Search results for "fumarate"
showing 10 items of 97 documents
Efficacy of quetiapine XR vs. placebo as concomitant treatment to mood stabilizers in the control of subthreshold symptoms of bipolar disorder: Resul…
2017
Patients with bipolar disorder (BD) do not always achieve full remission between episodes. Subthreshold symptoms (depressive, manic or mixed) represent a major cause of relapse and disability in these patients. Immediate release (IR) and extended release (XR) formulations of quetiapine are both indicated for short and long-term treatment of BD. The aim of this study was to evaluate the efficacy of quetiapine XR vs placebo in subthreshold symptomatology when added to previous mood stabilizer treatment. A pilot phase IIIB, multicentre, prospective, placebo controlled, randomized, double blinded study of 12 weeks follow-up was performed (NCT01197846). Patients were randomized to quetiapine XR …
Effects of long-acting bronchodilators in COPD patients according to COPD severity and ICS use
2013
SummaryBackgroundIndacaterol is a once-daily, long-acting β2-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD. While its bronchodilator effects have been shown to be maintained in different patient subgroups, effects on clinical outcomes in certain subgroups are not yet defined.MethodsPost-hoc analysis of pooled clinical study data to investigate efficacy and safety of indacaterol compared with placebo and other long-acting bronchodilators (formoterol, salmeterol, open-label tiotropium) in patient subgroups defined by COPD severity (GOLD stage II or III; n = 4082) and ICS use at baseline (no/yes; n = 4088). Efficacy outcomes were troug…
Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabin…
2019
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed vira…
Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with mod…
2015
Background QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD. The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD. Methods This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o…
The role of NFATc2 in chronic autoimmune neuroinflammation
2014
Dimethyl fumarate (DMF), a fumaric acid ester with potential immunomodulatory and neuroprotective effect, was recently approved as treatment for relapsing–remitting multiple sclerosis (MS). DMF ameliorates the clinical course of experimental autoimmune encephalomyelitis (EAE), the murine model of MS, where it exerts a neuroprotective action, reducing demyelination and axonal loss. We hypothesized that these effects are mediated, at least in part, through its action on microglia. We used a microglial cell line (N9) activated with lipopolysaccharide (LPS) to analyze the effect of monomethyl fumarate (MMF), a bioactive metabolite of DMF, in vitro. We show that MMF reverts the molecular phenoty…
The Nature of the Stimulus and of the Fumarate Binding Site of the Fumarate Sensor DcuS of Escherichia coli
2005
DcuS is a membrane-associated sensory histidine kinase of Escherichia coli specific for C(4) -dicarboxylates. The nature of the stimulus and its structural prerequisites were determined by measuring the induction of DcuS-dependent dcuB'-'lacZ gene expression. C(4)-dicarboxylates without or with substitutions at C2/C3 by hydrophilic (hydroxy, amino, or thiolate) groups stimulated gene expression in a similar way. When one carboxylate was replaced by sulfonate, methoxy, or nitro groups, only the latter (3-nitropropionate) was active. Thus, the ligand of DcuS has to carry two carboxylate or carboxylate/nitro groups 3.1-3.8 A apart from each other. The effector concentrations for half-maximal i…
The NMR structure of the sensory domain of the membranous two-component fumarate sensor (histidine protein kinase) DcuS of Escherichia coli
2003
The structure of the water-soluble, periplasmic domain of the fumarate sensor DcuS (DcuS-pd) has been determined by NMR spectroscopy in solution. DcuS is a prototype for a sensory histidine kinase with transmembrane signal transfer. DcuS belongs to the CitA family of sensors that are specific for sensing di- and tricarboxylates. The periplasmic domain is folded autonomously and shows helices at the N and the C terminus, suggesting direct linking or connection to helices in the two transmembrane regions. The structure constitutes a novel fold. The nearest structural neighbor is the Per-Arnt-Sim domain of the photoactive yellow protein that binds small molecules covalently. Residues Arg107, H…
Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution
2020
Significance Magnetic resonance imaging is hindered by inherently low sensitivity, which limits the method for the most part to observing water molecules in the body. Hyperpolarized molecules exhibit strongly enhanced MRI signals which opens the door for imaging low-concentration species in vivo. Biomolecules can be hyperpolarized and injected into a patient allowing for metabolism to be tracked in real time, greatly expanding the information available to the radiologist. Parahydrogen-induced polarization (PHIP) is a hyperpolarization method renowned for its low cost and accessibility, but is generally limited by low polarization levels, modest molecular concentrations, and contamination by…
A Na+-coupled C4-dicarboxylate transporter (Asuc_0304) and aerobic growth of Actinobacillus succinogenes on C4-dicarboxylates
2014
Actinobacillus succinogenes, which is known to produce large amounts of succinate during fermentation of hexoses, was able to grow on C4-dicarboxylates such as fumarate under aerobic and anaerobic conditions. Anaerobic growth on fumarate was stimulated by glycerol and the major product was succinate, indicating the involvement of fumarate respiration similar to succinate production from glucose. The aerobic growth on C4-dicarboxylates and the transport proteins involved were studied. Fumarate was oxidized to acetate. The genome of A. succinogenes encodes six proteins with similarity to secondary C4-dicarboxylate transporters, including transporters of the Dcu (C4-dicarboxylate uptake), Dcu…
Identification of a novel recurrent 1q42.2-1qter deletion in high risk MYCN single copy 11q deleted neuroblastomas
2012
Neuroblastoma is an aggressive embryonal tumor that accounts for similar to 15% of childhood cancer deaths. Hitherto, despite the availability of comprehensive genomic data on DNA copy number changes in neuroblastoma, relatively little is known about the genes driving neuroblastoma tumorigenesis. In this study, high resolution array comparative genome hybridization (CGH) was performed on 188 primary neuroblastoma tumors and 33 neuroblastoma cell lines to search for previously undetected recurrent DNA copy number gains and losses. A new recurrent distal chromosome 1q deletion (del(1)(q42.2qter)) was detected in seven cases. Further analysis of available array CGH datasets revealed 13 additio…