/H3)hydroxybutyrate (beta-(/sup 2/H3)OHB) and gas chromatography-mass spectrometry analysis. Results were analyzed according to the single-pool (combined enrichments) or the two-accessible pools models. After 20-22 h of fasting, ketone body turnover rate was 30-50 mumol.kg-1.min-1, a rate achieved after several days of fasting in adults. At low ketosis, acetoacetate was the ketone body preferentially synthesized de novo and utilized irreversibly. When ketosis increased, acetoacetate irreversible disposal was not enhanced, since it was largely converted into beta-OHB, whereas beta-OHB irreversible disposal was very much increased. The single-pool and two-pool models gave similar ketone body turnover rates when (/sup 13/C)AcAc was the tracer, whereas the use of beta-(/sup 2/H3)OHB gave some more divergent results, especially at low ketosis. These studies demonstrate that ketogenesis is very active in short-term fasted children and that the use of a combined infusion of (/sup 13/C)AcAc and beta-(/sup 2/H3)OHB is a convenient way to give insight into individual ketone body kinetics.

  3. Validation of two-pool model for in vivo ketone body kinetics

    International Nuclear Information System (INIS)

    Previous studies have indicated that simultaneous infusions of two ketone body tracers ([13C]acetoacetate and [14C]beta-hydroxybutyrate) provide accurate estimates of exogenous ketone body inflow when an open two-pool model is employed. In the present studies, net hepatic ketone body production was determined from surgically placed arterial, portal venous, and hepatic venous catheters in conscious diabetic (n = 6) and 4-day fasted (n = 7) dogs. [13C]acetoacetate and [14C]beta-hydroxybutyrate were infused simultaneously, and ketone body production was calculated from either acetoacetate (AcAc) single-isotope data, beta-hydroxybutyrate (beta-OHB) single-isotope data, the sum of individual fluxes, or the two-pool model. In fasted animals, both the AcAc single-isotope calculation and the sum of individual fluxes overestimated net hepatic production by approximately 50% (P less than 0.05), whereas the beta-OHB single-isotope calculation and the two-pool model gave accurate estimates. In the diabetic animals, the beta-OHB single-isotope calculation underestimated net hepatic production by approximately 30% (P less than 0.05). The sum of individual fluxes overestimated net hepatic production by approximately 46% (P less than 0.05), whereas both the AcAc single-isotope calculation and the two-pool model gave accurate estimates. In conclusion, single-isotope methods give erroneous estimates of net hepatic production of ketone bodies. In contrast, a two-pool model provided an accurate estimate of net hepatic production and thus appears to be suitable for determination of ketone body kinetics in humans

  4. SYNTHESIS, CHARACTERIZATION AND BIOCIDAL ACTIVITY OF NOVEL HALOGENATED - 4-[(SUBSTITUTED-BENZOTHIAZOL-2-YL HYDRAZONO]-2-(SUBSTITUTED-PHENYL-5-METHYL /ETHOXY -2,4-DIHYDRO-PYRAZOL-3-ONE DERIVATIVES Synthese, Charakterisierung und biozide Aktivität NOVEL HALOGENIERTEN - 4 - [(substituiertes-benzothiazol-2-YL hydrazono] -2 -(Substituiertes Phenyl-5-Methyl / ETHOXY -2,4-DIHYDRO-pyrazol-3-ONE DERIVATE

    Directory of Open Access Journals (Sweden)

    V. Khatri, K. Sharma, V. Sareen, D. Shinde and S. Sareen

    2012-04-01

    Full Text Available Some new 4-[(substituted-benzothiazol-2-ylhydrazono]-2-(substituted-phenyl-5- methyl/ethoxy-2,4-dihydro-pyrazol-3-one(4 have been synthesized by reacting substituted 2- amino benzothiazol (1 with acetoacetic ester and malonic ester (2. 2-[(substituted-benzothiazol- 2-ylhydrazono]-3-oxo-butyric acid ethyl ester and 2-[(substituted-benzothiazol-2- ylhydrazono]- malonic acid diethyl ester (3 react with different hydrazines to give the title compounds(4. These compounds are evaluated for their antifungal and insecticidal activity. The structures of all these compounds have been confirmed by IR, 1H NMR, mass spectra and elemental analysis data.

  5. Intense Photoluminescence and Movement of OpticalAbsorption Edge in Alumina Aerogels

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Alumina aerogels with high porosity of nanometer size were prepared from Al, n-butanol andethyl acetoacetate by the sol-gel route and the N2 supercritical extraction drying technique.Optical experiment results showed that for alumina aerogels after annealing at 500℃ for 4 h pneintense blue emission band appeared in the wavelength range of 400 to 800 nm, and the opticalabsorption edge moved from 8.0 eV of coarse grain Al2O3 to 3~5 eV and with increasing theannealing temperature, this luminescence band presented blue shifts. The reasons of these newoptical properties are discussed in detail.

  6. Four-component one-pot synthesis of unsymmetrical polyhydroquinoline derivatives using 3-methyl-1-sulfonic acid imidazolium hydrogen sulfate as a catalyst

    Institute of Scientific and Technical Information of China (English)

    Nader Ghaffari Khaligh

    2014-01-01

    3-Methyl-1-sulfonic acid imidazolium hydrogen sulfate has been used as an efficient, halogen-free, and reusable Brönsted acidic ionic liquid catalyst for the synthesis of ethyl-4-aryl/heteryl- hexahy-dro-trimehtyl-5-oxoquinoline-3-carboxylates via the one-pot condensation of dimedone with ar-yl/heteryl aldehydes, ethyl acetoacetate, and ammonium acetate under solvent-free conditions. This method has the advantage of being clean and simple, as well as providing the desired product in high yield over a short reaction time. Furthermore, the catalyst could be recycled and reused four times without any discernible reduction in activity.

  7. Solubility of trans-1,2-Cyclohexanediol in Some Solvents%1,2-环己二醇在溶剂中的溶解度

    Institute of Scientific and Technical Information of China (English)

    周彩荣; 王海峰; 蒋登高

    2005-01-01

    The solubility of trans-1,2-cyclohexanediol in water, methyl acetate, acetic ester, propyl acetate, butyl acetate, methyl acrylate, ethyl acrylate, 2-pentanone and acetoacetic ester was measured at temperatures ranging from about 300 K to 330K, using a modification of the experimental technique of laser monitoring observation system. The solubilities were calculated by λh method, in which new parameters were introduced to express the activity coefficients of trans-1,2-cyclohexanediol, and determined from the experimental data. The new parameters provide good calculated results. The experimental data were also correlated with a simple model, and results were compared with present λh model.

  8. Highly efficient solvent-free synthesis of pyranopyrazoles by a Brønsted-acidic ionic liquid as a green and reusable catalyst

    Indian Academy of Sciences (India)

    Javad Ebrahimi; Ali Mohammadi; Vahid Pakjoo; Esan Bahramzade; Amir Habibi

    2012-09-01

    A simple, green and efficient protocol for synthesis of dihydropyrano[2,3-c]pyrazole derivatives is developed by a four component reaction of various benzaldehydes, ethyl acetoacetate, hydrazine hydrate and malononitrile in the presence of 3-methyl-1-(4-sulphonic acid)butylimidazolium hydrogen sulphate [(CH2)4SO3HMIM][HSO4], an acidic ionic liquid and as a catalyst, under solvent-free conditions. The key advantages of this process are high yields, shorter reaction times, easy work-up, purification of products by non-chromatographic method and the reusability of the catalyst.

  9. Enzymes involved in 3,5-diaminohexanoate degradation by Brevibacterium sp.

    OpenAIRE

    Barker, H. A.; Kahn, J. M.; Chew, S

    1980-01-01

    Cell-free extracts of Brevibacterium sp. L5 grown on DL-erythro-3,5-diaminohexanoate were found to contain a 3-keto-5-aminohexanoate cleavage enzyme that converts 3-keto-5-aminohexanoate and acetyl-coenzyme A (CokA) to 3-aminobutyryl-CoA and acetoacetate and a deaminase that coverts L-3-aminobutyryl-CoA to crotonyl-CoA. The cleavage enzyme has been purified extensively, and some of its properties have been determined for comparison with the 3-keto-6-acetamido-hexanoate cleavage enzyme of Pseu...

  10. A green synthesis of α,β-unsaturated carbonyl compounds from glyceraldehyde acetonide

    Directory of Open Access Journals (Sweden)

    Cláudia O. Veloso

    2011-01-01

    Full Text Available The catalytic behavior of Cs-exchanged and Cs-impregnated zeolites (X and Y was studied using the Knoevenagel condensation between glyceraldehyde acetonide and ethyl acetoacetate in order to produce the corresponding α,β-unsaturated carbonyl compound that is an important intermediate for fine chemicals. The influence of reaction temperature, type of zeolite, and basicity of the sites on the catalytic behavior of the samples was evaluated. All zeolites were active for the studied reaction. The formation of the main condensation product was favored at lower reaction temperatures. Products of further condensations were also observed especially for samples that were only dried before catalytic test.

  11. Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells

    OpenAIRE

    Rains, Justin L.; Jain, Sushil K.

    2011-01-01

    Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0–10 mM) or β-hydroxybutyrate (BHB) (0–10 mM) for 24 h prior to evaluating adhesion and a...

  12. Synthesis of New dihydropyrimidinones catalysed by dicationic ionic liquid

    Indian Academy of Sciences (India)

    Dhanaji V Jawale; Umesh R Pratap; Aparna A Mulay; Jyotirling R Mali; Ramrao A Mane

    2011-09-01

    A convenient multi step synthetic protocol for new dihydropyrimidinones bearing quinolynyl methoxy phenyl moiety has been developed from 2-chloro-3-formyl quinolines. The last step is one-pot Biginelli reaction of multicomponents, 4-((2-chloroquinolin-3-yl) methoxy) benzaldehydes, ethyl acetoacetate and urea mediated and catalysed by dicationic ionic liquid (3-methyl-1-[3-(methyl-1H-imidazolium-1-yl) propyl]-1H-imidazolium dibromide (C3 [min]2 2 [Br−] )). Simple work-up procedures and moderate to good yields of the pyrimidinones and the intermediates are the merits of the route.

  13. A microwave-catalyzed rapid, efficient and ecofriendly synthesis of substituted pyrazol-5-ones

    Directory of Open Access Journals (Sweden)

    RAHUL P. GAVANDE

    2003-10-01

    Full Text Available A series of 1-(3,4-dihydro-3-oxo-2H-1,4-benzoxazine-2-carbonyl-3-methyl-4-(substituted phenylhydrazono-2-pyrazolin-5-ones have been synthesized by the reaction of 2H-3,4-dihydro-3-oxo-1,4-benzoxazine-2-carboxylic acid hydrazide with substituted acetoacetic ester derivatives using acetic acid as solvent under microwave irradiation (MWI, as well as by conventional methods. The reaction rate is enhanced tremendously and the yields are improved under MWI as compared to conventional methods.

  14. Nano-TiCl4/SiO2: An efficient heterogeneous solid acid catalyst for the one pot cascade five-component synthesis of densely functionalized tetrahydropyridines

    Indian Academy of Sciences (India)

    Abdolhamid Bamoniri; Bi Bi Fatemeh Mirjalili; Reza Tarazian

    2015-05-01

    Nano-TiCl4/SiO2 was found to be an inexpensive and efficient heterogeneous solid acid catalyst for the synthesis of one-pot cascade synthesis of highly functionalized asymmetric tetrahydropyridines from the five-component condensation reaction of the para-substituted anilines and aromatic aldehydes with ethyl acetoacetate under thermal conditions. Novel methodology, environmentally benign conditions, clean protocol, easy work-up and high yields are the important advantages of this protocol. The products were characterized using physical and spectroscopic data such as FT-IR, 1H-NMR and in some cases 13C-NMR and CHN analysis.

  15. Unsaturated b-ketoesters and their Ni(II, Cu(II and Zn(II complexes

    Directory of Open Access Journals (Sweden)

    MUHAMMED BASHEER UMMATHUR

    2009-03-01

    Full Text Available A new series of b-ketoesters in which the keto group is attached to the olefinic linkage were synthesized by the reaction of methyl acetoacetate and aromatic aldehydes under specified conditions. The existence of these compounds predominantly in the intramolecularly hydrogen bonded enol form was well demonstrated from their IR, 1H-NMR and mass spectral data. Details on the formation of their [ML2] complexes with Ni(II, Cu(II and Zn(II and the nature of the bonding are discussed on the basis of analytical and spectral data.

  16. Microwave Assisted Convenient One-Pot Synthesis of Coumarin Derivatives via Pechmann Condensation Catalyzed by FeF3 under Solvent-Free Conditions and Antimicrobial Activities of the Products

    OpenAIRE

    Vahid Vahabi; Farhad Hatamjafari

    2014-01-01

    A rapid and efficient solvent-free one-pot synthesis of coumarin derivatives by Pechmann condensation reactions of phenols with ethyl acetoacetate using FeF3 as a catalyst under microwave irradiation is described. This one-pot synthesis on a solid inorganic support provides the products in good yields. The newly synthesized compounds were systematically characterized by IR, 1H-NMR, 13C-NMR, MS and elemental CHN analyses. The proposed solvent-free microwave irradiation method using the environ...

  17. The Hantzsch Ester Production in a Water-based Biphasic Medium, Using Infrared Irradiation as the Activating Source

    OpenAIRE

    Raquel Gómez Pliego; Roberto Osnaya; Isai Zamora; Benjamín Velasco Bejarano; Gabriel Arroyo; Eduardo Ramírez San Juan; José Trujillo; Francisco Delgado; René Miranda

    2007-01-01

    The reaction of a wide number of benzaldehydes (1a-n) with ethyl (2a) or methyl (2b) acetoacetate and aqueous ammonia (3) has been carried out in the absence of an organic solvent, and using for the first time infrared irradiation as the heating mode. Thus, under the green chemistry protocole, the corresponding mono-1,4-dihydropyridines (4a-j) and bis-1,4-dihydropyridines (4k-n) were obtained in good yields and short reaction times.

  18. Potential antibacterial activity of coumarin and coumarin-3-acetic acid derivatives.

    Science.gov (United States)

    Chattha, Fauzia Anjum; Munawar, Munawar Ali; Nisa, Mehrun; Ashraf, Mohammad; Kousar, Samina; Arshad, Shafia

    2015-05-01

    Coumarin and coumarin-3-acetic acid derivatives were synthesized by reacting phenols with malic acid, ethyl acetoacetate and ethyl acetylsuccinate in appropriate reaction conditions. All synthesized compounds were subjected to test for their antimicrobial activities against variety of gram positive (Bacillus subtilis, Staphylococcus aureus) and gram negative bacterial stains (Shigella sonnei, Escherichia coli) by agar dilution method. Several of them exhibited appreciable good antibacterial activity against the different strains of gram positive and gram negative bacteria. These findings suggest a great potential of these compounds for screening and use as antibacterial agents for further studies with a battery of bacteria.

  19. Microwave assisted synthesis of novel Hantzsch 1,4-dihydropyridines, acridine-l,8-diones and polyhydroquinolines bearing the tetrazolo [1,5-a]quinoline moiety and their antimicrobial activity assess

    Institute of Scientific and Technical Information of China (English)

    Niraj K. Ladani; Divyesh C. Mungra; Manish P. Patel; Ranjan G. Patel

    2011-01-01

    Microwave assisted efficient Hantzsch reaction via four-component coupling reactions of tetrazolo [l,5-a]quinoline-4-carbal-dehyde, dimedone/cyclohexane-l,3-dione, ethyl/methyl acetoacetate and ammonium acetate was described as the preparation of tetrazolo [l,5-a]quinoline based 1,4-dihydropyridines, acridine-l,8-diones and polyhydroquinolines. The process presented here is simple, rapid, environmentally welcoming and high yielding. All the derivatives were subjected to an in vitro antimicrobial screening against a representative panel of bacteria and fungi and results worth further investigations.

  20. Fe3O4@SiO2-NH2 Nanocomposite as a Robust and Effective Catalyst for the One-pot Synthesis of Polysubstituted Dihydropyridines.

    Science.gov (United States)

    Ghasemzadeh, Mohammad Ali; Abdollahi-Basir, Mohammad Hossein

    2016-01-01

    A practical, simple and efficient method for the synthesis of polysubstituted dihydropyridines was described via multicomponent reactions of aldehydes, arylamines, dimethyl acetylenedicarboxylate and malononitrile/ethyl acetoacetate in the presence of Fe3O4@SiO2-NH2 nanocomposites. The present methodology provides a novel and efficient method for the synthesis of dihydropyridine derivatives with some advantages, such as excellent yields, short reaction times, recoverability and low catalyst loading. The nanomagnetic catalyst could be readily recovered using an external magnet and reused several times without any significant loss in activity. The catalyst was fully characterized by FT-IR, SEM, XRD, EDX and VSM analysis. PMID:27640390

  1. DFT study on mechanism of the classical Biginelli reaction

    Institute of Scientific and Technical Information of China (English)

    Jin Guang Ma; Ji Ming Zhang; Hai Hui Jiang; Wan Yong Ma; Jian Hua Zhou

    2008-01-01

    The condensation of benzaldehyde, urea, and ethyl acetoacetate according to the procedure described by Biginelli was investigated at the B3LYP/6-31G(d), B3LYP/6-31+G(d,p), and B3LYP/6-311+G(3df,2p)//B3LYP/6-31+G(d,p) levels to explore the reaction mechanism. According to the mechanism proposed by Kappe, structures of five intermediates were optimized and four transition states were found. The calculation results proved that the mechanism proposed by Kappe is right.

  2. Acetoacetylation of Hydroxyethyl Cellulose

    Institute of Scientific and Technical Information of China (English)

    陈晓锋; 高彦芳; 杜奕; 刘德山

    2002-01-01

    The acetoacetyl group can be used to improve superabsorbent resins since it is more active than the hydroxyethyl group. The acetoacetyl group can be introduced into the side group of hydroxyethyl cellulose (HEC) to activate HEC using the ester exchange reaction between HEC and ethyl acetoacetate (EAA) to improve HEC grafting. This paper discusses the main factors affecting the reaction, such as the amount of EAA and catalyzer, the reaction temperature, and the reaction time. The acetoacetyl group was successfully introduced into HEC. Within specified ranges, increasing the amount of EAA, the reaction temperature and the reaction time will increase the acetoacetylation.

  3. Preparation of fructone catalyzed by water-soluble Br(φ)nsted acid ionic liquids

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan Wang; Rong Wang; Liang Chun Wu; Li Yi Dai

    2007-01-01

    Fructone (2-methyl-2-ethylacetoacetate-1,3-dioxolane), a flavouring material, has been synthesized from ethyl acetoacetate and glycol using five water-soluble Br(φ)nsted acid ionic liquids as catalysts for the first time. The used Br(φ)nsted acid ionic liquids include [Hmim]Tfa, [Hmim]Tsa, [Hmim]BF4, [Bmim]HSO4, [Bmim]H2PO4, and [Hmim]BF4 showed the highest catalytic activity for the preparation of fructone. After reaction, the product could be isolated from the reaction system automatically, and the ionic liquid could be directly reused without dehydration.

  4. High Glass Transition Temperature Renewable Polymers via Biginelli Multicomponent Polymerization.

    Science.gov (United States)

    Boukis, Andreas C; Llevot, Audrey; Meier, Michael A R

    2016-04-01

    A novel and straightforward one-pot multicomponent polycondensation method was established in this work. The Biginelli reaction is a versatile multicomponent reaction of an aldehyde, a β-ketoester (acetoacetate) and urea, which can all be obtained from renewable resources, yielding diversely substituted 3,4-dihydropyrimidin-2(1H)-ones (DHMPs). In this study, renewable diacetoacetate monomers with different spacer chain lengths (C3, C6, C10, C20) were prepared via simple transesterification of renewable diols and commercial acetoacetates. The diacetoacetate monomers were then reacted with renewable dialdehydes, i.e., terephthalaldehyde and divanillin in a Biginelli type step-growth polymerization. The obtained DHMP polymers (polyDHMPs) displayed high molar masses, high glass transition temperatures (Tg) up to 203 °C and good thermal stability (Td5%) of 280 °C. The Tg of the polyDHMPs could be tuned by variation of the structure of the dialdehyde or the diacetoacetate component. PMID:26800511

  5. Metabolic Rewiring by Oncogenic BRAF V600E Links Ketogenesis Pathway to BRAF-MEK1 Signaling.

    Science.gov (United States)

    Kang, Hee-Bum; Fan, Jun; Lin, Ruiting; Elf, Shannon; Ji, Quanjiang; Zhao, Liang; Jin, Lingtao; Seo, Jae Ho; Shan, Changliang; Arbiser, Jack L; Cohen, Cynthia; Brat, Daniel; Miziorko, Henry M; Kim, Eunhee; Abdel-Wahab, Omar; Merghoub, Taha; Fröhling, Stefan; Scholl, Claudia; Tamayo, Pablo; Barbie, David A; Zhou, Lu; Pollack, Brian P; Fisher, Kevin; Kudchadkar, Ragini R; Lawson, David H; Sica, Gabriel; Rossi, Michael; Lonial, Sagar; Khoury, Hanna J; Khuri, Fadlo R; Lee, Benjamin H; Boggon, Titus J; He, Chuan; Kang, Sumin; Chen, Jing

    2015-08-01

    Many human cancers share similar metabolic alterations, including the Warburg effect. However, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Here we demonstrate a "synthetic lethal" interaction between oncogenic BRAF V600E and a ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL). HMGCL expression is upregulated in BRAF V600E-expressing human primary melanoma and hairy cell leukemia cells. Suppression of HMGCL specifically attenuates proliferation and tumor growth potential of human melanoma cells expressing BRAF V600E. Mechanistically, active BRAF upregulates HMGCL through an octamer transcription factor Oct-1, leading to increased intracellular levels of HMGCL product, acetoacetate, which selectively enhances binding of BRAF V600E but not BRAF wild-type to MEK1 in V600E-positive cancer cells to promote activation of MEK-ERK signaling. These findings reveal a mutation-specific mechanism by which oncogenic BRAF V600E "rewires" metabolic and cell signaling networks and signals through the Oct-1-HMGCL-acetoacetate axis to selectively promote BRAF V600E-dependent tumor development. PMID:26145173

  6. Isolation of a new butanol-producing Clostridium strain: high level of hemicellulosic activity and structure of solventogenesis genes of a new Clostridium saccharobutylicum isolate.

    Science.gov (United States)

    Berezina, Oksana V; Brandt, Agnieszka; Yarotsky, Sergey; Schwarz, Wolfgang H; Zverlov, Vladimir V

    2009-10-01

    New isolates of solventogenic bacteria exhibited high hemicellulolytic activity. They produced butanol and acetone with high selectivity for butanol (about 80% of butanol from the total solvent yield). Their 16S rDNA sequence was 99% identical to that of Clostridium saccharobutylicum. The genes responsible for the last steps of solventogenesis and encoding crotonase, butyryl-CoA dehydrogenase, electron-transport protein subunits A and B, 3-hydroxybutyryl-CoA dehydrogenase, alcohol dehydrogenase, CoA-transferase (subunits A and B), acetoacetate decarboxylase, and aldehyde dehydrogenase were identified in the new C. saccharobutylicum strain Ox29 and cloned into Escherichia coli. The genes for crotonase, butyryl-CoA dehydrogenase, electron-transport protein subunits A and B, and 3-hydroxybutyryl-CoA dehydrogenase composed the bcs-operon. A monocistronic operon containing the alcohol dehydrogenase gene was located downstream of the bcs-operon. Genes for aldehyde dehydrogenase, CoA-transferase (subunits A and B), and acetoacetate decarboxylase composed the sol-operon. The gene sequences and the gene order within the sol- and bcs-operons of C. saccharobutylicum Ox29 were most similar to those of Clostridium beijerinckii. The activity of some of the bcs-operon genes, expressed in heterologous E. coli, was determined. PMID:19674858

  7. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis.

    Science.gov (United States)

    Zabek, Adam; Swierkot, Jerzy; Malak, Anna; Zawadzka, Iga; Deja, Stanisław; Bogunia-Kubik, Katarzyna; Mlynarz, Piotr

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC  APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis.

  8. Preparation of toluenes specifically labelled with C-14

    International Nuclear Information System (INIS)

    The attempt to prepare toluene-2 C-14 starting from ethyl acetoacetate failed because the reaction of sodium ethyl acetoacetate with dibromopropane could not be performed. This labelling was also attempted starting from methyl tetrahydropyran. This synthesis was not successful because the preparationof 2-methyl pimelic acid was impossible. Labellimg of carbon-3 of toluene starting from succinic acid could not be carried out because the Grignard reaction of a-ketoglutaric acid as unsuccessful. The radioactive syntheses started from propanediol resp. from c-butyrolactone. (The labelling of carbon-3 of toluene was not possible in this case because the reduction of malonic acid to propanediol could not be carried out). The synthesis course was identical for all labellings. The synthesis differed only in the introduction of the activiy from potassium cyanide C-14. The starting compounds were reacted to propanedinitril, which was saponified to glutaric acid. The acid was reduced to pentanediol. From the diol, dibromopentane was produced. Reaction with potassium cyanide yielded, after saponification, pimelic acid. The acid was cyclizated to cyclohexanone, which was reduced to cyclohexanol. The OH group was replaced by bromine and subsequently by a methyl group. Dehydration yielded toluene. The following labellings were carried out: Toluene-2, -2.6, -1.2.6, -1.2 C-14. (G.G.)

  9. Profile of organic acid concentrations in the digestive gland and hemolymph of Biomphalaria glabrata under estivation

    Directory of Open Access Journals (Sweden)

    José Clecildo Barreto Bezerra

    1999-11-01

    Full Text Available Using high performance liquid chromatography (HPLC analysis it was possible to determine simultaneously the concentration of organic acids (pyruvate, lactate, succinate, fumarate, malate, acetate, propionate, acetoacetate, and ß-hydroxybutyrate in the digestive gland and the extracellular concentration of these same acids in the hemolymph of estivating Biomphalaria glabrata, the intermediate host of Schistosoma mansoni. After a 7 day period of estivation, there was a significant increase in the tissue levels of lactate, succinate, malate and acetate compared to non-estivating snails. After 14 days of estivation, the levels of lactate and acetate were also significantly elevated. The hemolymph concentrations of pyruvate and acetate increased significantly after 7 days and acetate concentrations continued to be significantly increased up to 14 days of estivation. The other organic acids studied, such as ketone body acetoacetate and ß-hydroxybutyrate or the volatile acid propionate, did not accumulate. Their tissue concentrations, however, increased on the 7th day of estivation and reached normal levels within two weeks of estivation for some of them. One should take into consideration how the reduction in metabolism can be handled under aerobic conditions, and what role anaerobic pathways may play in both energy formation and redox balance processes.

  10. Changes of NF-KB activity in colon carcinoma cells treated with different crude extracts of abrotani herba

    Institute of Scientific and Technical Information of China (English)

    Feng Pan; Yuying Chen; Li Yang; Zhiheng Bian; Houjie Liang

    2008-01-01

    Objective: To study changes of NF-KB activity in colon carcinoma cell lines treated with different crude extracts of abrotani herba obtained through solvent extraction methods.Methods: Crude extracts of abrotani herba were extracted with ligarine, chloroform, acetoacetate and n-butanol in separating funnel.Exposure concentration of crude extracts were obtained through detecting viability of HT-29 cells by MTT.Then HT-29 cells and Lovo cells were treated with different crude extracts respectively.Changes of NF-KB activity in HT-29 cells and Lovo cells using different crude extracts were observed by EMSA.Results: Successfully extracted different crude extracts of abrotani herba and called them ligarine extract, chloroform extract,acetoacetate extract, n-butanol extract and remaining extract for short.NF-KB activity was significantly inhibited in HT-29 cells treated with chloroform extract, there were no significant differences in other groups compared with the control.The same change of NF-KB activity was observed in Lovo calls using different crude extracts of abrotani herba.Conclusion: NF-KB activity can be inhibited in colon carcinoma HT-29 calls and Lovo cells treated with chloroform extract obtained from abrotani herba through the method of solvent extraction.

  11. Ketone bodies and islet function: 45Ca handling, insulin synthesis, and release

    International Nuclear Information System (INIS)

    D-(-)-beta-Hydroxybutyrate and acetoacetate cause a rapid, sustained, and rapidly reversible stimulation of insulin release from rat pancreatic islets incubated in the presence, but not absence, of D-glucose. This coincides with stimulation of both proinsulin biosynthesis and 45Ca net uptake. The ketone bodies also decrease 45Ca outflow from prelabeled islets perifused in the absence of Ca2+ and, in contrast, enhance effluent radioactivity in the presence of Ca2+. In the presence of D-glucose, the secretory response to D-(-)-beta-hydroxybutyrate is concentration related in the 2.5-20 mM range, abolished in the absence of Ca2+ or presence of KCN, and enhanced by theophylline and forskolin. It corresponds grossly to a shift to the left of the sigmoidal curve relating insulin output to the ambient concentration of D-glucose. The secretory, biosynthetic, and cationic response to acetoacetate is less marked than that evoked by an equimolar concentration of D-(-)-beta-hydroxybutyrate. These features are compatible with the view that the insulinotropic action of ketone bodies would be causally linked to their metabolism in islet cells

  12. Ketone bodies and islet function: sup 45 Ca handling, insulin synthesis, and release

    Energy Technology Data Exchange (ETDEWEB)

    Malaisse, W.J.; Lebrun, P.; Yaylali, B.; Camara, J.; Valverde, I.; Sener, A. (Brussels Free Univ. (Belgium))

    1990-07-01

    D-(-)-beta-Hydroxybutyrate and acetoacetate cause a rapid, sustained, and rapidly reversible stimulation of insulin release from rat pancreatic islets incubated in the presence, but not absence, of D-glucose. This coincides with stimulation of both proinsulin biosynthesis and {sup 45}Ca net uptake. The ketone bodies also decrease {sup 45}Ca outflow from prelabeled islets perifused in the absence of Ca{sup 2+} and, in contrast, enhance effluent radioactivity in the presence of Ca{sup 2+}. In the presence of D-glucose, the secretory response to D-(-)-beta-hydroxybutyrate is concentration related in the 2.5-20 mM range, abolished in the absence of Ca{sup 2+} or presence of KCN, and enhanced by theophylline and forskolin. It corresponds grossly to a shift to the left of the sigmoidal curve relating insulin output to the ambient concentration of D-glucose. The secretory, biosynthetic, and cationic response to acetoacetate is less marked than that evoked by an equimolar concentration of D-(-)-beta-hydroxybutyrate. These features are compatible with the view that the insulinotropic action of ketone bodies would be causally linked to their metabolism in islet cells.

  13. Lactate as a cerebral metabolic fuel for glucose-6-phosphatase deficient children.

    Science.gov (United States)

    Fernandes, J; Berger, R; Smit, G P

    1984-04-01

    The main substrates for brain energy metabolism were measured in blood samples taken from the carotid artery and the internal jugular bulb of four children with glycogen storage disease caused by deficiency of glucose-6-phosphatase. Multiple paired arterial and venous blood samples were analyzed for glucose, lactate, pyruvate, D-beta-hydroxybutyrate, acetoacetate, glycerol and O2, and the arteriovenous differences of the concentrations were calculated. In the first three patients the substrates were measured in two successive conditions with lower and higher glucose-intake, respectively, inducing reciprocally higher and lower concentrations of blood lactate. In the fourth patient medium chain triglycerides were administered simultaneously with the glucose-containing gastric drip feeding. Lactate appeared to be taken up significantly. It consumed, if completely oxidized, between 40-50% of the total O2 uptake in most cases. Only once in one patient the uptake of lactate switched to its release, when the blood lactate level decreased to normal. D-beta-hydroxybutyrate and acetoacetate arteriovenous (A-V) differences were small to negligible and these ketone bodies, therefore, did not contribute substantially to the brain's energy expenditure. Glycerol was not metabolized by the brain. Lactate thus appeared to be the second brain fuel next to glucose. It may protect the brain against fuel depletion in case of hypoglycemia.

  14. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis.

    Science.gov (United States)

    Zabek, Adam; Swierkot, Jerzy; Malak, Anna; Zawadzka, Iga; Deja, Stanisław; Bogunia-Kubik, Katarzyna; Mlynarz, Piotr

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC  APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis. PMID:26476882

  15. Effects of accumulated 60Co γ-ray irradiation on the small molecular metabolites in rats urine

    International Nuclear Information System (INIS)

    Objective: To explore the effects of accumulated 60Co γ-ray irradiation on small molecular metabolites in rats urine. Methods: Ten healthy male SD rats were irradiated by 60Co γ-rays in 5 days and the accumulated doses were 0, 0.2, 0.4, 0.6, 0.8, 1.0 Gy, respectively. The metabolites in urine of different groups were measured with 1H-NMR combined with principal components analysis (PCA) and partial least square discriminate analysis (PLS-DA). Results: The metabolites in rat urine were obviously changed after irradiation. Compared with control group, the amount of acetoacetate decreased after irradiation (t=29.7-30.7, P<0.05), but its relative level was stable when the dose increased (P>0.05). Meanwhile,the relative level of hippuric acid increased (t=4.4-21.6, P<0.05) especially when the accumulated dose was higher than 1 Gy (t=21.6, P<0.05). The relative level of proline, taurine and trimethylamine-N-oxide increased after irradiation with the same trend(t=3.5-13.4, 4.7-11.5, 2.9-12.7, P<0.05). Conclusions: The acetoacetate, hippuric acid, proline, taurine, and trimethylamine-N-oxide may be applicable for biomarkers of accumulative irradiation on rat. (authors)

  16. 三种金花茶叶的薄层色谱鉴别研究%Studies on Idetification of three varieties Camellia byThin-Layer Chromatography

    Institute of Scientific and Technical Information of China (English)

    梁霄; 莫建光; 刘布鸣; 黄艳; 高微; 黎凯群; 黎奕良

    2014-01-01

    Objective To establish a method for identification of Camellia by Thin-Layer Chromatography (TLC).Methods The specific compouds,oleanolic acid,rutin and ginsenosides Rg1 were studied by TLC in three different Camellia species.Results These three kinds of ingredients were all separated very well by the Ligroin-acetoacetate -acetone (7∶2∶1 ),Acetoacetate -methanol-aquaefer-formic acid (9∶2∶1∶0.1 ),Chloroform-acetoacetate-methanol-aquaefer (3∶8∶4.4∶1.6 ),and under the same condi-tions,the spots of oleanolic acid,rutin and ginsenosides Rg1 were significantly in different three varieties of Camellia.Conclusion This method was simple ,quick,and can better control the quality of the Camellia.%目的:建立金花茶叶的薄层色谱鉴别方法。方法:采用薄层色谱法分别鉴别金花茶叶中的齐墩果酸、芦丁和人参皂苷Rg1等化学成分。结果:齐墩果酸、芦丁和人参皂苷Rg1分别在以石油醚-乙酸乙酯-丙酮(7∶2∶1)、乙酸乙酯-甲醇-水-甲酸(9∶2∶1∶0.1)和氯仿-乙酸乙酯-甲醇-水(3∶8∶4.4∶1.6)为展开剂的条件下获得理想分离,且在同一点样量和展开条件下,三个金花茶品种中的齐墩果酸、芦丁、人参皂苷Rg1斑点均有明显差异。结论:该方法简便、快速,可更好地控制金花茶叶的药材质量。

  17. Synthesis, spectral, catalytic and antimicrobial studies of PPh 3/AsPh 3 complexes of Ru(II) with dibasic tridentate O, N, S donor ligands

    Science.gov (United States)

    Balasubramanian, K. P.; Karvembu, R.; Prabhakaran, R.; Chinnusamy, V.; Natarajan, K.

    2007-09-01

    Complexes of the type [Ru(CO)(EPh 3)(B)(L)] (E = P or As; B = PPh 3, AsPh 3, py or pip; L = dianion of the Schiff bases derived from thiosemicarbazone with acetoacetanilide, acetoacet- o-toluidide and o-chloro acetoacetanilide) have been synthesized from the reactions of equimolar amounts of [RuHCl(CO)(EPh 3) 2(B)] and Schiff bases in benzene. The new complexes have been characterized by analytical and spectral (IR, electronic, NMR) data. The arrangement of PPh 3 groups around ruthenium metal was determined from 31P NMR spectra. An octahedral structure has been assigned for all the new complexes. All the complexes exhibited catalytic activity for the oxidation of benzyl alcohol and cyclohexanol in presence of N-methylmorpholine- N-oxide as co-oxidant. The complexes also exhibited antibacterial activity against E. coli, Aeromonas hydrophilla and Salmonella typhi. The activity was compared with standard streptomycin.

  18. SYNTHESIS, CROSSLINKING MECHANISM AND PROPERTIES OF A POLYACRYLATE/POLYURETHANE COMPOSITE COATING

    Institute of Scientific and Technical Information of China (English)

    TANG Liming; GUO Wei; ZHOU Qixiang

    1997-01-01

    A polyacrylate/polyurethane (P(A)/P(U)) composite coating has been prepared by crosslinking an acetoacetylated polyacrylate with a vinylic group terminated polyurethane at room temperature. A model Michael reaction between ethyl acetoacetate (EAA) and methyl acrylate (MA) was designed to study the crosslinking mechanism. It was found that the two active hydrogen atoms in acetoacetyl group can both add to vinylic groups and the yield of mono- and bis-adducts are much affected by the molar ratio of acetoacetyl to vinylic groups. Higher crosslinking degree and better properties could be obtained with decreasing the molar ratio of the two active groups from 1/1 to 0.6/1 in the composite coatings.

  19. Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel

    Directory of Open Access Journals (Sweden)

    Rodrigo González-Olvera

    2016-02-01

    Full Text Available An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which the aldehyde-1,2,3-triazoles reacted with ethyl acetoacetate and urea in the presence of Ce(OTf3 as the catalyst. The corrosion inhibition of steel grade API 5 L X52 in 1 M HCl by the synthesized compounds was investigated using the electrochemical impedance spectroscopy technique. The measurements revealed that these heterocycles are promising candidates to inhibit acidic corrosion of steel.

  20. "Synthesis and smooth muscle Calcium channel antagonist effects of new derivatives of 1,4-Dihydropyridine containing Nitroimidazol substituent "

    Directory of Open Access Journals (Sweden)

    Miri R

    2002-09-01

    Full Text Available A group of racemic 3-[(2-hydroxyethyl, (2-Methoxyethyl, (2-acetylethyl or (2-cyanoethyl], 5- methyl, ethyl or isopropyl-1, 4-dihydro-2, 6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl-3, 5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2-carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkys 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle (GPILSM which was induced by carbacol (1.67 χ 10^-7 M. All compounds exhibited calcium channel antagonist activity (IC50=10^-12 to 10^-13 M range comparable to nifedipine as reference drug (IC50=1.07±0.12x 10^-11 M.

  1. Schiff bases of N-(2-aminoethyl)-3-aminopropyltrimethoxysilane and its silatranes: Synthesis and characterization

    Indian Academy of Sciences (India)

    Gurjaspreet Singh; Amandeep Saroa; Sadhika Khullar; Sanjay K Mandal

    2015-04-01

    This paper aims at the introduction of azomethine group by the condensation reaction of N-(2-aminoethyl)-3-aminopropyltrimethoxysilane with different compounds containing carbonyl group such as 2’-hydroxyacetophenone, salicylaldehyde, pyrrole-2-carboxaldehyde, acetylacetone and ethyl acetoacetate. Further, transesterification reaction of these Schiff base modified silanes with triethanolamine as a tripodal ligand leads to the synthesis of corresponding silatranes 1–5 bearing Schiff base functionalized long chain in the axial position. All the synthesized compounds are characterized by spectroscopic methods, elemental analysis and mass spectrometry. The authentication of Schiff base modified silatranes is scrutinized by single X-ray crystal structure of silatrane 1. The thermal stability of the five silatranes is studied by thermo-gravimetric analysis (TGA).

  2. Study on Screening Valid Target of Anti -inflammatory and Analgesic Effets of Calystegia Soldanella%孝扇草抗炎镇痛有效部位的筛选研究

    Institute of Scientific and Technical Information of China (English)

    谭丽; 沈清; 黄真

    2012-01-01

    Objective: To separate and screen the valid target of anti - inflammatory and analgesic effects of Calystegia soldanella . Methods: Systematic solvent method is used to separate the ethanol extract of Calystegia soldanella ,ear edema induced by dimethylbenzene in mice was used to screen the valid target of the anti - inflammatory effects,mice hot -plate procedures and mice wthithing induced by acetic acid were used to screen the valid target of the analgesic effects. Results :The inhibition ratio of swelling induced by dimethylbenzene in mice of the ethanol - extracted acetoacetate - abstraction group of Calystegia soldanella is 50.53% (P < 0.05). The acetoacetate - abstraction group and the rest group could significantly prolong the mouse hot - plate - induced pain of the pain threshold of the mice( P <0.05 ,P <0.05). The ethanol - extracted acetoacetate - abstraction group and the n - buOH - abstraction group can significantly decrease ? acetic acid -induced writhing response in mice(P < 0.05, P < 0.05). Conclusion-.The ethanol -extracted acetoacetate -abstraction group of Calystegia soldanella is most propably the valid target of anti - inflammatory and analgesic.%目的:分离并筛选孝扇草抗炎镇痛作用的有效部位.方法:采用系统溶剂法对孝扇草醇提物进行初步分离;采用二甲苯致小鼠耳廓肿胀实验,筛选孝扇草抗炎作用有效部位;采用热板法和醋酸致小鼠扭体法实验,筛选其镇痛作用有效部位.结果:孝扇草醇提乙酸乙酯萃取部位对二甲苯致小鼠耳廓肿胀的抑制率为50.53%,与空白对照组比较有显著性差异(P<0.05);孝扇草醇提乙酸乙酯萃取部位和各溶剂萃取剩余部位均能显著提高小鼠痛阈值,与空白对照组比较有显著性差异(P <0.05,P<0.05);孝扇草醇提乙酸乙酯和正丁醇萃取部位均能明显减少醋酸致小鼠扭体反应次数,与空白组比较有显著性差异(P<0.05,P<0.05).结论:孝扇草醇提

  3. Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

    Directory of Open Access Journals (Sweden)

    Sudipta Pathak

    2013-11-01

    Full Text Available A convenient and efficient methodology for the synthesis of densely substituted pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused isocoumarins were formed in good yields. This synthetic method has several advantages such as the employment of solvent-free reaction conditions without the use of any toxic reagents and metal catalysts, the ease of product isolation, the use of a recyclable catalyst, the low cost, the easy availability of the starting materials, and the excellent yields of products.

  4. Evaluation of the Accuracy of Capillary Hydroxybutyrate Measurement Compared with Other Measurements in the Diagnosis of Diabetic Ketoacidosis: A Systematic Review.

    Science.gov (United States)

    Brooke, Joanne; Stiell, Marlon; Ojo, Omorogieva

    2016-08-23

    A complication of diabetes is diabetic ketoacidosis (DKA), which if left untreated is a life threatening condition. Prompt and accurate diagnosis of DKA is required for the commencement of life saving interventions. Measurements of ketone bodies in DKA have usually been through nitroprusside urine acetoacetate testing. The aim of this systematic review was to examine whether capillary β-hydroxybutyrate (β-OHB) testing is more accurate compared to other diagnostic methods of DKA. The following electronic databases were searched: EBSCO Host, MEDLINE, PSYCHInfo, CINAHL and Science Direct for publications from 1 January 2005 and up to and including 1 January 2016. Inclusion criteria were: Adults 18 years and over and known type 1 or type 2 diabetes. Retrospective and prospective observation studies were included. A total of nine studies met the inclusion criteria. Capillary β-OHB was found to have high sensitivity, specificity, positive predictive value and negative predictive value in identifying DKA compared to urinary ketone testing.

  5. Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

    Science.gov (United States)

    Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao

    2016-01-01

    This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697

  6. Silica-bonded N-propylpiperazine sodium n-propionate as recyclable catalyst for synthesis of 4H-pyran derivatives

    Institute of Scientific and Technical Information of China (English)

    Khodabakhsh Niknam; Nassim Borazjani; Reza Rashidian; Abbas Jamali

    2013-01-01

    Silica-bonded N-propylpiperazine sodium n-propionate (SBPPSP) was found to act as an efficient solid base for the preparation of a series of 4H-benzo[b]pyran derivatives. SBPPSP was used as a recyclable heterogeneous solid base catalyst for the synthesis of 3,4-dihydropyrano[c]chromenes, 2-amino-4H-pyrans, 1,4-dihydropyrano[2,3-c]pyrazoles, and 2-amino-4H-benzo[e]-chromenes via the condensation reaction of dimedone, ethyl acetoacetate, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, andα-naphthol, respectively, with aromatic aldehydes and malononitrile in refluxing aqueous ethanol. The heterogeneous solid base showed similar efficiency when reused in consecutive reac-tions.

  7. Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel.

    Science.gov (United States)

    González-Olvera, Rodrigo; Román-Rodríguez, Viridiana; Negrón-Silva, Guillermo E; Espinoza-Vázquez, Araceli; Rodríguez-Gómez, Francisco Javier; Santillan, Rosa

    2016-02-22

    An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which the aldehyde-1,2,3-triazoles reacted with ethyl acetoacetate and urea in the presence of Ce(OTf)₃ as the catalyst. The corrosion inhibition of steel grade API 5 L X52 in 1 M HCl by the synthesized compounds was investigated using the electrochemical impedance spectroscopy technique. The measurements revealed that these heterocycles are promising candidates to inhibit acidic corrosion of steel.

  8. Synthesis of Some Pyrazolone Derivatives and Evaluation of its Antibacterial and Cytotoxic Activity

    Directory of Open Access Journals (Sweden)

    Rishiram Prajuli

    2015-12-01

    Full Text Available A series of novel pyrazolone derivative were synthesized by two different schemes (scheme-1 by the reaction of phenyl hydrazine and ethyl acetoacetate with substituted benzaldehydes PYR-1 to PYR-4 and (by the reaction of synthesized chalcone with phenyl hydrazine PYR-5 and characterised with its physical parameters (M.P, colour, %yield, solubility etc.. The entire synthesized compound was tested for their antimicrobial activity against Gram-positive and Gram-negative strains of bacteria and brimeshrimp bioassay was conducted for evaluation of cytotoxic activity The Investigation of antimicrobial screening data revealed that most of the tested compounds showed moderate to good antimicrobial activity. And cytotoxicity activity of compounds was also found to be satisfactory.

  9. Ultrasound Irradiation Effects on the Michael Reaction Catalyzed by KF/basic Al2O3%超声波辐射下KF/basic Al2O3催化的Michael加成

    Institute of Scientific and Technical Information of China (English)

    李记太; 陈国锋; 李同双

    2002-01-01

    超声辐射下,对查尔酮与含活泼亚甲基的化合物诸如丙二酸二乙酯、硝基甲烷、乙酰乙酸乙酯、环己酮等,在KF/basic Al2O3催化下的Michael 反应进行了研究,该法具有反应时间短、产率高、操作简单、催化剂可以重复使用的优点.%The Michael reaction of chalcones as acceptors with several active methylene compounds such as diethyl malonate, nitromethane,ethyl acetoacetate and cyclohexone et al as donors catalyzed by KF/basic Al2O3 under ultrasound irradiation proceed very efficiently and furnish higher yield of adducts.

  10. Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, β-amyloid toxicity, and astrocyte function

    DEFF Research Database (Denmark)

    Hertz, Leif; Chen, Ye; Waagepetersen, Helle S

    2015-01-01

    Diet supplementation with ketone bodies (acetoacetate and β-hydroxybuturate) or medium-length fatty acids generating ketone bodies has consistently been found to cause modest improvement of mental function in Alzheimer's patients. It was suggested that the therapeutic effect might be more...... pronounced if treatment was begun at a pre-clinical stage of the disease instead of well after its manifestation. The pre-clinical stage is characterized by decade-long glucose hypometabolism in brain, but ketone body metabolism is intact even initially after disease manifestation. One reason...... for the impaired glucose metabolism may be early destruction of the noradrenergic brain stem nucleus, locus coeruleus, which stimulates glucose metabolism, at least in astrocytes. These glial cells are essential in Alzheimer pathogenesis. The β-amyloid peptide Aβ interferes with their cholinergic innervation...

  11. Nano Fe{sub 2}O{sub 3,} clinoptilolite and H{sub 3}PW{sub 12}O{sub 40} as efficient catalysts for solvent-free synthesis of 5(4H)-isoxazolone under microwave irradiation conditions

    Energy Technology Data Exchange (ETDEWEB)

    Fozooni, Samieh, E-mail: samieh.fozooni@uk.ac.ir, E-mail: s_fozooni@yahoo.com [Shahid Bahonar University, Kerman (Iran, Islamic Republic of). Mining Engineering Department. Zarand High Education Center; Hosseinzadeh, Nasrin Gholam; Akhgar, Mohammad Reza [Islamic Azad University, Kerman (Iran, Islamic Republic of). Department of Chemistry; Hamidian, Hooshang [Payame Noor University (PNU), Tehran (Iran, Islamic Republic of). Department of Chemistry

    2013-10-15

    A quick and solvent-free approach involving the exposure of neat reactants to microwave irradiation in conjunction with the use of clinoptilolite, H{sub 3}PW{sub 12}O{sub 40} and Fe{sub 2}O{sub 3} nanoparticle catalysts is described. In this work, condensation of hydroxylamine hydrochloride, sodium acetate, acetoacetic or benzoyl acetic ethyl ester and appropriate aldehydes by employing catalysts gave 5(4H)-isoxazolone only in one step. Catalyst amount, temperature effects and catalysts reusability were monitored. Among the catalysts, Fe{sub 2}O{sub 3} nanoparticles had better performance than other catalysts from viewpoint of yield and reaction time. The present protocol offers several advantages, such as short reaction time, reasonable yield, mild reaction condition and recycling catalysts with a very easy workup. (author)

  12. Evaluation of the Accuracy of Capillary Hydroxybutyrate Measurement Compared with Other Measurements in the Diagnosis of Diabetic Ketoacidosis: A Systematic Review.

    Science.gov (United States)

    Brooke, Joanne; Stiell, Marlon; Ojo, Omorogieva

    2016-01-01

    A complication of diabetes is diabetic ketoacidosis (DKA), which if left untreated is a life threatening condition. Prompt and accurate diagnosis of DKA is required for the commencement of life saving interventions. Measurements of ketone bodies in DKA have usually been through nitroprusside urine acetoacetate testing. The aim of this systematic review was to examine whether capillary β-hydroxybutyrate (β-OHB) testing is more accurate compared to other diagnostic methods of DKA. The following electronic databases were searched: EBSCO Host, MEDLINE, PSYCHInfo, CINAHL and Science Direct for publications from 1 January 2005 and up to and including 1 January 2016. Inclusion criteria were: Adults 18 years and over and known type 1 or type 2 diabetes. Retrospective and prospective observation studies were included. A total of nine studies met the inclusion criteria. Capillary β-OHB was found to have high sensitivity, specificity, positive predictive value and negative predictive value in identifying DKA compared to urinary ketone testing. PMID:27563914

  13. Microwave Assisted Convenient One-Pot Synthesis of Coumarin Derivatives via Pechmann Condensation Catalyzed by FeF3 under Solvent-Free Conditions and Antimicrobial Activities of the Products

    Directory of Open Access Journals (Sweden)

    Vahid Vahabi

    2014-08-01

    Full Text Available A rapid and efficient solvent-free one-pot synthesis of coumarin derivatives by Pechmann condensation reactions of phenols with ethyl acetoacetate using FeF3 as a catalyst under microwave irradiation is described. This one-pot synthesis on a solid inorganic support provides the products in good yields. The newly synthesized compounds were systematically characterized by IR, 1H-NMR, 13C-NMR, MS and elemental CHN analyses. The proposed solvent-free microwave irradiation method using the environmentally friendly catalyst FeF3 offers the unique advantages of high yields, shorter reaction times, easy and quick isolation of the products, excellent chemoselectivity, and a one-pot, green synthesis. The products were screened for antimicrobial activity, and the results showed that the compounds reacted against all the tested bacteria.

  14. Synthesis of functionalized pyrazolopyran derivatives: comparison of two-step vs. one-step vs. microwave-assisted protocol and X-ray crystallographic analysis of 6-amino-1,4-dihydro-3-methyl-4-phenylpyrano[2,3-c]pyrazole-5-carbonitrile

    Indian Academy of Sciences (India)

    Paritosh Shukla; Ashok Sharma; Sumati Anthal; Rajni Kant

    2015-09-01

    A library of pyrazolopyran heterocycles was synthesized first by the traditional heating techniques using two-step and one-step procedures and then by microwave-assisted (MWA) multicomponent condensation of ethyl acetoacetate, hydrazine, malonodinitrile and a variety of substituted aldehydes. A comparison of the foregoing methods was first done based on the yields and then based on the time taken for the completion of the reactions. It was found that although the traditional methods gave slightly better yields, the MWA syntheses lead to substantial reduction in reaction timings. The title compound crystallizes in the triclinic crystal system with space group P–1. The crystal structure as elucidated by X-ray diffraction methods shows the presence of different intermolecular interactions, and the nature and energetics associated with these interactions have been characterized using PIXEL software.

  15. Synthesis of Some Novel Biologically Active Disperse Dyes Derived from 4-Methyl-2,6-dioxo-1-propyl-1,2,5,6-tetrahydro-pyridine-3-carbonitrile as Coupling Component and Their Colour Assessment on Polyester Fabrics

    Directory of Open Access Journals (Sweden)

    Mohamed H. Elnagdi

    2012-07-01

    Full Text Available A series of novel azo-disperse dyes containing alkylhydrazonopyridinone structures were synthesized. 4-Methyl-2,6-dioxo-1-propyl-1,2,5,6-tetrahydropyridine-3-carbonitrile (8 is synthesized by one-pot synthesis using ethyl cyanoacetate, propylamine, and ethyl acetoacetate. Compound 8 is then coupled with aromatic and heteroaromatic diazonium salts to afford the corresponding aryl- and heteroaryl-4-methyl-2,6-dioxo-1-propyl-1,2,5,6-tetrahydropyridine-3-carbonitriles 12a,b and 13a–c. Structural assignments to the dyes were made using NMR spectroscopic methods. A high temperature dyeing method was employed to apply these dyes to polyester fabrics. Most of the dyed fabrics tested displayed very good light fastness levels and good wash fastness. Finally, the biological activity of the prepared dyes against Gram positive bacteria and Gram negative bacteria were evaluated.

  16. Isolation and characterization of a new gram-negative, acetone-degrading, nitrate-reducing bacterium from soil, Paracoccus solventivorans sp. nov.

    Science.gov (United States)

    Siller, H; Rainey, F A; Stackebrandt, E; Winter, J

    1996-10-01

    An acetone-degrading, nitrate-reducing, coccoid to rod-shaped bacterium, strain L1, was isolated from soil on the site of a natural gas company. Cells of the logarithmic growth phase reacted gram positive, while those of the stationary growth phase were gram negative. Single organisms were 0.4 to 0.5 by 0.9 to 1.5 microns in size, nonmotile, and non-spore forming and had poly-beta-hydroxybutyrate inclusions. The doubling time of strain L1 on acetone-CO2-nitrate at the optimal pH of 7 to 8 and the optimal temperature of 30 to 37 degrees C was 12 h. More than 0.2% NaCl or 10 mM thiosulfate inhibited growth. For oxygen or nitrate respiration, acetone and a few organic chemicals were utilized as carbon sources whereas many others could not be used (for details, see Results). Bicarbonate (or CO2) was essential for growth on acetone but not for growth on acetoacetate. The growth yields for acetone-CO2 and acetoacetate were 28.3 and 27.3 g/mol, respectively. With acetone as the carbon source, poly-beta-hydroxybutyrate accounted for up to 40% of the cellular dry weight. The DNA of strain L1 had a G + C content of 68.5 mol% (as determined by high-performance liquid chromatography of nucleotides) or 70 mol% (as determined by the TM method). The sequence of the gene coding for the 16S rRNA led to the classification of strain L1 in the paracoccus group of the alpha subclass of the Proteobacteria. The new isolate is named Paracoccus solventivorans sp. nov. DSM 6637. PMID:8863446

  17. Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.

    Science.gov (United States)

    Tani, Naoto; Michiue, Tomomi; Chen, Jian-Hua; Oritani, Shigeki; Ishikawa, Takaki

    2016-09-01

    A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings. PMID:27591535

  18. Ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease

    Science.gov (United States)

    Youm, Yun-Hee; Nguyen, Kim Y.; Grant, Ryan W.; Goldberg, Emily L.; Bodogai, Monica; Kim, Dongin; D'Agostino, Dominic; Planavsky, Noah; Lupfer, Christopher; Kanneganti, Thirumala D.; Kang, Seokwon; Horvath, Tamas L.; Fahmy, Tarek M.; Crawford, Peter A.; Biragyn, Arya; Alnemri, Emad; Dixit, Vishwa Deep

    2015-01-01

    Ketone bodies , β-hydroxybutyrate (BHB) and acetoacetate support mammalian survival during states of energy deficit by serving as alternative source of ATP1. BHB levels are elevated during starvation, high-intensity exercise or by the low carbohydrate ketogenic diet2. Prolonged caloric restriction or fasting reduces inflammation as immune system adapts to low glucose supply and energy metabolism switches towards mitochondrial fatty acid oxidation, ketogenesis and ketolysis2-6. However, role of ketones bodies in regulation of innate immune response is unknown. We report that BHB, but neither acetoacetate nor structurally-related short chain fatty acids, butyrate and acetate, suppresses activation of the NLRP3 inflammasome in response to several structurally unrelated NLRP3 activators, without impacting NLRC4, AIM2 or non-canonical caspase-11 inflammasome activation. Mechanistically, BHB inhibits NLRP3 inflammasome by preventing K+ efflux and reducing ASC oligomerization and speck formation. The inhibitory effects of BHB on NLRP3 were not dependent on chirality or classical starvation regulated mechanisms like AMPK, reactive oxygen species (ROS), autophagy or glycolytic inhibition. BHB blocked NLRP3 inflammasome without undergoing oxidation in TCA cycle, independently of uncoupling protein-2 (UCP2), Sirt2, receptor Gpr109a and inhibition of NLRP3 did not correlate with magnitude of histone acetylation in macrophages. BHB reduced the NLRP3 inflammasome mediated IL-1β and IL-18 production in human monocytes. In vivo, BHB attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases like Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory syndrome (FCAS) and urate crystal induce body cavity inflammation. Taken together, these findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be mechanistically linked to BHB-mediated inhibition of the NLRP3 inflammasome, and point to the potential

  19. Stereochemical features of unsaturated aminodiesters - intermediates in the synthesis of Richlocaine

    Directory of Open Access Journals (Sweden)

    Meyrambek Ospanov

    2014-10-01

    Full Text Available The article provides information on the methods for synthesis of unsaturated aminodiesters, which are the key intermediates in the synthesis of N-substituted 2,5-dimethyl-piperidin-4-ones, including 1,2,5-trimetilpieridin-3-one. The developed method includes reaction of methyl ester of methacrylic acid with alkyl (alkenyl amines. The obtained N-alkyl(alkenyl-(2-methyl-2- carbmetoxyethyl methylamine are attached to acetoacetic ester being in the enol form. The optimal conditions for synthesis of N-alkyl(alkenyl-(2-methyl-2-carbethoxyethenemethylamines have been established. Results of gas chromatographic analysis has showed that, at room temperature, the reaction in polar solvents is delayed for two days. In non-polar solvents, the reaction runs with simultaneous distillation of water as an azeotrope with the solvent. Increase of the radical size at N atom has little effect on the reaction rate. Introduction of allyl radical at the nitrogen atom, apparently due to steric hindrance, resulted in lower reactivity of the monoester with allyl radical by condensation with acetoacetic ester. The structure of (1-methyl-2-carbethoxyethene-(2-methyl-2-carbmethoxyethyl methylamine has been studied by PMR spectroscopy. Study of the effect of chirality on the NMR spectra showed that, if the molecule of the organic compound has an asymmetric carbon atom, it may lead to the disappearance of the magnetic equivalence of neighboring protons or group of protons. Presence of an asymmetric carbon atom in b-position to the amino group of enamine leads to the disappearance of the magnetic equivalence of the neighboring protons is observed in the form of two quartets. For enaminodiesters, equilibrium is shifted toward the trans-S-cis conformer where less steric hindrance is pronounced.

  20. Structural Insights into an Oxalate-producing Serine Hydrolase with an Unusual Oxyanion Hole and Additional Lyase Activity.

    Science.gov (United States)

    Oh, Juntaek; Hwang, Ingyu; Rhee, Sangkee

    2016-07-15

    In Burkholderia species, the production of oxalate, an acidic molecule, is a key event for bacterial growth in the stationary phase. Oxalate plays a central role in maintaining environmental pH, which counteracts inevitable population-collapsing alkaline toxicity in amino acid-based culture medium. In the phytopathogen Burkholderia glumae, two enzymes are responsible for oxalate production. First, the enzyme oxalate biosynthetic component A (ObcA) catalyzes the formation of a tetrahedral C6-CoA adduct from the substrates acetyl-CoA and oxaloacetate. Then the ObcB enzyme liberates three products from the C6-CoA adduct: oxalate, acetoacetate, and CoA. Interestingly, these two stepwise reactions are catalyzed by a single bifunctional enzyme, Obc1, from Burkholderia thailandensis and Burkholderia pseudomallei Obc1 has an ObcA-like N-terminal domain and shows ObcB activity in its C-terminal domain despite no sequence homology with ObcB. We report the crystal structure of Obc1 in its apo and glycerol-bound form at 2.5 Å and 2.8 Å resolution, respectively. The Obc1 N-terminal domain is essentially identical both in structure and function to that of ObcA. Its C-terminal domain has an α/β hydrolase fold that has a catalytic triad for oxalate production and a novel oxyanion hole distinct from the canonical HGGG motif in other α/β hydrolases. Functional analyses through mutagenesis studies suggested that His-934 is an additional catalytic acid/base for its lyase activity and liberates two additional products, acetoacetate and CoA. These results provide structural and functional insights into bacterial oxalogenesis and an example of divergent evolution of the α/β hydrolase fold, which has both hydrolase and lyase activity. PMID:27226606

  1. Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice

    Energy Technology Data Exchange (ETDEWEB)

    Fromenty, B.; Fisch, C.; Labbe, G.; Degott, C.; Deschamps, D.; Berson, A.; Letteron, P.; Pessayre, D. (Institut National de la Sante et de la Recherche Medicale U24, Clichy (France))

    1990-12-01

    Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from (U-14C)palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of (14C)CO2 from (U-14C)palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of (U-14C)palmitic acid. One hour after 100 mg.kg-1, the exhalation of (14C)CO2 from (1-14C)palmitic acid, (1-14C)octanoic acid or (1-14C)butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of (14C)CO2 from (1-14C)palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice.

  2. Blister Test for Measurements of Adhesion and Adhesion Degradation of Organic Polymers on AA2024-T3

    Science.gov (United States)

    Rincon Troconis, Brendy Carolina

    cleaning/desmutting and conversion coating (CC) on the adhesion strength of acetoacetate to AA2024-T3 and the effects of improper water rinse temperature after cleaner were assessed using the BT. The results showed that pretreatments improve the adhesion strength of acetoacetate primer on AA2024-T3, but the comparative behavior depends on the specific treatment. Process control is of paramount importance for the performance of acetoacetate coated systems applied on AA2024-T3. The lack of thermal activity in the water rinse after cleaning step produces deleterious effects on the adhesion and blistering resistance of CC. Finally, a test sample incorporating a coated and scribed Al alloy panel and uncoated through-hole fasteners (Ti, SS316, AA2024-T3) was designed to provide accelerated response during atmospheric corrosion testing in the field (long-term beach exposure) or in laboratory chambers (ASTM B117). The results after only three weeks of exposure to ASTM B117 correlated well with long-term beach exposure, allowing rapid ranking of different coating systems. Of the fastener materials studied, visual observation and volume lost determination indicated that the worst attack occurred near SS316 fasteners its effect was explained by Scanning Kelvin Probe measurements and the available cathodic current measured in chloride solution.

  3. [The different notions about beta-oxidation of fatty acids in peroxisomes, peroxisomes and ketonic bodies. The diabetic, acidotic coma as an acute deficiency of acetyl-CoA and ATP].

    Science.gov (United States)

    Kotkina, T I; Titov, V N; Parkhimovich, R M

    2014-03-01

    The mechanisms of beta-oxidation of fatty acids developed more than a century before have no compliance with actual physical chemical data. The oxidation of long-chain C 16:0 palmitic saturated fatty acid occurs not by sequential formation of eight molecules of acetyl-KoA but by force of formation of double bond and its hydrolysis on two short-chain C 8:0 fatty acids. Only short-chain fatty acids can become shorter under "chipping" of C 2-acetate with formation of C 4-butyric acid (butyrate) and its metabolites (beta-hidroxibutirate, acetoacetate, acetone). The critical moment of oxidation is a hydrolysis of acetoacetyl-KoA on two molecules of acetyl-KoA. The molecule of ATP is to be expended on hydrolysis. The foundation of nonspecific biological reaction of stress--ketoacidosis,--is a decrease in mitochondrions of acetyl-KoA pool formed both from glycogen and glucose and fatty acids. The oxalate acetate inputs into Krebs cycle inadequate amount of acetyl-KoA which limits synthesis of ATP. The insulin has no direct involvement into development of ketoacidosis but prepares conditions to facilitate nonspecific etiological factor to initiate diabetic ketoacidosis. These are the pooling of small amount of glycogen in cytozol and the predominance in cytozol of cells and adipocytes of palmitic triglycerides which are slowly hydrolyzed by hormone-dependent lipase to release non-esterified fatty acids into intercellular medium. The increase of their concentration in blood plasma precedes ketoacidosis which is developing in patients without diabetes mellitus too. When cells begin to oxidize unsaturated linoleic and linolenic acids with large number of double binds instead of medium-chain fatty acids, oleinic and palmitic fatty acids to support beta-oxidation in mitochondrions and synthesis of ATP the amount of butyric acid, beta-hidroxibutiryl-KoA and acetoacetyl-KoA increases and of acetyl-KoA decreases. The cause of fatal outcome is the development of metabolic acidosis

  4. Study on sedative, hypnotic and effects of pine needle on neurotransmitter%松针不同提取物镇静催眠作用及对脑神经递质的影响

    Institute of Scientific and Technical Information of China (English)

    赵桂芝; 寿旦; 俞忠明; 李洪玉

    2011-01-01

    目的:研究比较松针不同提取物的镇静、催眠及对脑神经递质的作用.方法:通过直接诱导小鼠睡眠,观察比较松针不同提取物对戊巴比妥钠阈上、阈下剂量致小鼠睡眠的协同作用;采用HPLC法测定给药后小鼠脑海马中γ-氨基丁酸和谷氨酸的含量.结果:松针正丁醇提取物和乙酸乙酯提取物能明显延长阈上剂量戊巴比妥钠致小鼠睡眠时间(P<0.01),增加阈下剂量戊巴比妥钠致小鼠睡眠只数(P<0.01);有效提取物可增加海马中γ-氨基丁酸含量(P<0.05).结论:松针正丁醇提取物和乙酸乙酯提取物均具有明显的镇静催眠作用.%Objective: To study the sedative and hypnotic effects of the different extracts of pine needle and the effect on neurotransmitter. Methods: Sedative and hypnotic experiments were made to observe the effects of different extracts of pine needle on spontaneous motion and hypnosis in mice. Determining the levels of aminobutyric acid and glutamic acid in administered mice of hippocamp by HPLC. Results: The n-butanol extract of pine needle and its acetoacetate extract could enhance the sleeping number of pentobarbital sodium (subthleshold dosage) and prolong the sleeping time of sodium pentobarbital (superthleshold dosage, P<0.01); Effective extract can affect neurotransmitter in hippocampal slices (P<0.05). Conclusion: The n-butanol extract of pine needle and its acetoacetate extract had sedative and hypnotic effect.

  5. The stability of free radicals in densely crosslinked acrylate polymer networks

    International Nuclear Information System (INIS)

    Four types of crosslinked polymeric systems based on pentaerythritetatraacrylate (PETA) and propylene glycol - 424 -diacetonate (PGDSAA) were studied from the standpoints of free radical decay and the network density. The networks samples were prepared by two step synthesis. At first the Michael dark reaction results for multifunctional acrylates and acetoacetates in polymer network. The crosslinking continued in the second step of network formation by a photo-polymerization of the residual vinyl monomer, and pendant double bonds build up in the primary network in the first step of the synthesis. The free radical accumulation to the steady state during the irradiation, and their decay in the dark periods were studied directly in ESR spectrometer at 25 grad C. The kinetic of the radicals decay after switch of the light was used to calculate the rate constants for bimolecular termination reaction kt. These values show on the existence of long lived free radicals in the investigated polymeric networks. The stability of radicals is approximately of two decimal orders higher in networks irradiated in nitrogen compared to irradiation in air. A loss of the hyperfine structure of the spectra during repeated irradiation cycles is explained by increasing spin-spin dipolar interactions when radicals are trapped in more rigid regions of the polymer matrix. (authors)

  6. 3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.P.; Robert, M.F.; Mitchell, G.A. [Hopital Sainte-Justine, Quebec (Canada)] [and others

    1996-04-01

    3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither a TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.

  7. Regulated release of Ca2+ from respiring mitochondria by Ca2+/2H+ antiport.

    Science.gov (United States)

    Fiskum, G; Lehninger, A L

    1979-07-25

    Simultaneous measurements of oxygen consumption and transmembrane transport of Ca2+, H+, and phosphate show that the efflux of Ca2+ from respiring tightly coupled rat liver mitochondria takes place by an electroneutral Ca2+/2H+ antiport process that is ruthenium red-insensitive and that is regulated by the oxidation-reduction state of the mitochondrial pyridine nucleotides. When mitochondrial pyridine nucleotides are kept in a reduced steady state, the efflux of Ca2+ is inhibited; when they are in an oxidized state, Ca2+ efflux is activated. These processes were demonstrated by allowing phosphate-depleted mitochondria respiring on succinate in the presence of rotenone to take up Ca2+ from the medium. Upon subsequent addition of ruthenium red to block Ca2+ transport via the electrophoretic influx pathway, and acetoacetate, to bring mitochondrial pyridine nucleotides into the oxidized state, Ca2+ efflux and H+ influx ensued. The observed H+ influx/Ca2+ efflux ratio was close to the value 2.0 predicted for the operation of an electrically neutral Ca2+/2H+ antiport process.

  8. 3-Amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno [2,3-d ]pyrimidine: An Effecient Key Precursor for Novel Synthesis of Some Interesting Triazines and Triazepines as Potential Anti-Tumor Agents

    Directory of Open Access Journals (Sweden)

    Sobhi M. Gomha

    2012-09-01

    Full Text Available A number of interesting heterocycles were prepared through interaction of the intermediate 3-amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno-[2,3-d]pyrimidine (1 and reagents such as hydrazonyl halides 2 to furnish triazine derivatives 4a–l. Reaction of 1 with phenacyl bromide afforded compound 5. Moreover, the title compound 1 was subjected to condensation with active methylene compounds (ethyl acetoacetate and ethyl benzoylacetate to give triazipinones 8a,b. The condensation with aromatic aldehydes afforded either the triazole derivatives 10a–d or Schiff base 11. In addition, the behaviour of compound 1 towards activated unsaturated compounds namely dimethyl acetylene dicarboxylate and ethoxymethylenemalonitrile was studied and it was found to furnish the triazine 13 and triazepine derivative 15, respectively. Combination of title compound 1 with chlorinated active methylene compounds delivered the triazine derivatives 18a–c. Reaction of 1 with chloroacetonitrile furnished compound 20. The structures of the products were elucidated based on their microanalyses and spectroscopic data. Finally, the antitumor activity of the new compounds 4a and 8a against human breast cell MCF-7 line and liver carcinoma cell line HepG2 were recorded.

  9. Acetone formation in the Vibrio family: a new pathway for bacterial leucine catabolism.

    Science.gov (United States)

    Nemecek-Marshall, M; Wojciechowski, C; Wagner, W P; Fall, R

    1999-12-01

    There is current interest in biological sources of acetone, a volatile organic compound that impacts atmospheric chemistry. Here, we determined that leucine-dependent acetone formation is widespread in the Vibrionaceae. Sixteen Vibrio isolates, two Listonella species, and two Photobacterium angustum isolates produced acetone in the presence of L-leucine. Shewanella isolates produced much less acetone. Growth of Vibrio splendidus and P. angustum in a fermentor with controlled aeration revealed that acetone was produced after a lag in late logarithmic or stationary phase of growth, depending on the medium, and was not derived from acetoacetate by nonenzymatic decarboxylation in the medium. L-Leucine, but not D-leucine, was converted to acetone with a stoichiometry of approximately 0.61 mol of acetone per mol of L-leucine. Testing various potential leucine catabolites as precursors of acetone showed that only alpha-ketoisocaproate was efficiently converted by whole cells to acetone. Acetone production was blocked by a nitrogen atmosphere but not by electron transport inhibitors, suggesting that an oxygen-dependent reaction is required for leucine catabolism. Metabolic labeling with deuterated (isopropyl-d(7))-L-leucine revealed that the isopropyl carbons give rise to acetone with full retention of deuterium in each methyl group. These results suggest the operation of a new catabolic pathway for leucine in vibrios that is distinct from the 3-hydroxy-3-methylglutaryl-coenzyme A pathway seen in pseudomonads. PMID:10601206

  10. Isotopomer Spectral Analysis: Utilizing Nonlinear Models in Isotopic Flux Studies.

    Science.gov (United States)

    Kelleher, Joanne K; Nickol, Gary B

    2015-01-01

    We present the principles underlying the isotopomer spectral analysis (ISA) method for evaluating biosynthesis using stable isotopes. ISA addresses a classic conundrum encountered in the use of radioisotopes to estimate biosynthesis rates whereby the information available is insufficient to estimate biosynthesis. ISA overcomes this difficulty capitalizing on the additional information available from the mass isotopomer labeling profile of a polymer. ISA utilizes nonlinear regression to estimate the two unknown parameters of the model. A key parameter estimated by ISA represents the fractional contribution of the tracer to the precursor pool for the biosynthesis, D. By estimating D in cells synthesizing lipids, ISA quantifies the relative importance of two distinct pathways for flux of glutamine to lipid, reductive carboxylation, and glutaminolysis. ISA can also evaluate the competition between different metabolites, such as glucose and acetoacetate, as precursors for lipogenesis and thereby reveal regulatory properties of the biosynthesis pathway. The model is flexible and may be expanded to quantify sterol biosynthesis allowing tracer to enter the pathway at three different positions, acetyl CoA, acetoacetyl CoA, and mevalonate. The nonlinear properties of ISA provide a method of testing for the presence of gradients of precursor enrichment illustrated by in vivo sterol synthesis. A second ISA parameter provides the fraction of the polymer that is newly synthesized over the time course of the experiment. In summary, ISA is a flexible framework for developing models of polymerization biosynthesis providing insight into pools and pathway that are not easily quantified by other techniques. PMID:26358909

  11. Classification of brain tumor extracts by high resolution ¹H MRS using partial least squares discriminant analysis

    Directory of Open Access Journals (Sweden)

    A.V. Faria

    2011-02-01

    Full Text Available High resolution proton nuclear magnetic resonance spectroscopy (¹H MRS can be used to detect biochemical changes in vitro caused by distinct pathologies. It can reveal distinct metabolic profiles of brain tumors although the accurate analysis and classification of different spectra remains a challenge. In this study, the pattern recognition method partial least squares discriminant analysis (PLS-DA was used to classify 11.7 T ¹H MRS spectra of brain tissue extracts from patients with brain tumors into four classes (high-grade neuroglial, low-grade neuroglial, non-neuroglial, and metastasis and a group of control brain tissue. PLS-DA revealed 9 metabolites as the most important in group differentiation: γ-aminobutyric acid, acetoacetate, alanine, creatine, glutamate/glutamine, glycine, myo-inositol, N-acetylaspartate, and choline compounds. Leave-one-out cross-validation showed that PLS-DA was efficient in group characterization. The metabolic patterns detected can be explained on the basis of previous multimodal studies of tumor metabolism and are consistent with neoplastic cell abnormalities possibly related to high turnover, resistance to apoptosis, osmotic stress and tumor tendency to use alternative energetic pathways such as glycolysis and ketogenesis.

  12. Reduction of ketones and alkyl iodides by SmI(2) and Sm(II)-HMPA complexes. Rate and mechanistic studies.

    Science.gov (United States)

    Prasad, E; Flowers, Robert A

    2002-06-19

    The effect of HMPA on the electron transfer (ET) rate of samarium diiodide reduction reactions in THF was analyzed for a series of ketones (2-butanone, methyl acetoacetate, and N,N-dimethylacetoacetamide) and alkyl iodides (1-iodobutane and 2-iodobutane) with stopped flow spectrophotometric studies. Activation parameters for the ET processes were determined by temperature-dependence studies over a range of 30-50 degrees C. The ET rate constants and the activation parameters obtained for the above systems in the presence of different equivalents of HMPA were compared to understand the mechanism of action of HMPA on various substrates. The results obtained from these studies indicate that coordination or chelation is possible in the transition state geometry for SmI(2)/ketone systems even in the presence of the sterically demanding ligand HMPA. After the addition of 4 equiv of HMPA the ET rate and activation parameters for ketone reduction by Sm is unaffected by further HMPA addition while a linear dependence of ET rate on the equivalents of HMPA was found in the SmI(2)/alkyl iodide system. The results of these studies are consistent with an inner-sphere-type ET for the reduction of ketones by SmI(2) (and SmI(2)[bond]HMPA complexes) and an outer-sphere-type ET for the reduction of alkyl iodides by SmI(2) or SmI(2)[bond]HMPA complexes.

  13. Synthesis of 2(5H)-pyrrinones and the inhibitory effects on the Biofilms of P.aeruginosa in vitro%2(5H)-吡咯酮衍生物的合成及对铜绿假单胞菌生物膜的体外作用

    Institute of Scientific and Technical Information of China (English)

    郭嘉亮; 刘兆祥; 巢伟; 孙平华

    2013-01-01

    以乙酰乙酸乙酯为原料,设计合成2(5H)-吡咯酮及其衍生物,所得化合物经1H NMR、13C NMR、MS和元素分析等确证.通过扫描电镜观察2(5H)-吡咯酮对黏液型铜绿假单胞菌P.aeruginosa(PA)体外生物被膜(biofilms,BF)的影响,可见BF被破坏,基质样物变稀疏,细菌群聚大为降低.活性实验结果表明,2(5H)-吡咯酮类化合物具有一定的抑制细菌群体感应的能力.%A series of pyrroles and 2 (5H) -pyrrinones were successfully synthesized from ethyl aceto-acetate, and characterized by 'H NMR, 13C NMR, MS spectra and elemental analysis. Scanning electron microscope (SEM) was used to evaluate the effects of the 2 (5H) -pyrrolones on the quorum sensing (QS) system and the bacterial biofilm (BF) formation biofilm formation. The biofilms of P. aeruginosa were inhibited, the base became sparseness, and the swarming was decreased. The results of biological activity tests indicated that 2 (5H) -pyrrinones showed potent ability to inhibit the formation of bacterial biofilms.

  14. Benzothiazolylazo derivatives of some β-dicarbonyl compounds and their Cu(II, Ni(II and Zn(II complexes

    Directory of Open Access Journals (Sweden)

    KRISHNANNAIR KRISHNANKUTTY

    2010-05-01

    Full Text Available The coupling of diazotized 2-aminobenzothiazole with 1,3-dicar-bonyl compounds (benzoylacetone, methyl acetoacetate and acetoacetanilide yielded a new series of tridentate ligand systems (HL. Analytical, IR, 1H--NMR, 13C-NMR and mass spectral data indicated that the compounds exist in the intramolecularly hydrogen bonded azo-enol tautomeric form in which one of the carbonyl groups of the dicarbonyl moiety had enolised and hydrogen bonded to one of the azo nitrogen atoms. The compounds formed stable complexes with Ni(II, Cu(II and Zn(II ions. The Cu(II complexes conform to [CuL(OAc] stoichiometry while the Ni(II and Zn(II complexes are in agreement with [ML2] stoichiometry. Analytical, IR, 1H-NMR, 13C-NMR and mass spectral data of the complexes are consistent with the replacement of the chelated enol proton of the ligand with a metal ion, thus leading to a stable six-membered chelate ring involving a cyclic nitrogen, one of the azo nitrogens and the enolate oxygen. The Zn(II chelates are diamagnetic while Cu(II and Ni(II complexes showed a normal paramagnetic moment.

  15. A Comparative Study of the Organic Acid Content of the Hemolymph of Schistosoma mansoni-Resistant and Susceptible Strains of Biomphalaria glabrata

    Directory of Open Access Journals (Sweden)

    José Clecildo Barreto Bezerra

    1997-05-01

    Full Text Available The freshwater snail Biomphalaria glabrata is an intermediate host of the trematode Schistosoma mansoni. However, some strains of B. glabrata are resistant to successful infection by S. mansoni larvae. The present work examines the profile of organic acids present in S. mansoni-resistant and -susceptible strains of B. glabrata, in order to determine whether the type of organic acid present is related to susceptibility. The organic acids were extracted from the hemolymph of two susceptible B. glabrata strains (PR, Puerto Rico and Ba, Jacobina-Bahia from Brazil, and from the resistant strains 13-16-R1 and 10R2, using solid phase extraction procedures followed by high performance liquid chromatography. The organic acids obtained were analyzed and identified by comparison with known standards. Pyruvate, lactate, succinate, malate, fumarate, acetate, propionate, ß-hydroxybutyrate and acetoacetate were detected in all hemolymph samples. Under standard conditions, the concentration of each of these substances varied among the strains tested and appeared to be specific for each strain. An interesting variation was the low concentration of pyruvate in the hemolymph of PR-snails. Only the concentration of fumarate was consistently different (p£ 0.05 between resistant and susceptible strains

  16. Dark fermentation: isolation and characterization of hydrogen-producing strains from sludges.

    Science.gov (United States)

    Rajhi, Haifa; Conthe, Mónica; Puyol, Daniel; Díaz, Emiliano; Sanz, José Luis

    2013-03-01

    To improve bacterial hydrogen production, ten hydrogen-producing strains belonging to Clostridium spp. were isolated from various sludges under low vacuum. Hydrogenogenesis by dark fermentation in batch cultures of these strains was optimal at about 35 degrees C and an initial pH of 6.5, which for all strains gradually dropped to ca. pH 4 during the fermentation. Clostridium roseum H5 and C. diolis RT2 had the highest hydrogen yields per total substrate (120 ml H2/g initial COD). Substrate consumption alone by C. beijerinckii UAM and C. diolis RT2 reached 573 and 475 ml H2/g consumed COD, respectively. Butyric acid fermentation was predominant, with butyrate and acetate as the major by-products and propionate, ethanol, and lactate as secondary metabolites. The acetate:butyrate ratios and fermentation pathways varied depending on the strains and environmental conditions. Hydrogenogenesis was studied in greater detail in C. saccharobutylicum H1. In butyric acid fermentation by this representative strain, acetoacetate was detected as an intermediate metabolite. Hydrogenogenesis was also analyzed in an enrichment culture, which behaved similarly to the axenic cultures. PMID:24151782

  17. Synthesis of Febuxostat%非布索坦的合成

    Institute of Scientific and Technical Information of China (English)

    郑凡; 钱珊; 杨莉; 吴勇

    2009-01-01

    Febuxostat,an antipodagrics,was synthesized from 4-hydroxybenzonitrile by reaction with thioacetamide to give 4-hydroxythiobenzamide,which was subjected to cyclization with 2-chloroethyl acetoacetate,Duff reaction with urotropine to afford ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate,followed by reaction with hydroxylamine hydrochloride,etherifi cation and then hydrolysis with an overall yield of 28%.%对羟基苄腈与硫代乙酰胺反应得到4-羟基硫代苯甲酰胺,与2-氯乙酰乙酸乙酯环合后与六亚甲基四胺进行Duff反应得到2-(3-甲酰基-4-羟基苯基)-4-甲基-5-噻唑甲酸乙酯,再相继与盐酸羟胺/甲醇钠反应、异丁基溴成醚后碱性水解,制得抗痛风药非布索坦,总收率为28%.

  18. Synthesis and Spectroscopic Studies of Mixed Ligand Complexes of Pt(II and Pd(II with Ethyl-α-Isonitrosoacetoacetate and Dienes

    Directory of Open Access Journals (Sweden)

    Anita Krishankant Taksande

    2015-12-01

    Full Text Available The mixed ligand complexes of the kind [M(L1 (L2] where M= Pt(II, Pd(II.L1 = primary ligand ethyl-α-isonitrosoacetoacetate derived from reaction between ethyl acetoacetate, acetic acid and sodium nitrite and L2=secondary ligand para-phenyldiamine (PPD are synthesized. All the prepared complexes were identified and confirmed by elemental analysis, molar conductance measurements, and infrared electronic absorption. Their complexes has been made based on elemental analysis, molar conductivity, UV-Vis, FT-IR and 1HNMR spectroscopy and magnetic moment measurements as well as thermal analysis (TGA and DTA. The elemental analysis information recommends that the stoichiometry of the complexes to be 1:2:1. The molar conductance measurements of the complexes indicate their non-electrolytic nature. The infrared spectral information showed the coordination sites of the free ligand with the central metal particle. The electronic absorption spectral information disclosed the existence of an octahedral geometry for Pt(II and Pd(II complexes. DOI: http://dx.doi.org/10.17807/orbital.v7i4.633 

  19. Keto-acids in Carbonaceous Meteorites

    Science.gov (United States)

    Cooper, G.; Chang, P. M.; Dugas, A.; Byrd, A.; Chang, P. M.; Washington, N.

    2005-01-01

    The Murchison and Murray meteorites are the best-characterized carbonaceous meteorites with respect to organic chemistry and are generally used as references for organic compounds in extraterrestrial material. Among the classes of organic compounds found in these meteorites are amino acids, carboxylic acids, hydroxy acids, purines, and pyrimidines. Such compounds, important in contemporary biochemistry, are thought to have been delivered to the early Earth in asteroids and comets and may have played a role in early life and/or the origin of life. Absent among (today's) critically important biological compounds reported in carbonaceous meteorites are keto acids, i.e., pyruvic acid, acetoacetic acid, and higher homologs. These compounds are key intermediates in such critical processes as glycolysis and the citric acid cycle. In this study several individual meteoritic keto acids were identified by gas chromatography-mass spectrometry (GC-MS) (see figure below). All compounds were identified as their trimethylsilyl (TMS), isopropyl ester (ISP), and tert-butyldimethylsilyl (tBDMS) derivatives. In general, the compounds follow the abiotic synthesis pattern of other known meteorite classes of organic compounds [1,2]: a general decrease in abundance with increasing carbon number within a class of compounds and many, if not all, possible isomers present at a given carbon number. The majority of the shown compounds was positively identified by comparison of their mass spectra to commercially available standards or synthesized standards.

  20. Alternative energy production pathways in Taenia crassiceps cysticerci in vitro exposed to a benzimidazole derivative (RCB20).

    Science.gov (United States)

    Fraga, Carolina Miguel; Da Costa, Tatiane Luiza; De Castro, Ana Maria; Reynoso-Ducoing, Olivia; Ambrosio, Javier; Hernández-Campos, Alicia; Castillo, Rafael; Vinaud, Marina Clare

    2016-04-01

    Biochemical studies of benzimidazole derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.

  1. Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

    Science.gov (United States)

    Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

    2016-01-01

    Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract. PMID:27517894

  2. "Synthesis and smooth muscle Calcium channel antagonist effect of Alkyl, Aminoalkyl 1,4-Dihydro-2,6-Dimethyl-4-Nitroimidazole-3,5 Pyridine Dicarboxylates "

    Directory of Open Access Journals (Sweden)

    Miri R

    2001-08-01

    Full Text Available The discovery that 1,4-dihydropyridine (DHP class of calcium channel antagonist inhibits the Ca+² influx represented a major therapeutic advance in the treatment of cardiovascular diseases such as hypertension, angina pectoris and other spastic smooth muscle disorders. A novel class of calcium channel antagonist of flunarizine containing arylpiperazinyl moiety has recently been reported. It was therefore of interest to determine the effect that selected C-3 substituents contained amino alkyl and arylpiperazine, in conjunction with a C-4 1-methyl-5-nitro-2-imidazolyl substituents on calcium channel antagonist activity. The unsymmetrical analogues were prepared by a procedure reported by Meyer in which 1-methyl-5-nitro-imidazol-2-carboxaldehyde was reacted with acetoacetic esters and alkyl 3-aminocrotonate. In vitro calcium channel antagonist activities were determined by the use of high K+ contraction of guinea pig ileal longitudinal smooth muscle. All compounds exhibited comparable calcium channel antagonist activity (IC50=10^-9 to 10^-11 M against reference drug nifedipine (IC50=2.75±0.36 x 10^-10 M.

  3. Effect of Chelating Agents on the Stability of Nano-TiO2 Sol Particles for Sol-Gel Coating.

    Science.gov (United States)

    Maeng, Wan Young; Yoo, Mi

    2015-11-01

    Agglomeration of sol particles in a titanium alkoxide (tetrabutyl orthotitanate (TBOT), > 97%) solution during the hydrolysis and condensation steps makes the sol solution difficult to use for synthesizing homogeneous sol-gel coating. Here, we have investigated the effect of stabilizing agents (acetic acid and ethyl acetoacetate (EAcAc)) on the agglomeration of Ti alkoxide particles during hydrolysis and condensation in order to determine the optimized conditions for controlling the precipitation of TiO2 particles. The study was conducted at R(AC) ([acetic acid]/[TBOT]) = 0.1-5 and R(EAcAc)([EAcAc]/[TBOT]) = 0.05-0.65. We also studied the effects of a basic catalyst ethanolamine (ETA), water, and HCl on sol stability. The chelating ligands in the precursor sol were analyzed with FT-IR. The coating properties were examined by focused ion beam. The stabilizing agents (acetic acid and EAcAc) significantly influenced the agglomeration and precipitation of TBOT precursor particles during hydrolysis. As R(AC) and R(EAcAc) increased, the agglomeration remarkably decreased. The stability of the sol with acetic acid and EAcAc arises from the coordination of the chelating ligand to TBOT that hinders hydrolysis and condensation. A uniform fine coating (thickness: 30 nm) on stainless steel was obtained by using an optimized sol with R(AC) = 0.5 and R(EAcAc) = 0.65. PMID:26726529

  4. Design, synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase, anti-xanthine oxidase, and cytotoxic activities.

    Science.gov (United States)

    Saïd, Abderrahim Ben; Romdhane, Anis; Elie, Nicolas; Touboul, David; Jannet, Hichem Ben; Bouajila, Jalloul

    2016-12-01

    The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a-e has been accomplished by reaction of 2-acetonitrile derivatives 1a-e with hydroxylamine. Cyclocondensation reaction of precursors 2a-e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a-e, 4a-e, and 5a-e, respectively. On the other hand, the reaction of precursors 2a-e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a-e which evolve under reflux of toluene to the new oxadiazoles 7a-e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC50 = 4.0 μM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 μM, respectively) while 2e is highly selective against OVCAR-3 (IC50 = 10 μM).

  5. Butenolide inhibits marine fouling by altering the primary metabolism of three target organisms

    KAUST Repository

    Zhang, Yifan

    2012-06-15

    Butenolide is a very promising antifouling compound that inhibits ship hull fouling by a variety of marine organisms, but its antifouling mechanism was previously unknown. Here we report the first study of butenolides molecular targets in three representative fouling organisms. In the barnacle Balanus (=Amphibalanus) amphitrite, butenolide bound to acetyl-CoA acetyltransferase 1 (ACAT1), which is involved in ketone body metabolism. Both the substrate and the product of ACAT1 increased larval settlement under butenolide treatment, suggesting its functional involvement. In the bryozoan Bugula neritina, butenolide bound to very long chain acyl-CoA dehydrogenase (ACADVL), actin, and glutathione S-transferases (GSTs). ACADVL is the first enzyme in the very long chain fatty acid β-oxidation pathway. The inhibition of this primary pathway for energy production in larvae by butenolide was supported by the finding that alternative energy sources (acetoacetate and pyruvate) increased larval attachment under butenolide treatment. In marine bacterium Vibrio sp. UST020129-010, butenolide bound to succinyl-CoA synthetase β subunit (SCSβ) and inhibited bacterial growth. ACAT1, ACADVL, and SCSβ are all involved in primary metabolism for energy production. These findings suggest that butenolide inhibits fouling by influencing the primary metabolism of target organisms. © 2012 American Chemical Society.

  6. Regulated release of Ca2+ from respiring mitochondria by Ca2+/2H+ antiport.

    Science.gov (United States)

    Fiskum, G; Lehninger, A L

    1979-07-25

    Simultaneous measurements of oxygen consumption and transmembrane transport of Ca2+, H+, and phosphate show that the efflux of Ca2+ from respiring tightly coupled rat liver mitochondria takes place by an electroneutral Ca2+/2H+ antiport process that is ruthenium red-insensitive and that is regulated by the oxidation-reduction state of the mitochondrial pyridine nucleotides. When mitochondrial pyridine nucleotides are kept in a reduced steady state, the efflux of Ca2+ is inhibited; when they are in an oxidized state, Ca2+ efflux is activated. These processes were demonstrated by allowing phosphate-depleted mitochondria respiring on succinate in the presence of rotenone to take up Ca2+ from the medium. Upon subsequent addition of ruthenium red to block Ca2+ transport via the electrophoretic influx pathway, and acetoacetate, to bring mitochondrial pyridine nucleotides into the oxidized state, Ca2+ efflux and H+ influx ensued. The observed H+ influx/Ca2+ efflux ratio was close to the value 2.0 predicted for the operation of an electrically neutral Ca2+/2H+ antiport process. PMID:36390

  7. Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides.

    Science.gov (United States)

    Lehninger, A L; Vercesi, A; Bababunmi, E A

    1978-04-01

    Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport. PMID:25436

  8. The citric acid-Mn III,IVO 2(birnessite) reaction. Electron transfer, complex formation, and autocatalytic feedback

    Science.gov (United States)

    Wang, Yun; Stone, Alan T.

    2006-09-01

    Citrate released by plants, bacteria, and fungi into soils is subject to abiotic oxidation by MnO 2(birnessite), yielding 3-ketoglutarate, acetoacetate, and Mn II. Citrate loss and generation of products as a function of time all yield S-shaped curves, indicating autocatalysis. Increasing the citrate concentration decreases the induction period. The maximum rate ( rmax) along the reaction coordinate follows a Langmuir-Hinshelwood dependence on citrate concentration. Increases in pH decrease rmax and increase the induction time. Adding Mn II, Zn II, orthophosphate, or pyrophosphate at the onset of reaction decreases rmax. Mn II addition eliminates the induction period, while orthophosphate and pyrophosphate addition increase the induction period. These findings indicate that two parallel processes are responsible. The first, relatively slow process involves the oxidation of free citrate by surface-bound Mn III,IV, yielding Mn II and citrate oxidation products. The second process, which is subject to strong positive feedback, involves electron transfer from Mn II-citrate complexes to surface-bound Mn III,IV, generating Mn III-citrate and Mn II. Subsequent intramolecular electron transfer converts Mn III-citrate into Mn II and citrate oxidation products.

  9. Changes of arterial blood ketone body ratio following hypoperfusion in old and adult rats

    Institute of Scientific and Technical Information of China (English)

    Ling YE; Shiwen WANG; Songtao YU; Wei CHEN

    2004-01-01

    Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P < 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )

  10. Suggested involvement of ketone bodies in the pathogenesis of the metabolic syndrome.

    Science.gov (United States)

    Alexandre, Adolfo

    2013-05-01

    Untreated brain mitochondria are strong producers of H2O2. High peroxide production (in the presence of glutamate and pyruvate) is strictly succinate-dependent. Importantly, it is inhibited by the ketone body acetoacetate (AcAc) starting at 10 μM (maximal effect at 0.5mM). Butyrate derives from the fermentation of prebiotics, is present physiologically in the colon and is a strong producer of AcAc: indeed butyrate induces in the colon the transcription of mitochondrial 3-hydroxy-3-methyl glutarylCoA (HMGCoA) synthase, a key enzyme in ketone body synthesis. Obesity and insulin resistance were shown to be dependent on increased permeability of the colon epithelium to bacterial lipopolysaccharide (LPS); the process is evident particularly upon ingestion of lipids (a peroxidative event, inhibited by vitamin E) and is likely sensitive to AcAc. The oxidation of butyrate and the production of AcAc in the colon appear to be inhibited by high luminal sulphides and high NH3, a situation that presumably facilitates LPS permeation (on the contrary beta-hydroxy-butyrate oxidation is not inhibited). It is proposed that these damaging events may be opposed by the delivery of ketone bodies directly to the colon. PMID:23466063

  11. Metabolic effect of islet B-cell function in insulin-treated diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Iversen, S;

    1989-01-01

    We studied the relationship between endogenous insulin secretion and fasting levels of plasma free fatty acids (FFA), plasma acetoacetate plus plasma 3-hydroxybutyrate (total ketone bodies), blood glucose, and HbA1 in 132 diabetic outpatients treated with conventional insulin regimens. Patients.......60 nmol/l, and one group with C-peptide stimulation greater than 0.60 nmol/l. According to clinical criteria the prevalence of insulin-dependent diabetes mellitus was approximately 90% in patients with C-peptide stimulation less than 0.32 nmol/l, approximately 25% in patients with C-peptide stimulation...... were divided into four groups according to plasma C-peptide concentration after intravenous stimulation with glucagon: one group with C-peptide stimulation less than 0.06 nmol/l, one group with C-peptide stimulation 0.06- less than 0.32 nmol/l, one group with C-peptide stimulation 0.32- less than 0...

  12. Michael addition reaction catalyzed by solid base%用固体碱催化Michael加成反应的研究

    Institute of Scientific and Technical Information of China (English)

    徐景士; 王红明; 陈慧宗

    2003-01-01

    Different Michael addition reactions catalyzed by solid base K2O/γ-Al2O3 and KF/γ-Al2O3, MgO/γ-Al2O3 prepared by microwave irradiation method were reported in this paper. For the K2O/γ-Al2O3, not only good yield was attained but also made the reaction of Acetonitrile that usually is regarded as inactive carbonion and α, β-unsatumted compound to carry out. The yield of Michael reaction of Ethyl acetoacetate and Crotonaldehyde catalyzed by KF/γ-Al2O3, MgO/γ-Al2O3, MgO/NaY all could reach to 80% and the latter could reach to 90%. At the same time, the catalysts of different content(the ratio of load) of MgO were also applied in this reaction, and it was found that the best content of MgO was 20% ~ 25%。

  13. Synthesis of new 2-amino-4H-pyran-3,5-dicarboxylate derivatives using nanocrystalline M{sup II}Zr{sub 4}(PO{sub 4}){sub 6} ceramics as reusable and robust catalysts under microwave irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Safaei-Ghomi, Javad, E-mail: safaei@kashanu.ac.ir [University of Kashan, Department of Organic Chemistry, Faculty of Chemistry (Iran, Islamic Republic of); Javidan, Abdollah [Imam Hossein University, Nano-Research Center (Iran, Islamic Republic of); Ziarati, Abolfazl [University of Tehran, School of Chemistry, College of Science (Iran, Islamic Republic of); Shahbazi-Alavi, Hossein [University of Kashan, Department of Organic Chemistry, Faculty of Chemistry (Iran, Islamic Republic of)

    2015-08-15

    In the present paper, we report the successful synthesis of nanocrystalline M{sup II}Zr{sub 4}(PO{sub 4}){sub 6} ceramics (M: Mn, Ni, Fe, Co). These nano-structures were characterized by X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometer (VSM). Size of nano-structures was in the range of 20–150 nm. Nano-M{sup II}Zr{sub 4}(PO{sub 4}){sub 6} as an efficient and green catalyst has been used for the preparation of 2-amino-4H-pyran-3,5-dicarboxylate derivatives by the three-component condensation reaction of ethyl cyanoacetate, ethyl acetoacetate, and various aromatic aldehydes under microwave irradiation. Extraordinarily, the best results were obtained using MnZr{sub 4}(PO{sub 4}){sub 6} nanocrystallines as an efficient catalyst. This method provides several advantages including easy work-up, excellent yields, short reaction times, using of microwave as green method, recoverability of the catalyst, and little catalyst loading.

  14. Ketones block amyloid entry and improve cognition in an Alzheimer's model.

    Science.gov (United States)

    Yin, Jun Xiang; Maalouf, Marwan; Han, Pengcheng; Zhao, Minglei; Gao, Ming; Dharshaun, Turner; Ryan, Christopher; Whitelegge, Julian; Wu, Jie; Eisenberg, David; Reiman, Eric M; Schweizer, Felix E; Shi, Jiong

    2016-03-01

    Sporadic Alzheimer's disease (AD) is responsible for 60%-80% of dementia cases, and the most opportune time for preventive intervention is in the earliest stage of its preclinical phase. As traditional mitochondrial energy substrates, ketone bodies (ketones, for short), beta-hydroxybutyrate, and acetoacetate, have been reported to provide symptomatic improvement and disease-modifying activity in epilepsy and neurodegenerative disorders. Recently, ketones are thought as more than just metabolites and also as endogenous factors protecting against AD. In this study, we discovered a novel neuroprotective mechanism of ketones in which they blocked amyloid-β 42, a pathologic hallmark protein of AD, entry into neurons. The suppression of intracellular amyloid-β 42 accumulation rescued mitochondrial complex I activity, reduced oxidative stress, and improved synaptic plasticity. Most importantly, we show that peripheral administration of ketones significantly reduced amyloid burden and greatly improved learning and memory ability in a symptomatic mouse model of AD. These observations provide us insights to understand and to establish a novel therapeutic use of ketones in AD prevention. PMID:26923399

  15. The Ketone Body, β-Hydroxybutyrate Stimulates the Autophagic Flux and Prevents Neuronal Death Induced by Glucose Deprivation in Cortical Cultured Neurons.

    Science.gov (United States)

    Camberos-Luna, Lucy; Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Massieu, Lourdes

    2016-03-01

    Glucose is the major energy substrate in brain, however, during ketogenesis induced by starvation or prolonged hypoglycemia, the ketone bodies (KB), acetoacetate and β-hydroxybutyrate (BHB) can substitute for glucose. KB improve neuronal survival in diverse injury models, but the mechanisms by which KB prevent neuronal damage are still not well understood. In the present study we have investigated whether protection by the D isomer of BHB (D-BHB) against neuronal death induced by glucose deprivation (GD), is related to autophagy. Autophagy is a lysosomal-dependent degradation process activated during nutritional stress, which leads to the digestion of damaged proteins and organelles providing energy for cell survival. Results show that autophagy is activated in cortical cultured neurons during GD, as indicated by the increase in the levels of the lipidated form of the microtubule associated protein light chain 3 (LC3-II), and the number of autophagic vesicles. At early phases of glucose reintroduction (GR), the levels of p62 declined suggesting that the degradation of the autophagolysosomal content takes place at this time. In cultures exposed to GD and GR in the presence of D-BHB, the levels of LC3-II and p62 rapidly declined and remained low during GR, suggesting that the KB stimulates the autophagic flux preventing autophagosome accumulation and improving neuronal survival.

  16. Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species.

    Science.gov (United States)

    Julio-Amilpas, Alberto; Montiel, Teresa; Soto-Tinoco, Eva; Gerónimo-Olvera, Cristian; Massieu, Lourdes

    2015-05-01

    Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury.

  17. Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

    Directory of Open Access Journals (Sweden)

    Santhosh Karanth

    2013-11-01

    Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr, despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr.

  18. Ionic liquid-based dispersive liquid-liquid microextraction for the determination of formaldehyde in wastewaters and detergents.

    Science.gov (United States)

    Arvand, Majid; Bozorgzadeh, Elahe; Shariati, Shahab; Zanjanchi, Mohammad Ali

    2012-12-01

    Spectrophotometry in combination with ionic liquid-based dispersive liquid-liquid microextraction (DLLME) was applied for the extraction and determination of formaldehyde in real samples. The method is based on the reaction of formaldehyde with methyl acetoacetate in the presence of ammonia. The variation in the absorbance of the reaction product was measured at 375 nm. An appropriate mixture of ethanol (disperser solvent) and ionic liquid, 1-hexyl-3-methylimidazoliumhexafluoro-phosphate [C(6)MIM][PF(6)] (extraction solvent) was rapidly injected into a water sample containing formaldehyde. After extraction, sedimented phase was analyzed by spectrophotometry. Under the optimum conditions, the calibration graph was linear in the range of 0.1-20 ng mL(-1) with the detection limit of 0.02 ng mL(-1) and limit of quantification of 0.08 ng mL(-1) for formaldehyde. The relative standard deviation (RSD%, n = 5) for the extraction and determination of 0.8 ng mL(-1) of formaldehyde in the aqueous samples was 2.5%. The results showed that DLLME is a very simple, rapid, sensitive, and efficient analytical method for the determination of trace amounts of formaldehyde in wastewaters and detergents, and suitable results were obtained.

  19. Direct photolysis of carbonyl compounds dissolved in cloud and fog~droplets

    Science.gov (United States)

    Epstein, S. A.; Tapavicza, E.; Furche, F.; Nizkorodov, S. A.

    2013-09-01

    Gas-phase photolysis is an important tropospheric sink for many carbonyl compounds; however the significance of direct photolysis of these compounds dissolved in cloud and fog droplets is uncertain. We develop a theoretical approach to assess the importance of aqueous photolysis for a series of carbonyls that possess carboxyl and hydroxyl functional groups by comparison with rates of other atmospheric processes. We use computationally and experimentally derived effective Henry's law constants, hydration equilibrium parameters, aqueous hydroxyl radical (OH) rate constants, and optical extinction coefficients to identify types of compounds that will (or will not) have competitive aqueous photolysis rates. We also present molecular dynamics simulations designed to estimate gas- and aqueous-phase extinction coefficients of unstudied atmospherically relevant compounds found in d-limonene and isoprene secondary organic aerosol. In addition, experiments designed to measure the photolysis rate of glyceraldehyde, an atmospherically relevant water-soluble organic compound, reveal that aqueous quantum yields are highly molecule-specific and cannot be extrapolated from measurements of structurally similar compounds. We find that only two out of the 92 carbonyl compounds investigated, pyruvic acid and acetoacetic acid, may have aqueous photolysis rates that exceed the rate of oxidation by dissolved OH. For almost all carbonyl compounds lacking α,β-conjugation that were investigated, atmospheric removal by direct photolysis in cloud and fog droplets can be neglected under typical atmospheric conditions.

  20. [Method selected for the determination of creatinine in plasma or serum. Choice of optimal conditions of measurement].

    Science.gov (United States)

    Labbé, D; Vassault, A; Cherruau, B; Baltassat, P; Bonète, R; Carroger, G; Costantini, A; Guérin, S; Houot, O; Lacour, B; Nicolas, A; Thioulouse, E; Trépo, D

    1996-01-01

    The method selected by the SFBC (Société française de biologie clinique) is derived from the colorimetric reaction of creatinine with alkaline picrate, measured kinetically, without any pretreatment step. The key parameters of the reaction determining the quality of the results are studied, with special regard to samples including known interferents. The aims of the study were to gain an optimal analytical sensitivity and to reduce main interferences (acetoacetate, bilirubine, glucose, protein) which plague the Jaffé reaction, through a comprehensive study of the reagents, of their concentrations and of the analytical procedures. The selected concentrations (in the test) are: 150 mmol/L sodium hydroxide, 10 mmol/L picric acid and 2 g/L sodium dodecyl sulfate. Ten millilitres of a BRIJ solution (30% volvol) are added to the reagent. The operating procedures are as follow: sample ratio 0.07 to 0.08; wavelength 505 to 510 nm; temperature 37 degrees C; incubation of the specimen with the alkaline reagent 5 mn (at least), before starting the reaction with picric acid. A seric calibrator is recommended. The first measurement is taken 20 to 40 s after starting the reaction. Total measurement time is 120 to 150 seconds.

  1. Microwave Assisted Synthesis and Unusual Coupling of Some Novel Pyrido[3,2-f][1,4]thiazepines

    Directory of Open Access Journals (Sweden)

    Mohamed M. Youssef

    2011-05-01

    Full Text Available 3-Amino-3-thioxopropanamide (1 reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2, which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazothieno[2,3-b]pyridin-3(2H-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods.

  2. Ketosis leads to increased methylglyoxal production on the Atkins diet.

    Science.gov (United States)

    Beisswenger, Benjamin G K; Delucia, Elizabeth M; Lapoint, Nancy; Sanford, Rebecca J; Beisswenger, Paul J

    2005-06-01

    In the popular and widely used Atkins diet, the body burns fat as its main fuel. This process produces ketosis and hence increased levels of beta-hydroxybutyrate (BOB) acetoacetate (AcAc) and its by-products acetone and acetol. These products are potential precursors of the glycotoxin methylglyoxal. Since methylglyoxal and its byproducts are recognized as a significant cause of blood vessel and tissue damage, we measured methylglyoxal, acetone, and acetol in subjects on the Atkins diet. We found that by 14-28 days, methylghyoxal levels rose 1.67-fold (P = 0.039) and acetol and acetone levels increased 2.7- and 6.12-fold, respectively (P = 0.012 and 0.028). Samples from subjects with ketosis showed even greater increases in methylglyoxal (2.12-fold), as well as acetol and acetone, which increased 4.19- and 7.9-fold, respectively; while no changes were seen in samples from noncompliant, nonketotic subjects. The increase in methylglyoxal implies that potential tissue and vascular damage can occur on the Atkins diet and should be considered when choosing a weight-loss program.

  3. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

    Science.gov (United States)

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

    2016-03-01

    Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. PMID:26766547

  4. Comparison of palmitic acid kinetics during glucose or ketone body infusions

    Energy Technology Data Exchange (ETDEWEB)

    Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

    1986-03-05

    Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of (1-/sup 14/C) palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat.

  5. Serum and urine trace metals in ketosis

    Energy Technology Data Exchange (ETDEWEB)

    Burch, R.E.; Hiner, C.; Sullivan, J.F.

    1974-01-01

    Three groups of male rats were housed in metabolic cages. The control group was fed ad libitum, a second group was fasted and diabetes was induced in the third group by the subcutaneous injection of alloxan. After 48 hours all animals were bled and livers, which were quick-frozen in situ, were obtained. Fasted and diabetic animals were ketotic as manifested by lowering urinary pH and elevated urinary and blood acetoacetate and ..beta..-hydroxybutyrate. Blood and hepatic content of acetate was elevated in diabetic versus control rats. Blood and hepatic content of acetate was not increased in fasted animals. In fasted rats total urinary Zn and Cu were decreased and Mg and Ca did not differ significantly from control values. In diabetic rats total urinary excretion of Mg was increased whereas urinary Zn, Cu and Ca levels did not differ significantly from control values. In fasted animals only serum Zn was diminished. In diabetic rats serum Cu and Ca were decreased and serum Mg was increased while serum Zn was unchanged. Thus, the ketosis of fasting differs from the ketosis of diabetes in several of its metabolic manifestations. 11 references, 9 figures.

  6. Breath Ketone Testing: A New Biomarker for Diagnosis and Therapeutic Monitoring of Diabetic Ketosis

    Directory of Open Access Journals (Sweden)

    Yue Qiao

    2014-01-01

    Full Text Available Background. Acetone, β-hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. Methods. We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and β-hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (−, 2 (±, 3 (+, 4 (++, or 5 (+++ according to urinary ketone concentrations. Results. There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. Conclusions. Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis.

  7. Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Muhammad Tayyab Akhtar

    2016-08-01

    Full Text Available Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM. Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM. Proton Nuclear Magnetic Resonance (1H-NMR spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

  8. Gender-specific metabolomic profiling of obesity in leptin-deficient ob/ob mice by 1H NMR spectroscopy.

    Directory of Open Access Journals (Sweden)

    Eun-Young Won

    Full Text Available Despite the numerous metabolic studies on obesity, gender bias in obesity has rarely been investigated. Here, we report the metabolomic analysis of obesity by using leptin-deficient ob/ob mice based on the gender. Metabolomic analyses of urine and serum from ob/ob mice compared with those from C57BL/6J lean mice, based on the (1H NMR spectroscopy in combination with multivariate statistical analysis, revealed clear metabolic differences between obese and lean mice. We also identified 48 urine and 22 serum metabolites that were statistically significantly altered in obese mice compared to lean controls. These metabolites are involved in amino acid metabolism (leucine, alanine, ariginine, lysine, and methionine, tricarbocylic acid cycle and glucose metabolism (pyruvate, citrate, glycolate, acetoacetate, and acetone, lipid metabolism (cholesterol and carnitine, creatine metabolism (creatine and creatinine, and gut-microbiome-derived metabolism (choline, TMAO, hippurate, p-cresol, isobutyrate, 2-hydroxyisobutyrate, methylamine, and trigonelline. Notably, our metabolomic studies showed distinct gender variations. The obese male mice metabolism was specifically associated with insulin signaling, whereas the obese female mice metabolism was associated with lipid metabolism. Taken together, our study identifies the biomarker signature for obesity in ob/ob mice and provides biochemical insights into the metabolic alteration in obesity based on gender.

  9. Stereoselective reduction of prochiral ketones by plant and microbial biocatalysts

    Directory of Open Access Journals (Sweden)

    K Javidnia

    2016-01-01

    Full Text Available Chiral alcohols are the key chiral building blocks to many enantiomerically pure pharmaceuticals. The biocatalytic approach in asymmetric reduction of corresponding prochiral ketones to the preparation of these optically pure substances is one of the most promising routes. The stereoselective reduction of different kinds of prochiral ketones catalyzed by various plants and microorganisms was studied in this work. Benzyl acetoacetate, methyl 3-oxopentanoate, ethyl 3-oxopentanoate, and ethyl butyryl acetate were chosen as the model substrates for β-ketoesters. Benzoyl acetonitrile, 3-chloro propiophenone, and 1-acetyl naphthalene were chosen as aromatic aliphatic ketones. Finally, 2-methyl benzophenone and 4-chloro benzophenone were selected as diaryl ketones. Plant catalysis was conducted by Daucus carota, Brassica rapa, Brassica oleracea, Pastinaca sativa, and Raphnus sativus.For microbial catalysis, Aspergillus foetidus, Penicillum citrinum, Saccharomyces carlbergensis, Pichia fermentans, and Rhodotrula glutinis were chosen. Chiral alcohols were obtained in high yields and with optical purity. A superiority in the microorganisms' performance in the bioreduction of prochiral ketones was detected. Among microorganisms, Rhodotrula glutinis showed remarkable results with nearly all substrates and is proposed for future studies.

  10. Stereoselective Reduction of Prochiral Ketones by Plant and Microbial Biocatalysts.

    Science.gov (United States)

    Javidnia, K; Faghih-Mirzaei, E; Miri, R; Attarroshan, M; Zomorodian, K

    2016-01-01

    Chiral alcohols are the key chiral building blocks to many enantiomerically pure pharmaceuticals. The biocatalytic approach in asymmetric reduction of corresponding prochiral ketones to the preparation of these optically pure substances is one of the most promising routes. The stereoselective reduction of different kinds of prochiral ketones catalyzed by various plants and microorganisms was studied in this work. Benzyl acetoacetate, methyl 3-oxopentanoate, ethyl 3-oxopentanoate, and ethyl butyryl acetate were chosen as the model substrates for β-ketoesters. Benzoyl acetonitrile, 3-chloro propiophenone, and 1-acetyl naphthalene were chosen as aromatic aliphatic ketones. Finally, 2-methyl benzophenone and 4-chloro benzophenone were selected as diaryl ketones. Plant catalysis was conducted by Daucus carota, Brassica rapa, Brassica oleracea, Pastinaca sativa, and Raphnus sativus. For microbial catalysis, Aspergillus foetidus, Penicillum citrinum, Saccharomyces carlbergensis, Pichia fermentans, and Rhodotrula glutinis were chosen. Chiral alcohols were obtained in high yields and with optical purity. A superiority in the microorganisms' performance in the bioreduction of prochiral ketones was detected. Among microorganisms, Rhodotrula glutinis showed remarkable results with nearly all substrates and is proposed for future studies. PMID:27168684

  11. Biginelli Condensation Assisted by Microwave Irradiation in Ionic Liquids%离子液体中微波促进的Biginelli缩合反应

    Institute of Scientific and Technical Information of China (English)

    邵国强

    2004-01-01

    The reaction of a one-pot three component Biginelli condensation can be dramatically accelerated by irradiating the reaction mixture of ethyl acetoacetate, aryl aldehyde and urea in an ionic liquid 1-butyl-3-methylimidazonium tetrafluoroborate([bmim]BF4) as a catalyst with a Microwave oven. Ten 5-ethoxycarbonyl-4-aryldihydropyrimidinones were synthesized in 10min with excellent yields. Their structures were comfirmed by IR and 1H NMR.%在微波辐射下,以离子液体1-丁基-3-甲基咪唑四氟硼酸盐([bmim]BF4)为催化剂,三组分一锅法Bigi-nelli缩合反应快速地合成了10种高收率的5-乙氧羰基-4-芳基二氢嘧啶酮衍生物的缩合产物,其结构经IR和1H NMR确证.

  12. Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of some new 4,6-dimethoxy-5-(heterocyclesbenzofuran starting from naturally occurring visnagin

    Directory of Open Access Journals (Sweden)

    E.R. El-Sawy

    2014-12-01

    Full Text Available Novel 3-(4,6-dimethoxybenzofuran-5-yl-1-phenyl-1H-pyrazole-4-carboxaldehyde (3 and 3-chloro-3-(4,6-dimethoxybenzofuran-5-ylpropenal (4 were prepared via Vilsmeier–Haack reaction of 1-(4,6-dimethoxybenzofuran-5-ylethanone (1 and its hydrazone derivative 2. Reaction of compound 4 with some hydrazine derivatives, namely hydrazine hydrate, phenylhydrazine and benzylhydrazine hydrochloride led to the formation of pyrazole derivatives 5–8, respectively. On the other hand, reaction of compound 4 with thiourea, urea or guanidine gave the pyrimidine derivatives 9–11, respectively. Reaction of amino compound 11 with acetic anhydride, benzoyl chloride and benzenesulphonyl chloride yielded N-substituted pyrimidine derivatives 12–14, respectively. Reaction of diazonium salt of compound 11 with sodium azide afforded azidopyrimidine derivative 15, which upon reaction with ethyl acetoacetate gave 1,2,3-triazole derivative 16. Acid catalyzed reaction of 11 with p-nitrobenzaldehyde gave Schiff base 17, which cyclized upon reaction with thioglycolic acid or chloroacetyl chloride to give thiazolidin-4-one 18 and azetidin-2-one 19, respectively. The newly synthesized compounds were tested for their anti-inflammatory, analgesic and anticonvulsant activities. Depending on the obtained results, the newly synthesized compounds possess significant anti-inflammatory, analgesic and anticonvulsant activities.

  13. Synthesis of Clevidipine Butyrate%氯维地平的合成

    Institute of Scientific and Technical Information of China (English)

    张婧; 纪宪勇; 孙翔; 王杰

    2011-01-01

    Clevidipine butyrate, an antihypertensive agent, was synthesized from 2-cyanoethyl acetoacetate (2), 2,3-dichlorobenzaldehyde and methyl 3-aminocrotonate by Hantzsch cyclocondensation and followed by selective hydrolysis with sodium sulfide at room temperature to give 4-(2,3-dichlorophenyl)-l,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid monomethyl ester, which was then subjected to reaction with chloromethyl butyrate with an overall yield of about 59% (based on 2).%3-羟基丙腈和双乙烯酮在三乙胺作用下制得乙酰乙酸(2ˉ氰基乙基)酯(2),再与2,3-二氯苯甲醛和3ˉ氨基巴豆酸甲酯经Hantzsch缩合闭环,接着用硫化钠在常温下选择性水解得4-(2,3-二氯苯基)-1-4-二氢-2,6-二甲基-3,5-吡啶二羧酸单甲酯,最后与正丁酸氯甲酯反应即得抗高血压药氯维地平,总收率约59%(以2计).

  14. Graphene quantum dots from graphite by liquid exfoliation showing excitation-independent emission, fluorescence upconversion and delayed fluorescence.

    Science.gov (United States)

    Sarkar, Suprabhat; Gandla, Dayakar; Venkatesh, Yeduru; Bangal, Prakriti Ranjan; Ghosh, Sutapa; Yang, Yang; Misra, Sunil

    2016-08-21

    Facile synthesis of 2-10 nm-sized graphene quantum dots (GQDs) from graphite powder by organic solvent-assisted liquid exfoliation using a sonochemical method is reported in this study. Synthesized GQDs are well dispersed in organic solvents like ethyl acetoacetate (EAA), dimethyl formamide (DMF) and also in water. MALDI-TOF mass spectrometry reveals its selective mass fragmentation. Detailed characterizations by various techniques like X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and high resolution transmission electron microscopy (HRTEM) confirm the formation of disordered, functional GQDs. Density functional theory (DFT) calculation confirms HOMO-LUMO energy gap variation with changing size and functionalities. Photoluminescence (PL) properties of as-prepared GQDs were studied in detail. The ensemble studies of GQDs showed excellent photoluminescence properties comprising normal and upconverted fluorescence, delayed fluorescence and room-temperature phosphorescence. PL decay dynamics of GQDs has been explored using time-correlated single-photon technique (TCSPC) as well as femtosecond fluorescence upconversion technique. In vitro cytotoxicity study reveals its biocompatibility and high cell viability (>91%) even at high concentration (400 μg mL(-1)) of GQDs in Chinese Hamster Ovary (CHO) cells. PMID:27302411

  15. Synthesis, in vitro anticancer and antimicrobial evaluation of novel substituted dihydropyrimidines

    Directory of Open Access Journals (Sweden)

    K Rana

    2014-01-01

    Full Text Available A series of 1,4-dihydropyrimidine derivatives 3(a-t were prepared from Biginelli reactions by using ethyl acetoacetate, substituted benzaldehyde and thiourea in the presence of piperidine and ethanol. The compounds 3(a-t were reacted with dimethylsulphate, diethylsulphate, butyl bromide and benzyl chloride to give the new series of compounds 4(a-t. The structures of the newly synthesized compounds 4(a-t were established by IR, 1 H NMR, Mass spectra and elemental analysis. The synthesized compounds were evaluated for their in vitro anticancer activity by using Sulforhodamine B assay method against the growth of four humans cancer cell lines, antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and for antifungal activity against Candida albicans and Aspergillus niger. The compounds exhibited good anticancer activity and moderate antibacterial and antifungal activities. Compounds 4b, 4c, 4d, 4g, 4i, 4n, 4o, 4q and 4s showed significant anticancer activity when compared with the doxorubicin as a standard reference drug.

  16. False-positive breath-alcohol test after a ketogenic diet.

    Science.gov (United States)

    Jones, A W; Rössner, S

    2007-03-01

    A 59-year-old man undergoing weight loss with very low calorie diets (VLCD) attempted to drive a car, which was fitted with an alcohol ignition interlock device, but the vehicle failed to start. Because the man was a teetotaller, he was surprised and upset by this result. VLCD treatment leads to ketonemia with high concentrations of acetone, acetoacetate and beta-hydroxybutyrate in the blood. The interlock device determines alcohol (ethanol) in breath by electrochemical oxidation, but acetone does not undergo oxidation with this detector. However, under certain circumstances acetone is reduced in the body to isopropanol by hepatic alcohol dehydrogenase (ADH). The ignition interlock device responds to other alcohols (e.g. methanol, n-propanol and isopropanol), which therefore explains the false-positive result. This 'side effect' of ketogenic diets needs further discussion by authorities when people engaged in safety-sensitive work (e.g. bus drivers and airline pilots) submit to random breath-alcohol tests. PMID:16894360

  17. Catalytic synthesis of 5-ethoxycarbonyl-4-(4-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-ketone with H6P2W18O62/SiO2%H6P2W18O62/SiO2催化合成5-乙氧羰基-4-(4-羟基苯基)-6-甲基-3,4-二氢嘧啶-2(1H)-酮

    Institute of Scientific and Technical Information of China (English)

    刘晓霞; 肖欢; 杨水金

    2015-01-01

    5-Ethoxycarbonyl-4-(4-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-ketone was synthesized by using H6P2W18O62/SiO2 as the catalyst and p-hydroxy benzaldehyde,ethyl acetoacetate and urea as raw materials. Catalytic activity of this reaction using H6P2W18O62/SiO2 as the catalyst was explored. The effects of reaction on the yield of the product were investigated and the optimum conditions were determined as follows:fixing p-hydroxy benzaldehyde consumption is 0.04 mol,n(p-hydroxy benzaldehyde):n(ethyl acetoacetate):n(urea)=1∶1.5∶1.5,the mass ratio of the catalyst to total reactant is 1.5%,the reaction temperature is 80℃, and the reaction time is 1.0 h. The yield of the product was up to 94.4%.%采用H6P2W18O62/SiO2为催化剂,以对羟基苯甲醛、乙酰乙酸乙酯、尿素为原料合成5-乙氧羰基-4-(4-羟基苯基)-6-甲基-3,4-二氢嘧啶-2(1H)-酮.探讨H6P2W18O62/SiO2对本反应的催化活性,较系统地研究了反应物物质的量比、催化剂用量、反应时间、反应温度四因素对产物收率的影响.实验表明:H6P2W18O62/SiO2是合成5-乙氧羰基-4-(4-羟基苯基)-6-甲基-3,4-二氢嘧啶-2(1H)-酮的良好催化剂;在n (对羟基苯甲醛)∶n (乙酰乙酸乙酯)∶n (尿素)=1∶1.5∶1.5,催化剂的用量占反应物料总质量的1.5%,反应温度为80℃,反应时间为60 min的最佳条件下,其收率可达94.4%.

  18. 丙泊酚长链脂肪乳和中/长链脂肪乳注射液对肝脏能量代谢的影响%Effect of propofol long-chain fat emulsion injection and propofol medium/long-chain fat emulsion injection on hepatic energy metabolism

    Institute of Scientific and Technical Information of China (English)

    安丽; 高鸿; 欧炜; 杨扬

    2014-01-01

    目的:观察丙泊酚长链脂肪乳注射液(LCT )和丙泊酚中/长链脂肪乳注射液(MCT/LCT )短时间恒速输注对肝脏能量代谢的影响。方法选择年龄为18~50岁,术前 ASA分级Ⅰ~Ⅱ级的20例择期手术病人,随机分为2组,每组10例,分别行丙泊酚长链脂肪乳注射液4 mg · kg-1· h-1维持麻醉(L组)、丙泊酚中/长链脂肪乳注射液4 mg · kg-1· h-1维持麻醉(M组)。在气管插管后(T1)、维持输注丙泊酚麻醉2 h后(T 2),各取静脉血检测乙酰乙酸、β-羟丁酸值,计算血酮体比率(乙酰乙酸/β-羟丁酸)。结果 T1、T2时点两组乙酰乙酸、β-羟丁酸和血酮体比率之间比较,差异均无统计学意义(P>0.05)。结论丙泊酚长链脂肪乳注射液和丙泊酚中/长链脂肪乳注射液短时间持续输注对肝脏能量代谢没有明显的影响。%Objective To observe the effect of propofol long-chain fat emulsion injection (LCT ) and propofol medium /long-chain fat emulsion injection (MCT/LCT ) in short time infusion on hepatic energy metabolism .Methods Total of 20 patients aged 18~50 years with ASA ⅠorⅡ undergoing elec-tive surgery were randomized into 2 groups (n=10 for each) which were propofol long-chain fat emul-sion injection 4 mg · kg-1 · h-1 maintain anesthesia (group L ) ,and propofol medium /long-chain fat e-mulsion injection 4 mg · kg-1 · h-1 maintain anesthesia (group M ) .The blood samples were collected after tracheal intubation (T1 ) and maintain 2 hours after infusion of propofol (T2 ) ,for the measure-ment of acetoacetate ,β-hydroxybutyrate and calculating blood ketone body ratio (The ratio of acetoace-tate and β-hydroxybutyrate) .Results All indexes between T1 and T2 time comparison ,there were no statistically significant differences ( P> 0 .05 ) .Conclusion Propofol long-chain fat emulsion injection and propofol medium /long-chain fat emulsion injection short time

  19. Assessment of Early Postpartum Reproductive Performance in Two High Producing Estonian Dairy Herds

    Directory of Open Access Journals (Sweden)

    Kindahl H

    2003-09-01

    Full Text Available Early postpartum (6 weeks ovarian activity, hormonal profiles, uterine involution, uterine infections, serum electrolytes, glucose, milk acetoacetate and blood urea nitrogen (BUN levels were studied in 2 Estonian high producing dairy herd with annual milk production of 7688 (Farm A and 9425 (Farm B. From each farm 10 cows, with normal calving performance were used. Blood samples for the hormonal (PGF2α-metabolite, progesterone analyses were withdrawn. On day 25 PP blood serum samples were taken for the evaluation of metabolic/electrolyte status. On the same day estimation of milk acetoacetate values was done. The ultrasound (US was started on day 7 PP and was performed every 3rd day until the end of experiment. Uterine content, follicular activity and sizes of the largest follicle and corpus luteum were monitored and measured. Vaginal discharge and uterine tone were recorded during the rectal palpation. Each animal in the study was sampled for bacteriological examination using endometrial biopsies once a week. Two types of PGF2α-metabolite patterns were detected: elevated levels during 14 days PP, then decline to the basal level and then a second small elevation at the time of final elimination of the bacteria from the uterus; or elevated levels during first 7 days PP, then decline to the basal level and a second small elevation before the final elimination of bacteria. Endometritis was diagnosed in 5 cows in farm A and in 3 cows in farm B respectively. In farm A, 5 cows out of 10 ovulated during experimental period and in 1 cow cystic ovaries were found. In farm B, 3 cows out of 10 ovulated. In 3 cows cystic ovaries were found. Altogether 40% of cows had their first ovulation during the experimental period. Three cows in farm A and 5 cows in farm B were totally bacteria negative during the experimental period. The most frequent bacteria found were A. pyogenes, Streptococcus spp., E. coli., F. necrophorum and Bacteroides spp. The highest

  20. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  1. 乙酰乙酸基甲基丙烯酸乙酯的合成%Synthesis of acetoacetoxyethyl methacrylate

    Institute of Scientific and Technical Information of China (English)

    司动磊; 刘福胜

    2015-01-01

    Acetoacetoxyethyl methacrylate ( AAEM ) was synthesized via a transesterification involving hydroxyethyl methacrylate( HEMA) and ethyl acetoacetate ( AAA) as raw materials and solid acid as a catalyst. The reaction conditions were studied by single factor and orthogonal test methods. The obtained optimum reaction conditions were:n(AAA)∶n(HEMA) =3∶1,reaction temperature 130℃,reaction time 3 h,the quantity of catalyst was equal to 4. 5% HEMA,the quantity of inhibitor was equal to 0. 3% HE-MA. Under above conditions, the product yield and purity were over 93% and 97%, respectively. The structure of the obtained product was characterized by FTIR and 1 H NMR.%以甲基丙烯酸羟乙酯( HEMA)和乙酰乙酸乙酯( AAA)为原料,固体酸为催化剂,采用酯交换法合成了乙酰乙酸基甲基丙烯酸乙酯( AAEM)。采用单因素和正交实验的方法对反应条件进行了探究,确定较佳的反应条件为:n(AAA)∶n(HEMA)=3∶1,反应温度130℃,反应时间3 h,催化剂的用量4.5%(HEMA),阻聚剂的用量0.3%(HEMA)。在上述条件下,产品收率93%以上,含量97%,采用FTIR和1H NMR对产品结构进行了表征。

  2. STRUCTURE ACTIVITY RELATIONSHIP STUDIES OF SUBSTITUTED MANNICH BASES OF 2-OXO-4, 6-DIPHENYL-2, 6- IHYDROPYRAZOLO [1,5-a] [1,3,5] TRIAZINE-7-CARBONYL RING SYSTEM WITH VARIABLE ELECTRONEGETIVE ATOMS (UREA/THIOUREA/GUANIDINE FOR ANTIMICROBIAL AND ANTIFUNGAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Kaumil Navnitbhai Modi

    2011-06-01

    Full Text Available 2-oxo-4,6-diphenyl-2,6-dihydropyrazolo [1,5-a] [1,3,5] triazine-7- carbonyl ring system has been synthesised by the reaction between phenyl hydrazine and ethyl acetoacetate produced pyrazolone moiety which on benzoylation produced benzoyl derivative which on condensation with urea produced 7-methyl-4,6- diphenylpyrazolo-[1,5-a][1,3,5]triazin-2(6H-one ring which on alkaline oxidation with KMnO4/KOH produced carboxylic moiety. Treatment with thionyl chloride of produced acid chloride derivative. This on condensation with Mannich base produced by benzaldehyde and p-chloro benzaldehyde with urea/thiourea/guanidine produced the desired moiety. The synthesised compounds were characterised by N% and spectral datas and antimicrobial and antifungal screening has been performed by zone of inhibition studies and MIC calculation with standard antibiotic/antifungal drug against (gram+ve and (gram– ve bacteria and fungal strains on agar media after 24 hours incubation at 37°C for antimicrobial activity and 24°C for antifungal activity. Gram positive: Staphylococcus aureus ATCC 9144, Bacillus subtilis ATCC 6633, Gram negative: Escherichia coli ATCC 25922, Fungal strain: Candida albicans ATCC 10231 It has been observed that the Compound-6c (X=NH showed maximum antibacterial activity against Escherichia coli, Compound-6a (X=O against Bacillus subtilis and Compound- 6e (X=S against Staphylococcus aureus. Oxygen and Sulphur has two lone pairs whereas Nitrogen has one lone pair of electrons but the electronegativity of Oxygen (X=O; 3.5, electronegativity of Sulphur (X=S; 2.4 and electronegativity of Nitrogen (X=N+H; 3.1+2.2=5.3. MIC value of all the compounds have been found as 250Hg as Minimum Inhibitory Concentration by serial dilution method and MIC of Ampicillin is 25Hg and for Fluconazole is 5.5Hg.

  3. Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.

    Science.gov (United States)

    Orczyk-Pawilowicz, Magdalena; Jawien, Ewa; Deja, Stanislaw; Hirnle, Lidia; Zabek, Adam; Mlynarz, Piotr

    2016-01-01

    Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2nd and 3rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at α = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies.

  4. Synthesis of novel furobenzopyrone derivatives and evaluation of their antimicrobial and antiinflammatory activity

    Directory of Open Access Journals (Sweden)

    Srinivasan K

    2007-01-01

    Full Text Available Certain 4′-(4′′-substituted phenyl-4-methylfurobenzopyrones were synthesized and evaluated for antibacterial activity. Six of the synthesized compounds were also screened for their antiinflammatory activity. Substituted resorcinols were condensed with ethyl acetoacetate to afford different coumarins (2a-c. Various substituted phenacyl bromides (4a-g were prepared by the bromination of para-substituted acetophenones. The coumarins (2a-c and phenacyl bromides (4a-g were condensed to give oxoethers (5a-s. These were cyclised by using 1 M sodium hydroxide to afford the desired furobenzopyrone derivatives (FCa-s. All the compounds have been evaluated for their antibacterial activity against different strains of gram positive and gram negative bacteria. All the compounds have shown good activity against Pseudomonas aeruginosa . Compounds, 3-(4-chlorophenyl-5-methylfuro-[3,2-g][1]benzopyran-7-one, 3-(4-chlorophenyl-5,9-dimethylfuro[3,2-g][1]benzopyran-7-one and 4,5-dimethyl-3-phenylfuro[3,2-g][1]benzopyran-7-one (FCe, FCi, FCn were active against E. coli . A few compounds showed moderate activity against Bacillus subtilis also. Antiinflammatory activity of six selected compounds was also tested using the carrageenan-induced rat paw oedema method. Among them, 5-methyl-3-p-tolylfuro[3,2-g][1]benzopyran-7-one (FCg showed excellent activity. 5-Methyl-3-phenylfuro[3,2-g][1]benzopyran-7-one (FCa and 4,5-dimethyl-3-(4-nitrophenyl-furo[3,2-g][1]benzopyran-7-one (FCc showed activity comparable to that of the standard drug ibuprofen.

  5. Microstructure, Optical and Photocatalytic Properties of TiO₂ Thin Films Prepared by Chelating-Agent Assisted Sol-Gel Method.

    Science.gov (United States)

    Matĕjová, Lenka; Cieslarová, Monika; Matĕj, Zdenĕk; Danis, Stanislav; Peikertová, Pavlína; Sihor, Marcel; Lang, Jaroslav; Matĕjka, Vlastimil

    2016-01-01

    Single and multilayer TiO₂ thin films coated on two types of soda-lime glass substrates (microscope slides and cylinders) were prepared by a chelating agent-assisted sol-gel method, using ethyl acetoacetate as a chelating agent, dip-coating and calcination at 500 °C for 2 h in air. Phase composition, microstructural, morphological and optical properties of thin films were comprehensively investigated by using XRF, advanced XRD analysis, Raman and UV-vis spectroscopy and AFM. It was found out that the thickness of thin films increases linearly with increasing number of deposited layers, indicating a good adhesion of the titania solution to a glass substrate as well as to a previously calcined layer. 1 layer film crystallized to anatase-TiO₂(B) mixture with minor/negligible amount of nanosized brookite, 2-4 layers films crystallized to anatase-brookite-TiO₂(B) mixture. In contrast to other multilayers films, 4 layers film was highly inhomogeneous. The different phase composition of thin films was clarified based on the crystallization via titanate/s and metastable monoclinic TiO₂(B) as a consequence of several phenomena; the diffusion of Na⁺ ions from a soda-lime glass substrate, acidic conditions and repeated thermal treatment. The multilayer films were in average highly transparent (80-95%) in the visible light region with the sharp absorption edge in the UV light region. Additionally, the photocatalytic properties of selected multilayer films were compared in AO7 photodegradation. Photocatalytic experiments showed that thicker 4 layers film of tricrystalline anatase-brookite-TiO₂(B) phase mixture was similarly active as thinner 3 layers film of similar phase composition, which may be a consequence of the inhomogeneity of the thicker film. PMID:27398480

  6. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    International Nuclear Information System (INIS)

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg-1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  7. Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

    Directory of Open Access Journals (Sweden)

    Liangcai Zhao

    Full Text Available BACKGROUND: Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. METHODOLOGY/PRINCIPAL FINDINGS: Nuclear magnetic resonance (NMR-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. CONCLUSIONS/SIGNIFICANCES: The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

  8. Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

    Directory of Open Access Journals (Sweden)

    de Reggi Max

    2010-04-01

    Full Text Available Abstract Background The administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasis is on the penultimate step of the process, i.e. L-3-hydroxybutyryl-CoA dehydrogenase activity. We determined changes in enzyme activity and in circulating ketone body levels in the MPTP mouse model of Parkinson's disease. Since the active moiety of CoA is pantetheine, mice were treated with pantethine, its naturally-occurring form. Pantethine has the advantage of being known as an anti-inflammatory and hypolipidemic agent with very few side effects. Results We found that dehydrogenase activity and circulating ketone body levels were drastically reduced by the neurotoxin MPTP, whereas treatment with pantethine overcame these adverse effects. Pantethine prevented dopaminergic neuron loss and motility disorders. In vivo and in vitro experiments showed that the protection was associated with enhancement of glutathione (GSH production as well as restoration of respiratory chain complex I activity and mitochondrial ATP levels. Remarkably, pantethine treatment boosted the circulating ketone body levels in MPTP-intoxicated mice, but not in normal animals. Conclusions These finding demonstrate the feasibility of the enhancement of endogenous ketone body production and provide a promising therapeutic approach to Parkinson's disease as well as, conceivably, to other neurodegenerative disorders.

  9. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

    Science.gov (United States)

    Stilling, Roman M; van de Wouw, Marcel; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2016-10-01

    Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication. PMID:27346602

  10. Preparation of zirconia coatings by hydrolysis of zirconium alkoxide with hydrogen peroxide

    International Nuclear Information System (INIS)

    Zirconia has gained a great deal of attention because of its superior properties of mechanical strength, chemical resistance, and ionic conductivity. Zirconia coatings and thin films are receiving attention as tribological and thermal barrier coatings for engines, high-reflective coatings, solid electrolytes for fuel cells, oxygen sensors, etc. The sol-gel coating method has several advantages, such as low processing temperatures, homogeneity, control of micro-structure, and good productivity compared to chemical vapor deposition and physical vapor deposition. However, there are few reports concerning the preparation of zirconia coatings and thin films by the sol-gel method. Up to the present, zirconia coatings have been prepared from zirconium propoxide (not heated), zirconium tetrabutoxide modified by acetylacetone and ethyl acetoacetate, zirconium diethoxydichloride (ZrCl2(OC2H5)2), and a hydrosol prepared from a zirconium oxychloride solution. Coatings of 8.8-mol%-yttria-doped zirconia were fabricated using a transparent and spinnable sol prepared by hydrolysis of zirconium alkoxide with hydrogen peroxide and nitric acid. The sol gave a crack-free coating film consisting of fine grains. The crystalline phase was cubic after heating of 1,000 and 1,200 C and cubic and tetragonal at 1,350 C, with the coating being highly oriented in the (111) plane, especially at 1,000 C. Activation energy of the coating films was higher than that of the bulk. Transmittance through a film thickness of about 0.3 μm on each side was 75%

  11. Systemic and characteristic metabolites in the serum of streptozotocin-induced diabetic rats at different stages as revealed by a (1)H-NMR based metabonomic approach.

    Science.gov (United States)

    Diao, Chengfeng; Zhao, Liangcai; Guan, Mimi; Zheng, Yongquan; Chen, Minjiang; Yang, Yunjun; Lin, Li; Chen, Weijian; Gao, Hongchang

    2014-03-01

    Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids, and proteins. Investigating the changes in metabolic pathways during the evolution of diabetes mellitus may contribute to the understanding of its metabolic features and pathogenesis. In this study, serum samples were collected from diabetic rats and age-matched controls at different time points: 1 and 9 weeks after streptozotocin (STZ) treatment. (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with quantitative analysis was performed to study the metabolic changes. The serum samples were also subjected to clinical chemistry analysis to verify the metabolic changes observed by metabonomics. Partial least squares discriminant analysis (PLS-DA) demonstrated that the levels of serum metabolites in diabetic rats are different from those in control rats. These findings indicate that the metabolic characteristics of the two groups are markedly different at 1 and 9 weeks. Quantitative analysis showed that the levels of some metabolites, such as pyruvate, lactate, citrate, acetone, acetoacetate, acetate, glycerol, and valine, varied in a time-dependent manner in diabetic rats. These results suggest that serum metabolites related to glycolysis, the tricarboxylic acid cycle, gluconeogenesis, fatty acid β-oxidation, branched-chain amino acid metabolism, and the tyrosine metabolic pathways are involved in the evolution of diabetes. The metabolic changes represent potential features and promote a better understanding of the mechanisms involved in the development of diabetes mellitus. This work further suggests that (1)H NMR metabonomics is a valuable approach for providing novel insights into the pathogenesis of diabetes mellitus and its complications. PMID:24448714

  12. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease.

    Science.gov (United States)

    Youm, Yun-Hee; Nguyen, Kim Y; Grant, Ryan W; Goldberg, Emily L; Bodogai, Monica; Kim, Dongin; D'Agostino, Dominic; Planavsky, Noah; Lupfer, Christopher; Kanneganti, Thirumala D; Kang, Seokwon; Horvath, Tamas L; Fahmy, Tarek M; Crawford, Peter A; Biragyn, Arya; Alnemri, Emad; Dixit, Vishwa Deep

    2015-03-01

    The ketone bodies β-hydroxybutyrate (BHB) and acetoacetate (AcAc) support mammalian survival during states of energy deficit by serving as alternative sources of ATP. BHB levels are elevated by starvation, caloric restriction, high-intensity exercise, or the low-carbohydrate ketogenic diet. Prolonged fasting reduces inflammation; however, the impact that ketones and other alternative metabolic fuels produced during energy deficits have on the innate immune response is unknown. We report that BHB, but neither AcAc nor the structurally related short-chain fatty acids butyrate and acetate, suppresses activation of the NLRP3 inflammasome in response to urate crystals, ATP and lipotoxic fatty acids. BHB did not inhibit caspase-1 activation in response to pathogens that activate the NLR family, CARD domain containing 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome and did not affect non-canonical caspase-11, inflammasome activation. Mechanistically, BHB inhibits the NLRP3 inflammasome by preventing K(+) efflux and reducing ASC oligomerization and speck formation. The inhibitory effects of BHB on NLRP3 are not dependent on chirality or starvation-regulated mechanisms like AMP-activated protein kinase (AMPK), reactive oxygen species (ROS), autophagy or glycolytic inhibition. BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). BHB reduces NLRP3 inflammasome-mediated interleukin (IL)-1β and IL-18 production in human monocytes. In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome and urate crystal-induced peritonitis. Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB

  13. Applications of lasers in metallization of thermoplastic and thermosetting polymers

    Directory of Open Access Journals (Sweden)

    P. Rytlewski

    2013-04-01

    Full Text Available Purpose: This work focuses on the studies of chemical and physical changes induced by ArF-laser irradiation leading to formation of surfaces catalytically highly active and fully prepared for the direct electroless metallization for the case of thermoplastic and thermosetting polymer composites. The only pretreatment method for surface to be activated was laser irradiation. There are compared two polymer composites: thermoplastic and thermosetting with the same qualitative and quantitative contents of the selected copper compounds. Additionally, there is presented wide context of laser applications in electroless metallization of polymeric materials.Design/methodology/approach: The composites contained the same amount of copper(II oxide (CuO and copper(II acetoacetate Cu(acac2, while varied with the type of polymer matrix. There were chosen polyamide 6 as thermoplastic and polyurethane resin as thermosetting polymer matrixes. The composites were irradiated with various numbers of ArF excimer laser pulses (λ = 193 nm at constant fluence of 100 mJ/cm2. The metallization procedure of the laser-irradiated samples was performed by use of a commercial metallization bath and formaldehyde as a reducing agent. The samples were examined using FTIR, contact angle measurement and SEM techniques.Findings: It was found that laser irradiation induce catalytic properties in the studied composites. However, better catalytic properties were achieved for the thermoplastic than thermosetting polymer composites.Research limitations/implications: In order to better understand the differences in laser interactions between thermoplastic and thermosetting composites more examples of various polymer matrixes should be investigated.Practical implications: Suitable condition for laser irradiation of the composites associated with the best catalytic properties were proposes. Better catalytic properties were achieved for thermoplastic than thermosetting composite

  14. 2,4-二甲基吡咯-3,5-二羧酸二乙酯的合成--推荐一个大学有机化学实验%Synthesis of Diethyl 2,4-dimethyl-pyrrole-3,5-dicarboxylate:Recommending a University Organic Chemistry Experiment

    Institute of Scientific and Technical Information of China (English)

    汪剑波; 宗乾收; 沈锦锦; 毕成; 吴晨俊

    2016-01-01

    Using Knorr pyrrole synthesis, diethyl 2,4-dimethyl-pyrrole-3,5-dicarboxylate was synthesized via one-pot method with ethyl acetoacetate and sodium nitrite as starting materials in the presence of acetic acid and zinc powder. The experiment involves the experimental operation and analyses including temperature control, reflux, recrystal ization, melting point, IR and NMR spectroscopies. The advantages of the experiment are simple raw materials and high product yield. The experiment is helpful for cultivating and improving the synthesis ability of students, as wel as in-depth understanding of heterocyclic synthesis and spectral analysis.%采用Knorr吡咯合成法,以乙酰乙酸乙酯和亚硝酸钠为原料,在醋酸和锌粉作用下采用“一锅法”得到2,4-二甲基吡咯-3,5-二羧酸二乙酯。本实验涉及到控温、回流、重结晶、熔点测定、红外光谱及核磁共振等实验操作和分析检测方法。该实验原料简单易得、产物收率高,结合波谱解析方法,可以培养和提高学生合成实验的能力,加强学生对杂环合成和波谱解析的理解与分析。

  15. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

    Science.gov (United States)

    Stilling, Roman M; van de Wouw, Marcel; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2016-10-01

    Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication.

  16. Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, β-amyloid toxicity, and astrocyte function.

    Science.gov (United States)

    Hertz, Leif; Chen, Ye; Waagepetersen, Helle S

    2015-07-01

    Diet supplementation with ketone bodies (acetoacetate and β-hydroxybuturate) or medium-length fatty acids generating ketone bodies has consistently been found to cause modest improvement of mental function in Alzheimer's patients. It was suggested that the therapeutic effect might be more pronounced if treatment was begun at a pre-clinical stage of the disease instead of well after its manifestation. The pre-clinical stage is characterized by decade-long glucose hypometabolism in brain, but ketone body metabolism is intact even initially after disease manifestation. One reason for the impaired glucose metabolism may be early destruction of the noradrenergic brain stem nucleus, locus coeruleus, which stimulates glucose metabolism, at least in astrocytes. These glial cells are essential in Alzheimer pathogenesis. The β-amyloid peptide Aβ interferes with their cholinergic innervation, which impairs synaptic function because of diminished astrocytic glutamate release. Aβ also reduces glucose metabolism and causes hyperexcitability. Ketone bodies are similarly used against seizures, but the effectively used concentrations are so high that they must interfere with glucose metabolism and de novo synthesis of neurotransmitter glutamate, reducing neuronal glutamatergic signaling. The lower ketone body concentrations used in Alzheimer's disease may owe their effect to support of energy metabolism, but might also inhibit release of gliotransmitter glutamate. Alzheimer's disease is a panglial-neuronal disorder with long-standing brain hypometabolism, aberrations in both neuronal and astrocytic glucose metabolism, inflammation, hyperexcitability, and dementia. Relatively low doses of β-hydroxybutyrate can have an ameliorating effect on cognitive function. This could be because of metabolic supplementation or inhibition of Aβ-induced release of glutamate as gliotransmitter, which is likely to reduce hyperexcitability and inflammation. The therapeutic

  17. Advances in Synthesis and Aromatization of Hantzsch 1,4-Dihydropyridine Derivatives%Hantzsch 1,4-二氢吡啶衍生物的合成及其芳香化研究进展

    Institute of Scientific and Technical Information of China (English)

    尹显洪

    2003-01-01

      综述了Hantzsch 1,4-二氢吡啶衍生物的合成及其芳香化研究进展.Hantzsch 1,4-二氢吡啶衍生物的合成方法有:(1)乙酰乙酸乙酯、芳香醛和氨或伯胺反应;(2)1,3-二酮化合物、芳香醛和氨或伯胺反应;(3)烯胺化合物和芳香醛反应;(4)1,5-二酮与氨反应;(5) a,b-不饱和酮与烯胺或酮和氨反应等.在合成技术上有固相合成和微波辅助合成等.Hantzsch 1,4-二氢吡啶芳香化方法有:光化学反应、电化学反应、脱氢反应、氢转移反应等,本文主要对脱氢反应研究进展进行综述.%  The main methods of synthesis and aromatization of Hantzsch 1,4-dihydropyridine derivatives was reviewed in this paper. The former included the reactions of ethyl acetoacetate and aromaticaldehyde with ammonia or primary amine, the reactions of 1,3-diketone compounds and aromaticaldehyde with ammonia or primary amine, the reactions of enamine compounds with aromaticaldehyde, the reactions of 1,5-diketone with amine, the reactions of a,b-unsaturated ketone with enamine or ketone and amine. The synthetic technologies included solid-phase synthesis and microwave-assistant synthesis. The latter included photochemical reactions, electrochemical reactions, dehydrogenation reactions, hydrogen transfer reactions.

  18. Isopropanol production with engineered Cupriavidus necator as bioproduction platform

    Energy Technology Data Exchange (ETDEWEB)

    Grousseau, E; Lu, JN; Gorret, N; Guillouet, SE; Sinskey, AJ

    2014-03-07

    Alleviating our society's dependence on petroleum-based chemicals has been highly emphasized due to fossil fuel shortages and increasing greenhouse gas emissions. Isopropanol is a molecule of high potential to replace some petroleum-based chemicals, which can be produced through biological platforms from renewable waste carbon streams such as carbohydrates, fatty acids, or CO2. In this study, for the first time, the heterologous expression of engineered isopropanol pathways were evaluated in a Cupriavidus necator strain Re2133, which was incapable of producing poly-3-hydroxybutyrate [P(3HB)]. These synthetic production pathways were rationally designed through codon optimization, gene placement, and gene dosage in order to efficiently divert carbon flow from P(3HB) precursors toward isopropanol. Among the constructed pathways, Re2133/pEG7c overexpressing native C. necator genes encoding a beta-ketothiolase, a CoA-transferase, and codon-optimized Clostridium genes encoding an acetoacetate decarboxylase and an alcohol dehydrogenase produced up to 3.44 g l(-1) isopropanol in batch culture, from fructose as a sole carbon source, with only 0.82 g l(-1) of biomass. The intrinsic performance of this strain (maximum specific production rate 0.093 g g(-1) h(-1), yield 0.32 Cmole Cmole(-1)) corresponded to more than 60 % of the respective theoretical performance. Moreover, the overall isopropanol production yield (0.24 Cmole Cmole(-1)) and the overall specific productivity (0.044 g g(-1) h(-1)) were higher than the values reported in the literature to date for heterologously engineered isopropanol production strains in batch culture. Strain Re2133/pEG7c presents good potential for scale-up production of isopropanol from various substrates in high cell density cultures.

  19. Metabonomic alterations from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma facilitate the identification of biomarkers in serum for early diagnosis of pancreatic cancer.

    Science.gov (United States)

    Lin, Xianchao; Zhan, Bohan; Wen, Shi; Li, Zhishui; Huang, Heguang; Feng, Jianghua

    2016-08-16

    Pancreatic cancer is a highly malignant disease with a poor prognosis and it is essential to diagnose and treat the disease at an early stage. The aim of this study was to understand the underlying biochemical mechanisms of pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and to identify potential serum biomarkers for early detection of pancreatic cancer. 7,12-Dimethylbenz(a)anthracene (DMBA)-induced PanIN and PDAC rat models were established and the serum samples were collected. The serum samples were measured using (1)H nuclear magnetic resonance (NMR) spectroscopy and analyzed by chemometric methods including principal component analysis (PCA) and (orthogonal) partial least squares discriminant analysis ((O)PLS-DA). The related biochemical pathways were derived from KEGG analysis of the significantly different metabolites. As results, some serum metabolites demonstrated alarming metabolic changes in the precursor lesion of pancreatic cancer (PanIN-2 in this study). These changes involved elevated levels of ketone compounds including 3-hydroxybutyrate, acetoacetate, and acetone, some amino acids including asparagine, glutamate, threonine, and phenylalanine, glycoproteins and lipoproteins including N-acetylglycoprotein, LDL and VLDL, and some metabolites that have been shown to contribute to mutagenicity and cancer promotion such as deoxyguanosine and cytidine. More metabolites were shown to be significantly different between PanIN and PDAC, suggesting that a more complex set of changes occurs from noninvasive precursor lesion to invasive cancer. The serum metabonomic changes of rats with PanIN and PDAC may extend our understanding of pancreatic molecular pathogenesis, and the metabolic variations from PanIN to PDAC will be helpful to understand evolution processes of the pancreatic disease. NMR-based metabonomic analysis of animal models will be beneficial for the human study and will be helpful for the early detection of

  20. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Science.gov (United States)

    Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

    2010-03-01

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  1. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    International Nuclear Information System (INIS)

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  2. Enzymatic capacities of metabolic fuel use in cuttlefish (Sepia officinalis) and responses to food deprivation: insight into the metabolic organization and starvation survival strategy of cephalopods.

    Science.gov (United States)

    Speers-Roesch, Ben; Callaghan, Neal I; MacCormack, Tyson J; Lamarre, Simon G; Sykes, Antonio V; Driedzic, William R

    2016-08-01

    Food limitation is a common challenge for animals. Cephalopods are sensitive to starvation because of high metabolic rates and growth rates related to their "live fast, die young" life history. We investigated how enzymatic capacities of key metabolic pathways are modulated during starvation in the common cuttlefish (Sepia officinalis) to gain insight into the metabolic organization of cephalopods and their strategies for coping with food limitation. In particular, lipids have traditionally been considered unimportant fuels in cephalopods, yet, puzzlingly, many species (including cuttlefish) mobilize the lipid stores in their digestive gland during starvation. Using a comprehensive multi-tissue assay of enzymatic capacities for energy metabolism, we show that, during long-term starvation (12 days), glycolytic capacity for glucose use is decreased in cuttlefish tissues, while capacities for use of lipid-based fuels (fatty acids and ketone bodies) and amino acid fuels are retained or increased. Specifically, the capacity to use the ketone body acetoacetate as fuel is widespread across tissues and gill has a previously unrecognized capacity for fatty acid catabolism, albeit at low rates. The capacity for de novo glucose synthesis (gluconeogenesis), important for glucose homeostasis, likely is restricted to the digestive gland, contrary to previous reports of widespread gluconeogenesis among cephalopod tissues. Short-term starvation (3-5 days) had few effects on enzymatic capacities. Similar to vertebrates, lipid-based fuels, putatively mobilized from fat stores in the digestive gland, appear to be important energy sources for cephalopods, especially during starvation when glycolytic capacity is decreased perhaps to conserve available glucose. PMID:27138338

  3. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  4. The origin of free brain malonate

    Energy Technology Data Exchange (ETDEWEB)

    Riley, K.M.; Dickson, A.C.; Koeppen, A.H. (Research Service, Veterans Administration Medical Center, Albany, NY (United States))

    1991-02-01

    Rat brain contains substantial concentrations of free malonate (192 nmol/g wet weight) but origin and biological importance of the dicarboxylic acid are poorly understood. A dietary source has been excluded. A recently described malonyl-CoA decarboxylase deficiency is associated with malonic aciduria and clinical manifestations, including mental retardation. In an effort to study the metabolic origin of free malonate, several labeled acetyl-CoA precursors were administered by intracerebral injection. (2-14C)pyruvate or (1,5-14C)citrate produced radioactive glutamate but failed to label malonate. In contrast, (1-14C)acetate, (2-14C)acetate, and (1-14C)butyrate were converted to labeled glutamate and malonate after the same route of administration. The intracerebral injection of (1-14C)-beta-alanine as a precursor of malonic semialdehyde and possibly free malonate did not give rise to radioactivity in the dicarboxylate. The labeling pattern of malonic acid is compatible with the reaction sequence: acetyl-CoA----malonyl-CoA----malonate. The final step is thought to occur by transfer of the CoA-group from malonyl-CoA to succinate and/or acetoacetate. Labeling of malonate from acetate is most effective at the age of 7 days when the net concentration of the dicarboxylic acid in rat brain is still very low. At this age, butyrate was a better precursor of malonate than acetate. It is proposed that fatty acid oxidation provides the acetyl-CoA which functions as the precursor of free brain malonate. Compartmentation of malonate biosynthesis is likely because the acetyl-CoA precursors citrate and pyruvate are ineffective.

  5. Determining the Biochemical Properties of the Oxalate Biosynthetic Component (Obc)1 from Burkholderia mallei.

    Science.gov (United States)

    Lambert, Peter M; Nakata, Paul A

    2016-01-01

    Oxalic acid is produced by a variety of organisms ranging from simple microbes to complex animals. This acid has been proposed to fulfill various physiological and pathological functions which vary between organisms. In bacteria from the Burkholderia genus, oxalate secretion has been shown to be quorum sensing dependent and to support pathogenicity and cell viability. In light of the critical roles of oxalate in Burkholderia as well as other organisms, it is surprising that our understanding of how this simple dicarboxylate is biosynthesized remains incomplete. Here we report the expression, purification, and partial characterization of the first intact bacterial oxalate biosynthetic enzyme, Obc1, from B. mallei. An N-terminal His-tagged Bmobc1 was cloned into pDUET, expressed in E. coli BLR (DE3), and the recombinant enzyme purified by affinity chromatography. Oxalate biosynthetic enzyme assays coupled with HPLC analysis revealed that BmObc1 catalyzed the biosynthesis of oxalate, acetoacetate, and free CoA from oxaloacetate and a short chain acyl-CoA following Michaelis-Menten kinetics. Optimal enzyme activity was measured at pH 8.0 and a temperature around 44°C. Kinetic analysis conducted under conditions of saturating acetyl-CoA and varying oxaloacetate concentrations resulted in a calculated Km value for oxaloacetate of 94.3± 9.2 μM (mean ± SE). Under conditions of saturating oxaloacetate concentration and varying acyl-CoA (acetyl- or propionyl-CoA) concentrations kinetic analysis generated a calculated Km value of 26.8 ± 2.3 μM (mean ± SE) for acetyl-CoA and 104.4 ± 12.7 μM for propionyl-CoA. The significantly lower Km for acetyl-CoA suggests that it is strongly favored as a substrate over propionyl-CoA. PMID:27643499

  6. High acetone-butanol-ethanol production in pH-stat co-feeding of acetate and glucose.

    Science.gov (United States)

    Gao, Ming; Tashiro, Yukihiro; Wang, Qunhui; Sakai, Kenji; Sonomoto, Kenji

    2016-08-01

    We previously reported the metabolic analysis of butanol and acetone production from exogenous acetate by (13)C tracer experiments (Gao et al., RSC Adv., 5, 8486-8495, 2015). To clarify the influence of acetate on acetone-butanol-ethanol (ABE) production, we first performed an enzyme assay in Clostridium saccharoperbutylacetonicum N1-4. Acetate addition was found to drastically increase the activities of key enzymes involved in the acetate uptake (phosphate acetyltransferase and CoA transferase), acetone formation (acetoacetate decarboxylase), and butanol formation (butanol dehydrogenase) pathways. Subsequently, supplementation of acetate during acidogenesis and early solventogenesis resulted in a significant increase in ABE production. To establish an efficient ABE production system using acetate as a co-substrate, several shot strategies were investigated in batch culture. Batch cultures with two substrate shots without pH control produced 14.20 g/L butanol and 23.27 g/L ABE with a maximum specific butanol production rate of 0.26 g/(g h). Furthermore, pH-controlled (at pH 5.5) batch cultures with two substrate shots resulted in not only improved acetate consumption but also a further increase in ABE production. Finally, we obtained 15.13 g/L butanol and 24.37 g/L ABE at the high specific butanol production rate of 0.34 g/(g h) using pH-stat co-feeding method. Thus, in this study, we established a high ABE production system using glucose and acetate as co-substrates in a pH-stat co-feeding system with C. saccharoperbutylacetonicum N1-4. PMID:26928043

  7. Ketone bodies, potential therapeutic uses.

    Science.gov (United States)

    Veech, R L; Chance, B; Kashiwaya, Y; Lardy, H A; Cahill, G F

    2001-04-01

    Ketosis, meaning elevation of D-beta-hydroxybutyrate (R-3hydroxybutyrate) and acetoacetate, has been central to starving man's survival by providing nonglucose substrate to his evolutionarily hypertrophied brain, sparing muscle from destruction for glucose synthesis. Surprisingly, D-beta-hydroxybutyrate (abbreviated "betaOHB") may also provide a more efficient source of energy for brain per unit oxygen, supported by the same phenomenon noted in the isolated working perfused rat heart and in sperm. It has also been shown to decrease cell death in two human neuronal cultures, one a model of Alzheimer's and the other of Parkinson's disease. These observations raise the possibility that a number of neurologic disorders, genetic and acquired, might benefit by ketosis. Other beneficial effects from betaOHB include an increased energy of ATP hydrolysis (deltaG') and its linked ionic gradients. This may be significant in drug-resistant epilepsy and in injury and anoxic states. The ability of betaOHB to oxidize co-enzyme Q and reduce NADP+ may also be important in decreasing free radical damage. Clinical maneuvers for increasing blood levels of betaOHB to 2-5 mmol may require synthetic esters or polymers of betaOHB taken orally, probably 100 to 150 g or more daily. This necessitates advances in food-science technology to provide at least enough orally acceptable synthetic material for animal and possibly subsequent clinical testing. The other major need is to bring the technology for the analysis of multiple metabolic "phenotypes" up to the level of sophistication of the instrumentation used, for example, in gene science or in structural biology. This technical strategy will be critical to the characterization of polygenic disorders by enhancing the knowledge gained from gene analysis and from the subsequent steps and modifications of the protein products themselves.

  8. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Energy Technology Data Exchange (ETDEWEB)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

    2010-03-26

    As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  9. The synthesis and characterization of 7-hydroxy-4-methylcoumarin and the investigation of the fluorescence properties of its 7-hydroxy-4-methylcoumarin-chitosan films

    International Nuclear Information System (INIS)

    Chitosan fluorescent films containing 7-hydroxy-4-methylcoumarin (7H4MC) have been successfully prepared. Used chitosan was obtained from chitin isolated from skin of tiger prawns (Penaeus monodon) through the deproteination, demineralization, and deacetylation process. The yields of chitin and chitosan are 10.66% and 23.83%, respectively. The chitosan has 55.00% degree of deacetylation based on FTIR spectroscopy. Average molecular mass of chitosan which was determined by Ostwald viscometry method is 8.55 × 106 g/mol. The 7H4MC was synthesized from resorcinol and ethyl acetoacetate using amberlyst-15 as catalyst based on Pechmann reaction with chemical yields of 90.01% and the melting point of 189–190°C. The FTIR, 1H–NMR, and 13C–NMR spectroscopies confirmed the structure which corresponds to the structure of 7H4MC. The films of chitosan containing 7H4MC were prepared by solvent evaporation method in 2% (v/v) acetic acid. The 7H4MC content in each film was 0% (blank), 0.2%, 0.4%, 0.6%, and 0.8% (w/w). The UV-Vis spectrum of 7H4MC in methanol showed λmax at 235 and 337 nm. The observed fluorescence is the fluorescence color of cyan. The excitation wavelengths are 200, 235, 275, 337, and 365 nm. The highest intensity of cyan color fluorescence of chitosan containing 7H4MC films was obtained at the concentration of 0.2% of 7-hydroxy-4-methylcoumarin at the excitation wavelength of 275 nm

  10. Antioxidant, antityrosinase and antitumor activity comparison: the potential utilization of fibrous root part of Bletilla striata (Thunb. Reichb.f.

    Directory of Open Access Journals (Sweden)

    Fusheng Jiang

    Full Text Available This study was carried out to evaluate the utilization probability of the fibrous root part (FRP of Bletilla striata, which was usually discarded and harvesting pseudobulb part (PSP. The chemical composition, total phenolic content, DPPH radical scavenging activity, Ferric-reducing antioxidant power and tyrosinase inhibition activity were compared between FRP and PSP. Antioxidant and pro-oxidant effect as well as antitumor effect of the extract of FRP and PSP were analyzed by in vitro cell system as well. Thin layer chromatography and high performance liquid chromatography analysis indicated that the chemical compositions in the two parts were similar, but the content in FRP was much higher than PSP. Meanwhile, the FRP extracts showed higher phenolic content, stronger DPPH scavenging activity, Ferric-reducing antioxidant capacity and tyrosinase inhibition activity. Sub-fraction analysis revealed that the distribution characteristic of phenolic components and other active constituents in FRP and PSP were consistent, and mainly deposited in chloroform and acetoacetate fractions. Especially, the chloroform sub-fraction (sch of FRP showed extraordinary DPPH scavenging activity and tyrosinase inhibition activity, with IC50 0.848 mg/L and 4.3 mg/L, respectively. Besides, tyrosinase inhibition activity was even stronger than the positive compound arbutin (31.8 mg/L. Moreover, In vitro cell system analysis confirmed that FRP extract exerts comparable activity with PSP, especially, the sub-fraction sch of FRP showed better antioxidant activity at low dosage and stronger per-oxidant activity at high dosage, and both sch of FRP and PSP can dose-dependent induce HepG2 cells apoptosis, which implied tumor therapeutic effect. Considering that an additional 0.3 kg FRP would be obtained when producing 1.0 kg PSP, our work demonstrated that FRP is very potential to be used together with PSP.

  11. Effect of different doses of propofol and propofol medium/long-chain fat emulsion on blood ketone body ratio%不同剂量丙泊酚和丙泊酚中/长链脂肪乳对血酮体比率的影响

    Institute of Scientific and Technical Information of China (English)

    安丽; 高鸿; 欧炜; 刘艳秋

    2014-01-01

    Objective To observe the effect of different doses of propofol injection and propofol medium/long-chain fat emulsion injection in short time infusion on plasma ketone body ratio,to eva-lute its effecton hepatic energy metabolism.Methods Forty patients,aged 18-50 years old,ASA Ⅰ orⅡ undergoing selective surgery were randomly divided into 4 groups with 10 cases in each;propofol injection 4 mg·kg-1·h-1 maintain anesthesia (group L4 ),propofol injection 6 mg·kg-1·h-1 maintain anesthesia (group L6 ),propofol medium/long-chain fat emulsion injection 4 mg·kg-1·h-1 maintain anesthesia (group M4 ),propofol medium/long-chain fat emulsion injection 6 mg·kg-1·h-1 maintain anesthesia (group M6 ).MAP,HR,SpO2 and PET CO2 were recorded before anesthesia induction (T0 ),after tracheal intubation (T1 ),after 2 hours infusion of propofol (T2 )and operation completed (T3 ).The blood samples were collected at T1 and T2 to detect the level of acetoacetate,β-hydroxybu-tyrate and to calculate the blood ketone body ratio (the ratio of acetoacetate andβ-hydroxybutyrate). Results MAP,HR,SpO2 ,PET CO2 at T0-T3 and acetoacetate,β-hydroxybutyrate,blood ketone body ratio at T1 ,T2 showed no significant statistic difference.Conclusion Different doses of propofol and different doses of propofol medium/long-chain fat emulsion injection in short time continuous in-fusion has no obvious effect on hepatic energy metabolism;same dose of propofol injection and propo-fol medium/long-chain fat emulsion injection in short time continuous infusion has no obvious effect on hepatic energy metabolism.%目的:观察不同剂量丙泊酚注射液和丙泊酚中/长链脂肪乳注射液短时间输注血浆酮体比率的变化,以此评价其对肝脏能量代谢的影响。方法选择择期手术患者40例,年龄18~50岁,ASA Ⅰ或Ⅱ级,随机分为四组,每组10例,分别为:丙泊酚注射液4 mg·kg-1·h-1维持麻醉(L4组)、丙泊酚注射液6 mg·kg-1·h-1维持麻醉(L6组)、丙

  12. The synthesis and pharmacological evaluation of (±-2,3-seco-fentanyl analogues

    Directory of Open Access Journals (Sweden)

    LJ. DOSEN-MICOVIC

    2004-11-01

    Full Text Available An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1–5.5 (all new compounds were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting b-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methylphenethylamine, (93 % yield, was successively reacted with NaH and BuLi, to form the highly reactive a,g-dienolate anion 1.1a. Regio and chemoselective g-alkylation of the dienolate with various primary and secondary alkyl halides furnished the b-keto-amides 1.2–1.5 (76–91 %. Reductive amination of the keto-amides 1.1–1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1–2.5, afforded the b-anilino amides 3.1–3.5 (74–85 %. After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1–4.5 were obtained (87–97 %. The synthesis of (±-2,3-seco-fentanyls 5.1–5.5 was completed by N-acylation of the diamines 4.1–4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86–95 %. The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5–6 times more active than morphine in rats, while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance, the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers.

  13. CRITICAL POINTS IN THE FEEDING OF HIGH YIELDING DAIRY COWS IN ASSOCIATION WITH BCS AND METABOLIC PROFILE TEST

    Directory of Open Access Journals (Sweden)

    Z. GERGÁCZ

    2013-07-01

    Full Text Available The aim of the study was to analyse the relationship between the body condition and the results of metabolic profile tests done in the milk (DIM of dairy cows in different days. Moreover, critical points in the early pre- and postpartum period were also analysed. In the experiment, blood and urine samples were taken from 1984 clinically healthy cows (from 49 large scale dairy farms in Hungary, selected randomly from various groups of cows with different physiological stage of lactation and gestation, 3-5 hours after the morning feeding. During the experiment body condition scoring (BCS was measured on 1-5 scale, as well. It was concluded, that the BCS (body condition score decreased from the 1st day of lactation (3.48 onwards till the 44th day (2.65 and slightly increased till the day 218 (2.89. The haemoglobin value and the glucose concentration in blood samples were ranging within the physiological range and followed the tendency of BCS and the relationship between them and DIM was (P<0.001. There was a close negative correlation between the NEFA (non-esterified-fatty-acid concentration in blood samples and BCS change and it was found that these values were significantly different (P<0.01 compared to the DIM. The aceto-acetic acid concentration exceeded the upper limit of the physiological range indicating hyperketonaemia at DIM 18. The AST (aspartate aminotransferase, liver-enzyme activity value exceeded the upper limit of physiological range and followed the tendency of BCS change . The urea concentration in the blood exceeded the upper limit of the physiological range in all cows. The NABE (net acid-base empty value in the urine samples indicated acid load in the first two groups of samples (pre-, and post calving. During factor analysis I could differentiate three group factors and one individual. The most important factor is the acid-based factor (with urine pH and NEBA. The results of the present study also confirm that the body

  14. DIFFERENTIAL DIAGNOSIS OF ORGANIC ACIDEMIA: CLINICAL AND NEUROIMAGING FINDINGS

    Directory of Open Access Journals (Sweden)

    Mahmoud Reza ASHRAFI

    2012-03-01

    Full Text Available Clinical differential DiagnosisThe organic acidemias are important in the differential diagnosis of metabolic and neurologic derangement in the neonate and of new-onset neurologic signs in the older child.A-Organic aciduriaSeveral disorders, not classified as primary disorders of organic acid metabolism, have a characteristic urinary organic acid profile that suggests the appropriate diagnosis.• Mevalonicaciduria, a disorder of cholesterol biosynthesis, shows mevalonic acid in the urine.• Glutaricacidemia type II, a disorder of fatty acid oxidation, has multiple organic acids in abnormal concentration in urine. These organic acids include ethylmalonic acid, glutaric acid, dicarboxylic acids, and glycine conjugates of medium chain dicarboxylic acids.• The fatty acylCoA-glycine conjugates that signal incomplete fatty acid oxidation and serves as signals to the diagnosis of MCAD defeciency and other disorders of fatty acid oxidation and transport.• Biotinidase deficiency, a disorder of biotin recycling, results in the urinary excretion of several unusual organic acids, including 3-hydroxy-isovaleric, 3-hydroxypropionic, 3-hydroxybutyric acids, and acetoacetate. Propionyl glycine may also be seen.• Mitochondrial diseases with disordered oxidative phosphorylation often demonstrate the presence of abnormal organic acids in the urine.B-AcidosisNon-genetic conditions, such as shock, sepsis, DKA, liver and kidney failure, thiamine deficiency, RTA, some drug intoxication cause acidosis- genetic conditions are include: inherited metabolic disorders of lactate and pyruvate metabolism and oxidative phosphorylation, disorders of the Krebs cycle such as fumarase deficiency.C-HyperammonemiaDisorders of the urea cycle and the hyperammonemia-hypoglycemia syndrome.Neuroimaging• A variety of MRI abnormalities have been described in the organic academia, including distinctive basal ganglia lesions in glutaricacidemia type I (GA I, white matter changes in

  15. Synthesis, Antibacterial and Antifungal Activity of Some New Pyrazoline and Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Seham Y. Hassan

    2013-02-01

    Full Text Available A series of 2-pyrazolines 5–9 have been synthesized from α,β-unsaturated ketones 2–4. New 2-pyrazoline derivatives 13–15 bearing benzenesulfonamide moieties were then synthesized by condensing the appropriate chalcones 2–4 with 4-hydrazinyl benzenesulfonamide hydrochloride. Ethyl [1,2,4] triazolo[3,4-c][1,2,4]triazino[5,6-b]-5H-indole-5-ethanoate (26 and 1-(5H-[1,2,4]triazino[5,6-b] indol-3-yl-3-methyl-1H-pyrazol-5(4H-one (32 were synthesized from 3-hydrazinyl-5H-[1,2,4]triazino[5,6-b]indole (24. On the other hand ethyl[1,2,4]triazolo[3,4-c][1,2,4]triazino[5,6-b]-5,10-dihydroquinoxaline- 5-ethanoate (27 and 1-(5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxalin-3-yl-3-methyl-1H-pyrazol-5(4H-one (33 were synthesized from 3-hydrazinyl-5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxaline (25 by reaction with diethyl malonate or ethyl acetoacetate, respectively. Condensation of 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (1' with compound 24 or 25 afforded the corresponding Schiff's bases 36 and 37, respectively. Reaction of the Schiff's base 37 with benzoyl hydrazine or acetic anhydride afforded benzohydrazide derivative 39 and the cyclized compound 40, respectively. Furthermore, the pyrazole derivatives 42–44 were synthesized by cyclization of hydrazine derivative 25 with the prepared chalcones 2–4. All the newly synthesized compounds have been characterized on the basis of IR and 1H-NMR spectral data as well as physical data. Antimicrobial activity against the organisms E. coli ATCC8739 and P. aeruginosa ATCC 9027 as examples of Gram-negative bacteria, S. aureus ATCC 6583P as an example of Gram-positive bacteria and C. albicans ATCC 2091 as an example of a yeast-like fungus have been studied using the Nutrient Agar (NA and Sabouraud Dextrose Agar (SDA diffusion methods. The best performance was found for the compounds 16, 17, 19 and 20.

  16. NADPH-dependent reductive biotransformation with Escherichia coli and its pfkA deletion mutant: influence on global gene expression and role of oxygen supply.

    Science.gov (United States)

    Siedler, Solvej; Bringer, Stephanie; Polen, Tino; Bott, Michael

    2014-10-01

    An Escherichia coli ΔpfkA mutant lacking the major phosphofructokinase possesses a partially cyclized pentose phosphate pathway leading to an increased NADPH per glucose ratio. This effect decreases the amount of glucose required for NADPH regeneration in reductive biotransformations, such as the conversion of methyl acetoacetate (MAA) to (R)-methyl 3-hydroxybutyrate (MHB) by an alcohol dehydrogenase from Lactobacillus brevis. Here, global transcriptional analyses were performed to study regulatory responses during reductive biotransformation. DNA microarray analysis revealed amongst other things increased expression of soxS, supporting previous results indicating that a high NADPH demand contributes to the activation of SoxR, the transcriptional activator of soxS. Furthermore, several target genes of the ArcAB two-component system showed a lower mRNA level in the reference strain than in the ΔpfkA mutant, pointing to an increased QH2 /Q ratio in the reference strain. This prompted us to analyze yields and productivities of MAA reduction to MHB under different oxygen regimes in a bioreactor. Under anaerobic conditions, the specific MHB production rates of both strains were comparable (7.4 ± 0.2 mmolMHB  h(-1)  gcdw (-1) ) and lower than under conditions of 15% dissolved oxygen, where those of the reference strain (12.8 mmol h(-1)  gcdw (-1) ) and of the ΔpfkA mutant (11.0 mmol h(-1)  gcdw (-1) ) were 73% and 49% higher. While the oxygen transfer rate (OTR) of the reference strain increased after the addition of MAA, presumably due to the oxidation of the acetate accumulated before MAA addition, the OTR of the ΔpfkA strain strongly decreased, indicating a very low respiration rate despite sufficient oxygen supply. The latter effect can likely be attributed to a restricted conversion of NADPH into NADH via the soluble transhydrogenase SthA, as the enzyme is outcompeted in the presence of MAA by the recombinant NADPH-dependent alcohol

  17. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O' Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  18. Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis

    Directory of Open Access Journals (Sweden)

    Hafiani Assia

    2003-09-01

    Full Text Available Abstract Background Jerboa (Jaculus orientalis is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc and D-3-hydroxybutyrate (BOH are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process. Results We found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respectively for AcAc reduction and for BOH oxidation. The same differences were found in the hibernation state. 2/ In euthermic jerboa, the Michaelis constants, KM BOH and KM NAD+ are different in liver and in brain while KM AcAc, KM NADH and the dissociation constants, KD NAD+and KD NADH are similar. 3/ During prehibernating state, as compared to euthermic state, the liver BDH activity is reduced by half, while kinetic constants are strongly increased except KD NAD+. 4/ During hibernating state, BDH activity is significantly enhanced, moreover, kinetic constants (KM and KD are strongly modified as compared to the euthermic state; i.e. KD NAD+ in liver and KM AcAc in brain decrease 5 and 3 times respectively, while KD NADH in brain strongly increases up to 5.6 fold. 5/ Both protein content and mRNA level of BDH remain unchanged during the cold adaptation process. Conclusions These results cumulatively explained and are consistent with the existence of two BDH enzymatic forms in the liver and the brain. The apoenzyme would be subjected to differential conformational folding depending on the hibernation state. This regulation could be a result of either post-translational modifications and/or a modification of the mitochondrial membrane state

  19. C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.

    Science.gov (United States)

    Olson, Aaron K; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly Priddy, Colleen; Isern, Nancy; Portman, Michael A

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  20. Industrial Acetogenic Biocatalysts: A Comparative Metabolic and Genomic Analysis

    Science.gov (United States)

    Bengelsdorf, Frank R.; Poehlein, Anja; Linder, Sonja; Erz, Catarina; Hummel, Tim; Hoffmeister, Sabrina; Daniel, Rolf; Dürre, Peter

    2016-01-01

    Synthesis gas (syngas) fermentation by anaerobic acetogenic bacteria employing the Wood–Ljungdahl pathway is a bioprocess for production of biofuels and biocommodities. The major fermentation products of the most relevant biocatalytic strains (Clostridium ljungdahlii, C. autoethanogenum, C. ragsdalei, and C. coskatii) are acetic acid and ethanol. A comparative metabolic and genomic analysis using the mentioned biocatalysts might offer targets for metabolic engineering and thus improve the production of compounds apart from ethanol. Autotrophic growth and product formation of the four wild type (WT) strains were compared in uncontrolled batch experiments. The genomes of C. ragsdalei and C. coskatii were sequenced and the genome sequences of all four biocatalytic strains analyzed in comparative manner. Growth and product spectra (acetate, ethanol, 2,3-butanediol) of C. autoethanogenum, C. ljungdahlii, and C. ragsdalei were rather similar. In contrast, C. coskatii produced significantly less ethanol and its genome sequence lacks two genes encoding aldehyde:ferredoxin oxidoreductases (AOR). Comparative genome sequence analysis of the four WT strains revealed high average nucleotide identity (ANI) of C. ljungdahlii and C. autoethanogenum (99.3%) and C. coskatii (98.3%). In contrast, C. ljungdahlii WT and C. ragsdalei WT showed an ANI-based similarity of only 95.8%. Additionally, recombinant C. ljungdahlii strains were constructed that harbor an artificial acetone synthesis operon (ASO) consisting of the following genes: adc, ctfA, ctfB, and thlA (encoding acetoacetate decarboxylase, acetoacetyl-CoA:acetate/butyrate:CoA-transferase subunits A and B, and thiolase) under the control of thlA promoter (PthlA) from C. acetobutylicum or native pta-ack promoter (Ppta-ack) from C. ljungdahlii. Respective recombinant strains produced 2-propanol rather than acetone, due to the presence of a NADPH-dependent primary-secondary alcohol dehydrogenase that converts acetone to 2

  1. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  2. Milk metabolome relates enteric methane emission to milk synthesis and energy metabolism pathways.

    Science.gov (United States)

    Antunes-Fernandes, E C; van Gastelen, S; Dijkstra, J; Hettinga, K A; Vervoort, J

    2016-08-01

    Methane (CH4) emission of dairy cows contributes significantly to the carbon footprint of the dairy chain; therefore, a better understanding of CH4 formation is urgently needed. The present study explored the milk metabolome by gas chromatography-mass spectrometry (milk volatile metabolites) and nuclear magnetic resonance (milk nonvolatile metabolites) to better understand the biological pathways involved in CH4 emission in dairy cattle. Data were used from a randomized block design experiment with 32 multiparous Holstein-Friesian cows and 4 diets. All diets had a roughage:concentrate ratio of 80:20 (dry matter basis) and the roughage was grass silage (GS), corn silage (CS), or a mixture of both (67% GS, 33% CS; 33% GS, 67% CS). Methane emission was measured in climate respiration chambers and expressed as CH4 yield (per unit of dry matter intake) and CH4 intensity (per unit of fat- and protein-corrected milk; FPCM). No volatile or nonvolatile metabolite was positively related to CH4 yield, and acetone (measured as a volatile and as a nonvolatile metabolite) was negatively related to CH4 yield. The volatile metabolites 1-heptanol-decanol, 3-nonanone, ethanol, and tetrahydrofuran were positively related to CH4 intensity. None of the volatile metabolites was negatively related to CH4 intensity. The nonvolatile metabolites acetoacetate, creatinine, ethanol, formate, methylmalonate, and N-acetylsugar A were positively related to CH4 intensity, and uridine diphosphate (UDP)-hexose B and citrate were negatively related to CH4 intensity. Several volatile and nonvolatile metabolites that were correlated with CH4 intensity also were correlated with FPCM and not significantly related to CH4 intensity anymore when FPCM was included as covariate. This suggests that changes in these milk metabolites may be related to changes in milk yield or metabolic processes involved in milk synthesis. The UDP-hexose B was correlated with FPCM, whereas citrate was not. Both metabolites were

  3. Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis.

    Directory of Open Access Journals (Sweden)

    Benyam P Yoseph

    Full Text Available BACKGROUND: Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. METHODS: Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. RESULTS: Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01. This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. CONCLUSIONS: When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality

  4. Scientific Opinion on the safety and efficacy of primary aliphatic saturated or unsaturated alcohols/aldehydes/acids/acetals/esters with a second primary, secondary or tertiary oxygenated functional group including aliphatic lactones (chemical group 9 when used as flavourings for all animal species

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP

    2012-10-01

    Full Text Available

    Chemical group 9 consists of primary aliphatic saturated or unsaturated alcohols/aldehydes/acids/acetals/esters with a second primary, secondary or tertiary oxygenated functional group including aliphatic lactones, of which 30 are currently authorised for use as flavours in food. The FEEDAP Panel was unable to perform an assessment of 2-oxopropanal because of issues related to the purity of the compound. The FEEDAP Panel concludes that lactic acid, succinic acid, fumaric acid, 4-oxovaleric acid, ethyl lactate, butyl lactate, butyl-O-butyryllactate, hex-3-enyl lactate, hexyl lactate, ethyl acetoacetate, ethyl 4-oxovalerate, diethylsuccinate and diethyl malonate are considered to be safe for all animal species at the use levels proposed when used as feed flavourings; octano-1,4-lactone, nonano-1,4-lactone, decano-1,4-lactone and undecano-1,4-lactone are safe at 20 mg/kg complete feed; butyro-1,4-lactone, pentano-1,4-lactone, hexano-1,4-lactone, heptano-1,4-lactone, octano-1,5-lactone, nonano-1,5-lactone, decano-1,5-lactone and undecano-1,5-lactone at 5 mg/kg complete feed; dodecano-1,4-lactone, dodecano-1,5-lactone, tetradecano-1,5-lactone, and pentadecano-1,15-lactone at a maximum of 1.5 mg/kg complete feed for cattle, salmonids and non food producing animals and of 1 mg/kg complete feed for pigs and poultry. No safety concern was identified for the consumer from the use of compounds belonging to CG 9 up to the highest safe level in feedingstuffs for all animal species. All compounds should be considered as irritants to skin, eyes and respiratory tract, and as skin sensitizers. The compounds do not pose a risk to the environment when used at concentrations considered safe for the target species. Since all compounds are used in food as flavourings, no further demonstration of efficacy is necessary.

  5. Plasma Metabonomics Analysis of Tumor Patients of Phlegm-Stasis Syndrome%痰瘀证肿瘤患者血浆代谢组学研究

    Institute of Scientific and Technical Information of China (English)

    巴吐尔·买买提明; 哈木拉提·吾甫尔

    2011-01-01

    Objective To study metabonomic changes in plasma of tumor patients of phlegm-stasis syndrome by Chinese medicine and their in vivo metabolic mechanism. Methods 1H nuclear magnetic resonance (NMR) based metabonomic analysis was performed on plasma samples from 356 tumor patients of the phlegmstasis syndrome and 104 tumor patients of the non-phlegm-stasis syndrome, and 50 healthy subjects. The spectrogram integral results were analyzed by orthogonal partial least-squares discriminant analysis (OPLS-DA). Results Compared with healthy subjects, various amino acids including leucine, alanine, citrulline, tyrosine, histidine, arginine, methionine, isoleucine, valine, acetylcysteine, etc. in the plasma of patients of the phlegm-stasis syndrome were significantly lowered (P <0. 05). Glucose, glycoprotein, glutamine, myo-inositol, lactic acid, choline, creatine also significantly decreased ( P < 0. 05). But the plasmal formic acid, acetone, acetic acid, acetoacetate, pyruvate, β-hydrocxy butyrate, carnitine, malonic acid, and unsaturated fatty acid, very low density lipoprotein cholesterol (VLDL-C), low density lipoprotein cholesterol (LDL-C) increased in tumor patients of the phlegm-stasis syndrome. Compared with tumor patients of non-phlegm-stasis syndrome, patients of the phlegm-stasis syndrome had obvious lower plasmal contents of leucine, alanine, citrulline, tyrosine, histidine, isoleucine, valine, glutamine, myo-inositol, scyllo-inositol, lactic acid, creatine ( P < 0. 05), higher plasmal contents of acetone, acetoacetate, unsaturated fatty acid, VLDL-C, α-glucose, β-glucose, glycoprotein, and so on ( P<0. 05). Conclusions Tumor patients of the phlegm-stasis syndrome had strengthened in vivo fat metabolism and lowered various amino acids. The decreased antioxidation capacities resulted in aggravated cell membrane injuries. The in vivo metabolic disorder was more severe in tumor patients of the phlegm-stasis syndrome than in tumor patients of the non

  6. Effects of extracts of Dragon's blood on fibroblast proliferation and extracellular matrix hyaluronic acid%血竭提取物对成纤维细胞增殖及合成透明质酸的影响

    Institute of Scientific and Technical Information of China (English)

    李丹; 惠瑞; 胡咏武; 韩岩; 郭树忠

    2015-01-01

    Objective To investigate the effects of Dragon' s blood extract on proliferation and secret extracellular matrix function of fibroblasts in vitro.Methods Dragon ' s blood was extracted by chloroform,acetoacetic ester,alcohol.Human fibroblast were cultured in vitro in media containing gradient dilutions of Dragon's blood extracts (0.002,0.02,0.2,2,20 mg/ml),which was followed by cell proliferation assessed with MTT assay on 0,12,24,36,48,60,72 h.Under the optimal concentration,the cell growth curves were drawn and the flow cytometry (FCM) was used to determine the changes of cell cycle.On 0,12,24,36,48,60,72 h,the concentration of hyaluronic acid in the supernatant of fibroblast culture was measured by radioimmunoassay.Results 0.2-2 mg/ml Dragon' s blood extracts enhanced the proliferation of fibroblasts in a dose-dependent manner.2 mg/ml was the optimal dilution of Dragon' s blood extract,and it increased the ratio of S cells in cell cycle[(25.80 ± 3.10) %] than control group[(7.50 ± 0.70)%,P < 0.01].From 12 h to 72 h,in 2 mg/ml Dragon's blood group,concentration of Hyaluronic acid secreted by fibroblasts gradually increased,but were less than control(P < 0.01).Conclusions Dragon ' s blood acetoacetic ester extract improved the proliferation of cultured human fibroblasts in vitro,might be beneficial to promote wound healing.%目的 研究血竭提取物对成纤维细胞生物学作用的影响.方法 将血竭经过氯仿、乙酸乙酯、乙醇依次回流提取分别得到3种血竭提取液,培养液稀释后行成纤维细胞培养.噻唑蓝法MTT检测浓度分别为0.002、0.02、0.2、2、20 mg/ml的血竭提取物,在0、12、24、36、48、60、72h7个检测点对体外培养成纤维细胞增殖的影响,并绘制最适浓度下细胞生长曲线.流式细胞术FCM分析最适浓度培养下成纤维细胞的细胞周期变化.应用放射免疫分析法检测0、12、24、36、48、60、72 h细胞培养上清液中透明质酸(hyaluronic acid

  7. Lipoperoxidação, perda de viabilidade celular e diminuição da liberação de IL-8 de neutrófilos humanos na presença de corpos cetônicos

    Directory of Open Access Journals (Sweden)

    MIRIANE COSTA GILENO

    2010-06-01

    Full Text Available

    Portadores de diabetes tipo-1 são acometidos por episódios freqüentes de acidose causada pelo aumento no metabolismo de ácido graxos com conseqüente acúmulo de acetoacetato (AcAc e β-hidroxibutirato (β -OB. Neste trabalho estudou-se o efeito de concentrações patológicas destes metabólitos na lipoperoxidação, viabilidade e liberação da quimiocina CXCL8 (IL-8 por neutrófilos em cultura. Neutrófilos de indivíduos saudáveis foram isolados por gradiente de densidade (Histopaque 1077/1119 e incubados com os corpos cetônicos. A lipoperoxidação foi determinada pela presença de substâncias reagentes ao ácido tiobarbitúrico (TBARS. A viabilidade celular foi avaliada pela liberação da enzima lactato desidrogenase. A liberação de CXCL8 para o meio extracelular foi medida após cultura de 24 horas de neutrófilos estimulados por zymosan opsonizado por ensaio imunoenzimático (ELISA. O AcAc causou um aumento na lipoperoxidação dos neutrófilos e este efeito foi dependente da sua concentração (p < 0.05; r = 0.99146; não se observou efeito do β-HOB. No estudo do efeito citotóxico, houve aumento dose-dependente da liberação da LDH até 40 mM de AcAc (p < 0.05; não se observou efeito do β-HOB. A liberação de CXCL8 foi suprimida de modo dose dependente por AcAc e β-HOB. Estes resultados sugerem que o acúmulo de corpos cetônicos pode contribuir para aumentar o tempo de remissão de doenças e mesmo estar relacionado com a gravidade destas em indivíduos diabéticos. Palavras-chave: Acetoacetato. Lipoperoxidação. Neutrófilos. Interleucina-8. Diabetes mellitus. ABSTRACT Lipoperoxidation, loss of cell viability and inhibition of release of IL-8 BY human neutrophils in the presence of ketone bodies Type-1 diabetes patients suffer from frequent episodes of acidosis caused by an increased fatty acid metabolism and consequently increased plasma level of acetoacetate (AcAc and β-hydroxybutyrate (

  8. Determination of fluorouracil concentration in tissues by HPLC%高效液相色谱法测定氟尿嘧啶的组织浓度

    Institute of Scientific and Technical Information of China (English)

    余俊先; 蔡军; 史丽敏; 王康里; 罗晓; 温爱萍; 李任; 王汝龙

    2011-01-01

    Objective: An HPLC method was developed to determine the concentration of fluorouracil in tissues, which was a metabolite of capecitabine in tissues. Methods: Plasma contained fluorouracil with bromouracil as the internal standard was extracted with acetoacetate, then the organic layer was evaporated to dryness under nitrogen stream and the residue was reconstituted with mobile phase for HPLC assay. Gastric carcinoma tissues and perienchyma through exairesis were homogenated with blank plasma and dealt with the same as described above. The mobile phase consisted of acetointrile: water (1: 99) at a flow rate of 1.0 mL·min-1, and the detection wavelength was 254 nm. Results: The retention times of fluorouracil and bromouracil were 3.20 minutes and 7.50 minutes, respectively. The assay exhibited excellent linearity with the range of 0.02 - 1.0 μg·mL-1 (r = 0.999 6). The reproducibility, extraction recovery, the variability of intra- and inter- day assay were consistent with requirement for determining biological specimen. Fluorouracil, metabolite of capecitabine, in gastric carcinoma central tissues (1.095 μg·g-1) was significantly higher than that in normal gastric tissues (0.047 μg·g-1). Conclusion: The method is suitable for determining the concentration of fluorouracil in tissues, and applicable to the study of capecitabine metabolism in human.%目的:建立高效液相色谱法测定卡培他滨代谢物氟尿嘧啶的组织浓度.方法:取氟尿嘧啶血浆溶液,加入溴尿嘧啶为内标,经乙酸乙酯提取后氮气吹干,流动相复溶进样分析;手术切除的胃癌及其周边组织用空白血浆匀浆,匀浆液处理方法同上.流动相为乙腈-水(1:99),流速1.0mL·min-1,检测波长254nm.结果:氟尿嘧啶与内标溴尿嘧啶保留时间分别为3.20min和7.50min.氟尿嘧啶的标准曲线范围0.02~1.0μg·mL-1(r=0.9996),方法的重现性、回收率、精密度和稳定性均符合生物样品分析要求.卡培他滨代谢物

  9. Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats Metabolismo dos corpos cetônicos durante as lesões de isquemia e reperfusão cerebrais após oclusão bilateral das artérias carótidas comuns em ratos

    Directory of Open Access Journals (Sweden)

    Mário Henrique Girão Faria

    2007-04-01

    Full Text Available PURPOSE: To evaluate the in vivo alterations on ketone bodies metabolism after cerebral ischemia/reperfusion through an experimental model of brain ischemia induced by simple occlusion of common carotid arteries (CCAs in Wistar rats. METHODS: Forty-eight male Wistar rats were randomly distributed on two groups (S - Sham; T - Test and further redistributed into four times sets of study. After bilateral occlusion of CCAs for 30min, the animals of group T were allowed reperfusion for 0, 5, 10 and 15min. Samples of cerebral tissue and systemic arterial blood were collected and the metabolites acetoacetate (ACT and beta-hydroxybutyrate (BHB were determined. RESULTS: Cerebral ACT and BHB levels increased significantly in Group T after 30min of carotid occlusion (time 0. The highest brain ketone bodies (ACT+BHB concentration was verified at 5min of reperfusion, decreasing after 10min of recirculation. Systemic ketone bodies levels increased similarly between test and sham groups. Group S demonstrated a significant increase in cerebral and systemic ACT and BHB concentrations mainly after 40-45min of study. CONCLUSIONS: The partial transient acute global brain ischemia induced by the bilateral carotid occlusion in Wistar rats triggered ketogenesis probably due to a central stimulation of catecholamine secretion. There was an increased cerebral uptake of ketone bodies following brain ischemia, reaffirming these metabolites as alternative energy substrates under conditions of cerebral metabolic stress as well as its potential role on neuroprotection. The greatest changes in ketone bodies metabolism were verified at initial minutes of recirculation as a result of the reperfusion injury phenomenon.OBJETIVO: Avaliar as alterações in vivo no metabolismo dos corpos cetônicos após isquemia/reperfusão cerebral através de um modelo experimental de isquemia cerebral induzido pela simples oclusão das artérias carótidas comuns (CCAs em ratos Wistar. M

  10. Observation of curative effect of modified atkins diet in treatment of adults with refractory epilepsy%改良的阿特金斯饮食治疗成人难治性癫痫的疗效观察

    Institute of Scientific and Technical Information of China (English)

    尚丽; 王曼; 龚德山; 张翠荣; 王开颜

    2015-01-01

    目的:评估改良的阿特金斯饮食( MAD)治疗成人难治性癫痫的疗效。方法19例成人难治性癫痫患者接受MAD治疗,随访1~15个月。记录发作频率及不良反应。结果1个月有效率为63%,保留率100%;3个月有效率57%,保留率89%;6个月有效率为47%,保留率为47%。患者治疗前发作频率为4~152次/月,平均25次/月;治疗后1个月发作频率为0~100次/月,平均8次/月。住院期间患者β-羟丁酸(1.5±0.6)mmol/L,血糖(4.6±0.4)mmol/L;随访期间乙酰乙酸波动于触~揣。与治疗前比较,治疗后第1个月和第3个月三酰甘油水平显著升高(均P<0.05),但均值仍在正常范围;总胆固醇及低密度脂蛋白水平差异无统计学意义。不良反应表现为体质量减轻7例,高脂血症6例,乏力4例,便秘3例,腹泻2例,呕吐及肾结石1例。结论 MAD治疗成人难治性癫痫安全有效,没有手术指征的成人难治性癫痫患者排除禁忌后可选择MAD。%Objective To evaluate the efficacy of modified atkins diet ( MAD ) in treatment of adults with refractory epilepsy.Methods Nineteen adult patients with refractory epilepsy were initiated on the MAD and followed 1-15 months.Seizure frequencies and adverse effects were recorded.Results The effective rate was 63%, and retention rate was 100%at 1 month after MAD treatment.The effective rate was 57%, and retention rate was 89%at 3 month after MAD treatment.The effective rate was 47%, and retention rate was 47% at 6 month after MAD treatment.The seizure frequencies was 4-152 times per month before treatment, and the average was 25 times per month;the seizure frequencies was 0-100 times per month at 1 month after treatment, and average was 8 per month. The serumβ-hydroxybutyric acid level was (1.5 ±0.6)mmol/L, blood glucose level was (4.6 ±0.4)mmol/L in the hospitalization period;the level of acetoacetic acid

  11. No-mediated mitochondria damage induce liver function failure in rats sepsis%一氧化氮介导的线粒体损害诱发败血症肝功衰竭的研究

    Institute of Scientific and Technical Information of China (English)

    涂巍; 曲文志; 赵嫚; 于作夫; 金光华; 王勤勇; 胡松

    2008-01-01

    nucleotide in the hepatocytes with the high-performance liquid chromatography ( HPLC),and determined the content of the ketone body in the hepatocytes of the two groups with the enzymatic method,then calculated the ketone body ratio ( acetoacetate/β-hydroxy butyrate,KBR).Results The production of NO in the CLP group is twice to third as many as that in the Sham group ,IL-1β can decrease the content of ATP and the KBR in the hepatocytes of the two groups,and the decrease degree in the CLP group is greater than that in the Sham group.When the L-arginine was injected,the production of NO in the hepatocytes in the CLP group is increased,and the level of ATP and KBR is decreased.NG-methyl-L-arginine (L-NMMA),the inhibitor of NO syntbetase,can inhibit the production of NO,and recuperate the decrease of ATP and KBR.Conclusion Enhanced production of NO primed by the septic response may be associated with hepatic dysfunction in the liver of septic rats.The regulation of the production of NO may be an effective method in the prevention of the hepatic dysfunction in sepsis.

  12. Cloning, expression and characterization of a short-chain dehydrogenase from Pseudomonasfluorescens%荧光假单胞菌短链脱氢酶的克隆、表达及酶学性质分析

    Institute of Scientific and Technical Information of China (English)

    薛群; 应向贤; 杨池; 汪钊

    2011-01-01

    为了研究荧光假单胞菌中短链脱氢酶的生理角色和催化特性,从荧光假单胞菌Pseudomonas fluorescens GIMl.49基因组DNA克隆表达了一个短链脱氢酶的编码基因pfd,并分析了该基因产物的酶学性质.基因pfd全长684 bp,编码227个氨基酸,推算分子量为24.2 kDa.将携带短链脱氢酶基因的重组质粒pET28b-pfd转入大肠杆菌BL21(DE3)进行表达,得到了28 kDa的表达产物.重组荧光假单胞菌短链脱氢酶(PFD)能氧化4-氯-3-羟基丁酸乙酯、1-苯乙醇、苯甲醇、仲丁醇和还原4-氯-乙酰乙酸乙酯、2-溴-苯乙酮、4-溴-苯乙酮等底物.以4-氯-3-羟基丁酸乙酯为底物时活力最高,Km值为186.40 mmol/L,Vmax为89.56 U/mg.氧化4-氯-3-羟基丁酸乙酯时,最适反应温度和pH分别为12℃和10.5,倾向于利用NAD+作辅酶;而还原4-氯-乙酰乙酸乙酯时,最适温度和pH为24℃和8.8,倾向于利用NADPH作辅酶.重组PFD能耐受50%(V/V)的甲醇等有机助溶剂,Ca2+(1 mmol/L)和EDTA(5 mmol/L)对其酶活有一定的促进作用.上述结果表明,重组PFD是一个新型的短链脱氢酶,其代谢角色推测与卤代次级醇的氧化降解有关.%To explore the physiological role and biocatalytic properties of short-chain dehydrogenases from Pseudomonas fluorescens GIM1.49, we cloned the structural gene pfd and characterized its over-expressed product. The length of gene pfd was 684 bp encoding a short-chain dehydrogenase with 227 amino acid residues and calculated molecular mass of 24.2 kDa. The recombinant plasmid pET28b-pfy was constructed and functionally expressed in Escherichia coli BL21(DE3), resulting in the over-production of recombinant short-chain dehydrogenase PFD with a size of 28 kDa. The enzyme could oxidize alcohols including 4-chloro-3-hydroxbutanoate ester and reduce 4-chloro-acetoacetate ester using either NAD(H) or NADP(H) as coenzyme. The enzyme showed the highest activity against 4-chloro-3-hydroxbutanoate ester as