Search results for "Steroid"
showing 10 items of 1005 documents
The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease
2009
After more than two decades of research into phosphodiesterase 4 (PDE4) inhibitors, roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) may become the first agent in this class to be approved for patient treatment worldwide. Within the PDE family of 11 known isoenzymes, roflumilast is selective for PDE4, showing balanced selectivity for subtypes A-D, and is of high subnanomolar potency. The active principle of roflumilast in man is its dichloropyridyl N-oxide metabolite, which has similar potency as a PDE4 inhibitor as the parent compound. The long half-life and high potency of this metabolite allows for once-daily, oral administration of a single, 500…
A comparison of cytoplasmic and nuclear estradiol and progesterone receptors in human fallopian tube and endometrial tissue
1981
Quantitative and qualitative aspects of the in vitro binding of 3 H-estradiol and 3 H-progesterone to receptor components from human endometrium and fallopian tube cytoplasmic and nuclear fractions were studied. The steroid binding macromolecules formed in vitro could be extracted from nuclei by 0.4M KCl and detected by glycerol gradient centrifugation. Both estradiol- and progesterone-binding compounds formed only one peak (under high ionic strength conditions) with a sedimentation coefficient of about 4-5S. The number of cytoplasmic and nuclear binding sites for both estradiol and R5020 varied dramatically throughout the menstrual cycle: the estradiol and progesterone receptor concentrati…
A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk.
2011
Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular "xenosensors" like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicate…
The effects of ibuprofen on activated sludge: Shift in bacterial community structure and resistance to ciprofloxacin
2017
Abstract Ibuprofen (IBP) is ranked at the 4th place among 57 pharmaceutical compounds according to the number of citations in prioritization documents. The response of microbial community of activated sludge to IBP was studied at the concentrations of 50–5000 mg/L. Batch incubation was performed in an OxiTop® device for 21 days. The reduction of biological oxygen demand depended on the IBP concentration and varied in the range from 321 to 107 mg O 2 /L. Massive DNA sequencing analysis of the activated sludge revealed that Proteobacteria became more dominant when grown in the presence of IBP. Microbial diversity was reduced in the presence of 500–1000 mg/L IBP, but increased again in the pre…
The Mutation without childrenrgl Causes Ecdysteroid Deficiency in Third-Instar Larvae of Drosophila melanogaster
2000
Larvae homozygous for the recessive lethal allele without children(rgl) (woc(rgl)) fail to pupariate. Application of exogenous 20-hydroxyecdysone elicits puparium formation and pupation. Ecdysteroid titer measurements on mutant larvae show an endocrine deficiency in the brain-ring gland complex, which normally synthesizes ecdysone, resulting in a failure of the larvae to achieve a threshold whole body hormone titer necessary for molting. Ultrastructural investigation revealed extensive degeneration of the prothoracic cells of the ring gland in older larvae. The woc gene, located in polytene chromosomal region 97F, consists of 11 exons. A 6.8-kb transcript is expressed throughout development…
Mucoadhesive Solid Lipid Microparticles (SLM) for sustained release of corticosteroids to the lungs
2016
Pulmonary delivery is the preferred route of drug administration in the treatment of many respiratory disease, such as asthma and chronic obstructive pulmonary disease (COPD). Over the years, several kinds of carriers have been studied for sustained release of corticosteroids and bronchodilators to the lungs. Solid Lipid Microparticles (SLM) due to their biocompatibility and size (3-5 µm) can reach the bronchial epithelium directly, circumvent first pass metabolism and avoid systemic toxicity [1,2]. In this work we describe the preparation and the characterization of two different systems subjected to chitosan and alginate coating for sustained release of fluticasone propionate (FP) into th…
Structural characterization of triorganotin(IV) complexes with sodium fusidate and DFT calculations
2010
Abstract Three new complexes of the steroid sodium fusidate (sodium 2-[(1 S ,2 S ,5 R ,6 S ,7 S ,10 S ,11 S ,13 S , 14 Z ,15 R ,17 R )-13-(acetyloxy)-5,17-dihydroxy-2,6,10,11-tetramethyl tetracyclo[8.7.0.0 2,7 .0 11,15 ] heptadecan-14-ylidene]-6-methylhept-5-enoate = (NaFusidate, Na FA )]), with triorganotin(IV) moieties have been prepared and investigated by conventional techniques as FTIR, Mossbauer, ESI-MS and NMR spectroscopy. The isolated compounds showed stoichiometries organotin(IV)/fusidate 1/1, R 3 Sn(IV) FA (R = Me, FA1 ; Bu, FA2 ; Ph, FA3 ). The ligand coordination sites were determined by FTIR spectroscopic measurements. In the complexes, the carboxylate group of the fusidate li…
Inhibition of pro-inflammatory enzymes by inuviscolide, a sesquiterpene lactone from Inula viscosa
2006
Abstract This work concerns the pharmacological activity of inuviscolide, a sesquiterpenoid from Inula viscosa. It exerts inhibitory effects on elastase, cyclooxygenase 1 and secretory phospholipase A2. Furthermore, it reduces the skin leukocyte infiltration in a murine model of dermatitis induced by repeated application of 12-O-tetradecanoylphorbol 13-acetate.
Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways.
1999
The aim of this study was to re-examine the human hepatic metabolism of diclofenac, with special focus on the generation of minor hydroxylated metabolites implicated in the idiosyncratic hepatotoxicity of the drug. Different experimental approaches were used: human hepatocytes, human microsomes, and engineered cells expressing single human CYP (cytochromes P450). Human hepatocytes formed 3'-hydroxy-, 4'-hydroxy-, 5-hydroxy- 4',5-dihydroxy-, and N,5-dihydroxydiclofenac, as well as several lactams. Formation of 4'- and 5-hydroxydiclofenac by human liver microsomes followed a Michaelis-Menten kinetics (Km 9 +/- 1 microM; Vmax 432 +/- 15 pmol/min/mg and Km 43 +/- 5 microM; and Vmax 15.4 +/- 0.6…
The pyrrole moiety as a template for COX-1/COX-2 inhibitors
2000
Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a new class of COX-1/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX-1 and RIA for COX-2. Variation of the substitution pattern led to a series of active compounds which showed inhibition for COX-1 and COX-2. Structural requirements for the development of COX-1/COX-2 inhibitors are discussed.