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https://www.readbyqxmd.com/read/28727699/efficacy-of-palmitoylethanolamide-for-pain-a-meta-analysis
#1
Bekir Berker Artukoglu, Chad Beyer, Adi Zuloff-Shani, Ephraim Brener, Michael Howard Bloch
BACKGROUND: Palmitoylethanolamide (PEA) is a cannabimimetic compound that has been investigated as an analgesic agent in animal models and clinical trials. OBJECTIVES: We conducted a meta-analysis to examine the efficacy of PEA for treating pain in randomized, controlled trials. STUDY DESIGN: Systematic review and meta-analysis. SETTING: This meta-analysis examined all randomized, controlled trials involving the effect of PEA on pain score...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727604/preclinical-development-of-ebi-005-an-il-1-receptor-1-inhibitor-for-the-topical-ocular-treatment-of-ocular-surface-inflammatory-diseases
#2
Joseph Kovalchin, Bracken King, Allyson Masci, Elizabeth Hopkins, Jeremy Fry, Jay Hou, Christian Li, Kelly Tenneson, Steve Weber, Gary Wolfe, Kathy Collins, Eric S Furfine
OBJECTIVE: Topical interleukin (IL)-1 receptor (R)1 blockade is therapeutically active in reducing signs and symptoms of dry eye disease. Herein, we describe in vitro and in vivo nonclinical Investigational New Drug (IND)-enabling studies of EBI-005, a novel protein chimera of IL-1β and IL-1 receptor antagonist (IL-1Ra or anakinra) that potently binds IL-1R1 and blocks signaling. These studies provide an assessment of receptor affinity, drug bioavailability, immunogenic response, safety, and tolerability in mice and rabbits...
July 18, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/28727431/pd-catalyzed-iodide-promoted-%C3%AE-arylation-of-ketones-for-the-regioselective-synthesis-of-isocoumarins
#3
Alessandra Casnati, Raimondo Maggi, Giovanni Maestri, Nicola Della Ca', Elena Motti
A variety of isocoumarins have been synthesized directly from 2-halobenzoates and ketones through a palladium-catalyzed α-arylation step followed by an intramolecular cyclization process. The addition of iodide anions to the reaction mixture increased yields and selectivities especially when 2-bromobenzoates were employed. This phosphine-free one-pot synthesis features a high functional group tolerance and gives access to richly decorated isocoumarins. This general methodology was successful in the total synthesis of Xyridin A, an important natural product with antibacterial and antifungal activity...
July 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28726739/5-aza-2-2-difluroro-deoxycytidine-nuc013-a-novel-nucleoside-dna-methyl-transferase-inhibitor-and-ribonucleotide-reductase-inhibitor-for-the-treatment-of-cancer
#4
Richard Daifuku, Zhenbo Hu, Yogen Saunthararajah
Tumor suppressor genes can be silenced genetically as well as epigenetically. One approach to reversing epigenetic suppression of tumor suppressor genes is to inhibit DNA methyl transferase. 5-aza-2',2'-diflurorodeoxycytidine (NUC013) is a novel DNA methyl transferase and ribonucleotide reductase inhibitor that is a more potent inhibitor of growth than decitabine in the NCI 60 cancer cell line panel. NUC013 is more active than decitabine against p53-null/mutant cancer cell lines (p = 0.027) but is even more so against p53 wild-type (WT) cell lines (p = 0...
July 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28726715/overexpression-of-the-osimp-gene-increases-the-accumulation-of-inositol-and-confers-enhanced-cold-tolerance-in-tobacco-through-modulation-of-the-antioxidant-enzymes-activities
#5
Rong-Xiang Zhang, Li-Jun Qin, De-Gang Zhao
Inositol is a cyclic polyol that is involved in various physiological processes, including signal transduction and stress adaptation in plants. l-myo-inositol monophosphatase (IMPase) is one of the metal-dependent phosphatase family members and catalyzes the last reaction step of biosynthesis of inositol. Although increased IMPase activity induced by abiotic stress has been reported in chickpea plants, the role and regulation of the IMP gene in rice (Oryza sativa L.) remains poorly understood. In the present work, we obtained a full-length cDNA sequence coding IMPase in the cold tolerant rice landraces in Gaogonggui, which is named as OsIMP...
July 20, 2017: Genes
https://www.readbyqxmd.com/read/28726711/the-use-of-constructed-wetlands-for-the-treatment-and-reuse-of-urban-wastewater-for-the-irrigation-of-two-warm-season-turfgrass-species-under-mediterranean-climatic-conditions
#6
Mario Licata, Teresa Tuttolomondo, Claudio Leto, Salvatore La Bella, Giuseppe Virga
Constructed wetlands (CWs) represent low-cost technology for the treatment and reuse of wastewater in urban areas. This study aimed to evaluate the pollutant removal efficiency of a CW system and to assess the effects of irrigation using treated urban wastewater on soil and on two warm-season turf species. The research was carried out in Sicily (Italy) on a pilot-scale horizontal subsurface flow system which was fed with treated urban wastewater following secondary treatment from an activated-sludge wastewater treatment plant...
July 2017: Water Science and Technology: a Journal of the International Association on Water Pollution Research
https://www.readbyqxmd.com/read/28726644/arabidopsis-calmodulin-like-protein-cml36-is-a-calcium-ca-2-sensor-that-interacts-with-the-plasma-membrane-ca-2-atpase-isoform-aca8-and-stimulates-its-activity
#7
Alessandra Astegno, Maria Cristina Bonza, Rosario Vallone, Valentina La Verde, Mariapina D'Onofrio, Laura Luoni, Barbara Molesini, Paola Dominici
Calmodulin-like (CML) proteins are major EF hand-containing, calcium (Ca(2+))-binding proteins with crucial roles in plant development and in coordinating plant stress tolerance. Given their abundance in plants, the properties of Ca(2+) sensors and identification of novel target proteins of CMLs deserve special attention. To this end, we recombinantly produced and biochemically characterized CML36 from Arabidopsis thaliana We analyzed Ca(2+) and Mg(2+) binding to the individual EF hands, observed metal-induced conformational changes, and identified a physiologically relevant target...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726638/understanding-inhibitor-resistance-in-mps1-kinase-through-novel-biophysical-assays-and-structures
#8
Yoshitaka Hiruma, Andre Koch, Nazila Hazraty, Foteini Tsakou, Rene H Medema, Robbie P Joosten, Anastassis Perrakis
Monopolar spindle 1 (Mps1/TTK) is a protein kinase essential in mitotic checkpoint signalling, preventing anaphase until all chromosomes are properly attached to spindle microtubules. Mps1 has emerged as a potential target for cancer therapy, and a variety of compounds have been developed to inhibit its kinase activity. Mutations in the catalytic domain of Mps1 that give rise to inhibitor resistance, but retain catalytic activity and do not display cross-resistance to other Mps1 inhibitors, have been described...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726394/human-cst-prefers-g-rich-but-not-necessarily-telomeric-sequences
#9
Robert A Hom, Deborah Sharon Wuttke
The human CST (CTC1-STN1-TEN1) heterotrimeric complex plays roles in both telomere maintenance and DNA replication through its ability to interact with ssDNA of a variety of sequences. The precise sequence specificity required to execute these functions is unknown. Telomere-binding proteins have been shown to specifically recognize key telomeric sequence motifs within ssDNA while accommodating non-specifically recognized sequences through conformationally plastic interfaces. To better understand the role CST plays in these processes, we have produced highly purified heterotrimer and elucidated the sequence requirements for CST recognition of ssDNA in vitro...
July 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28726200/intranasal-insulin-restores-metabolic-parameters-and-insulin-sensitivity-in-rats-with-metabolic-syndrome
#10
K V Derkach, A O Ivantsov, O V Chistyakova, I B Sukhov, D M Buzanakov, A A Kulikova, A O Shpakov
We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28726190/effect-of-peripheral-%C3%AE-%C3%AE-and-%C3%AE%C2%BA-opioid-ligands-on-the-development-of-tolerance-to-ethanol-induced-analgesia
#11
S K Sudakov, E V Alekseeva, G A Nazarova
We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of μ-, δ-, and κ-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric κ-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric μ-opioid receptors decelerated the development of this tolerance...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28726132/phase-i-dose-escalation-study-of-nms-1286937-an-orally-available-polo-like-kinase-1-inhibitor-in-patients-with-advanced-or-metastatic-solid-tumors
#12
Glen J Weiss, Gayle Jameson, Daniel D Von Hoff, Barbara Valsasina, Cristina Davite, Claudia Di Giulio, Francesco Fiorentini, Rachele Alzani, Patrizia Carpinelli, Alessandro Di Sanzo, Arturo Galvani, Antonella Isacchi, Ramesh K Ramanathan
Background Pharmacological inhibition of polo-like kinase 1 (PLK1) represents a new approach for the treatment of solid tumors. This study was aimed at determining the first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD) of NMS-1286937, a selective ATP-competitive PLK1-specific inhibitor. Secondary objectives included evaluation of its safety and pharmacokinetic (PK) profile in plasma, its antitumor activity, and its ability to modulate intracellular targets in biopsied tissue...
July 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#13
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28725426/colony-stimulating-factor-1-receptor-csf1r-inhibitors-in-cancer-therapy
#14
REVIEW
Michael A Cannarile, Martin Weisser, Wolfgang Jacob, Anna-Maria Jegg, Carola H Ries, Dominik Rüttinger
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725344/complete-response-of-mediastinal-clear-cell-sarcoma-to-pembrolizumab-with-radiotherapy
#15
Samuel Marcrom, Jennifer F De Los Santos, Robert M Conry
BACKGROUND: Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28725328/heterozygous-familial-hypercholesterolemia-with-apoe-haplotype-a-prospective-harbinger-of-a-catastrophic-cardiovascular-event
#16
Glenmore Lasam, Siddesh Shambhu, Robert Fishberg
We report a very young man with heterozygous familial hypercholesterolemia (FH) with APOE haplotype and a significant cardiac family history who underwent cardiac catheterization for intermittent episodes of exertional dyspnea and was noted to have a severe triple vessel coronary artery disease (CAD). He underwent coronary artery bypass graft (CABG) surgery which was uneventful. He was discharged on antiplatelet, beta blocker, nitrate, and statin. On routine health maintenance evaluation, he had no cardiac complaints and had been tolerating well his activities of daily living...
June 2017: Cardiology Research
https://www.readbyqxmd.com/read/28725251/custom-made-micro-applicators-for-high-dose-rate-brachytherapy-treatment-of-chronic-psoriasis
#17
Ivan M Buzurovic, Desmond A O'Farrell, Mandar S Bhagwat, Jorgen L Hansen, Thomas C Harris, Scott Friesen, Robert A Cormack, Phillip M Devlin
PURPOSE: In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR) brachytherapy. The custom-made micro applicators (CMMA) were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. MATERIAL AND METHODS: The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands...
June 2017: Journal of Contemporary Brachytherapy
https://www.readbyqxmd.com/read/28725229/the-synergistic-priming-effect-of-exogenous-salicylic-acid-and-h2o2-on-chilling-tolerance-enhancement-during-maize-zea-mays-l-seed-germination
#18
Zhan Li, Jungui Xu, Yue Gao, Chun Wang, Genyuan Guo, Ying Luo, Yutao Huang, Weimin Hu, Mohamed S Sheteiwy, Yajing Guan, Jin Hu
Chilling stress is an important constraint for maize seedling establishment in the field. To examine the role of salicylic acid (SA) and hydrogen peroxide (H2O2) in response to chilling stress, we investigated the effects of seed priming with SA, H2O2, and SA+H2O2 combination on maize resistance under chilling stress (13°C). Priming with SA, H2O2, and especially SA+H2O2 shortened seed germination time and enhanced seed vigor and seedling growth as compared with hydropriming and non-priming treatments under low temperature...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#19
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28725145/hiv-pharmaceutical-care-in-primary-healthcare-improvement-in-cd4-count-and-reduction-in-drug-related-problems
#20
C G R C Molino, Renata Cavalcanti Carnevale, Aline Teotonio Rodrigues, Patricia Moriel, Priscila Gava Mazzola
Background: Highly active antiretroviral therapy (HAART) is complex and many factors contribute to a patient's response to initial therapy including adherence, drug effectiveness, and tolerance. Close HAART follow-up is needed, particularly when there are concurrent therapies such as prophylactic antibiotics and medications for the treatment of comorbidities. Objective: To assess the effectiveness of pharmacist intervention in reducing drug related problems in HIV/AIDS outpatients (intervention group) and in improving clinical parameters in the intervention group compared to the control group...
July 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
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