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https://www.readbyqxmd.com/read/28801320/in-stable-copd-long-acting-muscarinic-antagonist-plus-long-acting-beta-agonists-resulted-in-less-exacerbations-pneumonia-and-larger-improvement-in-fev-1-than-long-acting-beta-agonists-plus-inhaled-corticosteroids
#1
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#2
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28793049/possible-mechanisms-involved-in-the-vasorelaxant-effect-produced-by-clobenzorex-in-aortic-segments-of-rats
#3
J Lozano-Cuenca, A González-Hernández, O A López-Canales, J R Villagrana-Zesati, J D Rodríguez-Choreão, R Morín-Zaragoza, E F Castillo-Henkel, J S López-Canales
Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7...
August 7, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28782490/unmet-needs-in-schizophrenia
#4
Maurizio Pompili, Herbert Y Meltzer
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
August 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28781727/cross-state-dependent-learning-interaction-between-scopolamine-and-morphine-in-mice-the-role-of-dorsal-hippocampus
#5
Morteza Maleki, Majid Hassanpour-Ezatti, Majid Navaeian
INTRODUCTION: The current study aimed at investigating the existence of the cross state-dependent learning between morphine and scopolamine (SCO) in mice by passive avoidance method, pointing to the role of CA1 area. METHODS: The effects of pre-training SCO (0.75, 1.5, and 3 μg, Intra-CA1), or morphine (1, 3, and 6 mg/kg, intraperitoneal (i.p.) was evaluated on the retrieval of passive avoidance learning using step-down task in mice (n=10). Then, the effect of pretest administration of morphine (1...
May 2017: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/28777299/ultrafast-and-slow-cholinergic-transmission-different-involvement-of-acetylcholinesterase-molecular-forms
#6
REVIEW
Yves Dunant, Victor Gisiger
Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) Ultrafast transmission. Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief impulses (1-4 ms) at high frequencies. The collagen-tailed A12 acetylcholinesterase is concentrated in the synaptic cleft of NMJs and NEJs, were it curtails the postsynaptic response by ultrafast ACh hydrolysis...
August 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28776261/roles-of-na-ca-2-and-k-channels-in-the-generation-of-repetitive-firing-and-rhythmic-bursting-in-adrenal-chromaffin-cells
#7
REVIEW
Christopher J Lingle, Pedro L Martinez-Espinosa, Laura Guarina, Emilio Carbone
Adrenal chromaffin cells (CCs) are the main source of circulating catecholamines (CAs) that regulate the body response to stress. Release of CAs is controlled neurogenically by the activity of preganglionic sympathetic neurons through trains of action potentials (APs). APs in CCs are generated by robust depolarization following the activation of nicotinic and muscarinic receptors that are highly expressed in CCs. Bovine, rat, mouse, and human CCs also express a composite array of Na(+), K(+), and Ca(2+) channels that regulate the resting potential, shape the APs, and set the frequency of AP trains...
August 3, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28775269/hipp-neurons-in-the-dentate-gyrus-mediate-the-cholinergic-modulation-of-background-context-memory-salience
#8
Syed Ahsan Raza, Anne Albrecht, Gürsel Çalışkan, Bettina Müller, Yunus Emre Demiray, Susann Ludewig, Susanne Meis, Nicolai Faber, Roland Hartig, Burkhart Schraven, Volkmar Lessmann, Herbert Schwegler, Oliver Stork
Cholinergic neuromodulation in the hippocampus controls the salience of background context memory acquired in the presence of elemental stimuli predicting an aversive reinforcement. With pharmacogenetic inhibition we here demonstrate that hilar perforant path-associated (HIPP) cells of the dentate gyrus mediate the devaluation of background context memory during Pavlovian fear conditioning. The salience adjustment is sensitive to reduction of hilar neuropeptide Y (NPY) expression via dominant negative CREB expression in HIPP cells and to acute blockage of NPY-Y1 receptors in the dentate gyrus during conditioning...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28772121/cell-type-specific-translation-profiling-reveals-a-novel-strategy-for-treating-fragile-x-syndrome
#9
Sophie R Thomson, Sang S Seo, Stephanie A Barnes, Susana R Louros, Melania Muscas, Owen Dando, Caoimhe Kirby, David J A Wyllie, Giles E Hardingham, Peter C Kind, Emily K Osterweil
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX); however, the differentially translating mRNAs that contribute to altered neural function are not known. We used translating ribosome affinity purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1(-/y)) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28768531/the-effect-of-glycopyrronium-and-indacaterol-as-monotherapy-and-in-combination-on-the-methacholine-dose-response-curve-of-mild-asthmatics-a-randomized-three-way-crossover-study
#10
Christianne M Blais, Beth E Davis, Donald W Cockcroft
BACKGROUND: Methacholine dose-response curves illustrate pharmacologic bronchoprotection against methacholine-induced airway hyperresponsiveness and can be used to quantitate changes in airway sensitivity (position), reactivity (slope), and maximal responsiveness following drug administration. Our objective was to determine the influence of single-dose glycopyrronium (long-acting muscarinic antagonist) and indacaterol (ultra-long acting β2 agonist), as monotherapy and in combination, on the methacholine dose-response curve of mild asthmatics and to compare these findings with a non-asthmatic control curve...
August 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28767773/long-acting-muscarinic-antagonists-vs-long-acting-%C3%AE-2-agonists-in-copd-exacerbations-a-systematic-review-and-meta-analysis
#11
Israel Silva Maia, Mariângela Pimentel Pincelli, Victor Figueiredo Leite, João Amadera, Anna Maria Buehler
Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid...
July 31, 2017: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
https://www.readbyqxmd.com/read/28767678/pharmacoperone-rescue-of-vasopressin-2-receptor-mutants-reveals-unexpected-constitutive-activity-and-coupling-bias
#12
Jo Ann Janovick, Timothy P Spicer, Thomas D Bannister, Louis Scampavia, P Michael Conn
Pharmacoperones are small molecules that diffuse into cells and rescue misfolded, mistrafficked protein mutants, restoring their function. These substances act with high target specificity, serving as templates to fold (or refold) receptors, enzymes, ion channels or other proteins and enable them to pass the scrutiny of the cellular quality control system ("rescue"). In the present study we demonstrate that a rescued mutant (L83Q) of the vasopressin type 2 receptor (V2R), shows a strong bias for Gs coupling unlike the WT V2 receptor, which couples to both Gs and Gq/11...
2017: PloS One
https://www.readbyqxmd.com/read/28766156/a-primer-on-nerve-agents-what-the-emergency-responder-anesthesiologist-and-intensivist-needs-to-know
#13
Keith Candiotti
PURPOSE: The purpose of this review article is to familiarize first responders, anesthesiologists, and intensivists with the medical management of patients exposed to nerve agents. SOURCE: This review is based on the current medical literature available to the general medical community. PRINCIPAL FINDINGS: Nerve agents are some of the deadliest substances known to humanity. Though they kill primarily via muscle paralysis, which leads to respiratory arrest, these agents affect virtually every organ system in the body...
August 1, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28764154/effect-of-agonist-and-antagonist-on-the-in-vitro-contractility-of-inflamed-vermiform-appendix
#14
Phani Bhushan Singh, Pushpakant Tiwary, Sanjeev K Singh, Ratna Pandey, Atanu Roy, Amrita Ghosh Kar, Somprakas Basu, Anil Kumar Tiwari
INTRODUCTION: Appendicitis poses a great health problem worldwide. Previous studies demonstrated structural damage to neuronal network and interstitial cell of Cajal in appendicitis. Above observations suggest for the alterations in appendicular motility/contractility in appendicitis. But the mechanisms involved in mediating the contractility in inflamed vermiform appendix is not known till date. AIM: The present in vitro study was performed to find out the mechanisms responsible for contractility in the inflamed human vermiform appendix...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28763112/systematic-literature-review-of-clinical-trials-evaluating-pharmacotherapy-for-overactive-bladder-in-elderly-patients-an-assessment-of-trial-quality
#15
REVIEW
Kristin D Kistler, Yingxin Xu, Kelly H Zou, Fady Ntanios, Douglass S Chapman, Xuemei Luo
AIMS: Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. METHODS: MEDLINE(®) , Embase(®) , and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as "elderly")...
August 1, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28762161/muscarinic-receptors-in-adrenal-chromaffin-cells-physiological-role-and-regulation-of-ion-channels
#16
REVIEW
Masumi Inoue, Hidetada Matsuoka, Keita Harada, Lung-Sen Kao
Adrenal medullary chromaffin cells in mammals are innervated by sympathetic preganglionic nerve fibers, as are sympathetic ganglion neurons. Acetylcholine in the ganglion neurons is well established as mediating fast and slow excitatory postsynaptic potentials through nicotinic and muscarinic acetylcholine receptors (AChRs), respectively. The role of muscarinic AChRs during neuronal transmission in chromaffin cells varies among different mammals. Furthermore, the ion channel mechanisms associated with the muscarinic AChR-mediated increase in excitability of chromaffin cells are complicated and different from the excitation of ganglion neurons, which has been ascribed to the inhibition of M-type K(+) channels...
July 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28758583/new-trends-in-the-treatment-of-schizophrenia
#17
Herbert Y Meltzer
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28757318/new-treatment-option-for-copd-two-long-acting-bronchodilators-in-a-single-metered-dose-inhaler
#18
REVIEW
Timothy H Self, Samantha Ellingson
Combination long-acting inhaled bronchodilators are central to the management of moderate to very severe chronic obstructive pulmonary disease (COPD) patients. Glycopyrrolate is a long-acting muscarinic antagonist (LAMA), and formoterol fumarate is a long-acting beta2 agonist (LABA). In randomized controlled trials, this LAMA/LABA combination in a metered dose inhaler (MDI) was shown to be effective in improving pulmonary function and quality of life. Clinicians now have the availability of three delivery systems for LAMA/LABA therapy, including MDI, dry-powder inhaler, and Soft Mist inhaler...
July 27, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28754132/interactions-between-glycopyrronium-and-indacaterol-on-cholinergic-neurotransmission-and-contractile-response-in-bovine-trachealis
#19
Michele Baroffio, Giovanni Barisione, Vito Brusasco
BACKGROUND: Muscarinic-receptor antagonists and β-adrenoceptor agonists are used, alone or in combination, as first-line treatment for chronic obstructive pulmonary disease. Both drugs decrease airway smooth muscle tone by post-junctional mechanisms but they may have opposing effects on pre-junctional acetylcholine (ACh)-release. METHODS: We studied the effects of the muscarinic-receptor antagonist glycopyrronium (GLY), the β-adrenoceptor agonist indacaterol (IND) and their combination on electrically-induced ACh-release and contractile response in isolated bovine trachealis...
July 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28752576/influence-of-prostanoids-in-the-diuretic-and-natriuretic-effects-of-extracts-and-kaempferitrin-from-bauhinia-forficata-link-leaves-in-rats
#20
Priscila de Souza, Luisa Mota da Silva, Thaise Boeing, Lincon Bordignon Somensi, Camile Cecconi Cechinel-Zanchett, Adriana Campos, Clarissa de Medeiros Amorim Krueger, Jairo Kenupp Bastos, Valdir Cechinel-Filho, Sérgio Faloni de Andrade
Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis, no scientific investigation has focused on demonstrating its efficacy in preclinical trials. For that, normotensive male Wistar and spontaneously hypertensive rats were used to test the effect of extracts and kaempferitrin obtained from Bauhinia forficata leaves in the experimental model of diuresis. Cumulative urine volume, Na(+) and K(+) excretion, calcium, creatinine, prostaglandin E2 , pH, density, and conductivity were measured at the end of the experiment (after 8 or 24 h)...
July 28, 2017: Phytotherapy Research: PTR
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