Search results for " Stab"
showing 10 items of 1773 documents
Controlled Iontophoretic Delivery in Vitro and in Vivo of ARN14140—A Multitarget Compound for Alzheimer’s Disease
2019
ARN14140 is a galantamine-memantine conjugate that acts upon both cholinergic and glutamatergic pathways for better management of Alzheimer's disease. Poor oral bioavailability and pharmacokinetics meant that earlier preclinical in vivo studies employed intracerebroventricular injection to administer ARN14140 directly to the brain. The aim of the present study was to evaluate the feasibility of using constant current transdermal iontophoresis for the noninvasive systemic delivery of ARN14140 and to quantify the amounts present in the blood and the brain. Preliminary experiments in vitro were performed using porcine skin and validated with human skin. Cumulative ARN14140 permeation across th…
Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis
2007
Glutathione depletion is a key factor in the development of acute pancreatitis. Our aim was to study the regulation of glutamate cysteine ligase, the rate-limiting enzyme in glutathione synthesis, in edematous or necrotizing pancreatitis in rats. Glutathione levels were kept low in necrotizing pancreatitis for several hours, with no increase in protein or mRNA levels of glutamate cysteine ligase subunits, despite binding of RNA polymerase II to their promoters and coding regions. The survival signal pathway mediated by ERK and c-MYC was activated, and c-MYC was recruited to the promoters. The failure in gene up-regulation seems to be due to a marked increase in cytosolic ribonuclease activi…
Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability a…
2010
The aim of this study was to investigate the cathodal iontophoresis of dexamethasone sodium phosphate (DEX-P) in vitro and in vivo and to determine the feasibility of delivering therapeutic amounts of the drug for the treatment of chemotherapy-induced emesis. Stability studies, performed to investigate the susceptibility of the phosphate ester linkage to hydrolysis, confirmed that conversion of DEX-P to dexamethasone (DEX) upon exposure to samples of human, porcine and rat dermis for 7 h was limited (82.2+/-0.4%, 72.5+/-4.8% and 78.6+/-6.0% remained intact) and did not point to any major inter-species differences. Iontophoretic transport of DEX-P across dermatomed porcine skin (0.75 mm thic…
Endothelial Dysfunction in Tristetraprolin-deficient Mice Is Not Caused by Enhanced Tumor Necrosis Factor-α Expression
2014
Cardiovascular events are important co-morbidities in patients with chronic inflammatory diseases like rheumatoid arthritis. Tristetraprolin (TTP) regulates pro-inflammatory processes through mRNA destabilization and therefore TTP-deficient mice (TTP(-/-) mice) develop a chronic inflammation resembling human rheumatoid arthritis. We used this mouse model to evaluate molecular signaling pathways contributing to the enhanced atherosclerotic risk in chronic inflammatory diseases. In the aorta of TTP(-/-) mice we observed elevated mRNA expression of known TTP targets like tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-1α, as well as of other pro-atherosclerotic mediators, l…
BRAIN-TARGETED SOLID LIPID NANOPARTICLES CONTAINING RILUZOLE: PREPARATION, CHARACTERIZATION AND BIODISTRIBUTION
2009
Aim: Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Materials & method: Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodi…
A mathematical model for the phase of sexual reproduction in monogonont rotifers
2000
Recently, the optimal sex allocation in monogonont rotifers is studied in [1], and, as a closely related question, the relative frequencies of the relevant types of mictic females. The authors focus on the evolution of the age at which young mictic females lose their fertilization susceptibility and they address the threshold age of fertilization that maximizes resting egg production. Assuming that a stationary population is achieved, with stable age distribution, they obtain their results, without knowing the stationary population. Our aim is to study this problem in the framework of the theory of nonlinear age-dependent population dynamics developed by G. F. Webb in [13], which is more ap…
Multiple marker approach to risk stratification in patients with stable coronary artery disease
2010
Aims Multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina. Methods and results We investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic …
Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: Pleiotropic evidence from plasma mRNA analyses
2013
Objective: Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasmamRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C). Design and methods: Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molec…
Differential stabilization of cytochrome P-450 isoenzymes in primary cultures of adult rat liver parenchymal cells.
1991
Cytochrome P-450 dependent hydroxylation of testosterone was measured in 7-day-old cultures of primary rat liver parenchymal cells. Determinations were carried out in monocultures of parenchymal cells and co-cultures of parenchymal cells with rat liver nonparenchymal epithelial cells, or mouse embryo fibroblasts. In the monoculture system, testosterone metabolism was drastically reduced and hardly measurable after 7 days in culture. In the co-culture systems, individual P-450 isoenzymes were stabilized on different levels. P-450s p and presumably c were well preserved, P-450 a was reduced but clearly measurable, P-450 h was totally lost whereas P-450s b and e were not measurable after 7 day…
Atorvastatin treatment increases plasma bilirubin but not HMOX1 expression in stable angina patients.
2015
In vitro and animal studies indicate that statins increase heme oxygenase-1 gene (HMOX1) expression, which then, presumably, increases plasma bilirubin concentration. However, clinical confirmation that statins concomitantly increase HMOX1 expression and plasma bilirubin concentration is lacking. We hypothesized that in patients with stable angina atorvastatin therapy (20 mg/day for 10 weeks) concomitantly increases total bilirubin concentration and HMOX1 expression, as assessed non-invasively by plasma analysis.In 44 patients with stable angina plasma concentrations of total bilirubin, HMOX1 mRNA and HMOX1 protein were measured before and after the statin treatment, as well as plasma conce…