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https://www.readbyqxmd.com/read/29779229/codeinone-reductase-isoforms-with-differential-stability-efficiency-and-product-selectivity-in-opium-poppy
#1
Mehran Dastmalchi, Limei Chang, Miguel A Torres, Kenneth K S Ng, Peter J Facchini
Codeinone reductase (COR) catalyzes the reversible NADPH-dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (Papaver somniferum). COR also irreversibly reduces neopinone, which forms by spontaneous isomerization in aqueous solution from codeinone, to neopine. In a parallel pathway involving 3-O-desmethylated analogs, COR converts morphinone to morphine, and neomorphinone to neomorphine. Similar to neopine, neomorphine formation by COR is irreversible...
May 19, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29779224/ir-catalyzed-silyl-directed-peri-borylation-of-c-h-bonds-in-fused-polycyclic-arenes-and-heteroarenes
#2
Bo Su, John F Hartwig
peri-Disubstituted naphthalenes exhibit interesting physical properties and unique chemical reactivity, due to the parallel arrangement of the bonds to the two peri-disposed substituents. Regioselective installation of a functional group at the position peri to 1-substituted naphthalenes is challenging due to the steric interaction between the existing substituent and the position at which the second one would be installed. We report an iridium-catalyzed borylation of the C-H bond peri to a silyl group in naphthalenes and analogous polyaromatic hydrocarbons...
May 20, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29779020/acetaminophen-reduces-acute-and-persistent-incisional-pain-after-hysterectomy
#3
Onur Koyuncu, Sedat Hakimoglu, Mustafa Ugur, Cagla Akkurt, Selim Turhanoglu, Daniel Sessler, Alparslan Turan
OBJECTIVE: Acetaminophen is effective for acute surgical pain, but whether it reduces persistent incision pain remains unknown. We tested the primary hypothesis that patients given perioperative acetaminophen have less incisional pain three months after surgery. Our secondary hypotheses were that patients randomized to acetaminophen have less postoperative pain and analgesic consumption, and better functional recovery at three months. METHODS: 140 patients having abdominal hysterectomy were randomly assigned to: 1)intravenous acetaminophen (4 g/day for 72 postoperative hours); or, 2) saline placebo...
May 15, 2018: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/29778948/bioisosteres-of-ethyl-8-ethynyl-6-pyridin-2-yl-4h-benzo-f-imidazo-1-5-a-1-4-diazepine-3-carboxylate-hz-166-as-novel-alpha-2-3-selective-potentiators-of-gaba-a-receptors-improved-bioavailability-enhances-anticonvulsant-efficacy
#4
J M Witkin, J L Smith, X Ping, S D Gleason, M M Poe, G Li, X Jin, J Hobbs, J M Schkeryantz, J S McDermott, A I Alatorre, J N Siemian, J W Cramer, D C Airey, K R Methuku, V V N P B Tiruveedhula, T M Jones, J Crawford, M J Krambis, J L Fisher, J M Cook, R Cerne
HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778875/purification-of-recombinant-trichodysplasia-spinulosa-associated-polyomavirus-vp1-derived-virus-like-particles-using-chromatographic-techniques
#5
Mindaugas Zaveckas, Karolis Goda, Danguole Ziogiene, Alma Gedvilaite
Trichodysplasia spinulosa-associated polyomavirus (TSPyV) has been linked to a rare and recently characterized skin disease occurring in immunocompromised patients. In analogy with other polyomaviruses, the major capsid protein VP1 of TSPyV can self-assemble into virus-like particles (VLPs). VLPs are increasingly applied for the vaccination and diagnostics. Mostly, non-scalable and labor intensive ultracentrifugation-based techniques are used for the purification of VLPs. In this work, we developed a purification procedure for TSPyV VP1 VLPs based on two chromatographic steps, ion-exchange monolith and core bead chromatography...
May 9, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29778834/generating-para-water-from-para-hydrogen-a-gedankenexperiment
#6
Konstantin L Ivanov, Geoffrey Bodenhausen
A novel conceptual approach is described that is based on the transfer of hyperpolarization from para-hydrogen in view of generating a population imbalance between the two spin isomers of H2 O. The approach is analogous to SABRE (Signal Amplification By Reversible Exchange) and makes use of the transfer of spin order from para-hydrogen to H2 O in a hypothetical organometallic complex. The spin order transfer is expected to be most efficient at avoided level crossings. The highest achievable enrichment levels of para- and ortho-water are discussed...
May 17, 2018: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/29778605/proteomic-and-biochemical-comparison-of-the-cellular-interaction-partners-of-human-vps33a-and-vps33b
#7
Morag R Hunter, Geoffrey G Hesketh, Tomasz H Benedyk, Anne-Claude Gingras, Stephen C Graham
Multi-subunit tethering complexes control membrane fusion events in eukaryotic cells. CORVET and HOPS are two such complexes, both containing the Sec1/Munc18 protein subunit VPS33A. Metazoans additionally possess VPS33B, which has considerable sequence similarity to VPS33A but does not integrate into CORVET or HOPS complexes and instead stably interacts with VIPAR. It has been recently suggested that VPS33B and VIPAR comprise two subunits of a novel multi-subunit tethering complex (named "CHEVI"), perhaps analogous in configuration to CORVET and HOPS...
May 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29778200/the-nucleoside-analog-gs-441524-strongly-inhibits-feline-infectious-peritonitis-fip-virus-in-tissue-culture-and-experimental-cat-infection-studies
#8
B G Murphy, M Perron, E Murakami, K Bauer, Y Park, C Eckstrand, M Liepnieks, N C Pedersen
Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM...
June 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#9
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29777877/multi-walled-carbon-nanotubeinduced-inhalation-toxicity-recognizing-nano-bis-demethoxy-curcumin-analog-as-an-ameliorating-candidate
#10
Arul Prakash Francis, Thiyagarajan Devasena, Selvam Ganapathy, Venkata Rajsekhar Palla, Prakhya Balakrishna Murthy, Sundara Ramaprabhu
Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#11
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29777569/improving-metabolic-stability-with-deuterium-the-discovery-of-hwl-066-a-potent-and-long-acting-free-fatty-acid-receptor-1-agonists
#12
Chunxia Liu, Zheng Li, Wei Shi, Huilan Li, Nasi Wang, Yuxuan Dai, Chen Liao, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid affording compound 4 (HWL-066)...
May 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29777431/modified-anterior-palatoplasty-and-double-suspension-sutures-with-or-without-tonsillectomy-in-selected-patients-with-obstructive-sleep-apnea-a-preliminary-report
#13
Sherif M Askar, Mohammad W El-Anwar, Ali Awad
BACKGROUND: Retropalatal region might be considered the most common site of obstruction in patients with snoring and OSA. We aimed at presentation of two combined techniques: modified anterior palatoplasty (MAP) and bilateral double suspension suture (DSS). METHODS: This prospective study was conducted on OSA patients with retro-palatal collapse only that was confirmed by nasoendoscopy during Muller's maneuver and drug induced sleep endoscopy. MAP and DSS were performed for all patients...
May 18, 2018: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/29777144/benefits-in-radical-mastectomy-protocol-a-randomized-trial-evaluating-the-use-of-regional-anesthesia
#14
Marcio Matsumoto, Eva M Flores, Pedro P Kimachi, Flavia V Gouveia, Mayra A Kuroki, Alfredo C S D Barros, Marcelo M C Sampaio, Felipe E M Andrade, João Valverde, Eduardo F Abrantes, Claudia M Simões, Rosana L Pagano, Raquel C R Martinez
Surgery is the first-line treatment for early, localized, or operable breast cancer. Regional anesthesia during mastectomy may offer the prevention of postoperative pain. One potential protocol is the combination of serratus anterior plane block (SAM block) with pectoral nerve block I (PECS I), but the results and potential benefits are limited. Our study compared general anesthesia with or without SAM block + PECS I during radical mastectomy with axillary node dissection and breast reconstruction using evaluations of pain, opioid consumption, side effects and serum levels of interleukin (IL)-1beta, IL-6 and IL-10...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777050/the-yeast-telomerase-recruitment-module-requires-a-specific-rna-architecture
#15
Nancy Laterreur, Bruno Lemieux, Hannah Neumann, Jean-Christophe Berger-Dancause, Daniel Lafontaine, Raymund J Wellinger
Telomerases are ribonucleoprotein (RNP) enzymes that are related to reverse transcriptases. While they maintain genome stability, their composition varies significantly between species. Yeast telomerase RNPs contain an RNA that is comparatively large and its overall folding shows long helical segments with distal functional parts. Here we investigated the essential stem IVc module of the budding yeast telomerase RNA, called Tlc1. The distal part of stem IVc includes a conserved sequence element CS2a and structurally conserved features to which bind the Pop1/Pop6/Pop7 proteins and which together function analogously to the P3 domains of the RNase P/MRP RNPs...
May 18, 2018: RNA
https://www.readbyqxmd.com/read/29777023/xanthates-metabolism-by-flavoprotein-containing-monooxygenases-fmo-and-antimycobacterial-activity
#16
Stanislav Yanev, Tsveta Stoyanova, Violeta Valcheva, Paul R Ortiz De Montellano
Ethionamide (ETH) plays a central role in the treatment of tuberculosis in patients resistant to the first-line drugs. The ETH, thioamide, and thiourea class of antituberculosis agents are pro-drugs that are oxidatively converted to their active S-oxides by the flavin monooxygenase EtaA of M. tuberculosis, thus initiating the chain of reactions that result in inhibition of mycolic acid biosynthesis and cell lysis. As part of a search for new lead candidates, we report here that several xanthates are oxidized by purified EtaA to S-oxide metabolites (perxanthates) that are implicated in the antimycobacterial activity of these compounds...
May 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29776930/modifying-the-lantibiotic-mutacin-1140-for-increased-yield-activity-and-stability
#17
Mengxin Geng, Leif Smith
Mutacin 1140 belongs to the epidermin family of type AI lantibiotics. This family has a broad spectrum of activity against Gram-positive bacteria. The binding of mutacin 1140 to lipid II leads to the inhibition of cell wall synthesis. Pharmacokinetic experiments on type AI lantibiotics are generally discouraging for clinical applications due to their short half-life. The unprotected dehydrated and protease susceptible residues outside of the lanthionine rings may play a role in their short half-life in physiological settings...
May 18, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29776852/indications-for-mars-mri-in-patients-treated-with-articular-surface-replacement-xl-total-hip-arthroplasty
#18
James W Connelly, Vincent P Galea, Inari Laaksonen, Sean J Matuszak, Rami Madanat, Orhun Muratoglu, Henrik Malchau
BACKGROUND: The purpose of this study was to identify which patient and clinical factors are predictive of adverse local tissue reaction (ALTR) and to use these factors to create a highly sensitive algorithm for indicating metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) in Articular Surface Replacement (ASR) XL total hip arthroplasty patients. Our secondary aim was to compare our algorithm to existing national guidelines on when to take MARS-MRI in metal-on-metal total hip arthroplasty patients...
April 19, 2018: Journal of Arthroplasty
https://www.readbyqxmd.com/read/29776742/discovery-of-novel-n-hydroxy-2-arylisoindoline-4-carboxamides-as-potent-and-selective-inhibitors-of-hdac11
#19
Matthew W Martin, Jennifer Y Lee, David R Lancia, Pui Yee Ng, Bingsong Han, Jennifer R Thomason, Maureen S Lynes, C Gary Marshall, Chiara Conti, Alan Collis, Monica Alvarez Morales, Kshama Doshi, Aleksandra Rudnitskaya, Lili Yao, Xiaozhang Zheng
N-Hydroxy-2-arylisoindoline-4-carboxamides are potent and selective inhibitors of HDAC11. The discovery, synthesis, and structure activity relationships of this novel series of inhibitors are reported. An advanced analog (FT895) displays promising cellular activity and pharmacokinetic properties that make it a useful tool to study the biology of HDAC11 and its potential use as a therapeutic target for oncology and inflammation indications.
May 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29776741/a-small-diversity-library-of-%C3%AE-methyl-amide-analogs-of-sulindac-for-probing-anticancer-structure-activity-relationships
#20
Bini Mathew, Timothy S Snowden, Michele C Connelly, R Kiplin Guy, Robert C Reynolds
Non-steroidal anti-inflammatory drugs (NSAIDs) have a variety of potential indications that include management of pain and inflammation as well as chemoprevention and/or treatment of cancer. Furthermore, a specific form of ibuprofen, dexibuprofen or the S-(+) form, shows interesting neurological activities and has been proposed for the treatment of Alzheimer's disease. In a continuation of our work probing the anticancer activity of small sulindac libraries, we have prepared and screened a small diversity library of α-methyl substituted sulindac amides in the profen class...
May 10, 2018: Bioorganic & Medicinal Chemistry Letters
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