Search results for "pine"
showing 10 items of 2022 documents
Elucidating the constructs happiness and wellbeing: A mixed-methods approach
2015
International audience; In this study we examine the constructs "happiness" and "wellbeing" in a sample of Canadian women and men in mid-adulthood. Through a sequential mixed-methods approach, we utilize Sen and Nussbaum's conceptualizations of capabilities to inform the themes generated from semi-structured interviews. We find that participants understand happiness and wellbeing as two distinct constructs that are illuminated in the metaphors happiness as balance and the gears of wellbeing. Second, we corroborate these constructs through a principal component analysis of questionnaire data. We conclude that happiness and wellbeing are not static entities, but rather iterative processes tha…
Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
2013
Abstract Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non–small cell lung cance…
Phase I Assessment of New Mechanism-Based Pharmacodynamic Biomarkers for MLN8054, a Small-Molecule Inhibitor of Aurora A Kinase
2011
Abstract The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the ski…
Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.
2011
Abstract Cannabinoid CB1 receptors (CB1Rs) regulate the neurodegenerative damage of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R stimulation exerts protective effects is still unclear. Here we show that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice. Furthermore, mice lacking CB1Rs showed a more severe clinical course and, in parallel, exacerbated alterations of sEPSC duration af…
Tetanus Toxin Inhibits Neuroexocytosis Even When Its Zn2+-dependent Protease Activity Is Removed
1995
Tetanus toxin (TeTX) is a dichain protein that blocks neuroexocytosis, an action attributed previously to Zn(2+)-dependent proteolysis of synaptobrevin (Sbr) by its light chain (LC). Herein, its cleavage of Sbr in rat cerebrocortical synaptosomes was shown to be minimized by captopril, an inhibitor of certain metalloendoproteases, whereas this agent only marginally antagonized the inhibition of noradrenaline release, implicating a second action of the toxin. This hypothesis was proven by preparing three mutants (H233A, E234A, H237A) of the LC lacking the ability to cleave Sbr and reconstituting them with native heavy chain. The resultant dichains were found to block synaptosomal transmitter…
Cholinesterase Activity and Hematological Parameters as Biomarkers of Sublethal Molinate Exposure in Anguilla anguilla
2000
Cholinesterase (ChE) activity was measured in plasma, whole blood [using 5,5'-dithiobis(2-nitrobenzoic acid) and 2-PDS as chromophores], brain, and whole eyes of Anguilla anguilla exposed to a sublethal concentration of 11.15 mg/L (one-third of the 96-h LC(50)) of the carbamate herbicide molinate. ChE activity was evaluated after 6, 24, 48, 72, and 96 h of pesticide exposure. Results indicated that ChE activity in eel tissues decreased as time of exposure increased, especially in eel blood. Eels exposed to molinate were transferred to a pesticide-free water for a recovery period of 4 days and ChE activity was also evaluated. Results indicated that ChE activity for those animals with preexpo…
Effect of genetics polymorphism of carbamazepine – metabolizing enzymes in epileptic patients
2013
Transbuccal tablets of carbamazepine: formulation, release and absorption pattern.
2006
Tranbsuccal drug administration is an attractive method, as it has several advantages especially with respect to peroral delivery. Here we report: i) the aptitude of carbamazepine (CBZ) to penetrate porcine buccal mucosa and reconstituted human oral (RHO) epithelium; ii) three different tablet formulations for transbuccal administration; iii) the drug release rate from tablets. CBZ permeation through the buccal mucosa was investigated by using two different bi-compartmental open models: Franz cells for porcine buccal mucosa and Transwell diffusion cells system for RHO epithelium. Results, expressed as drug flux (Js) and permeability coefficients (Kp), indicated that CBZ well penetrates the …