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A Varga

Publications and source records attributed to A Varga.

131 records · Page 8Linked to original sources
PubMedDate not supplied

[An experimental study of the action of 5-fluorouracil on the function and cytomorphology of the exocrine pancreas].

The authors have taken up previous studies by Martin (1969), and by Johnson (1973), and carried out an experimental study on white rats aimed at evaluating the morpho-functional changes of cells from the exocrine pancreas under the influence of 5-fluorouracil (Ftorafur), a cytostatic drug which is a general inhibitor of protein synthesis by cells. Ftorafur was injected in amounts of 2.3 mg/100 g of body weight, and a significant reduction was noted in the secretion of bicarbonates, amylase and lipase by the pancreas of the animals. Cytologic changes were also noted in the pancreatic tissue of these animals, indicating, on the one hand, a deficient protein and enzyme synthesis by the pancreatic cells, and a blocking of the mechanism of discharge of zymogen granules, on the other hand. The most intensive morpho-functional changes were noted following repeated administration of Ftorafur, probably due to the cumulative effects of this substance at the level of secretory pancreatic cells. The authors consider that 5-fluorouracil inhibits to a considerable degree the synthesis of pancreatic enzymes, and as such it can be used as a therapeutic means for the reduction of the external secretion of the pancreas.

Animals↗
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Reversal of multidrug resistance by amitriptyline in vitro.

Amitriptyline, a tricyclic antidepressant, was able to reverse the multidrug resistance efflux pump of human colon cancer subline SW 620 and multidrug resistant (mdr) mouse lymphoma cells by decreasing rhodamine 123 efflux. The inhibitory effect of amitriptyline on the efflux pump was dose dependent. An investigation was made of the effects of mouse tumour necrosis factor (TNF) alpha and interferon (IFN) gamma on the efflux pump activity of mdr cells together with amitriptyline compared to the par cells (mdr-). After long-term cytokine pretreatment of mdr cells, the amitriptyline was more effective, due to some synergism between the amitriptyline and TNF-alpha.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Multidrug resistance reversal in mouse lymphoma cells by heterocyclic compounds.

Due to the close homology between bacterial and tumor cell transporter proteins, some antiplasmid and anticancer compounds were tested for their ability to reserve the multidrug resistance (mdr) of lymphoma cells. Some known anticancer medicines such as platidiam, novantron, fluorouracil, bleomycin and methotrexate were ineffective/while vinca alkaloids exerted a strong reversal effect on the mdr of lymphoma cells. The structurally related reserpine and yohimbine do not affect the activity of efflux pump. Some selected antitumor phenothiazines and benzo[a]phenothiazines, including trifluoperazine inhibit the P-glycoprotein (pgp) function. This fact is independent from the antiproliferative- or differentiation inducing effects. Since the polylactosamine specific tomato lectin prevents the action of the chemosensitizers tested, it is supposed that the site of action of phenothiazines can be at the 1st loop in the transmembrane glycoprotein. The efflux pump activity of the pgp in brain capillary endothel which is responsible for blood brain barrier (BBB) was also inhibited by some phenothiazines. However, the tomato lectin sensitivity of pgp was different in mouse lymphoma and human brain capillary endothelial cells. The mdr-gene expression of the mouse lymphoma cells (which were transfected with the human mdr-1 gene) could be reduced by phenothiazines such as promethazine and trifluoperazine, when the cells were cultured in the presence of 0.5 microgram/mL phenothiazines. Further synergism was found between two resistance modifiers i.e. verapamil and trifluoperazine on the inhibition of mdr-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

The inhibition of SOS-responses and MDR by phenothiazine-metal complexes.

The gene of multidrug resistance (mdr) is inducible by different environmental stresses (SOS gene). We tested the inhibitory action of some new metal complexes of phenothiazines on megacin encoding bacterial gene induced by mitomycin-C as an example of "SOS induction" and on efflux pump of mouse lymphoma cells. The interaction of compounds to DNA was measured by thermal stability of DNA. It was found that metal co-ordination complexes of trifluoperazine (TFP) and chlorpromazine (CPZ) added before mitomycin administration have an inhibitory action on megacine induction. The TFP-V(IV) complex was effective at a lower concentration than TFP alone. The inhibitory effect of some metal coordinating complexes (TFP-Cu(II) and TFP- V(IV)) exceeded the action of TFP alone on efflux pumps. We propose that these compounds can form a complex with the regulatory protein or DNA resulting in the inhibition of SOS response and inhibit the mdr function by inactivating the P-glycoprotein as well.

ATP Binding Cassette Transporter, Subfamily B, Mem↗