Search results for "kinetics"
showing 10 items of 2224 documents
Retinoic acid inhibits nitric oxide synthase-2 expression through the retinoic acid receptor-alpha.
2000
Retinoids are multipotent modulators of cellular functions and suppress cytokine-induced production of nitric oxide (NO) in several cell types. We have explored the mechanisms by which retinoic acid (RA) regulates NO production in rat aortic smooth muscle cells (VSMC), which express NOS2 in response to proinflammatory cytokines. RA inhibited interleukin-1beta (IL-1beta)-induced NOS2 mRNA expression and NO production. These effects were attenuated by the retinoic acid receptor (RAR) antagonist CD3106, indicating that they were mediated through retinoic acid receptors (RARs). The synthetic retinoid agonists CD336 (which specifically binds RARalpha) and CD367 (which binds all RARs) but not ago…
Local Delivery of Nimodipine by Prolonged-Release Microparticles—Feasibility, Effectiveness and Dose-Finding in Experimental Subarachnoid Hemorrhage
2012
Background and purposeTo investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).Methods70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as …
Fate and effects of the trehalase inhibitor trehazolin in the migratory locust (Locusta migratoria).
2009
Abstract Trehalose is the main haemolymph sugar in many insect species. To be utilized trehalose must be hydrolysed into its glucose units by trehalase (EC 3.2.1.28). Inhibitors of trehalase have attracted interest as possible pesticides and tools for studying the regulation of trehalose metabolism in insects. To make full use of these inhibitors requires knowledge of their fate and effects in vivo. To this end we have measured trehazolin in locusts using a method based on the specific inhibition of a trehalase preparation. After injection of 20 μg, trehazolin decreased in haemolymph with a half-life of 2.6 days and after 10 days almost 95% had disappeared. Trehazolin did not reach the intr…
Sirolimus exposure and the occurrence of cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation
2018
Sirolimus appears to protect against cytomegalovirus (CMV) in organ transplant recipients. The effect of this drug in allogeneic hematopoietic stem cell transplantation recipients remains unexplored. By means of multivariate continuous-time Markov model analyses, we identified 3 independent covariates that significantly impacted the risk of CMV DNAemia: recipient/donor CMV serostatus, tacrolimus exposure, and sirolimus exposure. CMV-seropositive recipients with CMV-seronegative donors had a significantly higher probability of having detectable CMV DNAemia. Increasing the tacrolimus trough concentration from 0 to 16 ng/mL increased the probability of patients having detectable CMV DNAemia by…
Labetalol absorption kinetics: Rat small intestine and colon studies
2006
Labetalol is a widely used drug for the management of hypertension, which is preferably administered by the oral route despite its low bioavailability. The objective of this study is to ascertain the mechanisms underlying its absorption as an approach to help in predicting the influence of dosage changes, possible drug-drug and drug-fruit juice interactions. Perfusion experiments have been performed in rats in two sites of absorption: the intestine and the colon. The nonlinearity of the process has been established by means of the assay of a wide range of concentrations (2-2000 microM). Fitting of the concentration versus time data allows the estimation of passive diffusion constant in the …
Effect of chamber characteristics, loading and analysis time on motility and kinetic variables analysed with the CASA-mot system in goat sperm.
2017
Several factors unrelated to the semen samples could be influencing in the sperm motility analysis. The aim of the present research was to study the effect of four chambers with different characteristics, namely; slide-coverslip, Spermtrack, ISAS D4C10, and ISAS D4C20 on the sperm motility. The filling procedure (drop or capillarity) and analysis time (0, 120 and 240s), depth of chamber (10 or 20μm) and field on motility variables were analysed by use of the CASA-mot system in goat sperm. Use of the drop-filling chambers resulted in greater values than capillarity-filling chambers for all sperm motility and kinetic variables, except for LIN (64.5% compared with 56.3% of motility for drop- a…
Thyroid hormone controls carnitine status through modifications of gamma-butyrobetaine hydroxylase activity and gene expression.
2002
The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through…
The Effects of Chlorotrianisene (Tace) on Kinetics of 3H-testosterone Metabolism in Patients with Carcinoma of the Prostate
1982
Summary— Alterations in the metabolism of testosterone and plasma levels of testosterone, luteinising hormone (LH), follicle stimulating hormone (FSH), prolactin and oestradiol were studied in 6 patients with newly diagnosed prostatic carcinoma before and during treatment with chlorotrianisene at a daily dosage of 48 mg for 14 days. Parameters of plasma kinetics were determined according to the single injection technique and the 2-compartment model, and the plasma hormones by radioimmunoassay. Chlorotrianisene altered neither plasma levels of testosterone, gonadotrophins, prolactin and oestradiol, nor metabolic clearance rate, production rate and other kinetic parameters of testosterone. Th…
Sex differences in GABAA receptor binding in rat brain measured by an improved in vitro binding assay.
1990
The distribution of GABAA receptor sites was studied in female and male rat brain by an improved in vitro binding assay using 3H-muscimol and carefully washed membrane fractions. The binding studies revealed a single class of binding sites exhibiting the properties of GABAA receptors. The specific binding of 3H-muscimol was measured in four brain areas: the preoptic brain area, mediobasal hypothalamus, corticomedial amygdala and cerebral cortex. The equilibrium dissociation constants (KD) ranged from 11.2 to 23.3 nM in diestrous females and from 13.1 to 50.4 nM in males, the maximal number of binding sites (Bmax) from 3290 to 10240 fmol/mg protein in females and from 5495 to 17449 fmol/mg p…
Modelling intestinal absorption of salbutamol sulphate in rats
2005
The objective was to develop a semiphysiological population pharmacokinetic model that describes the complex salbutamol sulphate absorption in rat small intestine. In situ techniques were used to characterize the salbutamol sulphate absorption at different concentrations (range: 0.15-18 mM). Salbutamol sulphate at concentration of 0.29 mM was administered in presence of verapamil (10 and 20 mM), grapefruit juice and sodium azide (NaN3) (0.3, 3 and 6 mM). Different pharmacokinetic models were fitted to the dataset using NONMEM. Parametric and non-parametric bootstrap analyses were employed as internal model evaluation techniques. The validated model suggested instantaneous equilibrium betwee…