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Adam Ingram, Megan Valente
Beta-blockers such as metoprolol, carvedilol, and bisoprolol are indicated for the treatment of patients with reduced ejection fraction heart failure. Heart failure treatment guidelines call for titration of these medications to specific target doses for morbidity and mortality benefit. Hepatic enzymes are responsible for metabolizing these medications; however, these enzymes are subject to genetic variations (polymorphisms) that can increase or decrease enzyme activity. Metoprolol relies almost exclusively on this enzyme for degradation to inactive metabolites, whereas carvedilol relies on this enzyme only partially for metabolism, and the portion of drug that is metabolized by CYP2D6 becomes active metabolites...
January 1, 2018: Journal of Pharmacy Practice
Pengying Liao, Xiongdiao Lan, Dankui Liao, LiXia Sun, Liqin Zhou, Jianhua Sun, Zhangfa Tong
Carapax Trionycis (the shell of the turtle Pelodiscus sinensis) was hydrolyzed by six different commercial proteases. The hydrolysate prepared from papain showed stronger inhibitory activity against angiotensin I-converting enzyme (ACE) than other extracts. Two noncompetitive ACE inhibitory peptides were purified successively by ultrafiltration, gel filtration chromatography, ion exchange column chromatography, and high-performance liquid chromatography (HPLC). The amino acid sequences of them were identified as KRER and LHMFK, with IC50 values of 324...
June 19, 2018: Journal of Agricultural and Food Chemistry
Tippawan Jantafong, Sakchai Ruenphet, Darsaniya Punyadarsaniya, Kazuaki Takehara
Aim: The aim of this study was to determine the effectiveness of the fourth-generation quaternary ammonium compounds, didecyl dimethyl ammonium bromide (DDAB), on the efficacy of bacterial and viral decontamination against pathogens commonly found in livestock industry including Salmonella infantis (SI), Escherichia coli , and avian influenza virus (AIV). Materials and Methods: The DDAB was prepared at 500, 250, and 125 parts per million (ppm) for absent and present organic material...
May 2018: Veterinary World
Jun Young Sonn, Jongbin Lee, Min Kyung Sung, Hwajung Ri, Jung Kyoon Choi, Chunghun Lim, Joonho Choe
Sleep and metabolism are physiologically and behaviorally intertwined; however, the molecular basis for their interaction remains poorly understood. Here, we identified a serine metabolic pathway as a key mediator for starvation-induced sleep suppression. Transcriptome analyses revealed that enzymes involved in serine biosynthesis were induced upon starvation in Drosophila melanogaster brains. Genetic mutants of astray ( aay ), a fly homolog of the rate-limiting phosphoserine phosphatase in serine biosynthesis, displayed reduced starvation-induced sleep suppression...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Lennart Tonneijck, Marcel H A Muskiet, Jos W Twisk, Mark H H Kramer, A H Jan Danser, Jaap A Joles, Mark M Smits, Daniël H van Raalte
The prolonged treatment effects of a short-acting GLP-1RA (glucagon-like peptide-1 receptor agonist), such as lixisenatide, on fasting and postprandial systemic hemodynamics in type 2 diabetes mellitus patients are unknown. In this secondary analysis, we included 34 overweight insulin glargine-treated type 2 diabetes mellitus patients (mean±SD age, 62±7 years; HbA1c , 8.0±0.9%; systolic blood pressure [BP], 133.9±16.1 mm Hg; diastolic BP, 75.4±8.39 mm Hg) that were randomized to once-daily lixisenatide 20 μg or once-daily titrated insulin glulisine for 8 weeks...
June 18, 2018: Hypertension
Chaoyue Hu, Xumin Zhang, Yonghua Liu, Yang Gao, Xiaohong Zhao, Hua Zhou, Yu Luo, Yaling Liu, Xiaodong Wang
BACKGROUND: In a previous study, we found that titrating clopidogrel maintenance doses (MDs) according to vasodilator-stimulated phosphoprotein (VASP) monitoring minimised the rate of major adverse cardiovascular and cerebral events (MACCE) after percutaneous coronary intervention (PCI) without increasing bleeding in patients with high on-treatment platelet reaction to clopidogrel. This study aimed to investigate whether VASP-guided clopidogrel MD could reduce thromboembolism and bleeding in atrial fibrillation (AF) patients requiring anticoagulation and scheduled for PCI...
June 18, 2018: BMC Cardiovascular Disorders
Jeannie-Marie S Leoutsakos, Haijuan Yan, William S Anderson, Wael F Asaad, Gordon Baltuch, Anna Burke, M Mallar Chakravarty, Kristen E Drake, Kelly D Foote, Lisa Fosdick, Peter Giacobbe, Zoltan Mari, Mary Pat McAndrews, Cynthia A Munro, Esther S Oh, Michael S Okun, Jo Cara Pendergrass, Francisco A Ponce, Paul B Rosenberg, Marwan N Sabbagh, Stephen Salloway, David F Tang-Wai, Steven D Targum, David Wolk, Andres M Lozano, Gwenn S Smith, Constantine G Lyketsos
BACKGROUND: Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years...
June 9, 2018: Journal of Alzheimer's Disease: JAD
Harald Breivik, Tone Marte Ljosaa, Kristian Stengaard-Pedersen, Jan Persson, Hannu Aro, John Villumsen, Dorthe Tvinnemose
Objective Patients with osteoarthritis (OA) pain often have insufficient pain relief from non-opioid analgesics. The aim of this trial was to study efficacy and tolerability of a low dose 7-day buprenorphine transdermal delivery system, added to a NSAID or coxib regimen, in opioid-naïve patients with moderate to severe OA pain. Methods A 6 months randomised, double-blind, parallel-group study at 19 centres in Denmark, Finland, Norway, and Sweden, in which OA patients (>40 years) with at least moderate radiographic OA changes and at least moderate pain in a hip and/or knee while on a NSAID or a coxib were randomised to a 7-day buprenorphine patch (n = 100) or an identical placebo patch (n = 99)...
December 29, 2017: Scandinavian Journal of Pain
Leila Niemi-Murola, Jani Unkuri, Katri Hamunen
Introduction and aim Pain is a frequent symptom in emergency patients and opioids are commonly used to treat it at emergency departments and at pre-hospital settings. The aim of this systematic review is to examine the efficacy and safety of parenteral opioids used for acute pain in emergency medicine. Method Qualitative review of randomized controlled trials (RCTs) on parenteral opioids for acute pain in adult emergency patients. Main outcome measures were: type and dose of the opioid, analgesic efficacy as compared to either placebo or another opioid and adverse effects...
December 29, 2017: Scandinavian Journal of Pain
A Basnet, S Butler, P Hartvig Honoré, M Butler, T E Gordh, K Kristensen, O J Bjerrum
Aims The clinical relevance of adding the acetylcholinesterase inhibitor donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The two drugs have previously shown synergism following co-administration in nerve-injured rats [1,2]. Methods The study comprised two consecutive periods of minimum six weeks: (1) titration of gabapentin until highest tolerable dose or maximum 24GG mg daily; and (2) addition of donepezil 5 mg once daily to the fixed gabapentin dose...
December 29, 2017: Scandinavian Journal of Pain
Dongjin Wan, Lairong Wu, Yongde Liu, Hailiang Zhao, Jun Fu, Shuhu Xiao
In this study, cow dung biochar (CDB) and ferric chloride-modified CDB (Fe@CDB) were synthesized to remove low concentration perchlorate from water. The pseudo-second-order kinetics model was used and satisfactorily described perchlorate removal onto CDB and Fe@CDB. The Langmuir model fit the experimental isotherm data better than the Freundlich model. The maximum adsorption capacity obtained using the Langmuir model was 1787 μg/g for Fe@CDB and 304 μg/g for CDB. The detrimental effects of coexisting anions decreased as: NO3 -  > SO4 2 -  > Cl- ...
September 15, 2018: Science of the Total Environment
Johannes Lützenkirchen, Tim Scharnweber, Tuan Ho, Alberto Striolo, Marialore Sulpizi, Ahmed Abdelmonem
We present a measurement cell that allows simultaneous measurement of second harmonic generation (SHG) and streaming potential (SP) at mineral-water interfaces with flat specimen that are suitable for non-linear optical (NLO) studies. The set-up directly yields SHG data for the interface of interest and can also be used to obtain information concerning the influence of flow on NLO signals from that interface. The streaming potential is at present measured against a reference substrate (PTFE). The properties of this inert reference can be independently determined for the same conditions...
June 15, 2018: Journal of Colloid and Interface Science
Xiaoyan Dong, Yunpeng Liu, Guishan Zhang, Dandan Wang, Xuan Zhou, Jiahui Shao, Qirong Shen, Ruifu Zhang
Nitric oxide (NO) is an important gas signal that regulates many biological processes, and due to the high nitrogen recycling activity in the rhizosphere, NO is an important signaling molecule in this region. Thus, an understanding of the effect of NO on the rhizomicrobiome, especially on plant beneficial rhizobacteria, is important for the use of these bacteria in agriculture. In this study, the effect of exogenous NO on the beneficial rhizobacterium Bacillus amyloliquefaciens SQR9 was investigated. The results showed that low concentrations of NO increased the ability of the strain SQR9 to form biofilms, while high concentrations of NO inhibited the growth of this bacterium...
June 15, 2018: Biochemical and Biophysical Research Communications
V Subbiah, V Velcheti, B B Tuch, K Ebata, N L Busaidy, M E Cabanillas, L J Wirth, S Stock, S Smith, V Lauriault, S Corsi-Travali, D Henry, M Burkard, R Hamor, K Bouhana, S Winski, R D Wallace, D Hartley, S Rhodes, M Reddy, B J Brandhuber, S Andrews, S M Rothenberg, A Drilon
Purpose: Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Patients and Methods: Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models...
April 18, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Keitaro Sofue, Toshihide Itoh, Satoru Takahashi, Bernhard Schmidt, Ryuji Shimada, Noriyuki Negi, Kazuro Sugimura, Takamichi Murakami
OBJECTIVE: The aim of this study was to assess the ability of third-generation dual-source dual-energy computed tomography to quantify cisplatin concentration using a 3-material decomposition algorithm in an experimental phantom. MATERIALS AND METHODS: Fifteen agarose-based phantoms containing various concentrations of iodine (0, 1.0, 2.0 mg I/mL) and cisplatin (0, 0.5, 1.0, 2.0, 3.0 mg Pt/mL) were scanned using third-generation dual-source dual-energy computed tomography at 80 kV and 150 kV with tin prefiltration...
June 14, 2018: Investigative Radiology
Katherine R Tuttle, Mark C Lakshmanan, Brian Rayner, Robert S Busch, Alan G Zimmermann, D Bradley Woodward, Fady T Botros
BACKGROUND: Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than does insulin. We assessed the efficacy and safety of dulaglutide in patients with type 2 diabetes and moderate-to-severe chronic kidney disease. METHODS: AWARD-7 was a multicentre, open-label trial done at 99 sites in nine countries...
June 14, 2018: Lancet Diabetes & Endocrinology
Barbara Wienen-Schmidt, Hendrik R A Jonker, Tobias Wulsdorf, Hans-Dieter Gerber, Krishna Saxena, Denis Kudlinzki, Sridhar Sreeramulu, Giacomo Parigi, Claudio Luchinat, Andreas Heine, Harald Schwalbe, Gerhard Klebe
Biophysical parameters can accelerate drug development, e.g. rigid ligands may reduce entropic penal-ty and improve binding affinity. We studied systematically the impact of ligand rigidification on ther-modynamics using a series of fasudil derivatives inhibiting protein kinase A by crystallography, iso-thermal titration calorimetry, nuclear magnetic resonance and molecular dynamics simulations. The ligands varied in their internal degrees of freedom but conserve the number of heteroatoms. Counter-intuitively, the most flexible ligand displays the entropically most favored binding...
June 16, 2018: Journal of Medicinal Chemistry
Yusra Rahman, Shumaila Afrin, Mohammad Tabish
Studying the interaction of therapeutic molecules with serum albumin is important to understand their biopharmaceutics, pharmacokinetics and toxicity as well as their relation with the structure and function of protein. The biomolecular interaction of an anti-spasmodic drug, pirenzepine with bovine serum albumin (BSA) was investigated using multi-spectroscopic, calorimetric and docking studies. Fluorescence quenching of BSA on interaction with pirenzepine revealed the static mode of quenching. Pirenzepine exhibited a moderate binding to serum albumin with the binding constant value in the order of 104  M-1 ...
June 13, 2018: Archives of Biochemistry and Biophysics
Kajorngai Thajee, Lu Wang, Kate Grudpan, Eric Bakker
Potassium ion concentration can be successfully determined volumetrically by moving the titration from a homogeneous phase to a two phase solvent system. This is because potassium can be readily complexed in a selective and thermodynamically stable manner by ionophores such as valinomycin. Previous work demonstrated the successful titration of potassium by ion-exchange into an organic phase containing valinomycin, but the sample itself served as titrant, which is not sufficiently practical for routine applications...
October 31, 2018: Analytica Chimica Acta
Amit Kumar Jaiswal, Daya Shanker, Vikrant Sudan, Amit Singh
In the present study, the 75% alcoholic fractionation of excretory-secretory (ES) antigen isolated from 200 to 300 live P. epiclitum was assessed for its diagnostic potential for the detection of caprine amphistomosis by using antibody detection enzyme immunoassay. Prior to enzyme immunoassay, 75% alcoholic fractionation of excretory-secretory (ES) antigen was subjected to SDS- PAGE and western blot analysis for the presence of immunoreactive polypeptides. SDS-PAGE analysis of ES antigen resolved a total 7 polypeptides bands of size 56, 27, 25, 22...
June 15, 2018: Veterinary Parasitology
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