Search results for "pharmaceutical"

Simultaneous Inhibition of Peripheral CB1R and iNOS Mitigates Obesity-Related Dyslipidemia Through Distinct Mechanisms.

2020

Diabetic dyslipidemia, characterized by increased plasma triglycerides and decreased HDL cholesterol levels, is a major factor contributing to nonalcoholic steatohepatitis and cardiovascular risk in type 2 diabetes. Activation of the cannabinoid-1 receptor (CB1R) and activation of inducible nitric oxide synthase (iNOS) are associated with nonalcoholic steatohepatitis progression. Here, we tested whether dual-targeting inhibition of hepatic CB1R and iNOS improves diabetic dyslipidemia in mice with diet-induced obesity (DIO mice). DIO mice were treated for 14 days with (S)-MRI-1867, a peripherally restricted hybrid inhibitor of CB1R and iNOS. (R)-MRI-1867, the CB1R-inactive stereoisomer that …

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

2017

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), …

Impairment of Everyday Spatial Navigation Abilities in Mild Cognitive Impairment Is Weakly Associated with Reduced Grey Matter Volume in the Medial P…

2020

Alzheimer’s Disease Neuroimaging Initiative.

Phototherapy: Ruthenium-Containing Block Copolymer Assemblies: Red-Light-Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular…

2016

H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice

2020

Deregulation of the dynamic crosstalk between the gut microbiota, intestinal epithelial cells, and immune cells is critically involved in the development of inflammatory bowel disease and the overgrowth of opportunistic pathogens, including the human opportunistic fungus Candida albicans. In the present study, we assessed the effect of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a protein kinase A inhibitor, on the migration of macrophages to C. albicans through dextran sulphate sodium (DSS)-challenged Caco-2 cells. We also investigated the impact of H89 on intestinal inflammation and C. albicans clearance from the gut, and determined the diversity of the gut microbio…

Molecular epidemiology and drug-resistance mechanisms in carbapenem-resistant Klebsiella pneumoniae isolated in patients from a tertiary hospital in …

2020

Abstract Objectives The aim of this study has been to characterize carbapenem-resistant Klebsiella pneumoniae isolates and to determine the resistance mechanisms involved, the clonal relationship between strains and clinical and demographical data of the infected patients. Methods Clinical and demographical data from patients were collected and statistically analysed. Antimicrobial susceptibility testing was performed and resistance genes were detected both phenotypically and genotypically. Conjugation assays were performed to show horizontal transferability of resistance genes. Clonal relationship was also studied. Next-generation sequencing (NGS) was performed to obtain information regard…

Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis?

2017

International audience; Background: Moxifloxacin retains partial activity against some fluoroquinolone-resistant mutants of Mycobacterium tuberculosis. Levofloxacin is presumed to be as active as moxifloxacin against drug-susceptible tuberculosis and to have a better safety profile.Objectives: To compare the in vivo activity of levofloxacin and moxifloxacin against M. tuberculosis strains with various levels of fluoroquinolone resistance.Methods: BALB/c mice were intravenously infected with 106M. tuberculosis H37Rv and three isogenic mutants: GyrA A90V, GyrB E540A and GyrB A543V. Treatment with 50 or 100 mg/kg levofloxacin and 60 or 66 mg/kg moxifloxacin was given orally every 6 h, for 4 we…

Negative Impact of Citral on Susceptibility of Pseudomonas aeruginosa to Antibiotics

2021

Essential oils (EOs) or their components are widely used by inhalation or nebulization to fight mild respiratory bacterial infections. However, their interaction with antibiotics is poorly known. In this study we evaluated the effects of citral, the main component of lemongrass oil, on in vitro susceptibility of Pseudomonas aeruginosa to antibiotics. Exposure of strain PA14 to subinhibitory concentrations of citral increased expression of operons encoding the multidrug efflux systems MexEF-OprN and MexXY/OprM, and bacterial resistance to anti-pseudomonal antibiotics including imipenem (twofold), gentamicin (eightfold), tobramycin (eightfold), ciprofloxacin (twofold), and colistin (≥128-fold…

Chemoselective Dual Labeling of Native and Recombinant Proteins

2017

The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presenc…

Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs.

2018

Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis an…