Search results for " Drug"
showing 10 items of 3138 documents
The presence of KCl in the exposure medium strongly influences the mutagenicity of metabolites of polycyclic aromatic hydrocarbons in Escherichia col…
1994
Abstract Previous studies demonstrated that the ion composition of the exposure medium may strongly influence the mutagenicity of many compounds in the liquid preincubation modification of the reversion assay with his − Salmonella typhimurium strains. Similar influences were now observed in the reversion assay with trp − Escherichia coli strain WP2 uvrA . The exposure medium was 8 mM sodium phosphate buffer (pH 7.4), containing no other ions or 125 mM KCl. Omission of KCl resulted in an about 10-fold enhancement of the mutagenic activity of 7-methylbenz[ a ]anthracene 5,6-oxide, but in a strong decrease in the mutagenicity of 1-hydroxymethylpyrene sulphate, close to the limit of detection. …
Kinetic modelling of passive transport and active efflux of a fluoroquinolone across Caco-2 cells using a compartmental approach in NONMEM.
2005
The purpose was to develop a general mathematical model for estimating passive permeability and efflux transport parameters from in vitro cell culture experiments. The procedure is applicable for linear and non-linear transport of drug with time,10 or10% of drug transport, negligible or relevant back flow, and would allow the adequate correction in the case of relevant mass balance problems. A compartmental kinetic approach was used and the transport barriers were described quantitatively in terms of apical and basolateral clearances. The method can be applied when sink conditions are not achieved and it allows the evaluation of the location of the transporter and its binding site. In this …
Binucleate cells in the Ehrlich ascites tumor. Action of 5-fluorouracil.
1987
Time-dependent frequency distribution of binucleate cells (BC) was studied in Ehrlich ascites tumor (EAT) growing in mice. In animals that received no further treatment, the number of BC increased slowly from 2.6% to 16.5% of total cells within 8 days. In animals that were treated with different doses of 5-fluorouracil (FU) we found clearly higher numbers of BC. The number of BC increased with tumor age. The increase observed after treatment was reached more quickly in animals that had received the highest FU dose. The final number of BC was also dependent on the age of the tumor at the time of FU injection.
Induction of micronucleated and binucleate cells in Chinese hamster ovary (CHO) cells by cis-diamminedichloroplatinum (II): a morphological and morph…
1990
Abstract The mutagenicity and cytotoxicity of cis -diamminedichloroplatinum (II) (cisplatin) at doses of 5, 10 and 20 μg/ml in Chinese hamster ovary (CHO) cells have been examined. A morphological characterization of several cell types induced by cisplatin was carried out. The frequencies of both cells with micronuclei and binucleate cells as a time-dependent parameter have also been studied. Whilst the number of cells with micronuclei was found to decrease with time, the number of binucleate cells increased. The possible kinetic mechanism for the production of binucleate cells and cells with micronuclei is discussed. A morphometric analysis was also performed. The nuclear area in both trea…
A novel moniliformin derivative as pan-inhibitor of histone deacetylases triggering apoptosis of leukemia cells
2021
New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC13…
Galantamine modulates nicotinic receptor and blocks Aβ-enhanced glutamate toxicity
2004
Galantamine is a plant alkaloid that is used in the treatment of Alzheimer's disease. We have studied the effects of galantamine on beta-amyloid-enhanced glutamate toxicity using primary rat cultured cortical neurons. Nicotine and galantamine alone, and in combination, protected neurons against this neurotoxicity. The protection was not blocked by alpha4beta2 nicotinic acetylcholine receptor (nAChR) antagonists, but was partially blocked by alpha7 nAChR antagonists. Galantamine induced phosphorylation of Akt, an effector of phosphatidylinositol 3-kinase (PI3K), while PI3K inhibitors blocked the protective effect and Akt phosphorylation. The antibody FK1, which selectively blocks the alloste…
Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress
2000
Arachidonic acid administration caused apoptosis in Y79 cells, as shown by typical morphological changes, phosphatidylserine externalization, chromatin condensation, processing and activation of caspase-3 and cleavage of the endogenous caspase substrate poly-(ADP-ribose)-polymerase. Arachidonic acid also caused lamin B cleavage, suggesting caspase-6 activation. Arachidonic acid treatment was accompanied by increased formation of the lipid peroxidation end products malondialdehyde and 4-hydroxy-2-nonenal, lowering in reduced glutathione content and in mitochondrial membrane potential. Inhibiting glutathione synthesis sensitized Y79 cells to apoptosis-inducing stimuli, whilst replenishing red…
Unraveling In vivo brain transport of protein‐coated fluorescent nanodiamonds
2019
The blood–brain barrier is the biggest hurdle to overcome for the treatment of neurological disorders. Here, protein‐coated nanodiamonds are delivered to the brain and taken up by neurovascular unit cells after intravenous injection. Thus, for the first time, nanodiamonds with their unique properties and a flexible protein coating for the attachment of therapeutics emerge as a potential platform for nanotheranostics of neurological disorders.Nanotheranostics, combining diagnostics and therapy, has the potential to revolutionize treatment of neurological disorders. But one of the major obstacles for treating central nervous system diseases is the blood–brain barrier (BBB) preventing systemic…
Dissolution enhancement and in vitro performance of clarithromycin nanocrystals produced by precipitation–lyophilization–homogenization method
2014
The gastroduodenal diseases caused by Helicobacter pylori were commonly treated with antibiotic clarithromycin as a standard regimen. According to the poorly water-soluble of clarithromycin, the nanocrystal formulation was prepared. The aim of this study was to investigate an enhancement effect of clarithromycin nanocrystals produced by precipitation-lyophilization-homogenization (PLH) method on the saturation solubility, dissolution velocity, antibiotic activity, permeability through the gastric mucus and cellular permeability. Poloxamer 407 and sodium lauryl sulfate (SLS) were chosen as combined stabilizers in the nanocrystal system. The obtained clarithromycin nanocrystals were identifie…
Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.
2020
Abstract Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3–8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9–11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted fo…