Search results for "INHIBITOR"
showing 10 items of 3742 documents
Coronavirus Disease 2019–Associated Coagulopathy
2021
Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19-associated coagulopathy (CC), is now considered a major component of the pathophysiology of this novel infectious disease, leading to widespread thrombosis. While at first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multi-organ dysfunction syndrome. In this review article, we discuss recent insights into the pathophysiologic mecha…
Genetic determinants of ATR inhibitor sensitivity and resistance in Gastric Cancer
2019
Synthetic lethal approaches in identifying genetic determinants of drug response is a powerful method in selecting patents for targeted cancer therapies. Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR) is a valuable target to inhibit the DNA damage repair (DDR) pathway, that has been shown to be particularly effective in cancer cells harbouring other DDR defects, including truncating mutations in ARID1A, found in the 20% of gastric cancer (GC) patients. Although ATR inhibitors (ATRi) are emerging as promising cancer therapies, resistance mechanisms inevitably arise from these drugs as monotherapy, emphasising the importance of identifying genetic determinants of re…
A kinetic-catalytic method for iodide based on the simultaneous addition of inhibitor and substrate
1987
Abstract A kinetic-catalytic method of analysis, based on the addition of a mixture of inhibitor and substrate, at a constant rate, over the catalyst in the presence of the other component of the indicator reaction is studied. The method is applied to the determination of iodide using the Ce(IV)As(III) catalytic reaction and Hg(II) as inhibitor. Under suitable experimental conditions the absorbance of the unconsumed Ce(IV) is inversely proportional to the initial iodide concentration.
An in-depth evaluation of acalabrutinib for the treatment of mantle-cell lymphoma
2020
Introduction: Regimens involving intensive immuno-chemotherapy, followed by high-dose therapy and autologous stem cell transplant represent the standard treatment for younger fit patients with mantle cell lymphoma (MCL). Targeted approaches (i.e. ibrutinib, bortezomib, and lenalidomide) represent the backbone of therapy for relapsed cases. Areas covered: Acalabrutinib is a novel small molecule with a butynamide moiety specifically designed to irreversibly inhibit Bruton tyrosine kinase (BTK), which is more potent and selective than ibrutinib. Relevant publications have been identified through literature searches using the terms 'mantle cell lymphoma' and 'acalabrutinib'. Expert opinion: Aca…
Dental management of patients receiving anticoagulant and/or antiplatelet treatment
2013
Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can give rise to complications associated with important morbidity-mortality. The dental treatment of patients who tend to an increased risk of bleeding due to the use of anticoagulant and/or antiplatelet drugs raises a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis, and the optimized management of such patients, are therefore very important issues. Objectives: A study is made of the anticoagulant / antiplatelet drugs currently available on the market, with evaluation of the risks and benefits of suspending su…
1H NMR methodologies applied in the thermodynamic and structural characterization of organic supramolecular complexes
2021
Orientador: Anita Jocelyne Marsaioli Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química Resumo: Nesta tese consiste no estudo de interações supramoleculares utilizando diferentes metodologias de Ressonância Magnética Nuclear de hidrogênio (RMN de 1H), tais como ROESY 1D, RMN-DOSY e RMN-STD. Os sistemas supramoleculares foram abordados em dois casos de estudo diferentes. O Capítulo I tem como objeto de estudo interações do fármaco Dapsona com diferentes carreadores de fármacos (ß-CD, SBE-ß-CD e lipossoma de EPC), com a finalidade de encontrar formulações nas quais a Dapsona seja mais solúvel. Os complexos binários e ternário formados foram determinadas por medidas de …
Inhibitory effects on mitochondrial complex I of semisynthetic mono-Tetrahydrofuran acetogenin derivatives
2003
Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety or in the alkyl chain that links this terminal gamma-lactone with the alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.
Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta-Analysis and Systematic Review
2018
Objectives: To evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementia. Design: Systematic review and meta-analysis. Setting: Two authors independently searched major electronic databases from inception until June 17, 2017, for longitudinal (without a control group) and cohort (with a control group) studies reporting CV outcomes in relation to AChEIs. Randomized controlled trials were excluded because they included relatively healthy subjects. Participants: Individuals with dementia and controls. Measurements: Changes in CV parameters were summarized using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Even…
High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors
2016
International audience; Inhibitors of uridine diphosphate-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC, which catalyses the first, irreversible step in lipid A biosynthesis) are a promising new class of antibiotics against Gram-negative bacteria. The objectives of the present study were to: (i) compare the antibiotic activities of three LpxC inhibitors (LPC-058, LPC-011 and LPC-087) and the reference inhibitor CHIR-090 against Gram-negative bacilli (including MDR and XDR isolates); and (ii) investigate the effect of combining these inhibitors with conventional antibiotics.MethodsMICs were determined for 369 clinical isolates (234 Enterobacteriaceae and 135 non-fermentati…
The relation between neuronal chloride transporter activities, GABA inhibition, and neuronal activity
2020
Abstract The intracellular chloride concentration [Cl−]i in neurons is regulated by a set of transmembrane transporters, with the Cl−-loader NKCC1 and the Cl−-extruder KCC2 as most relevant members. The expression of these transporters is tightly regulated, with the general trend that KCC2 expression is low in immature neurons, which are thus characterized by a high [Cl−]i. As [Cl−]i is the main factor determining the polarity of GABAergic responses, such a high [Cl−]i is related to depolarizing GABAergic responses. However, depolarizing GABAergic responses are not per se excitatory, but can also contribute to shunting inhibition. The excitatory/inhibitory action of GABAergic responses is m…