Search results for "RATS"
showing 10 items of 3537 documents
Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models
2010
Oncolytic virotherapy is a potential treatment modality under investigation for various malignancies including malignant brain tumors. Unlike some other natural or modified viruses that show oncolytic activity against cerebral neoplasms, the rodent parvovirus H-1 (H-1PV) is completely apathogenic in humans. H-1PV efficiently kills a number of tumor cells without harm to corresponding normal ones. In this study, the concept of H-1PV-based virotherapy of glioma was tested for rat (RG-2 cell-derived) and for human (U87 cell-derived) gliomas in immunocompetent and immunodeficient rat models, respectively. Large orthotopic rat and human glioma cell-derived tumors were treated with either single …
Inorganic Polyphosphate in Human Osteoblast-like Cells
1998
Significant amounts of inorganic polyphosphates and of polyphosphate-degrading exopolyphosphatase activity were detected in human mandibular-derived osteoblast-like cells. The amount of both soluble and insoluble long-chain polyphosphate in unstimulated osteoblast-like cells was higher than in human gingival cells, erythrocytes, peripheral blood mononuclear cells, and human blood plasma. The cellular content of polyphosphate in osteoblast-like cells strongly decreased after a combined treatment of the cells with the stimulators of osteoblast proliferation and differentiation, dexamethasone, beta-glycerophosphate, epidermal growth factor, and ascorbic acid. The amount of soluble long-chain p…
Binge administration of 3,4-methylenedioxymethamphetamine ("ecstasy") impairs the survival of neural precursors in adult rat dentate gyrus.
2006
3,4-Methylenedioxymethamphetamine (MDMA) is a potent stimulant and hallucinogenic drug whose ability to regulate neurogenesis in the adult has not been previously investigated. We used 5'-bromo-2-deoxyuridine (BrdU) and Ki-67 as mitotic markers, and doublecortin (DCX) as a marker of immature neurons, to study proliferation, survival and maturation of adult-generated cells in the dentate gyrus (DG) of the hippocampus following binge administration of MDMA (8 injections of 5 mg/kg at 6 h intervals). The results showed that MDMA treatment did not affect cytogenesis in the DG, but significantly decreased the survival rate of cells incorporated after 2 weeks to the granular layer of the DG by ca…
Mathematical modeling of oral absorption and bioavailability of a fluoroquinolone after its precipitation in the gastrointestinal tract
2013
The objective was to characterize the in vivo absorption and bioavailability (BA) of a low solubility, high permeability fluoroquinolone (CNV97101) that precipitates in the gastrointestinal (GI) tract by mathematical modeling approach. In situ rat intestinal perfusion studies were performed to characterize the absorption mechanism. The oral fraction absorbed in vivo was lower than the predicted based on the in situ intestinal permeability. Two additional routes of administration, intraduodenal (ID) and intraperitoneal (IP) were investigated to explore if precipitation in stomach and subsequent partial re-dissolution were the causes of the lower in vivo BA. Ex vivo precipitation studies with…
Rat and human liver cytosolic epoxide hydrolases: evidence for multiple forms at level of protein and mRNA.
1990
Two forms of human liver cytosolic epoxide hydrolase (cEH) with diagnostic substrate specificity for trans-stilbene oxide (cEHTSO) and cis-stilbene oxide (cEHCSO) have been identified, and cEHCSO was purified to apparent homogeneity. The enzyme had a monomer molecular weight of 49 kDa and an isoelectric point of 9.2. Pure cEHCSO hydrolyzed CSO at a rate of 145 nmole/min/mg. TSO was not metabolized at a detectable level, and like cEHTSO, the enzyme was about three times more active at pH 7.4 than at pH 9.0. Unlike cEHTSO, cEHCSO was efficiently inhibited by 1 mM 1-trichloropropene oxide (90.5%) and 1 mM STO (92%). Similarly, liver cEH purified 541-fold from fenofibrate induced Fischer 344 ra…
Drug-metabolizing enzyme activities in freshly isolated oval cells and in an established oval cell line from carcinogen-fed rats
1994
The activities of several different phase I and phase II drug-metabolizing enzymes were measured in freshly isolated oval cells from rats fed a choline-deficient/DL-ethionine-supplemented diet for 6 weeks and also in vitro in the established oval cell line OC/CDE 6. No cytochrome P450 was spectrophotometrically measurable in both preparations and two cytochrome P450-dependent monoxygenase activities, aminopyrine N-demethylase and ethoxyresorufin O-deethylase, could not be detected in the oval cells of both sources. However, cytosolic glutathione transferase, microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities were clearly measurable in oval cells. Similar enzyme activiti…
The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells
2006
Disruption of cell proliferation control by polycyclic aromatic hydrocarbons (PAHs) may contribute to their carcinogenicity. We investigated role of the aryl hydrocarbon receptor (AhR) in disruption of contact inhibition in rat liver epithelial WB-F344 'stem-like' cells, induced by the weakly mutagenic benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and by the strongly mutagenic benzo[a]pyrene (BaP). There were significant differences between the effects of BaA and BbF, and those of the strongly genotoxic BaP. Both BaA and BbF increased percentage of cells entering S-phase and cell numbers, associated with an increased expression of Cyclin A and Cyclin A/cdk2 complex activity. Their eff…
In vitro mammalian metabolism of the mitosis inhibitor zoxamide and the relationship to its in vitro toxicity.
2009
The in vitro mammalian metabolism of the fungicide zoxamide is related to its in vitro mammalian toxicity. After incubation of zoxamide with rat liver microsomes leading to practically 100% metabolism (mostly hydroxylated zoxamide), the cytotoxicity (methyl thiazole tetrazolium (MTT) test) and the mitosis-inhibiting potential (shown by cell count and by cell cycle analysis) for V79 were not distinguishable from those of zoxamide, demonstrating that the hydroxylation of zoxamide did not change the cytotoxicity or mitosis-inhibiting potential as determined by these assays. After incubation of zoxamide with rat liver S9 predominantly leading to conjugation with glutathione, and after incubatio…
Detection of oxidative mutagenesis by isoniazid and other hydrazine derivatives in Escherichia coli WP2 tester strain IC203, deficient in OxyR: stron…
1998
Abstract Strain IC203, deficient in the OxyR function, was sensitive to both cytotoxic and mutagenic effects of isoniazid (INH) whereas its parent, WP2 uvrA /pKM101, was resistant to these effects. Four other hydrazine compounds, hydrazine hydrate (HZH), phenylhydrazine (PHZ), hydralazine (HLZ) and nialamide (NLD), were mutagenic in WP2 uvrA /pKM101. Increases in mutagenicity were observed in IC203 for HZH and PHZ but not for HLZ and NLD. Growth inhibition zones by HZH, PHZ and NLD were larger in IC203 than in WP2 uvrA /pKM101. The enhancements in the effects of INH, HZH and PHZ in IC203 with respect to its oxyR + parent are considered to be caused by the production of reactive oxygen speci…
Heat-induced action potential discharges in nociceptive primary sensory neurons of rats.
2009
Although several transducer molecules for noxious stimuli have been identified, little is known about the transformation of the resulting generator currents into action potentials (APs). Therefore we investigated the transformation process for stepped noxious heat stimuli (42-47 degrees C, 3-s duration) into membrane potential changes and subsequent AP discharges using the somata of acutely dissociated small dorsal root ganglion (DRG) neurons (diameteror=32.5 microm) of adult rats as a model for their own peripheral terminals. Three types of heat-induced membrane potential changes were differentiated: type 1, heat-induced AP discharges (approximately 37% of the neurons); type 2, heat-induce…