14 research outputs found
Improvement in the Number of Analytic Features Detected by Non-Targeted Metabolomic Analysis: Influence of the Chromatographic System and the Ionization Technique
Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors
The phosphoinositide 3-kinases (PI3Ks) constitute an important family of lipid kinase enzymes that control a range of cellular processes through their regulation of a network of signal transduction pathways, and have emerged as important therapeutic targets in the context of cancer, inflammation and cardiovascular diseases. Since the mid-late 1990s, considerable progress has been made in the discovery and development of small molecule ATP-competitive PI3K inhibitors, a number of which have entered early phase human trials over recent years from which key clinical results are now being disclosed. This review summarizes progress made to date, primarily on the discovery and characterization of class I and dual class I/IV subtype inhibitors, together with advances that have been made in translational and clinical research, notably in cancer
Cross-platform Q-TOF validation of global exo-metabolomic analysis: Application to human glioblastoma cells treated with the standard PI 3-Kinase inhibitor LY294002☆
Comparison of the Pharmacokinetics of Subcutaneous and Intravenous Administration of a Phosphorothioate Oligodeoxynucleotide in Cynomolgus Monkeys
Biodistribution and Metabolism of a Mixed Backbone Oligonucleotide (GEM 231) Following Single and Multiple Dose Administration in Mice
Effect of PEGylation on the toxicity and permeability enhancement of chitosan
The aim of the present work is to investigate if conditions can be devised where PEGylation of chitosan would reduce its toxicity toward the nasal mucosa while maintaining its ability to open the cellular tight junctions and, consequently, produce an enhancement of macromolecular permeability. A series of mPEG-g-chitosan copolymers with varying levels of mPEG substitution, mPEG molecular weight, and chitosan molecular weight were synthesized by grafting carboxylic acid-terminated mPEGs (M w 1.9 and 5.0 × 10 3 g mol -1) to chitosans (M w 28.9 and 82.0 × 10 3 g mol -1) using a NHS/EDC coupling system. The synthesized mPEG-g-chitosans were fully characterized using a number of techniques, including FT-IR, 1H NMR, and SEC-MALLS and their physicochemical properties were analyzed by TGA and DSC. Thereafter, the conjugates were tested for their cytotoxicity and tight junction modulating property in a relevant cell model, a mucus producing Calu-3 monolayer. mPEG-g-chitosan conjugates exhibited reduced toxicity toward cells, as compared to unmodified chitosan counterparts. Furthermore, the conjugates demonstrated a dramatic effect on cell monolayer transepithelial electrical resistance (TEER) and enhancement of permeability of model macromolecules. TEER and permeability-enhancing effects, as measurable indicators of tight junction modulation, were found to be pH-dependent and were notably more pronounced than those exhibited by unmodified chitosans. This work therefore demonstrates that conditions can be contrived where PEGylation improves the toxicity profile of chitosan, while preserving its effect on epithelial tight junctions in the nose
Grammaire bilingue : française et basque / par J.-B. Archu = Bi mihiren gramatika : uskara eta Franzesa / egina J.-B. Archu.
Texto paralelo en francés y euskeraDialecto : texto en euskera Bajo-navarroS. XIX -- Periodo : primer euskera modernoEuskalkia : behenafarreraXIX. md. -- Aroa : lehen euskara modernoaDigitalización Vitoria-Gasteiz Fundación Sancho el Sabio 2008Rústica3e éd. = 3. argit