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Glutaric Acid

Thao V Nguyen, Andrea C Alfaro, Fabrice Merien, Tim Young, Roffi Grandiosa
Massive mortalities due to pathogens are routinely reported in bivalve cultivation that have significant economic consequences for the global aquaculture industry. However, host-pathogen interactions and infection mechanisms that mediate these interactions are poorly understood. In addition, gender-specific immunological responses have been reported for some species, but the reasons for such differences have not been elucidated. In this study, we used a GC/MS-based metabolomics platform and flow cytometry approach to characterize metabolic and immunological responses in haemolymph of male and female mussels (Perna canaliculus) experimentally infected with Vibrio sp...
August 12, 2018: Journal of Invertebrate Pathology
Evagelia C Laiakis, Tytus D Mak, Steven J Strawn, Yi-Wen Wang, Bo-Hyun Moon, Pelagie Ake, Albert J Fornace
Exposures to ionizing radiation (IR) may either be accidental or intentional, for medical purposes or even through terrorist actions. As certain populations emerge to be more radiosensitive than others, it is imperative to assess those individuals and treat them accordingly. To demonstrate the feasibility of rapid identification of such cases, we utilized the highly radiosensitive mouse model Atm-/- in the C57BL/6 background, and evaluated the urinary responses in 8-10 week old male mice at early time points (4, 24, and 72 h) after exposure to their respective LD50/30 doses [4 Gy for Atm-/- , and 8 Gy for wild type (WT)]...
August 10, 2018: Environmental and Molecular Mutagenesis
Dingkang Chen, Zhiyun Du, Zhirong Lin, Ping Su, Hanyi Huang, Zhirong Ou, Wanyi Pan, Shiya Huang, Kun Zhang, Xi Zheng, Li Lin, Lanyue Zhang
Angelica pubescens, a plant of the family Umbelliferae, has been widely used as traditional Chinese medicine for the treatment of many diseases; however, there has been minimal modern research focused on the pharmacological activity of oils extracted from Angelica pubescens, in particular, the potential anti-photoaging effects. Therefore, in the present study, we analyzed the chemical composition of Angelica pubescens oil (AO) and evaluated its bioactivity against photoaging in ultraviolet (UV) -B radiation-induced hairless mice...
July 11, 2018: Chemistry & Biodiversity
Nandita Mehta, Gurleen Kaur
Glutaric aciduria Type 1 (GA-1) is an autosomal recessive metabolic disorder that results from deficiency of enzyme glutaryl-CoA dehydrogenase. This gives rise to elevated neurotoxic glutaric acid and 3-hydroxyglutaric acid as well as nontoxic glutarylcarnitine in body fluids. The enzyme defect leads to secondary damage to central nervous system due to the accumulation of glutaric acid. Approximately 90% people will develop the neurological disease during a finite period of brain development (3-36 months) following an acute encephalopathic crisis often precipitated by gastroenteritis, immunization, surgical intervention, and intercurrent febrile illness...
April 2018: Anesthesia, Essays and Researches
Xiaoping Xu, Yi Li, Xiaoling Lu, Yuyun Sun, Jianming Luo, Yingjian Zhang
OBJECTIVE: Cisplatin has limited clinical applications due to drug resistance. PAMAM dendrimer was chosen as a vehicle to counteract cisplatin-resistance and its mechanism was assessed. METHODS: Generation 5 Polyamidoamine dendrimer (G5) was modified by glutaric anhydride (GA) and then conjugated with cisplatin. The cisplatin release of G5-GA-cisplatin was evaluated at pH 5.5 and pH 7.4. The cytotoxicity of G5-GA-cisplatin and free cisplatin was compared in cisplatin-resistant breast cancer cell line MCF-7R...
October 1, 2018: Journal of Nanoscience and Nanotechnology
Sampada Koranne, Anasuya Sahoo, Joseph F Krzyzaniak, Suman Luthra, Kapildev K Arora, Raj Suryanarayanan
Tablets containing a theophylline-glutaric acid (TG) cocrystal dissociated rapidly forming crystalline theophylline (20-30%), following storage at 40 °C/75% RH for 2 weeks. Control tablets of TG cocrystal containing no excipients were stable under the same conditions. The dissociation reaction was water-mediated, and the theophylline concentration (the dissociation product), monitored by synchrotron X-ray diffractometry, was strongly influenced by the formulation composition. Investigation of the binary compacts of the TG cocrystal with each excipient revealed the influence of excipient properties (hydrophilicity, ionizability) on cocrystal stability, providing mechanistic insights into a dissociation reaction...
July 16, 2018: Molecular Pharmaceutics
Henry H Nguyen, Abdullah Khathlan, Marvin J Fritzler, Mark G Swain
BACKGROUND: Chronic Hepatitis C Virus (HCV) infection has been commonly linked to the development of autoimmunity, in part through activation of B cells. B cells are also postulated to play a pathogenic role in the autoimmune liver disease Primary Biliary Cholangitis (PBC). Patients with concurrent PBC and HCV infection carry an increased risk of more progressive disease, although the mechanism underlying this effect is poorly understood. Utilizing a case series of patients with concurrent PBC and HCV, the aim of this study was to evaluate for the potential impact of HCV eradication upon autoimmunity/autoantibody production...
June 25, 2018: BMC Gastroenterology
Judith Aron-Wisnewsky, Edi Prifti, Eugeni Belda, Farid Ichou, Brandon D Kayser, Maria Carlota Dao, Eric O Verger, Lyamine Hedjazi, Jean-Luc Bouillot, Jean-Marc Chevallier, Nicolas Pons, Emmanuelle Le Chatelier, Florence Levenez, Stanislav Dusko Ehrlich, Joel Dore, Jean-Daniel Zucker, Karine Clément
OBJECTIVES: Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes...
June 13, 2018: Gut
Emily L Goodband, Gonçalo Serrano, Fernando Constantino-Casas, Joy Archer, Penny J Watson, Tim L Williams
The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (-80°C) serum samples were identified...
2018: Veterinary Record Open
Mei Zhao, Guohui Li, Yu Deng
Glutarate is a linear chain dicarboxylic acid having wide applications in the production polyesters and polyamides such as nylon-4,5 and nylon-5,5. Previous studies focused on the biological production of glutarate from lysine with low yields and titers. Here, we report the glutarate production by Escherichia coli using a five-step reverse adipate-degradation pathway (RADP) identified in Thermobifida fusca By expressing the enzymes of RADP, the glutarate was detected by strain Bgl146 in shaken flasks. After fermentation optimization, the titer of glutarate by Bgl146 was increased to 4...
June 1, 2018: Applied and Environmental Microbiology
Nathania J Leong, Dharmini Mehta, Victoria M McLeod, Brian D Kelly, Rashmi Pathak, David J Owen, Christopher J H Porter, Lisa M Kaminskas
PEGylated polylysine dendrimers have demonstrated potential as inhalable drug delivery systems that can improve the treatment of lung cancers. Their treatment potential may be enhanced by developing constructs that display prolonged lung retention, together with good systemic absorption, the capacity to passively target lung tumors from the blood and highly selective, yet rapid liberation in the tumor microenvironment. This study sought to characterize how the nature of cathepsin B-cleavable peptide linkers, used to conjugate doxorubicin (Dox) to a PEGylated (PEG570) G4 polylysine dendrimer, affects drug liberation kinetics and intravenous and pulmonary pharmacokinetics in rats...
May 29, 2018: Journal of Pharmaceutical Sciences
Donogh Maguire, Dinesh Talwar, Paul G Shiels, Donald McMillan
The WHO 2016 report indicates that worldwide obesity is rising, with over 600 million people in the obese range (BMI>30). The recommended daily calorie intake for adults is 2000 kcal and 2500 kcal for women and men respectively. The average American consumes 3770 kcal/day and the average person in the UK consumes 3400 kcal/day. With such increased caloric intake, there is an increased load on metabolic pathways, in particular glucose metabolism. Such metabolism requires micronutrients as enzyme co-factors...
June 2018: Clinical Nutrition ESPEN
Alberto Tejero Rioseras, Kapil Dev Singh, Nora Nowak, Martin T Gaugg, Tobias Bruderer, Renato Zenobi, Pablo M-L Sinues
The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathway for cellular respiration in aerobic organisms. It provides and collects intermediates for many other interconnecting pathways and acts as a hub connecting metabolism of carbohydrates, fatty acids, and amino acids. Alteration in intracellular levels of its intermediates has been linked with a wide range of illnesses ranging from cancer to cellular necrosis or liver cirrhosis. Therefore, there exists an intrinsic interest in monitoring such metabolites...
June 5, 2018: Analytical Chemistry
Sunitha Sadula, Basudeb Saha
Energy-efficient catalytic conversion of biomass intermediates to functional chemicals can make bio-products viable. Herein, we report an efficient and low temperature aerobic oxidation of xylose to xylaric acid, a promising bio-based chemical for the production of glutaric acid, over commercial catalysts in water. Among several heterogeneous catalysts investigated, Pt/C exhibits the best activity. Systematic variation of reaction parameters in the pH range of 2.5 to 10 suggests that the reaction is fast at higher temperatures but high C-C scission of intermediate C5 -oxidized products to low carbon carboxylic acids undermines xylaric acid selectivity...
July 11, 2018: ChemSusChem
Tapan Parikh, Abu T M Serajuddin
PURPOSE: The purpose of this study was to explore the feasibility of developing amorphous solid dispersion (ASD) by inducing acid-base interaction at an elevated temperature using hot melt extrusion. METHODS: Itraconazole and glutaric acid, which do not form salt with each other, were selected as, respectively, model basic drug and weak organic acid. A 1:4:1w/w mixture of itraconazole, glutaric acid and a polymer, Kollidon®VA64, was melt extruded at 95°C. The ground extrudate was characterized by DSC and PXRD and then tested for dissolution at pH 1...
April 25, 2018: Pharmaceutical Research
Chawanphat Muangnoi, Ponsiree Jithavech, Pahweenvaj Ratnatilaka Na Bhuket, Wiwat Supasena, Wisut Wichitnithad, Pasarapa Towiwat, Nuansri Niwattisaiwong, Ian S Haworth, Pornchai Rojsitthisak
In this work, a curcumin-diglutaric acid (CurDG) prodrug was synthesized by conjugation of curcumin with glutaric acid via an ester linkage. The water solubility, partition coefficient, release characteristics, and antinociceptive activity of CurDG were compared to those of curcumin. The aqueous solubility of CurDG (7.48 μg/mL) is significantly greater than that of curcumin (0.068 μg/mL). A study in human plasma showed that the CurDG completely releases curcumin within 2 h, suggesting the ability of CurDG to serve as a prodrug of curcumin...
August 2018: Bioscience, Biotechnology, and Biochemistry
Svetlana N Rylova, Christian Stoykow, Luigi Del Pozzo, Keelara Abiraj, Maria Luisa Tamma, Yvonne Kiefer, Melpomeni Fani, Helmut R Maecke
Copper-64 is an attractive radionuclide for PET imaging and is frequently used in clinical applications. The aim of this study was to perform a side-by-side comparison of the in vitro and in vivo performance of 64Cu-NODAGA-JR11 (NODAGA = 1,4,7-triazacyclononane,1-glutaric acid,4,7-acetic acid, JR11 = p-Cl-Phe-cyclo(D-Cys-Aph(Hor)-D-Aph(cbm)-Lys-Thr-Cys)D-Tyr-NH2), a somatostatin receptor 2 antagonist, with the clinically used sst2 agonist 64Cu-DOTA-TATE ((TATE = D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)Thr). In vitro studies demonstrated Kd values of 5...
2018: PloS One
Ermelinda Lucente, Hongguang Liu, Yang Liu, Xiang Hu, Enza Lacivita, Marcello Leopoldo, Zhen Cheng
Bombesin receptor 2 (BB2 ) and integrin αv β3 receptor are privileged targets for molecular imaging of cancer because of their overexpression in a number of tumor tissues. The most recent developments in heterodimer-based radiopharmaceuticals concern BB2 - and integrin αv β3 -targeting compounds, consisting of bombesin (BBN) and cyclic arginine-glycine-aspartic acid peptides (RGD), connected through short length linkers. Molecular imaging probes based on RGD-BBN heterodimer design exhibit improved tumor targeting efficacy compared to the single-receptor targeting peptide monomers...
May 16, 2018: Bioconjugate Chemistry
Brett A Case, Max A Kruziki, Sadie M Johnson, Benjamin J Hackel
The Gp2 domain is a protein scaffold for synthetic ligand engineering. However, the native protein function results in a heterogeneous distribution of charge on the conserved surface, which may hinder further development and utility. We aim to modulate charge, without diminishing function, which is challenging in small proteins where each mutation is a significant fraction of protein structure. We constructed rationally guided combinatorial libraries with charge-neutralizing or charge-flipping mutations and sorted them, via yeast display and flow cytometry, for stability and target binding...
May 16, 2018: Bioconjugate Chemistry
Jonathan Martens, Giel Berden, Herman Bentlage, Karlien L M Coene, Udo F Engelke, David Wishart, Monique van Scherpenzeel, Leo A J Kluijtmans, Ron A Wevers, Jos Oomens
The identification of molecular biomarkers is critical for diagnosing and treating patients and for establishing a fundamental understanding of the pathophysiology and underlying biochemistry of inborn errors of metabolism. Currently, liquid chromatography/high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy are the principle methods used for biomarker research and for structural elucidation of small molecules in patient body fluids. While both are powerful techniques, several limitations exist that often make the identification of unknown compounds challenging...
May 2018: Journal of Inherited Metabolic Disease
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