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https://www.readbyqxmd.com/read/28535993/structural-basis-for-asymmetric-conductance-of-the-influenza-m2-proton-channel-investigated-by-solid-state-nmr-spectroscopy
#1
Venkata S Mandala, Shu Yu Liao, Byungsu Kwon, Mei Hong
The influenza M2 protein forms an acid-activated proton channel that is essential for virus replication. The transmembrane H37 selects for protons under low external pH (pHout) while W41 ensures proton conduction only from the N-terminus to the C-terminus and prevents reverse current under low internal pH (pHin). Here we address the molecular basis for this asymmetric conduction by investigating the structure and dynamics of a mutant channel, W41F, which permits reverse current under low pHin. Solid-state NMR experiments show that W41F M2 retains the pH-dependent α-helical conformations and tetrameric structure of the wild-type channel, but has significantly altered protonation and tautomeric equilibria at H37...
May 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28525887/an-updated-meta-analysis-of-amantadine-for-treating-dyskinesia-in-parkinson-s-disease
#2
Min Kong, Maowen Ba, Chao Ren, Ling Yu, Shengjie Dong, Guoping Yu, Hui Liang
In recent years, a few of randomized controlled trials (RCTs) about amantadine for treating dyskinesia in Parkinson's disease (PD) were completed. Here, we conducted a systematic literature review about the clinical research to provide the updated evidence for treating dyskinesia. Electronic search of Medline, PubMed, Cochrane Library, and other databases up to May 2016 for relevant studies was performed. We selected the Unified Parkinson's Disease Rating Scale IV (UPDRS IV) and Dyskinesia Rating Scales (DRS) as efficacy outcomes of amantadine on dyskinesia...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506531/parkinson-s-disease-and-pregnancy-an-updated-review
#3
REVIEW
Mara Seier, Amie Hiller
Pregnancy does not often occur in the setting of Parkinson's disease (PD) as the most common age of onset is beyond the childbearing years, yet management of these two conditions is crucial for the health of both mother and child. Here we review treatment data of PD during pregnancy, primarily from case reports and drug registries, and focus on available evidence regarding the pregnancy risks for patient and fetus. Historically, it was reported that many women had worsening of symptoms during pregnancy but this may be because anti-parkinsonian medications were not recommended or were under dosed...
May 11, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28492457/the-role-of-amantadine-withdrawal-in-3-cases-of-treatment-refractory-altered-mental-status
#4
Leah D Fryml, Kristen R Williams, Christopher G Pelic, James Fox, Gregory Sahlem, Sophie Robert, Gonzalo J Revuelta, Edward Baron Short
Amantadine, which was originally developed as an antiviral medication, functions as a dopamine agonist in the central nervous system and consequently is utilized in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and neuroleptic malignant syndrome. For reasons that are not entirely understood, abrupt changes in amantadine dosage can produce a severe withdrawal syndrome. Existing medical literature describes case reports of amantadine withdrawal leading to delirium, which at times has progressed to neuroleptic malignant syndrome...
May 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/28490139/development-of-a-competitive-immunochromatographic-assay-for-the-sensitive-detection-of-amantadine-in-chicken-muscle
#5
Songsong Wu, Fangfei Zhu, Liming Hu, Jun Xia, Guomao Xu, Daofeng Liu, Qi Guo, Kai Luo, Weihua Lai
Amantadine (AMD) is a prohibitive veterinary medicine in the entire world. In this study, a sensitive colloidal gold immunochromatographic assay (CGICA) was established for the rapid semi-quantitative detection of AMD in chicken muscle. Under optimal conditions, the detection results were obtained in 12min with a limit of detection for 1.80ng/mL. CGICA presented a good linear range from 2.5ng/mL to 25ng/mL, with only 11.5% cross-reactivity with rimantadine. The recovery rates for the fortified samples were ranged from 81% to 120%...
October 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28487425/a-variant-pfcrt-isoform-can-contribute-to-plasmodium-falciparum-resistance-to-the-first-line-partner-drug-piperaquine
#6
Satish K Dhingra, Devasha Redhi, Jill M Combrinck, Tomas Yeo, John Okombo, Philipp P Henrich, Annie N Cowell, Purva Gupta, Matthew L Stegman, Jonathan M Hoke, Roland A Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J Egan, David A Fidock
Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28449715/functional-implications-of-microbial-and-viral-gut-metagenome-changes-in-early-stage-l-dopa-na%C3%A3-ve-parkinson-s-disease-patients
#7
J R Bedarf, F Hildebrand, L P Coelho, S Sunagawa, M Bahram, F Goeser, P Bork, U Wüllner
BACKGROUND: Parkinson's disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker...
April 28, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28442707/polyanionic-cyclodextrin-induced-supramolecular-nanoparticle
#8
He-Lue Sun, Ying-Ming Zhang, Yong Chen, Yu Liu
Ionizable cyclodextrins have attracted increasing attention in host-guest chemistry and pharmaceutical industry, mainly due to the introduction of favorable electrostatic interactions. The ionizable cyclodextrins could not only enhance its own solubility but also induce oppositely charged guests to form more stable complex. However, the aggregation induced by charged cyclodextrins has rarely been reported. In this work, guided by the concept of molecular-induced aggregation, a series of carboxyl modified cyclodextrins were synthesized via "click" and hydrolysis reaction...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28433777/design-and-expeditious-synthesis-of-organosilanes-as-potent-antivirals-targeting-multidrug-resistant-influenza-a-viruses
#9
Yanmei Hu, Yuanxiang Wang, Fang Li, Chunlong Ma, Jun Wang
The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28418820/case-241-hemiparkinsonism-hemiatrophy-spect-with-99m-tc-trodat-1-and-muscle-mr-imaging-abnormalities
#10
Thiago Cardoso Vale, Flávia Cristina de Lima Pinto, José Luiz Pedroso, Marília Alves Dos Reis, Ilza Rosa Batista, Rodrigo Affonseca Bressan, René Leandro Magalhães Rivero, Renato Adam Mendonça, Orlando G Barsottini
History A 43-year-old right-handed man presented with a history of progressive mild left-sided weakness and slowness of movements. Symptoms began 4 years earlier, and the patient noticed a progressive decline in his daily routine due to gait difficulties in the past year. There was no history of head trauma, surgery, drug therapy, smoking, or alcohol abuse, nor was there any relevant family history. Examination revealed normal cognition (29 of 30 points on the Mini-Mental State Examination and 27 of 30 points on the Montreal Cognitive Assessment) and normal cerebellar, sensory, cranial nerve, and autonomic function...
May 2017: Radiology
https://www.readbyqxmd.com/read/28418242/slow-but-steady-wins-the-race-dissimilarities-among-new-dual-inhibitors-of-the-wild-type-and-the-v27a-mutant-m2-channels-of-influenza-a-virus
#11
Marta Barniol-Xicota, Sabrina Gazzarrini, Eva Torres, Yanmei Hu, Jun Wang, Lieve Naesens, Anna Moroni, Santiago Vázquez
New insights on the amantadine resistance mechanism of the V27A mutant were obtained through the study of novel, easily accessible 4-(1- and 2-adamantyl)piperidines, identified as dual binders of the wild-type and V27A mutant M2 channels of influenza A virus. Their antiviral activity and channel blocking ability were determined using cell-based assays and two-electrode voltage clamp (TEVC) technique on M2 channels, respectively. In addition, electrophysiology experiments revealed two interesting findings: (i) these inhibitors display a different behavior against the wild-type versus V27A mutant A/M2 channels, and (ii) the compounds display antiviral activity when they have kd equal or smaller than 10(-6) while they do not exhibit antiviral activity when kd is 10(-5) or higher although they may show blocking activity in the TEV assay...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28401407/molecular-analysis-of-amantadine-resistant-influenza-a-h1n1-pdm09-virus-isolated-from-slum-dwellers-of-dhaka-bangladesh
#12
Mozibur Rahman, Sheikh Ariful Hoque, Mohammad Ariful Islam, Sabita Rezwana Rahman
Influenza is a highly contagious viral infection associated with excessive hospitalizations and deaths throughout the world. Continuous antigenic shift and drift is not only responsible for this devastating effect of influenza but also causes ineffectiveness of antiviral drugs and vaccines. In this study, we investigated the effectiveness of ribavirin, oseltamivir, and amantadine drugs in vitro against nine influenza A isolates collected during June 2012-August 2013 from different slums in Dhaka city. The effectiveness of these drugs was determined by measuring the inhibition of virus-induced cytopathic effect on MDCK cells through MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)...
June 2017: Virus Genes
https://www.readbyqxmd.com/read/28391443/non-human-primate-models-of-pd-to-test-novel-therapies
#13
REVIEW
Marc Morissette, Thérèse Di Paolo
Non-human primate (NHP) models of Parkinson disease show many similarities with the human disease. They are very useful to test novel pharmacotherapies as reviewed here. The various NHP models of this disease are described with their characteristics including the macaque, the marmoset, and the squirrel monkey models. Lesion-induced and genetic models are described. There is no drug to slow, delay, stop, or cure Parkinson disease; available treatments are symptomatic. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-Dopa) still remains the gold standard symptomatic treatment of Parkinson...
April 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28387447/withdrawn-interventions-for-fatigue-and-weight-loss-in-adults-with-advanced-progressive-illness
#14
REVIEW
Cathy Payne, Philip J Wiffen, Suzanne Martin
BACKGROUND: Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. Appropriate interventions may bring considerable improvements in function and quality of life to seriously ill people and their families, reducing physical, psychological and spiritual distress. OBJECTIVES: To conduct an overview of the evidence available on the efficacy of interventions used in the management of fatigue and/or unintentional weight loss in adults with advanced progressive illness by reviewing the evidence contained within Cochrane reviews...
April 7, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28383359/amantadine-for-antipsychotic-related-weight-gain-meta-analysis-of-randomized-placebo-controlled-trials
#15
Wei Zheng, Shibin Wang, Gabor S Ungvari, Chee H Ng, Xin-Hu Yang, Yu-Hong Gu, Ming Li, Ying-Qiang Xiang, Yu-Tao Xiang
PURPOSE: Weight gain associated with antipsychotics in schizophrenia has been an ongoing concern. This meta-analysis examined the efficacy and safety of amantadine as an adjunctive treatment of weight gain in schizophrenia by systematically searching and analyzing randomized controlled trials (RCTs). RCTs comparing adjunctive amantadine with placebo in adult patients with schizophrenia were included in the meta-analysis. METHODS: Two independent investigators searched the literature and extracted data...
June 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28362799/organic-cation-transporter-1-oct1-is-involved-in-pentamidine-transport-at-the-human-and-mouse-blood-brain-barrier-bbb
#16
Gayathri N Sekhar, Ana R Georgian, Lisa Sanderson, Gema Vizcay-Barrena, Rachel C Brown, Paula Muresan, Roland A Fleck, Sarah A Thomas
Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT). At the blood-brain barrier (BBB), it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell lines expressed the organic cation transporters (OCT1, OCT2 and OCT3), however, P-gp was only expressed in hCMEC/D3 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28334651/dispersive-micro-solid-phase-extraction-of-amantadine-rimantadine-and-memantine-in-chicken-muscle-with-magnetic-cation-exchange-polymer
#17
Dawei Chen, Hong Miao, Yunfeng Zhao, Yongning Wu
This study demonstrated a novel dispersive micro solid phase extraction (DMSPE) method for extraction of adamantane drugs (amantadine, rimantadine and memantine) in chicken muscle. The adamantane drugs were extracted from chicken muscle using 1% acidic acetonitrile as extraction solvent. The cleanup of fatty matrices from analytes was achieved by the DMSPE technique using magnetic cation exchange polymer as adsorbent. In this procedure, the experimental parameters and conditions were optimized in detail for the improvement of extraction efficiency...
April 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28318897/efficacy-of-off-label-augmentation-in-unipolar-depression-a-systematic-review-of-the-evidence
#18
REVIEW
Julia Kleeblatt, Felix Betzler, Laura L Kilarski, Tom Bschor, Stephan Köhler
Treatment of unipolar depression with currently available antidepressants is still unsatisfactory. Augmentation with lithium or second generation antipsychotics is an established practice in non-responders to antidepressant monotherapy, but is also associated with a substantial non-response rate and with non-tolerance. Based on a systematic review of the literature, including meta-analyses, randomized controlled trials (RCTs), non-randomized comparative studies and case studies, off-label augmentation agents (administered in addition to an antidepressant, without FDA approval for treatment of MDD) were identified and evaluated regarding their efficacy using levels of evidence...
March 16, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28298229/a-novel-benzo-heterocyclic-amine-derivative-n30-inhibits-influenza-virus-replication-by-depression-of-inosine-5-monophospate-dehydrogenase-activity
#19
Jin Hu, Linlin Ma, Huiqiang Wang, Haiyan Yan, Dajun Zhang, Zhuorong Li, Jiandong Jiang, Yuhuan Li
BACKGROUD: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5'- monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH. RESULTS: The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro...
March 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28287432/a-biologically-based-computational-approach-to-drug-repurposing-for-anthrax-infection
#20
Jane P F Bai, Theodore Sakellaropoulos, Leonidas G Alexopoulos
Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus...
March 10, 2017: Toxins
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