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https://www.readbyqxmd.com/read/28545167/synthesis-of-s-2-s-3-4-chlorophenyl-n-4-chlorophenyl-sulfonyl-4-phenyl-4-5-dihydro-1h-pyrazole-1-carboximidamido-3-methyl-d3-butanamide-d5-octa-deuterated-jd5037
#1
Malliga R Iyer, Resat Cinar, Nathan J Coffey, Robert J Chorvat, George Kunos
JD5037 (1) is a potent and selective, peripherally acting inverse agonist of the cannabinoid (CB1 R) receptor. Peripheral CB1 receptor antagonists/inverse agonists have great potential in the treatment of metabolic disorders like type 2 diabetes, obesity and NASH. We report the synthesis of octa-deuterated [(2) H8 ]-JD5037 (S, S) (8) along with its (S, R) diastereomer (13) from commercially available L-valine-d8 starting material. The [(2) H8 ]-JD5037 compound will be used to quantitate unlabeled JD5037 during clinical ADME studies and will be used as an LC-MS/MS bioanalytical standard...
May 25, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28542386/correlation-between-plasma-endothelin-1-levels-and-severity-of-septic-liver-failure-quantified-by-maximal-liver-function-capacity-limax-test-a-prospective-study
#2
Magnus F Kaffarnik, Navid Ahmadi, Johan F Lock, Tilo Wuensch, Johann Pratschke, Martin Stockmann, Maciej Malinowski
AIM: To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test) and endothelin-1, TNF-α and IL-6 in septic surgical patients. METHODS: 28 septic patients (8 female, 20 male, age range 35-80y) were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10...
2017: PloS One
https://www.readbyqxmd.com/read/28537724/palladium-catalyzed-enantioselective-arylation-of-aryl-sulfenate-anions-a-combined-experimental-and-computational-study
#3
Tiezheng Jia, Mengnan Zhang, Samuel P McCollom, Ana Bellomo, Sonia Montel, Jianyou Mao, Spencer D Dreher, Christopher J Welch, Erik L Regalado, R Thomas Williamson, Brian C Manor, Neil C Tomson, Patrick J Walsh
A novel approach to produce chiral diaryl sulfoxides from aryl benzyl sulfoxides and aryl bromides via an enantioselective arylation of aryl sulfenate anions is reported. A (JosiPhos)Pd-based catalyst successfully promotes the asymmetric arylation reaction with good functional group compatibility. A wide range of enantioenriched diaryl, aryl heteroaryl, and even diheteroaryl sulfoxides were generated. Many of the sulfoxides prepared herein would be difficult to prepare via classic enantioselective oxidation of sulfides, including Ph(Ph-d5)SO (90% ee, 95% yield)...
May 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28534606/standardized-reporting-of-functioning-information-on-icf-based-common-metrics
#4
Birgit Prodinger, Alan Tennant, Gerold Stucki
BACKGROUND: In clinical practice and research a variety of clinical data collection tools are used to collect information on people's functioning for clinical practise and research and National Health Information Systems. Reporting on ICF-based common metrics enables standardized documentation of functioning information in national health information systems. OBJECTIVE: The objective of this methodological note on applying the ICF in rehabilitation is to demonstrate how to report functioning information collected with a data collection tool on ICF-based common metrics...
May 23, 2017: European Journal of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/28530752/active-metal-template-synthesis-of-a-neutral-indolocarbazole-containing-2-rotaxane-host-system-for-selective-oxoanion-recognition
#5
Asha Brown, Thomas Lang, Kathleen M Mullen, Paul D Beer
An active metal template strategy was used to synthesise a neutral indolocarbazole containing [2]rotaxane anion host system. (1)H NMR anion binding investigations reveal that the [2]rotaxane recognises a range of monoanions in acetone-d5 : D2O 95 : 5 with an unusual interlocked host selectivity for acetate and dihydrogenphosphate oxoanions over halides. The rotaxane displays an overall selectivity for the sulfate dianion, favouring a 2 : 1 host : guest binding stoichiometry at low sulfate concentration and a 1 : 1 stoichiometry in the presence of excess sulfate...
May 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28521812/radiotherapy-improves-serum-fatty-acids-and-lipid-profile-in-breast-cancer
#6
Sana Shaikh, Naseem Aslam Channa, Farha Naz Talpur, Muhammad Younis, Naila Tabassum
BACKGROUND: Breast cancer is a disease with diverse clinical symptoms, molecular profiles, and its nature to response its therapeutic treatments. Radiotherapy (RT), along with surgery and chemotherapy is a part of treatment in breast cancer. The aim of present study was to investigate pre and post treatment effects of radiotherapy in serum fatty acids and its lipids profile in patients with breast cancer. METHODS: In this comparative as well as follow up study, Serum fatty acids were performed by gas chromatography to investigate fatty acids and Microlab for analysis of lipid profile...
May 18, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28520922/gc-ms-method-for-quantification-of-mephedrone-in-human-blood-sample
#7
Khaled M Mohamed
Abuse of mephedrone (4-methylmethcathinone) has emerged among the last few years. Intoxication and fatality associated with mephedrone have been reported in the literature. The present work describes a simple and rapid gas chromatography-mass spectrometry (GC-MS) method for detection and quantification of mephedrone in human blood samples using GC-MS. Blood was deproteinated with acetonitrile and the supernatant was derivatized and extracted in a single step with ethyl chloroformate and ethyl acetate. Methamphetamine-d5 was used as an internal standard (IS)...
May 18, 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/28515379/alternative-internal-standard-calibration-of-an-indirect-enzymatic-analytical-method-for-2-mcpd-fatty-acid-esters
#8
Kazuo Koyama, Kinuko Miyazaki, Kousuke Abe, Yoshitsugu Egawa, Toru Fukazawa, Tadashi Kitta, Takashi Miyashita, Toru Nezu, Hidenori Nohara, Takashi Sano, Yukinari Takahashi, Hideji Taniguchi, Hiroshi Yada, Kumiko Yamazaki, Yomi Watanabe
An indirect enzymatic analysis method for the quantification of fatty acid esters of 2-/3-monochloro-1,2-propanediol (2/3-MCPD) and glycidol was developed, using the deuterated internal standard of each free-form component. A statistical method for calibration and quantification of 2-MCPD-d5, which is difficult to obtain, is substituted by 3-MCPD-d5 used for calculation of 3-MCPD. Using data from a previous collaborative study, the current method for the determination of 2-MCPD content using 2-MCPD-d5 was compared to three alternative new methods using 3-MCPD-d5...
May 17, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28511917/evidence-of-the-role-of-the-vagal-nerves-as-a-monitor-in-the-gastrointestinal-renal-axis-of-natriuresis-in-human-effects-of-vagotomy
#9
Constantinos E Alifieris, Dimitrios T Trafalis, Aris D Efstratopoulos, Emmanuel K Alifieris
This study aimed to investigate the mechanism of gastrointestinal regulation of natriuresis. Sixteen subjects without (group I) and sixteen subjects with a truncal vagotomy (group II), were given a daily diet of 18mmol of sodium for 5days (D1-D5). The sodium deficit for this period was calculated for each subject and on the morning of day-6 (D6), their cumulative deficit (E) was given as 3% NaCl. In both groups the subjects were divided to receive the hypertonic saline either orally (Ior, IIor) or intravenously (Iiv, IIiv)...
May 10, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28511864/metabolism-and-disposition-of-14-c-methycyclosiloxanes-in-rats
#10
Jeanne Y Domoradzki, Christopher M Sushynski, Jacob M Sushynski, Debra A McNett, Cynthia Van Landingham, Kathleen P Plotzke
Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) are low molecular weight cyclic volatile methyl siloxanes (cVMSs) primarily used as intermediates or monomers in the production of high molecular weight silicone polymers. The use of D4 as a direct ingredient in personal care products has declined significantly over the past 10 years, although it may be present as a residual impurity in a variety of consumer products. D5 is still used as an intentional ingredient in cosmetics, consumer products and in dry cleaning...
May 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28507463/radiotherapy-induced-skin-reactions-induce-fibrosis-mediated-by-tgf-%C3%AE-1-cytokine
#11
Cherley Borba Vieira de Andrade, Isalira Peroba Rezende Ramos, Alan César Nunes de Moraes, Ana Lúcia Rosa do Nascimento, Camila Salata, Regina Coeli Dos Santos Goldenberg, Jorge José de Carvalho, Carlos Eduardo Veloso de Almeida
PURPOSE: This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Methods and Materials: Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin was observed 5, 10, and 25 days (D) after ionizing radiation exposition. RESULTS: Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor β1 is associated with this process...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28503991/platelet-concentrates-modulate-myeloid-dendritic-cell-immune-responses
#12
Katrina K Ki, Helen M Faddy, Robert L Flower, Melinda M Dean
Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3(+) DC were assessed following exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry)...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28495611/hiv-1-tat-protein-enhances-sensitization-to-methamphetamine-by-affecting-dopaminergic-function
#13
James P Kesby, Julia A Najera, Benedetto Romoli, Yiding Fang, Liana Basova, Amanda Birmingham, Maria Cecilia G Marcondes, Davide Dulcis, Svetlana Semenova
Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period...
May 8, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28494354/development-of-collection-storage-and-analysis-procedures-for-the-quantification-of-cyclic-volatile-methylsiloxanes-in-wastewater-treatment-plant-effluent-and-influent
#14
Scott M Knoerr, Jeremy A Durham, Debra A McNett
A reliable and accurate method for collection and analysis of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) in wastewater treatment plant influent, effluent and surface waters was developed. Due to the use of cyclic volatile methylsiloxanes (cVMS) in industrial and consumer products including some personal care products, the wastewater stream represents a potential post-use disposal route and cVMS may subsequently enter the environment through wastewater treatment plant effluents...
May 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28493358/structural-identification-of-degradants-of-moexipril-by-lc-ms-ms
#15
C Purushotham Reddy, K Ramakrishna, K M V Narayana Rao
A gradient LC-MS method was developed for the identification and characterization of degradants of moexipril using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Moexipril was subjected to hydrolysis (acid, base and neutral), oxidation, photolytic and thermal degradation conditions as mentioned in ICH guidelines Q1A (R2). The drug degraded under hydrolysis, oxidation and photolytic conditions, but it was stable under thermal conditions. In total, five degradants were formed and separated on an Agilent XDB C-18 column (4...
May 10, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28491063/isa-2011b-a-phosphatidylinositol-4-phosphate-5-kinase-%C3%AE-inhibitor-impairs-cd28-dependent-costimulatory-and-pro-inflammatory-signals-in-human-t-lymphocytes
#16
Martina Kunkl, Nicla Porciello, Marta Mastrogiovanni, Cristina Capuano, Federica Lucantoni, Chiara Moretti, Jenny L Persson, Ricciarda Galandrini, Raffaella Buzzetti, Loretta Tuosto
Phosphatidylinositol 4,5-biphosphate (PIP2) is a membrane phospholipid that controls the activity of several proteins regulating cytoskeleton reorganization, cytokine gene expression, T cell survival, proliferation, and differentiation. Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) are the main enzymes involved in PIP2 biosynthesis by phosphorylating phosphatidylinositol 4-monophosphate (PI4P) at the D5 position of the inositol ring. In human T lymphocytes, we recently found that CD28 costimulatory molecule is pivotal for PIP2 turnover by recruiting and activating PIP5Kα...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28472381/a-simulation-study-on-the-dosimetric-benefit-of-real-time-motion-compensation-in-spot-scanning-proton-therapy-for-prostate
#17
Yusuke Fujii, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Takaaki Fujii, Naoki Miyamoto, Kikuo Umegaki, Kentaro Nishioka, Shinichi Shimizu, Hiroki Shirato
For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique...
May 4, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28471470/establishing-score-equivalence-of-the-functional-independence-measure-motor-scale-and-the-barthel-index-utilising-the-international-classification-of-functioning-disability-and-health-and-rasch-measurement-theory
#18
Birgit Prodinger, Rory J O'Connor, Gerold Stucki, Alan Tennant
INTRODUCTION: Two widely used outcome measures to assess functioning in neurological rehabilitation are the Functional Independence Measure (FIM™) and the Barthel Index. The current study aims to establish the equivalence of the total score of the FIM™ motor scale and the Barthel Index through the application of the International Classification of Functioning, Disability and Health, and Rasch measurement theory. METHODS: Secondary analysis of a large sample of patients with stroke, spinal cord injury, and multiple sclerosis, undergoing rehabilitation was conducted...
April 28, 2017: Journal of Rehabilitation Medicine
https://www.readbyqxmd.com/read/28457720/quantitative-analysis-of-the-transporter-mediated-drug-drug-interaction-between-atorvastatin-and-rifampicin-using-a-stable-isotope-iv-method
#19
Shinji Yamashita, Tsubasa Hasegawa, Masaki Tachihara, Keiko Minami, Haruki Higashino, Kazutaka Togashi, Kuninori Mutaguchi, Makoto Kataoka
This study aims to investigate the drug-drug interactions (DDIs) between orally administered atorvastatin (ATV) and rifampicin (RIF) in rats. The isotope-IV method was used for the analysis of the increased systemic exposure (AUCpo) of ATV, in which a small amount of deuterium-labeled ATV (ATV-d5) was intravenously injected after oral administration of ATV. By assuming ATV-d5 showed same pharmacokinetic properties with ATV, this method enabled to calculate the systemic clearance (CLtot) and the oral bioavailability (Foral) of ATV for each individual rat in a single experiment...
April 27, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28444793/dietary-mannoheptulose-does-not-alter-glucose-or-lipid-metabolism-in-adult-labrador-retrievers
#20
L L McKnight, J France, D Wright, G Davenport, A K Shoveller
Mannoheptulose (MH), a glycolytic inhibitor, has been preliminarily investigated as a novel functional food ingredient for dogs. This study aimed to determine the effects of dietary MH, delivered as an extract of un-ripened avocados, on fatty acid and glucose kinetics in healthy adult Labrador Retriever dogs (n = 12 dogs). The study was a double-blindcrossover with each dog receiving both dietary treatments, control (CON) and MH (400 mg/kg of diet), in random order. Glucose and glycerol plasma turnover (Ra) and oxidation (Ox) were measured in fasting and in response to repeated meal feeding ("fed") with stable isotope tracers (U-(13) C-glucose, 1,1,2,3,3-D5 -glycerol) and indirect calorimetry...
April 26, 2017: Journal of Animal Physiology and Animal Nutrition
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