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https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#1
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28214642/short-term-results-of-carotid-endarterectomy-and-stenting-after-the-introduction-of-carotid-magnetic-resonance-imaging-a-single-institutional-retrospective-study
#2
Ryu Fukumitsu, Kazumichi Yoshida, Yoshitaka Kurosaki, Koichi Torihashi, Nobutake Sadamasa, Masaomi Koyanagi, Osamu Narumi, Tsukasa Sato, Masaki Chin, Akira Handa, Sen Yamagata, Susumu Miyamoto
OBJECTIVE: While carotid artery stenting (CAS) has been gaining popularity as an alternative to carotid endarterectomy (CEA), the perioperative stroke rate following contemporary CAS remains significantly higher than that in CEA. The purpose of this study was to assess perioperative (within 30-day) therapeutic results in patients with carotid stenosis (CS) after the introduction of preoperative carotid magnetic resonance plaque evaluation in a single center offering both CEA and CAS. METHODS: Based on prospectively collected data for patients with CS who were scheduled for carotid revascularization, retrospective analysis was conducted of 295 consecutive CS patients...
February 15, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#3
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213566/a-randomised-phase-iib-study-of-mavrilimumab-a-novel-gm-csf-receptor-alpha-monoclonal-antibody-in-the-treatment-of-rheumatoid-arthritis
#4
Gerd R Burmester, Iain B McInnes, Joel Kremer, Pedro Miranda, Mariusz Korkosz, Jiri Vencovsky, Andrea Rubbert-Roth, Eduardo Mysler, Matthew A Sleeman, Alex Godwood, Dominic Sinibaldi, Xiang Guo, Wendy I White, Bing Wang, Chi-Yuan Wu, Patricia C Ryan, David Close, Michael E Weinblatt
OBJECTIVES: Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. METHODS: In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3...
February 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28213334/reactive-oxygen-a-novel-antimicrobial-mechanism-for-targeting-biofilm-associated-infection
#5
REVIEW
Matthew S Dryden, Jonathan Cooke, Rami J Salib, Rebecca E Holding, Timothy Biggs, Ali A Salamat, Raymond N Allan, Rachel S Newby, Fenella Halstead, Beryl Oppenheim, Thomas Hall, Sophie C Cox, Liam M Grover, Zain Al-Hindi, Lilyann Novak-Frazer, Malcolm D Richardson
Reactive oxygen species (ROS) is a novel therapeutic strategy for topical or local application to wounds, mucosa or internal structures where there may be heavy bacterial bioburden with biofilm and chronic inflammation. Bacterial biofilms are a significant problem in clinical settings owing to their increased tolerance towards conventionally prescribed antibiotics and their propensity for selection of further antibacterial resistance. There is therefore a pressing need for the development of alternative therapeutic strategies that can improve antibiotic efficacy towards biofilms...
February 14, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#6
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28212843/natural-extranuclear-androgen-receptor-ligands-as-endocrine-disruptors-of-cancer-cell-growth
#7
Marilena Kampa, George Notas, Elias Castanas
Even though the term endocrine disruption primarily designates environmental chemicals that can interfere with the action of hormones, in recent years it has been extended to include also plant derived compounds that can reach the human body, naturally, or have been identified and studied as alternative pharmaceutical agents. In fact, for a large number of them, their antihormonal action was appreciated by different traditional herbal medicines. In the present review we report the majority of the plant derived compounds that exhibit an antiandrogenic effect and the known mechanisms of action...
February 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28212616/general-practitioners-views-on-long-term-prescription-and-use-of-problematic-and-potentially-inappropriate-medication-for-oldest-old-patients-a-qualitative-interview-study-with-gps-cim-triad-study
#8
Nadine Janis Pohontsch, Kathrin Heser, Antje Löffler, Britta Haenisch, Debora Parker, Tobias Luck, Steffi G Riedel-Heller, Wolfgang Maier, Frank Jessen, Martin Scherer
BACKGROUND: Potentially inappropriate medication (PIM) is defined as medication with uncertain therapeutic effects and/or potential adverse drug reactions outweighing the clinical benefits. The prescription rate of PIM for oldest-old patients is high despite the existence of lists of PIM (e.g. the PRISCUS list) and efforts to raise awareness. This study aims at identifying general practitioners' views on PIM and aspects affecting the (long-term) use of PIM. METHODS: As part of the CIM-TRIAD study, we conducted semi-structured, qualitative interviews with 47 general practitioners, discussing 25 patients with and 22 without PIM (according to the PRISCUS list)...
February 17, 2017: BMC Family Practice
https://www.readbyqxmd.com/read/28212592/novel-insights-into-gonadotropin-releasing-hormone-action-in-the-pituitary-gonadotrope
#9
Jessica L Brown, Mark Roberson
The hypothalamic-pituitary-gonadal axis controls reproduction via a series of hormones regulating gonadal function through interconnected feedback loops. Secretion of hypothalamic-derived gonadotropin-releasing hormone (GnRH) integrates inputs from higher brain centers to coordinate the activity of the pituitary gonadotrope and the biosynthesis and secretion of the gonadotropins which ultimately regulate gonadal function. Failure of GnRH to serve as the central integrator of this system has been associated with hypogonadotropic-hypogonadism and clinical infertility, while pharmacological application of GnRH analogs and gonadotropins have important implications of the treatment of such infertility...
February 17, 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28211870/non-apoptotic-functions-of-caspases-in-myeloid-cell-differentiation
#10
REVIEW
Stéphanie Solier, Michaela Fontenay, William Vainchenker, Nathalie Droin, Eric Solary
Subtle caspase activation is associated with the differentiation of several myeloid lineages. A tightly orchestrated dance between caspase-3 activation and the chaperone HSP70 that migrates to the nucleus to protect the master regulator GATA-1 from cleavage transiently occurs in basophilic erythroblasts and may prepare nucleus and organelle expel that occurs at the terminal phase of erythroid differentiation. A spatially restricted activation of caspase-3 occurs in maturing megakaryocytes to promote proplatelet maturation and platelet shedding in the bloodstream...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211007/daclizumab-a-review-in-relapsing-multiple-sclerosis
#11
Matt Shirley
Daclizumab (Zinbryta(®); previously known as daclizumab high-yield process) is a therapeutic monoclonal antibody that has recently been approved for the treatment of relapsing forms of multiple sclerosis (MS) in adults. Daclizumab is a humanized IgG1 monoclonal antibody directed against CD25, the alpha subunit of the high-affinity interleukin-2 receptor. As demonstrated in the phase III DECIDE trial, once-monthly subcutaneous daclizumab was superior to once-weekly intramuscular interferon (IFN) β-1a in reducing the clinical relapse rate and radiological measures of disease in patients with relapsing-remitting MS...
February 17, 2017: Drugs
https://www.readbyqxmd.com/read/28210823/non-ablative-erbium-yag-laser-for-the-treatment-of-type-iii-stress-urinary-incontinence-intrinsic-sphincter-deficiency
#12
Adrian Gaspar, Hugo Brandi
The objective of this pilot study was to determine the safety and efficacy of a new non-ablative erbium YAG laser procedure for the treatment of type III stress urinary incontinence (intrinsic sphincter deficiency) in women. Twenty-two patients with a Valsalva leak point pressure less than 60 cm H2O were recruited and treated with a non-ablative erbium laser delivering low fluence pulses inside the whole length of the urethra through a specially designed cannula. Treatment consisted of two treatment sessions with a 3-week interval in-between...
February 16, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28210463/frequency-of-inducible-clindamycin-resistance-among-gram-positive-cocci-in-a-tertiary-hospital-tehran-iran
#13
Hiva Saffar, Afsaneh Rajabiani, Alireza Abdollahi, Shirin Habibi, Zohreh Baseri
BACKGROUND AND OBJECTIVES: Accurate designation of antimicrobial susceptibility pattern of the infecting microorganisms is an important crucial factor in making appropriate therapeutic decisions. Macrolide, lincosamide and streptogramin B antibiotics are in a family, reserved as an alternative approach in treatment of resistant Gram positive cocci. Amongst them, clindamycin has been considered as the preferred agent due to its excellent pharmacokinetic properties. The inducible resistance to clindamycin in Gram positive staphylococci and streptococci cannot be recognized by routine broth or agar based susceptibility tests and D-zone testing is necessary...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28209757/cdk4-6-therapeutic-intervention-and-viable-alternative-to-taxanes-in-crpc
#14
James P Stice, Suzanne E Wardell, John D Norris, Alexander P Yllanes, Holly M Alley, Victoria O Haney, Hannah S White, Rachid Safi, Peter S Winter, Kimberly J Cocce, Rigel J Kishton, Scott A Lawrence, Jay C Strum, Donald P McDonnell
: Resistance to second generation AR antagonists and CYP17 inhibitors in patients with castrationresistant prostate cancer (CRPC) develops rapidly through reactivation of the androgen signaling axis and has been attributed to androgen receptor (AR) overexpression, production of constitutively active AR splice variants, or the selection for AR mutants with altered ligand binding specificity. It has been established that androgens induce cell cycle progression, in part, through upregulation of cyclin D1 (CCND1) expression and subsequent activation of cyclin-dependent kinases 4 and 6 (CDK4/6)...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209661/non-topical-management-of-recalcitrant-paediatric-atopic-dermatitis
#15
REVIEW
Jin Ho Chong, Mark Jean Aan Koh
Atopic dermatitis (AD) is a common chronic, pruritic skin disease in children. As the incidence of AD increases, especially in high-income countries, paediatricians may see an increasing number of recalcitrant AD cases in their practice. Although these cases are principally managed by paediatric dermatologists, it is important for paediatricians to be aware of the use and side effects of non-topical treatment like phototherapy and systemic agents as well as the evidence for alternative treatment, which caregivers may ask about...
February 16, 2017: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/28209365/gelatin-and-non-gelatin-capsule-dosage-forms
#16
REVIEW
Rampurna P Gullapalli, Carolyn L Mazzitelli
Capsules offer an alternate to tablets for oral delivery of therapeutic compounds. One advantage of capsules over tablets is their amenability to deliver not only solids but also non-aqueous liquids and semisolids as a unit dose solid dosage form. Shell component is an essential part of capsule dosage forms. Capsule shells, available as hard or soft shells, are formulated from gelatin or a non-gelatin polymeric material such as hypromellose and starch, water, and with or without a non-volatile plasticizer. The capsule shells may also be formulated to modify the release of their fill contents in a site-specific manner in the gastrointestinal tract...
February 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28208769/localisation-microscopy-of-breast-epithelial-erbb-2-receptors-and-gap-junctions-trafficking-after-%C3%AE-irradiation-neuregulin-1%C3%AE-and-trastuzumab-application
#17
Götz Pilarczyk, Ines Nesnidal, Manuel Gunkel, Margund Bach, Felix Bestvater, Michael Hausmann
In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion-a process attenuated by trastuzumab antibody application...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208731/in-vivo-imaging-of-local-gene-expression-induced-by-magnetic-hyperthermia
#18
Olivier Sandre, Coralie Genevois, Eneko Garaio, Laurent Adumeau, Stéphane Mornet, Franck Couillaud
The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28207863/identification-of-age-dependent-motor-and-neuropsychological-behavioural-abnormalities-in-a-mouse-model-of-mucopolysaccharidosis-type-ii
#19
Hélène F E Gleitz, Claire O'Leary, Rebecca J Holley, Brian W Bigger
Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this...
2017: PloS One
https://www.readbyqxmd.com/read/28207424/skeletal-muscle-wasting-new-role-of-nonclassical-renin-angiotensin-system
#20
Claudio Cabello-Verrugio, Juan C Rivera, Dominga Garcia
PURPOSE OF REVIEW: Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. RECENT FINDINGS: Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle...
February 16, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
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