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https://www.readbyqxmd.com/read/28733581/structural-determinants-at-the-m2-muscarinic-receptor-modulate-the-rgs4-girk-response-to-pilocarpine-by-impairment-of-the-receptor-voltage-sensitivity
#1
I-Shan Chen, Kazuharu Furutani, Yoshihisa Kurachi
Membrane potential controls the response of the M2 muscarinic receptor to its ligands. Membrane hyperpolarization increases response to the full agonist acetylcholine (ACh) while decreasing response to the partial agonist pilocarpine. We previously have demonstrated that the regulator of G-protein signaling (RGS) 4 protein discriminates between the voltage-dependent responses of ACh and pilocarpine; however, the underlying mechanism remains unclear. Here we show that RGS4 is involved in the voltage-dependent behavior of the M2 muscarinic receptor-mediated signaling in response to pilocarpine...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733085/functional-consequences-of-chemically-induced-%C3%AE-arrestin-binding-to-chemokine-receptors-cxcr4-and-ccr5-in-the-absence-of-ligand-stimulation
#2
Marcel Liebick, Sarah Henze, Viola Vogt, Martin Oppermann
Chemokine receptor signaling is a tightly regulated process which was for a long time exclusively attributed to heterotrimeric G proteins. β-Arrestins constitute a separable signaling arm from classical heterotrimeric G proteins, in addition to their well-established roles in receptor desensitization and endocytosis. In order to clearly dissect β-arrestin- from G protein-dependent effects we forced the recruitment of β-arrestin to CXCR4 and CCR5 independently of agonist-promoted receptor activation through chemically-induced dimerization...
July 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28732431/the-efficacy-of-oral-immunotherapy-in-patients-with-cow-s-milk-allergy
#3
Mohsen Ebrahimi, Mohammad Gharagozlou, Ali Mohebbi, Nasim Hafezi, Gholamreza Azizi, Masoud Movahedi
Cow's milk allergy is the most common type of food allergy that decrease the quality of life of patients and their families. The aim of this study was to evaluate the efficacy of oral immunotherapy in patients with cow's milk allergy. 14 patients above 3 years of age with a history of cow's milk allergy confirmed by positive double blind placebo controlled food challenge (DBPCFC) test, presence of serum IgE against cow's milk and positive SPT (skin prick test) were enrolled in this study. During the immunotherapy all patients received increasing amounts of cow's milk during three phases...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28731314/desensitization-to-chemical-and-food-sensitivities-by-low-dose-immunotherapy-ascertained-by-provocation-neutralization-is-associated-with-reduced-influx-of-calcium-ions-into-lymphocytes
#4
Basant K Puri, John McLaren Howard, Jean A Monro
Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels...
April 26, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28731218/explosives-in-the-cage-metal-organic-frameworks-for-high-energy-materials-sensing-and-desensitization
#5
REVIEW
Shan Wang, Qianyou Wang, Xiao Feng, Bo Wang, Li Yang
An overview of the current status of coordination polymers and metal-organic frameworks (MOFs) pertaining to the field of energetic materials is provided. The explosive applications of MOFs are discussed from two aspects: one for detection of explosives, and the other for explosive desensitization. By virtue of their adjustable pore/cage sizes, high surface area, tunable functional sites, and rich host-guest chemistry, MOFs have emerged as promising candidates for both explosive sensing and desensitization...
July 21, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28730896/cannabinoid-hyperemesis-syndrome-potential-mechanisms-for-the-benefit-of-capsaicin-and-hot-water-hydrotherapy-in-treatment
#6
John R Richards, Jeff M Lapoint, Guillermo Burillo-Putze
INTRODUCTION: Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. OBJECTIVES: In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation...
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28728802/-psychotherapies-for-the-treatment-of-phantom-limb-pain
#7
Katherine Cárdenas, Mariana Aranda
INTRODUCTION: The phantom limb pain has been described as a condition in which patients experience a feeling of itching, spasm or pain in a limb or body part that has been previously amputated. Such pain can be induced by a conflict between the representation of the visual and proprioceptive feedback of the previously healthy limb. The phantom limb pain occurs in at least 42 to 90% of amputees. Regular drug treatment of phantom limb pain is almost never effective. METHODS: A systematic review of the literature was conducted in Medline and Cochrane using the MESH terms "phantom limb pain" and "psychotherapy", published in the last 10 years, in English and Spanish, finding 49 items...
July 2017: Revista Colombiana de Psiquiatría
https://www.readbyqxmd.com/read/28725322/recurrent-body-rash-warranted-second-desensitization-with-acyclovir-in-a-myeloma-patient-a-case-report
#8
Jack T Seki, Pamela Ng, Wallace Lam, Julie Cote, Anca Prica
A 75-year-old woman developed a moderately severe rash about a week and a half after the start of bortezomib (Btb)-based chemotherapy for IgG lambda multiple myeloma; at the time, she was also receiving acyclovir as antiviral prophylaxis in addition to herpes zoster (HZ) vaccination. HZ reactivation rate is high in Btb recipients; therefore, the timing of antiviral prevention is critical in relation to Btb. Attempts were made to identify the offending agent based on the timing of drugs administered and the appearance of skin lesions in relation to other drugs...
August 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28724750/disruption-of-a-structurally-important-extracellular-element-in-the-glycine-receptor-leads-to-decreased-synaptic-integration-and-signaling-resulting-in-severe-startle-disease
#9
Natascha Schaefer, Alexandra Berger, Johannes van Brederode, Fang Zheng, Yan Zhang, Sophie Leacock, Laura Littau, Sibylle Jablonka, Sony Malhotra, Maya Topf, Friederike Winter, Daria Davydova, Joseph W Lynch, Christopher J Paige, Christian Alzheimer, Robert J Harvey, Carmen Villmann
Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorder. We found that lack of synaptic integration of GlyRs, together with disrupted receptor function is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation Q177K located in the extracellular β8-β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8-β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in cys-loop receptors...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28722651/ephrin-a-epha-specific-co-adaptation-as-a-novel-mechanism-in-topographic-axon-guidance
#10
Felix Fiederling, Markus Weschenfelder, Martin Fritz, Anne von Philipsborn, Martin Bastmeyer, Franco Weth
Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722364/-allergy-to-human-seminal-plasma
#11
Laura Moi, Igor Salvadé, Camillo Ribi
Hypersensitivity to human seminal plasma is rare, but probably under-diagnosed. It should be suspected in women with unexplained anaphylaxis, vulvo-vaginitis, pelvic pain and dyspareunia. The diagnosis relies on the clinical presentation, the exclusion of other causes, a positive skin test result to seminal plasma and the detection of IgE directed to allergenic proteins (such as prostate specific antigen). Use of condoms is the best preventive measure. Premedication with antihistamines or anti-inflammatory agents is often unreliable...
April 5, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28718768/selective-and-regulated-trapping-of-nicotinic-receptor-weak-base-ligands-and-relevance-to-smoking-cessation
#12
Anitha P Govind, Yolanda F Vallejo, Jacob R Stolz, Jing-Zhi Yan, Geoffrey T Swanson, William N Green
To better understand smoking cessation, we examined the actions of varenicline (Chantix) during long-term nicotine exposure. Varenicline reduced nicotine upregulation of α4β2-type nicotinic receptors (α4β2Rs) in live cells and neurons, but not for membrane preparations. Effects on upregulation depended on intracellular pH homeostasis and were not observed if acidic pH in intracellular compartments was neutralized. Varenicline was trapped as a weak base in acidic compartments and slowly released, blocking (125)I-epibatidine binding and desensitizing α4β2Rs...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28713569/kctd12-modulation-of-gaba-b-receptor-function
#13
Melody Li, Carol J Milligan, Haiyan Wang, Andrew Walker, Leonid Churilov, Andrew J Lawrence, Christopher A Reid, Seth C Hopkins, Steven Petrou
The molecular composition and functional diversity of native GABAB receptors (GABABR) are still poorly understood, thus hindering development of selective GABABR ligands. Potassium channel tetramerization domain-containing protein (KCTD) 12 is a GABABR auxiliary subunit and mouse KCTD12 can alter GABABR function. In this study, we sought to characterize the effects of human KCTD12 on GABABR kinetics and pharmacology, using an automated electrophysiological assay. Seizure susceptibility and ethanol consumption were also investigated in a KCTD12 knockout mouse model...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28711716/impact-of-paroxetine-on-proximal-%C3%AE-adrenergic-receptor-signaling
#14
Shuchi Guo, Rhonda L Carter, Laurel A Grisanti, Walter J Koch, Douglas G Tilley
β-adrenergic receptors (βAR) regulate numerous functions throughout the body, however G protein-coupled receptor kinase (GRK)-dependent desensitization of βAR has long been recognized as a maladaptive process in the progression of various disease states. Thus, the development of small molecule inhibitors of GRKs for the study of these processes and as potential therapeutics has been at the forefront of recent research efforts. Via structural and biochemical analyses, the selective serotonin reuptake inhibitor (SSRI) paroxetine was identified as a GRK2 inhibitor that enhances βAR-dependent cardiomyocyte and cardiac contractility and reverses cardiac dysfunction and myocardial βAR expression in mouse models of heart failure...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28708827/deciphering-the-regulation-of-p2x4-receptor-channel-gating-by-ivermectin-using-markov-models
#15
Laurent Mackay, Hana Zemkova, Stanko S Stojilkovic, Arthur Sherman, Anmar Khadra
The P2X4 receptor (P2X4R) is a member of a family of purinergic channels activated by extracellular ATP through three orthosteric binding sites and allosterically regulated by ivermectin (IVM), a broad-spectrum antiparasitic agent. Treatment with IVM increases the efficacy of ATP to activate P2X4R, slows both receptor desensitization during sustained ATP application and receptor deactivation after ATP washout, and makes the receptor pore permeable to NMDG+, a large organic cation. Previously, we developed a Markov model based on the presence of one IVM binding site, which described some effects of IVM on rat P2X4R...
July 14, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28703891/duration-of-action-of-mepivacaine-and-lidocaine-in-equine-palmar-digital-perineural-blocks-in-an-experimental-lameness-model
#16
Mona Hoerdemann, Rachael L Smith, Giselle Hosgood
OBJECTIVE: To establish and compare the onset and duration of action of 2 local anesthetics based on objective lameness and skin sensitivity assessment. STUDY DESIGN: Interventional crossover experimental trial with balanced randomization. ANIMALS: Eight horses. METHODS: Reversible forelimb lameness was induced in 8 horses. A palmar digital nerve block (PDNB) was applied with mepivacaine or lidocaine (both 2%). Quantitative lameness and skin sensitivity data were collected with an inertial sensor system and a force gauge, respectively...
July 13, 2017: Veterinary Surgery: VS
https://www.readbyqxmd.com/read/28702058/effectiveness-of-audiovisual-distraction-in-behavior-modification-during-dental-caries-assessment-and-sealant-placement-in-children-with-autism-spectrum-disorder
#17
Kausar Sadia Fakhruddin, Hisham Yehia El Batawi
BACKGROUND: The aim of this study was to evaluate the effectiveness of audiovisual (AV) distraction in behavior modification during dental caries assessment and sealant placement in children with autism spectrum disorder. MATERIALS AND METHODS: This study was conducted on 28 children diagnosed with autism spectrum disorder, aged 6.5-9.8 years. Children underwent one introductory (desensitization) appointment and three treatment sessions. During the introductory session, children had the procedures explained to them, they watched a movie projected on a screen while oral screening and assessment of cooperation level were carried out...
May 2017: Dental Research Journal
https://www.readbyqxmd.com/read/28702033/how-streptomyces-anulatus-primes-grapevine-defenses-to-cope-with-gray-mold-a-study-of-the-early-responses-of-cell-suspensions
#18
Parul Vatsa-Portugal, Aziz Aziz, Marine Rondeau, Sandra Villaume, Hamid Morjani, Christophe Clément, Essaid Ait Barka
Gray mold, caused by Botrytis cinerea, is one of the most destructive diseases of grapevine and is controlled with an intense application of fungicides. As alternatives to chemicals, beneficial microbes may promote plant health by stimulating the plant's immune system. An actinomycete, Streptomyces anulatus S37, has been screened from the rhizosphere microbiome of healthy Vitis vinifera on the basis of its ability to promote grapevine growth and to induce resistance against various phytopathogens, including B...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28701711/amplification-mode-differs-along-the-length-of-the-mouse-cochlea-as-revealed-by-connexin-26-deletion-from-specific-gap-junctions
#19
Victoria A Lukashkina, Tetsuji Yamashita, Jian Zuo, Andrei N Lukashkin, Ian J Russell
The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters' cells (DCs) and pillar cells (PCs), coupled by gap-junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving-voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697974/a-possible-desensitized-state-conformation-of-the-human-%C3%AE-7-nicotinic-receptor-a-molecular-dynamics-study
#20
L Chiodo, T E Malliavin, L Maragliano, G Cottone
The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing...
June 30, 2017: Biophysical Chemistry
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