Search results for "metabolite"
showing 10 items of 551 documents
Application of Cell Culture for the Production of Bioactive Compounds from Sponges: Synthesis of Avarol by Primmorphs from Dysidea avara
2000
Among all metazoan phyla, sponges are known to produce the largest number of bioactive compounds. However, until now, only one compound, arabinofuranosyladenine, has been approved for application in humans. One major obstacle is the limited availability of larger quantities of defined sponge starting material. Recently, we introduced the in vitro culture of primmorphs from Suberites domuncula, which contain proliferating cells. Now we have established the primmorph culture also from the marine sponge Dysidea avara and demonstrate that this special form of sponge cell aggregates produces avarol, a sesquiterpenoid hydroquinone, known to display strong cytostatic activity especially against ma…
Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease
2013
Background Glucocorticoid functions are markedly impaired in patients with chronic obstructive pulmonary disease (COPD). The phosphodiesterase 4 inhibitor roflumilast N-oxide (RNO) is the active metabolite of roflumilast approved as a treatment to reduce the risk of exacerbations in patients with severe COPD. Objective We sought to characterize the differential effects of RNO versus corticosteroids and their potential additive/synergistic effect in neutrophils from patients with COPD, thus providing scientific rationale for the combination of roflumilast with corticosteroids in the clinic. Methods Peripheral blood neutrophils were isolated from patients with COPD (n = 32), smokers (n = 7), …
Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.
2015
ABSTRACT Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-E…
Kinetic experiments on the binding of metyrapone to liver microsomes
1969
Kinetic experiments on the inhibition of oxidative microsomal O- and N-demethylations by metyrapone (2-methyl-1, 2-bis(3-pyridyl)-l-propanone, Su 4885) were carried out using mouse liver microsomes as the enzyme source. The model substrates were p-nitroanisole and N-monomethyl-p-nitroaniline. It was shown that the inhibition is competitive. The K i for metyrapone is 0.42 × 10−4 M and for the reduced metabolite of metyrapone 1.15×10−4 M. Their spectral dissooiation constants as determined from difference spectra have almost the same values. From this it is concluded that the degree of inhibition is correlated to the amount of metyrapone bound to cytochrome P-450. Metyrapone does not seem to …
Gemcitabine sensitizes lung cancer cells to Fas/FasL system-mediated killing
2014
Gemcitabine is a chemotherapy agent commonly used in the treatment of non-small cell lung cancer (NSCLC) that has been demonstrated to induce apoptosis in NSCLC cells by increasing functionally active Fas expression. The aim of this study was to evaluate the Fas/Fas ligand (FasL) system involvement in gemcitabine-induced lung cancer cell killing. NSCLC H292 cells were cultured in the presence or absence of gemcitabine. FasL mRNA and protein were evaluated by real-time PCR, and by Western blot and flow cytometry, respectively. Apoptosis of FasL-expressing cells was evaluated by flow cytometry, and caspase-8 and caspase-3 activation by Western blot and a colorimetric assay. Cytotoxicity of ly…
Determination of 3-(4′-methylbenzylidene)camphor and its metabolite 3-(4′-carboxybenzylidene)camphor in human semen by solid-phase extraction and liq…
2015
An analytical method for the determination of the controversial UV filter 3-(4′-methylbenzylidene)camphor (MBC) and its metabolite 3-(4′-carboxybenzylidene)camphor (CBC) in human semen is presented. The method is based on the simultaneous hydrolysis of phase II conjugates and protein precipitation, followed by solid-phase extraction (SPE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) detection. The proposed method was validated by analyzing spiked analyte-free human semen samples. Matrix-matched calibration using an analyte-free semen pool was employed. Satisfactory recoveries (92–114%) were obtained using this calibration methodology, thus showing the accuracy of the propos…
High-performance liquid chromatographic determination of spironolactone and its major metabolite canrenone in urine using ultraviolet detection and c…
1994
A rapid and simple column liquid chromatographic method involving a column-switching system for the determination of spironolactone and its main metabolite canrenone in urine is described. Purification and concentration was performed using an Hypersil ODS-C18, 30 microns (20 x 2.1 mm I.D.) pre-column. The most polar urinary compounds were removed by washing the pre-column with water, and the analytes were subsequently switched to a LiChrospher RP C18, 5 microns (125 x 4 mm I.D.) analytical column and separated by means of an acetonitrile-water mobile-phase. Under the proposed conditions, the extraction efficiency was approximately 100% over the 0.5-10.0 micrograms/ml concentration range. Th…
A solid-phase extraction liquid chromatography-tandem mass spectrometry method for the percutaneous absorption assessment of 3-(4′-methylbenzylidene)…
2013
The UV filter 3-(4′-methylbenzylidene)camphor (MBC) is a common ingredient in sunscreen cosmetic products. However, different in vitro and in vivo studies suggest that MBC can cause endocrine disrupting effects. This report focuses on the development of an analytical method based on solid-phase extraction (SPE) prior to liquid chromatography tandem mass spectrometry (LC-MS/MS) for the determination of MBC and its main phase I metabolite, named 3-(4′-carboxybenzylidene)camphor (CBC), in urine from users of sunscreen cosmetic products containing MBC. The formation of phase II metabolites (i.e., glucuronide and sulphate conjugates) was also considered by carrying out an enzymatic hydrolysis of…
Bioanalysis of digoxin and its metabolites using direct serum injection combined with liquid chromatography and on-line immunochemical detection.
1994
Abstract An automated dual-column liquid chromatographic assay for digoxin is described. Serum samples are directly injected onto a restricted-access solid-phase extraction support. After liquid chromatographic (LC) separation on a C18 analytical column, antigenic analytes are detected by means of post-column immunochemical detection (ICD) using fluorescein-labelled antibodies against digoxigenin. The detection limit of this assay is 160 pg/ml (preconcentration of 1.0 ml serum). With the present method digoxin and three of its cross-reactive metabolites were determined in serum taken from patients which were orally administered a 1-mg dose of digoxin. The results obtained with LC—ICD were c…
Simultaneous determination of olanzapine, clozapine and demethylated metabolites in serum by on-line column-switching high-performance liquid chromat…
2001
An automated method for simultaneous routine quantification of the antipsychotic drugs clozapine, olanzapine and their demethylated metabolites is described. The method included adsorption on a cyanopropyl (CPS) coated clean-up column (10 microm; 10 x 2.0 mm I.D.), washing off interfering serum constituents to waste, and separation on C18 ODS Hypersil reversed phase material (5 microm; 250 x 4.6 mm I.D.) using acetonitrile-water-tetramethylethylenediamine (37:62.6:0.4, v/v/v) adjusted to pH 6.5 with concentrated acetic acid. UV-detection was performed at 254 nm. The limit of quantification was 10-20 ng/ml. Relative day to day standard variations ranged between 4.5 and 13.5%. The method is s…