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https://www.readbyqxmd.com/read/29164296/pharmacokinetic-and-toxicodynamic-evaluation-of-oxaliplatin-induced-neuropathy-and-hematological-toxicity-in-rats
#1
Yukako Ito, Shinji Kobuchi, Risa Shimizu, Yosuke Katsuyama
PURPOSE: Oxaliplatin (L-OHP) is a third-generation, platinum-based chemotherapeutic agent and is widely used in gastroenterological cancer regimens. It is important to complete chemotherapy cycles to improve treatment efficacy for cancer patients. However, undesirable side effects, including acute and chronic neuropathies, and myelosuppression, lead to the discontinuation of chemotherapy in some treatment regimens. To predict and prevent the onset of side effects, and to establish appropriate dose adjustment, pharmacokinetic and toxicodynamic studies were performed to investigate the effects of L-OHP in rats...
November 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29163064/turtle-flexion-reflex-motor-patterns-show-windup-mediated-partly-by-l-type-calcium-channels
#2
Keith P Johnson, Stephen M Tran, Emily A Siegrist, Krishna B Paidimarri, Matthew S Elson, Ari Berkowitz
Windup is a form of multisecond temporal summation in which identical stimuli, delivered seconds apart, trigger increasingly strong neuronal responses. L-type Ca(2+) channels have been shown to play an important role in the production of windup of spinal cord neuronal responses, initially in studies of turtle spinal cord and later in studies of mammalian spinal cord. L-type Ca(2+) channels have also been shown to contribute to windup of limb withdrawal reflex (flexion reflex) in rats, but flexion reflex windup has not previously been described in turtles and its cellular mechanisms have not been studied...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29159981/understanding-the-metabolic-burden-of-recombinant-antibody-production-in-saccharomyces-cerevisiae-using-a-quantitative-metabolomics-approach
#3
Jorg C de Ruijter, Essi V Koskela, Jatin Nandania, Alexander D Frey, Vidya Velagapudi
The cellular changes induced by heterologous protein expression in the yeast Saccharomyces cerevisiae have been analyzed on many levels and found to be significant. However, even though high-level protein production poses a metabolic burden, evaluation of the expression host at the level of the metabolome has often been neglected. We present a comparison of metabolite profiles of a wild-type strain with those of three strains producing recombinant antibody variants of increasing size and complexity: a scFv fragment, a scFv-Fc fusion protein, and a full-length IgG molecule...
November 20, 2017: Yeast
https://www.readbyqxmd.com/read/29156381/structure-based-methods-to-predict-mutational-resistance-to-diarylpyrimidine-non-nucleoside-reverse-transcriptase-inhibitors
#4
Syeda Maryam Azeem, Alecia N Muwonge, Nehaben Thakkar, Kristina W Lam, Kathleen M Frey
Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance...
November 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29156206/cytokine-release-syndrome-who-is-at-risk-and-how-to-treat
#5
REVIEW
Noelle Frey
T-cell engaging therapies such as blinatumomab and anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized our approach to patients with relapsed and refractory acute lymphoblastic leukemia (ALL). However, the immune activation responsible for high remission rates is also responsible for the unique treatment-related toxicity of cytokine release syndrome (CRS). The clinical signs of CRS include fever, hemodynamic instability, and capillary leak, which correlate with T-cell activation and elevated cytokine levels...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155722/automated-gait-analysis-in-mice-with-chronic-constriction-injury
#6
Dong-Wook Kang, Jae-Gyun Choi, Ji-Young Moon, Suk-Yun Kang, Yeonhee Ryu, Jin Bong Park, Hyun-Woo Kim
The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some disadvantages such as subjective data and the requirement of a skilled, experienced experimenter. To date, a variety of modifications have improved the von Frey method, but it still has a few limitations. Recent reports have suggested that gait analysis produces more accurate and objective data from the neuropathic animals. This protocol demonstrates how to perform the automated gait analysis to determine the degree of neuropathic pain in mice...
October 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155701/an-ultrasonic-tool-for-nerve-conduction-block-in-diabetic-rat-models
#7
Yee Fun Lee, Chou-Ching Lin, Jung-Sung Cheng, Gin-Shin Chen
Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU can reversibly block the conduction of peripheral nerves without damaging the nerves while using an appropriate ultrasonic parameter. Temporary and partial block of the action potentials of nerves shows that HIFU has the potential to be a useful clinical treatment for pain relief. This work demonstrates the procedures for suppressing the action potentials of neuropathic nerves in diabetic rats in vivo using an HIFU transducer...
October 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29149151/sacroplasty-a-ten-year-analysis-of-prospective-patients-treated-with-percutaneous-sacroplasty-literature-review-and-technical-considerations
#8
Michael E Frey, Christopher Warner, Samuel M Thomas, Karan Johar, Heathpaul Singh, Maheen S Mohammad, Douglas P Beall
BACKGROUND: The treatment of sacral fractures has evolved since its first description in 1982. Several techniques for sacral augmentation have been developed since 2001, and the rate of improvement is rapid with over 50% reduction in pain achieved prior to post-procedure discharge of the patient. Pain reduction occurs primarily within the first 3 months and is sustained at 12 months; however, the long-term outcomes have not previously been studied. OBJECTIVES: We aim to evaluate the long-term efficacy of sacroplasty versus non-surgical management (NSM) in treating sacral insufficiency fractures (SIFs), including the effect on pain relief, opioid and other analgesic use, patient satisfaction, and complication rates...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29148614/double-regioselective-asymmetric-c-allylation-of-isoxazolinones-iridium-catalyzed-n-allylation-followed-by-an-aza-cope-rearrangement
#9
Stefan Rieckhoff, Jan Meisner, Johannes Kästner, Wolfgang Frey, René Peters
Isoxazolinones are biologically and synthetically interesting densely functionalized heterocycles, which for a long time were not accessible in enantioenriched form by asymmetric catalysis. Next to the deficit of enantioselective methods, the functionalization of isoxazolinones is often plagued by regioselectivity issues due to the competition of various nucleophilic centers within the heterocycles. Here we report the first regio- and enantioselective C-allylations of isoxazolinones. They also allowed for high regioselectivity in favor of the linear allylation products, although Ir phosphoramidite catalysts were used, which commonly result in branched isomers...
November 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29147842/tetrandrine-alleviates-nociception-in-a-rat-model-of-migraine-via-suppressing-s100b-and-p-erk-activation-in-satellite-glial-cells-of-the-trigeminal-ganglia
#10
Guangcheng Qin, Bei Gui, Jingmei Xie, Lixue Chen, Lianlian Chen, Zhiwei Cui, Jiying Zhou, Ge Tan
Sensitization and activation of the trigeminal ganglia have been implicated in the pathology of migraine. Satellite glial cells (SGCs), a specialized type of glial cells that ensheathe trigeminal neurons, may be critical for peripheral nociceptive sensitization. Tetrandrine (TET), an alkaloid extracted from a traditional Chinese herb, exerts an inhibitory effect on glial activation in vitro and has been used in various neurologic diseases. The current study investigated the effect of TET on nitroglycerin (NTG)-induced trigeminal sensitization and examined potential signaling pathways related to SGC activation in the model of migraine...
November 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29144151/workflow-interruptions-and-employee-work-outcomes-the-moderating-role-of-polychronicity
#11
Daniela Pachler, Angela Kuonath, Julia Specht, Silja Kennecke, Maria Agthe, Dieter Frey
Workflow interruptions are one of the most commonly experienced stressors at work. This research expands existing literature on workflow interruptions in a diary field study. We apply a within-person approach and investigate detrimental effects of daily workflow interruptions on both daily satisfaction with performance and daily emotional exhaustion. Furthermore, we introduce polychronicity (the trait-like preference of a person to deal with several activities at the same time) as a buffering factor in this relationship...
November 16, 2017: Journal of Occupational Health Psychology
https://www.readbyqxmd.com/read/29141959/an-integrative-strategy-to-identify-the-entire-protein-coding-potential-of-prokaryotic-genomes-by-proteogenomics
#12
Ulrich Omasits, Adithi R Varadarajan, Michael Schmid, Sandra Goetze, Damianos Melidis, Marc Bourqui, Olga Nikolayeva, Maxime Québatte, Andrea Patrignani, Christoph Dehio, Juerg E Frey, Mark D Robinson, Bernd Wollscheid, Christian H Ahrens
Accurate annotation of all protein-coding sequences (CDSs) is an essential prerequisite to fully exploit the rapidly growing repertoire of completely sequenced prokaryotic genomes. However, large discrepancies among the number of CDSs annotated by different resources, missed functional short open reading frames (sORFs), and overprediction of spurious ORFs represent serious limitations. Our strategy toward accurate and complete genome annotation consolidates CDSs from multiple reference annotation resources, ab initio gene prediction algorithms and in silico ORFs (a modified six-frame translation considering alternative start codons) in an integrated proteogenomics database (iPtgxDB) that covers the entire protein-coding potential of a prokaryotic genome...
November 15, 2017: Genome Research
https://www.readbyqxmd.com/read/29140997/topical-anaesthesia-reduces-sensitivity-of-castration-wounds-in-neonatal-piglets
#13
Sabrina Lomax, Charissa Harris, Peter A Windsor, Peter J White
The aim of this study was to do determine the efficacy of the topical anaesthetic Tri-Solfen® in the amelioration of the pain of castration in piglets. The trial was conducted over a three day period, and blocked across six litters with 12 piglets treated on days one and two, and 16 on day three. The piglets were randomly allocated by weight and litter to 1 of 4 treatment groups: (i) sham castration (SHAM; n = 10); (ii) surgical castration with no anaesthetic intervention (CAST; n = 10); (iii) surgical castration with post-operative topical anaesthesia (TRI; n = 10); (iv) surgical castration with a pre-operative intra-testicular lignocaine hydrochloride injection (LIG; n = 10)...
2017: PloS One
https://www.readbyqxmd.com/read/29138092/abnormal-cortical-neuroplasticity-induced-by-paired-associative-stimulation-after-traumatic-spinal-cord-injury-a-preliminary-study
#14
Viviana Versace, Patrick B Langthaler, Yvonne Höller, Vanessa N Frey, Francesco Brigo, Luca Sebastianelli, Leopold Saltuari, Raffaele Nardone
We aimed at assessing in this pilot study whether patients with spinal cord injury (SCI) show alterations of sensorimotor plasticity within the primary motor cortex (M1). Since learning in human M1 occurs through LTP-like mechanisms, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in M1, in subjects with chronic SCI. We found that PAS protocol significantly increased corticospinal excitability as long as 30minutes in healthy subjects and in SCI patients with good motor recovery, while it was followed by a non-significant increase of MEP amplitude in the SCI patients with poor functional recovery...
November 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29137311/crenolanib-is-a-type-i-tyrosine-kinase-inhibitor-that-inhibits-mutant-kit-d816-isoforms-prevalent-in-systemic-mastocytosis-and-core-binding-factor-leukemia
#15
Kerstin Maria Kampa-Schittenhelm, Julia Frey, Lara A Haeusser, Barbara Illing, Ashly A Pavlovsky, Gunnar Blumenstock, Marcus Matthias Schittenhelm
Activating D816 mutations of the class III receptor tyrosine kinase KIT are associated with the majority of patients with systemic mastocytosis (SM), but also core binding factor (CBF) AML, making KIT mutations attractive therapeutic targets for the treatment of these cancers. Crenolanib is a potent and selective inhibitor of wild-type as well as mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β. Notably, crenolanib inhibits constitutively active mutant-FLT3 isoforms resulting from amino acid substitutions of aspartic acid at codon 835, which is homologous to codon 816 in the KIT gene - suggesting sensitivity against mutant-KIT D816 isoforms as well...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136128/the-proton-activated-receptor-gpr4-modulates-intestinal-inflammation
#16
Yu Wang, Cheryl de Vallière, Pedro H Imenez Silva, Irina Leonardi, Sven Gruber, Alexandra Gerstgrasser, Hassan Melham, Achim Weber, Katharina Leucht, Lutz Wolfram, Martin Hausmann, Carsten Krieg, Koray Thomasson, Onur Boyman, Isabelle Frey-Wagner, Gerhard Rogler, Carsten A Wagner
BACKGROUND AND AIMS: During active inflammation tissue intraluminal intestinal pH is decreased in patients with inflammatory bowel disease (IBD). Acidic pH may play a role in IBD pathophysiology. Recently, proton sensing G-protein coupled receptors were identified, including GPR4, OGR1 (GPR68), and TDAG8 (GPR65). We investigated whether GPR4 is involved in intestinal inflammation. METHODS: The role of GPR4 was assessed in murine colitis models: chronic dextran sulphate sodium (DSS) administration and by crossbreeding into an IL-10 deficient background for development of spontaneous colitis...
November 9, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29134825/assessing-the-need-for-a-comprehensive-acne-quality-of-life-scale-for-face-and-torso-acne
#17
Chelsea McLellan, Marc Philip Frey, Jerry Tan
PURPOSE: While acne, a common condition, largely involves the face, chest, and back, current acne quality-of-life measures focus primarily on facial acne. The purpose of this study was to assess the need for a comprehensive quality-of-life measure intended for use with patients who have facial and/or torso acne. METHODS: We evaluated the need for a comprehensive quality-of-life scale for facial and torso acne based on data from an epidemiological survey (N = 690) in which participants were grouped according to the location of their acne (face, torso, or both) and where quality of life was assessed...
November 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/29134241/ct-based-evaluation-of-volumetric-bone-density-in-fragility-fractures-of-the-pelvis-a-matched-case-control-analysis
#18
D Schönenberg, R Guggenberger, D Frey, H-C Pape, H-P Simmen, G Osterhoff
This matched case-control study compared the computed tomography (CT)-based regional bone density of patients with fragility fractures of the sacrum to a control without fracture. Patients with a sacral fracture demonstrated a significantly lower regional bone density of the sacrum, the sacral bone density not being correlated with the BMD by DXA of the spine. INTRODUCTION: The aim of this study is to compare the computed tomography-based regional bone density measured by Hounsfield units (HUs) in patients with and without fragility fractures of the sacrum...
November 13, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/29134031/the-dipteran-family-celyphidae-in-the-new-world-with-discussion-of-and-key-to-world-genera-insecta-diptera
#19
Stephen D Gaimari
The family Celyphidae (Diptera, Lauxanioidea) is verified as part of the New World fauna, with a second specimen discovered of a species described from French Guiana in 1844 by P.J.M. Macquart. As this species possesses characteristics that clearly suggest a separate lineage from the Old World celyphids, a new genus is proposed, Atopocelyphusgen. n., with the type species, Celyphus ruficollis Macquart, in the new combination Atopocelyphus ruficollis (Macquart), comb. n. A key to world genera of Celyphidae is presented, along with discussion of generic concepts...
2017: ZooKeys
https://www.readbyqxmd.com/read/29131630/role-of-regioisomeric-bicyclo-3-3-0-octa-2-5-diene-ligands-in-rh-catalysis-synthesis-structural-analysis-theoretical-study-and-application-in-asymmetric-1-2-and-1-4-additions
#20
Tina Mühlhäuser, Alex Savin, Wolfgang Frey, Angelika Baro, Andreas J Schneider, Heinz-Günter Döteberg, Florian Bauer, Andreas Köhn, Sabine Laschat
In order to study the impact of regioisomeric diene ligands on the formation and catalytic activity of Rh complexes, a series of C2- and CS-symmetric 2,5-disubstituted bicyclo[3.3.0]octa-2,5-dienes C2-L and CS-L, respectively, were synthesized from Weiss diketone by simultaneous deprotonation/electrophilic trapping of both oxo functions, and the catalytic behavior was studied in the presence of [RhCl(C2H4)2]2. Complexes [RhCl(C2-L)]2 bearing C2-symmetric ligands catalyzed effectively the asymmetric arylation of N-tosylaldimines to (S)-diarylamines with yields and ee values up to 99%...
November 21, 2017: Journal of Organic Chemistry
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