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Drug Impairment

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https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#1
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430602/fluoxetine-attenuates-the-impairment-of-spatial-learning-ability-and-prevents-neuron-loss-in-middle-aged-appswe-psen1de9-double-transgenic-alzheimer-s-disease-mice
#2
Jing Ma, Yuan Gao, Lin Jiang, Feng-Lei Chao, Wei Huang, Chun-Ni Zhou, Wei Tang, Lei Zhang, Chun-Xia Huang, Yi Zhang, Yan-Min Luo, Qian Xiao, Hua-Rong Yu, Rong Jiang, Yong Tang
Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429626/promising-immunotherapy-against-fungal-diseases
#3
Wilfried Posch, Marion Steger, Doris Wilflingseder, Cornelia Lass-Flörl
Despite the relatively high efficacy of antifungal drugs, invasive fungal infections (IFIs) are still associated with tremendous morbidity and mortality, since late diagnosis makes an antifungal drug therapy inefficient. Therefore, antifungal immunotherapies to specifically strengthen the host´s own immune mechanisms constitute an additional promising strategy in taking action against fungal pathogens. Areas covered: The authors summarize efforts in research and clinical trials to provide safe and efficient immunotherapeutic options against invasive fungal diseases...
April 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28429294/ocular-cubosome-drug-delivery-system-for-timolol-maleate-preparation-characterization-cytotoxicity-ex-vivo-and-in-vivo-evaluation
#4
Jiayuan Huang, Tingting Peng, Yanrong Li, Zhengwen Zhan, Youmei Zeng, Ying Huang, Xin Pan, Chuan-Yu Wu, Chuanbin Wu
Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization...
April 20, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28429110/inhibition-of-the-crf1-receptor-influences-the-activity-of-antidepressant-drugs-in-the-forced-swim-test-in-rats
#5
Andrzej Wróbel, Anna Serefko, Aleksandra Szopa, Karol Rojek, Ewa Poleszak, Krystyna Skalicka-Woźniak, Jarosław Dudka
Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of the central corticotropin-releasing factor (CRF) system are factors in the pathogenesis of depression. Though several antagonists of the CRF1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between CRF1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of SN003, a CRF1 receptor blocker, on the activity of imipramine and fluoxetine in the forced swim test (FST) in rats which presented some signs of depression...
April 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28428744/mutational-analysis-at-intersubunit-interfaces-of-an-anionic-glutamate-receptor-reveals-a-key-interaction-important-for-channel-gating-by-ivermectin
#6
Nurit Degani-Katzav, Revital Gortler, Marina Weissman, Yoav Paas
The broad-spectrum anthelmintic drug ivermectin (IVM) activates and stabilizes an open-channel conformation of invertebrate chloride-selective glutamate receptors (GluClRs), thereby causing a continuous inflow of chloride ions and sustained membrane hyperpolarization. These effects suppress nervous impulses and vital physiological processes in parasitic nematodes. The GluClRs are pentamers. Homopentameric receptors assembled from the Caenorhabditis elegans (C. elegans) GluClα (GLC-1) subunit can inherently respond to IVM but not to glutamate (the neurotransmitter)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28428592/antibiotic-prophylaxis-for-infective-endocarditis-some-rarely-addressed-issues
#7
R Pippi
Although quite consistent indications on antibiotic prophylaxis for infective endocarditis (IE) have been reported internationally, several common dental practice issues are still not clear: which dental procedures require antibiotic prophylaxis? In the case of multiple procedures can the same antibiotic be used? How can dentists identify high-risk conditions for IE? Do dentists verify patient antibiotic intake? What are the requirements of antibiotic prophylaxis in cases of coexistence of diseases which involve host defence impairment? What are the modalities of second choice drug administration? And finally, are chlorhexidine mouthwashes before dental procedures combined with antibiotics useful or not? Uncertainty also persists as far as the real need for prophylaxis is concerned and although several sources have suggested that a wide prospective randomised controlled study may be the definitive solution, problems exist in performing such a study...
April 21, 2017: British Dental Journal
https://www.readbyqxmd.com/read/28428505/-neurolysis-and-spinal-analgesia-in-cancer-pain-management
#8
Seiji Hattori, Junko Tachibana
Cancer pain appears as a complex pain and often progressive.WhenWHO pain management strategy and/or palliative care failed to relieve their pain, patients are given high dose opioids or anonymous adjuvant drugs and have no chance to meet specialized pain treatment. This section briefly covers the outline of neurolysis and spinal analgesia for these cancer patients with severe pain. Purpose of nerve block and neurolysis are to block the incoming signal of pain in order to reduce pain, reduce analgesic dose, recover ADL, and finally to be discharged from the hospital...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28428363/phlpp-a-putative-cellular-target-during-insulin-resistance-and-type-2-diabetes
#9
Alpana Mathur, Vivek Kumar Pandey, Poonam Kakkar
Progressive research in the past decade converges to the impact of PHLPP (Pleckstrin homology domain and leucine rich repeat protein phosphatase) in regulating the cellular metabolism through PI3K/Akt inhibition. Defects in the PKB/Akt signaling coordinates with impaired insulin secretion and insulin resistance, identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we discuss the impact of PHLPP isoforms in insulin signaling and its associated cellular events including mitochondrial dysfunction, DNA damage, autophagy and cell death...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28428202/precision-physiology-and-rescue-of-brain-ion-channel-disorders
#10
REVIEW
Jeffrey Noebels
Ion channel genes, originally implicated in inherited excitability disorders of muscle and heart, have captured a major role in the molecular diagnosis of central nervous system disease. Their arrival is heralded by neurologists confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and cognitive impairment with few effective treatments. As detection of rare structural variants in channel subunit proteins becomes routine, it is apparent that primary sequence alone cannot reliably predict clinical severity or pinpoint a therapeutic solution...
April 20, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28428072/membrane-lipid-alterations-in-the-metabolic-syndrome-and-the-role-of-dietary-oils
#11
REVIEW
Javier S Perona
The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28427912/hepataprotective-effects-of-ginsenoside-rg1-a-review
#12
REVIEW
Yan Gao, Shifeng Chu, Zhao Zhang, Naihong Chen
BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng has been used as efficient tonic and for the treatment of various diseases including hepatic disorders. Ginseng saponins, also known as ginsenosides, are principal constituents and have been treated to be responsible for disparate ginseng health benefits. The current review mainly focuses on ginsenoside Rg1, a compound isolated from traditional Chinese herbal medicine Panax ginseng Meyer. AIMS: To summary the hepataprotective effects and related mechanisms of ginsenoside Rg1, we conclude this review by combining the literature and our own researches...
April 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28427779/fish-oil-lc-pufas-do-not-affect-blood-coagulation-parameters-and-bleeding-manifestations-analysis-of-8-clinical-studies-with-selected-patient-groups-on-omega-3-enriched-medical-nutrition
#13
Stephanie Jeansen, Renger F Witkamp, Jossie A Garthoff, Ardy van Helvoort, Philip C Calder
BACKGROUND & AIMS: The increased consumption of fish oil enriched-products exposes a wide diversity of people, including elderly and those with impaired health to relatively high amounts of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). There is an ongoing debate around the possible adverse effects of n-3 LC-PUFAs on bleeding risk, particularly relevant in people with a medical history of cardiovascular events or using antithrombotic drugs. METHODS: This analysis of 8 clinical intervention studies conducted with enteral medical nutrition products containing fish oil as a source of n-3 LC-PUFAs addresses the occurrence of bleeding-related adverse events and effects on key coagulation parameters (Prothrombin Time [PT], (activated) and Partial Thromboplastin Time [(a)PTT])...
March 29, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28427041/the-efficacy-of-donepezil-administration-on-acetylcholinesterase-activity-and-altered-redox-homeostasis-in-alzheimer-s-disease
#14
Pinar Atukeren, Mahir Cengiz, Hakan Yavuzer, Remise Gelisgen, Esma Altunoglu, Sena Oner, Fusun Erdenen, Damla Yuceakın, Himmet Derici, Ufuk Cakatay, Hafize Uzun
Alzheimer's disease (AD) is a serious multifactorial disorder with progressive neurodegenerative outcomes related with impaired redox homeostasis. Inhibition of the enzyme acetylcholinesterase (AChE), as one of the major therapeutic strategies, is considered to be offering only symptomatic relief and moderate disease modifying effect. We intended to investigate the effects of acetylcholinesterase inhibition via donepezil on protein carbonyl (PCO), advanced protein oxidation products (AOPP) and ischemia modified albumin (IMA) as protein oxidation markers and ferric reducing antioxidant power (FRAP), prooxidant-antioxidant balance (PAB), total thiol (T-SH), protein thiol (P-SH) as antioxidant status markers and also kynurenine (KYN), N-formyl kynurenine (N-FKYN) and protein bound dityrosine (DT) levels all in one demonstrating the redox homeostasis in Alzheimer patients also correlated with AChE activity...
April 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28426552/altered-neural-responses-to-heat-pain-in-drug-na%C3%A3-ve-patients-with-parkinson-s-disease
#15
Katarina Forkmann, Wiebke Grashorn, Katharina Schmidt, Odette Fründt, Carsten Buhmann, Ulrike Bingel
Pain is a frequent but still neglected non-motor symptom of Parkinson's disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using fMRI we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn&Yahr I-III) and 23 healthy controls (HC). PD patients were naïve to dopaminergic medication in order to avoid confounding drug effects...
April 18, 2017: Pain
https://www.readbyqxmd.com/read/28425222/class-iii-antiarrhythmic-drugs-amiodarone-and-dronedarone-impair-kir-2-1-backward-trafficking
#16
Yuan Ji, Hiroki Takanari, Muge Qile, Lukas Nalos, Marien J C Houtman, Fee L Romunde, Raimond Heukers, Paul M P van Bergen En Henegouwen, Marc A Vos, Marcel A G van der Heyden
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system...
April 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28424738/protective-effects-of-li-fei-xiao-yan-prescription-on-lipopolysaccharide-induced-acute-lung-injury-via-inhibition-of-oxidative-stress-and-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#17
Lie-Qiang Xu, Xiu-Ting Yu, Shu-Hua Gui, Jian-Hui Xie, Xiu-Fen Wang, Zu-Qing Su, Yu-Cui Li, Xiao-Ping Lai, Janis Ya-Xian Zhan, You-Liang Xie
Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28424585/efr3a-insufficiency-attenuates-the-degeneration-of-spiral-ganglion-neurons-after-hair-cell-loss
#18
Haixia Hu, Bin Ye, Le Zhang, Quan Wang, Zhiwei Liu, Suying Ji, Qiuju Liu, Jingrong Lv, Yan Ma, Ying Xu, Hao Wu, Fude Huang, Mingliang Xiang
Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to facilitate the survival of hippocampal newborn neurons in adult mice. Previously, we found Efr3a expression in the auditory neural pathway is upregulated soon after the destruction of hair cells. Here we conducted a time-course analysis of drug-caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice (Efr3a(-/+), Efr3a KD) and their wild type littermates...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424565/invasive-pneumococcal-disease-still-lots-to-learn-and-a-need-for-standardized-data-collection-instruments
#19
T J Marrie, G J Tyrrell, Sumit R Majumdar, Dean T Eurich
Background. Large studies of invasive pneumococcal disease (IPD) are frequently lacking detailed clinical information. Methods. A population-based 15-year study of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years formed the study group. Males outnumbered females and Aboriginal and homeless persons were overrepresented. High rates of smoking, excessive alcohol use, and illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had functional limitations prior to admission...
2017: Canadian Respiratory Journal: Journal of the Canadian Thoracic Society
https://www.readbyqxmd.com/read/28424405/the-bruton-s-tyrosine-kinase-inhibitor-ibrutinib-exerts-immunomodulatory-effects-through-regulation-of-tumor-infiltrating-macrophages
#20
Lingyan Ping, Ning Ding, Yunfei Shi, Lixia Feng, Jiao Li, Yalu Liu, Yufu Lin, Cunzhen Shi, Xing Wang, Zhengying Pan, Yuqin Song, Jun Zhu
The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies. However, the precise mechanism of action of the drug remains to be fully elucidated. Tumor-infiltrating macrophages presented in the tumor microenvironment have been shown to promote development and progression of B-cell lymphomas through crosstalk mediated by secreted cytokines and chemokines. Because Btk has been implicated in Toll-like receptor (TLR) signaling pathways that regulate macrophage activation and production of proinflammatory cytokines, we investigated the immunomodulatory effects of Btk inhibitor on macrophages...
April 5, 2017: Oncotarget
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