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J Drobník

Publications and source records attributed to J Drobník.

At least 19 recordsLinked to original sources
PubMed2002

[Genetically modified organisms--problems and legislation].

Genetically modified organisms are defined by law as entities capable of replication and/or transmission of hereditary material that had been altered by the insertion or removal of a DNA fragment. By the EU legal regulation as well as by the Czech law, such organisms are considered risky whereas other products of breeding, though obtained by, e.g., induced mutagenesis, are claimed as safe. Organisms transferred from other ecosystems are also considered safe. The Czech law on the use of genetically modified organisms is based on registers of users and organisms for specific use. Application for the registration that is valid as an approval should be submitted to the Ministry of Environment. The applicant is obliged to present the risk assessment of the particular use of genetically modified organisms. Genetically modified organisms are connected with certain risk to ecology, however health risks are brought about almost exclusively by microorganisms. Modified organisms used for food production are thoroughly tested for substantial equivalency with standard crops and with respect to health parameters of the protein(s) newly introduced due to genetic modification. Detail tests as well as their cost are close to the testing of new drugs. European as well as Czech rules for food labelling are motivated by the psychology of consumers rather than by health impact. They result to absurdities but do not meet the task of public psychology. This is why the EU authorities are looking for measures to change the present situation that other wise would bring Europe well behind the developed countries.

Czech Republic↗
PubMed1994

[Glycosaminoglycans in the peritoneal fluid of infertile women with endometriosis].

The authors examined the glycosaminoglycan level in the peritoneal fluid of 54 infertile women with or without endometriosis. The peritoneal fluid was collected during a routine laparoscopic examination. Glycosaminoglycans were assayed in complexes with Alcian blue. There was a higher concentration of glycosaminoglycans in peritoneal fluid during the follicular phase of women with endometriosis. The authors did not prove a statistically significant difference between women with and without endometriosis.

Adolescent↗
PubMed1987

Hydrogels in endovascular embolization. III. Radiopaque spherical particles, their preparation and properties.

The synthesis and properties of spherical radiopaque hydrogel particles designed for endovascular occlusion are reported. These particles were prepared by the hydroxyl acylation of low crosslinked poly (2-hydroxyethyl methacrylate) beads with a nontoxic radiopaque compound based on triiodobenzoic acid, without affecting their properties which are advantages in medical practice. The effect of the iodine content on the size of dry and swollen particles is discussed. It has been found that an iodine content of about 25-30 wt% is desirable in order to obtain an easily recognizable X-ray image. These particles make the immediate control of embolus application easy and enable periodical inspection of the polymer to check the successful blockage of the vessel. They also open up the method of endovascular occlusion to further improvement.

Contrast Media↗
PubMed1987

Cyclic AMP levels of C6 glioma cells treated with cis-dichlorodiammine platinum (cis-DDP).

Rat C6 glioma cells were cultured for 3-4 days in MEM supplemented with bovine serum. After 10 min incubation of cells with 0.075, 1.0 or 7.5 micrograms ml-1 cis-DDP the basal cAMP levels (7.87 +/- 0.4 pmoles mg-1 protein) were not affected. In the presence of a phosphodiesterase inhibitor, IBMX, an increase of cAMP occurred; the later was more pronounced in cis-DDP treated cells than in the controls. This suggests that both adenylate cyclase and cAMP-phosphodiesterase were proportionally influenced at this period and that the stimulatory effect of cis-DDP on AC could be demonstrated only when increased activity of PDE had been blocked by IBMX. At later time intervals (10 h-40 h), a 5- to 17-fold elevation of cAMP levels was observed even in the absence of IBMX. Pretreatment of the cells with cis-DDP significantly potentiated cAMP accumulation in response to NE alone and to cis-DDP plus NE could be prevented to a large extent by propranolol; in cis-DDP treated cells the propranolol protection was more effective, both in the absence and the presence of IBMX. The pretreatment of cells with an alpha-blocker, Regitin, did not significantly influence cAMP accumulation. The results indicate that the cis-DDP stimulated cAMP response to NE is mediated via an interaction with beta-adrenergic receptors. The late increase in cAMP content may be a mediator of the morphological changes in these cells following exposure to cis-DDP.

Animals↗
PubMed1987

Chromotest estimation of SOS functions as a screening method for antitumor platinum complexes.

The chromotest which measures the induction of SOS functions in an Escherichia coli strain bearing the lacZ gene under the sfiA gene control was evaluated as a screening method for platinum complexes with antitumor activity. Four types of complexes were used: (a) those with two nitrogen ligands in cis position and chlorine or carboxylic acid as anionic ligand; (b) four nitrogen atoms surrounding platinum; (c) complexes involving sulphur and amino group of methionine; (d) complexes of tetravalent platinum. The trans-diaminodichloro complex was used as negative control. Groups (b) and (c) were inactive in the chromotest which correlated well with their absence of antitumor activity. Antitumor activity and a positive chromotest also correlated in group (d). In group (a), which includes complexes with well established antitumor activity, the chromotest separated complexes with fast and slow rate of hydrolysis. The results fitted well in the mutation induction test.

Alkaline Phosphatase↗
PubMed1987

Comparative pharmacokinetics of four platinum cytostatics in rats.

The time-course of plasma and red blood cells platinum concentration was investigated after the administration of cis-dichlorodiammineplatinum II (cisplatinum), cis-dichlorodiammine-trans-dihydroxyplatinum IV (oxoplatinum), cis-dichloro-trans-dihydroxy-bis-isopropylamine-platinum IV (CHIP) and cis-diammine-1,1-cyclobutanedicarboxylate-platinum II (CBDCA) to male Wistar rats. A physiologically based three-compartment open model was used for pharmacokinetic evaluation. This model provides an estimation of free and protein-bound platinum time-courses from the total platinum species decrease. The total plasma clearance of total platinum increased in the order cisplatinum, CHIP, oxoplatinum and CBDCA. Plasma half-live of gamma-phase, which probably represents the elimination of protein-bound platinum species is similar (51-72 h) in all drugs under study and is longer than that of 131I-HSA (33 h). The platinum concentration in red blood cells shows plateau for all complexes studied at long time intervals and its elimination is very slow.

Animals↗
PubMed1986

Pharmacokinetics and plasma protein binding of two platinum cytostatics CHIP and CBDCA in rats.

Plasma protein binding and pharmacokinetic parameters of CHIP (cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV) and CBDCA (cis-diammine-1,1-cyclobutane dicarboxylate platinum II) were investigated in male Wistar rats. The plasma clearance of total and non-protein-bound platinum was determined and compared with that of 99mTc-DTPA. For binding experiments, a novel, simple, and quick method based on adsorption of non-protein-bound platinum species to charcoal was used. The clearance of total platinum after CHIP and CBDCA administration was markedly lower than the glomerular filtration rate (determined as the clearance of 99mTc-DTPA). The renal clearance of non-protein-bound platinum corresponded to 168% and 50% of the glomerular filtration rate for CHIP and CBDCA, respectively. These studies suggested that CHIP was excreted by the rat kidney.

Animals↗
PubMed1986

Antitumor activity of four polymer bound trans-1,2-diaminocyclohexaneplatinum(II)-4-carboxyphtalate complexes tested in different model systems.

Four polymer bound Pt-complexes have been tested in in vivo and in in vitro systems. No substantial difference in effectivity against P388 leukemia in vivo was found when free trans-1,2-diaminocyclohexaneplatinum(II)-4-carboxyphtalate (TMA) was compared with the polymer bound complexes. The compound with the highest ID50 value in soft agar assay exhibited low effectivity in in vivo testing. Polymer bound Pt-complexes with faster release of the active molecule exhibited in in vivo and in soft agar assay slightly lower activity, when compared with suspension culture test system. Cross resistance of polymer bound complexes was investigated on three cell lines with induced drug resistance against different Pt-complexes. Cross resistance was found between TMA (free and polymer bound) and trans-1,2-diaminocyclohexaneplatinum(II)citrate (PEX) as well as trans-1,2-diaminocyclohexaneplatinum(II)glucarate (PTU) but there was no cross resistance between TMA and cis-diamminedichloroplatinum(II) (cis-DDP).

Animals↗
PubMed1985

Characterization of the adsorptive pinocytic capture of a polyaspartamide modified by the incorporation of tyramine residues.

Previously it has been shown (Duncan, R., Starling, D., Rypácek, F., Drobník, J. and Lloyd, J.B. (1982) Biochim. Biophys. Acta 717, 248-254) that incorporation of tyramine residues into poly (alpha, beta-(N-2-hydroxyethyl]-DL-aspartamide (PHEA) greatly increases its rate of pinocytic uptake by rat visceral yolk sacs cultured in vitro. Here we describe the relationship between the tyramine content (1.2-21.9 mol%) of modified PHEA and its rate of uptake by yolk sacs. Above a level of substitution of approximately 10 mol% the rate of uptake rises rapidly, and the concentration-dependence of capture is indicative of uptake by adsorptive pinocytosis. Serum proteins were shown to compete effectively for membrane binding sites, indicating a nonspecific interaction of PHEA-derivatives with the yolk sac membrane. PHEA derivatives of the same tyramine content, but of different mean molecular weights (Mr), were captured at the same rates.

Adsorption↗
PubMed1985

Retention and biliary excretion of poly-alpha, beta-[N(2-hydroxyethyl)-D,L-aspartamide] (PHEA) and its tyramine derivative (PHEA-Tyr) by isolated perfused rat liver. The role of molecular weight and chemical structure.

Isolated rat liver was perfused with fractions of fluorescent labelled poly-alpha,beta-[N(2-hydroxyethyl)-D,L-aspartamide] (PHEA), (Mw:8000, 51 400 and 70 000) and its tyramine derivative, PHEA-Tyr (19 mol% tyramine side chains; Mw:8000 and 35 000) under conditions approximating an "in vivo" situation. By an analysis of the recovered polymers it was shown, firstly that accumulation of polymers, which occurred most apparently in the Kupffer cells, was neither affected by the presence of tyramine side chains nor influenced by the molecular weight of polymers; secondly that the tyramine side chains slightly increased the biliary excretion of PHEA-Tyr, and thirdly with both types of polymers the excretion of high-molecular-weight fractions in the bile was strongly suppressed.

Animals↗
PubMed1984

Immunostimulatory effect of cis-diamine dichloroplatinum (II).

Cis-diamine dichloroplatinum (II) (DDP) injected i.p. or i.v. at the dosage of 0.83 mg/kg to BALB/c mice on days 0, 7 and 14 elicited antibodies against proteins (RSA, BGG) and haptens (TNP, FITC) detectable by ELISA or by passive haemagglutination. Significant increase in antibody production was observed with either route of DDP application. A similar set of antibodies against antigens which do not cross-react with the immunizing proteins was observed when mice were immunized with complexes formed by an in vitro incubation of RSA and BGG with DDP. Thus, proteins modified in vivo or in vitro by DDP may stimulate the production of antibodies of unexpected specificities.

Adjuvants, Immunologic↗
PubMed1984

Cisplatin-induced tubular injury studied by water-soluble synthetic polymers.

Accumulation of a synthetic water-soluble polymer, poly-alpha, beta-[N(2-hydroxyethyl)-D,L-aspartamide-co-N(4-hydroxyphenethyl )- D,L-aspartamide] in the cells of kidney proximal tubules was used as an indicator for the functional localization of Cisplatin (CDDP) induced tubular injury in rats. Tubular accumulation of polymer was examined using 131I and fluorescence labelling for quantitative as well as morphological evaluation. It was found that reabsorption of the polymer, in which mainly the epithelium of proximal convolutions is involved, remains unaffected upon CDDP treatment in the course of one to six days after the drug administration. This finding supports on the functional level the morphological localization of CDDP injury into the straight segment of the proximal tubule.

Animals↗
PubMed1984

Unequal inhibition of protein synthesis in mitochondria of Zajdela hepatoma and rat liver after in vivo treatment with cis-diamminedichloroplatinum (II).

The effect of in vivo administered cis Pt(II) on mitochondrial and overall cellular protein synthesis in hepatocytes from regenerating rat liver and Zajdela hepatoma was examined. In both types of cells the overall cellular protein synthesis was inhibited by the drug approximately to the same extent (about 50%). Protein synthesis in mitochondria of Zajdela hepatoma was practically unaffected by the drug, whereas that in rat liver was inhibited similarly as was the overall cellular protein synthesis. Cis Pt(II) treatment had no detectable effect on the electrophoretic pattern of peptides synthesized in mitochondria of rat liver and Zajdela hepatoma. Relative content of cytochrome oxidase subunit IV to subunit II in Zajdela hepatoma mitochondria decreased upon cis Pt(II) treatment. The amount of platinum bound to Zajdela hepatoma mitochondria upon in vivo cis Pt(II) treatment was about two times lower than that bound to mitochondria of rat liver. It is concluded that protein synthesis in Zajdela hepatoma mitochondria is more resistant to in vivo cis Pt(II) treatment than the process in mitochondria of rat liver, and that this effect results from lower binding of cis Pt(II) and/or its derivatives to the tumor mitochondria.

Animals↗
PubMed1984

Cinematographic study of the effects of cis-diammine-dichloroplatinum on mouse L cells.

Cells of mouse fibroblasts line L were grown one hour in the presence of cisplatin. Their fate was then followed by time-lapse microcinematography during six days. Up to the concentration 3.2 mumol 1(-1) there was little effect observed. Higher concentrations induced prolongation of mitosis and interphase, finally resulting in non-cycling cells with complete and persistent division arrest at 25 mumol 1(-1). After 72 hours following the treatment the cellular and nuclear volumes in non-cycling cells began to grow progressively. The mobility and the ruffling activity of the cell membrane were unaltered. Thus, energy generation, the function of the cytoskeleton, and synthetic processes seemed unchanged. The effect of cisplatin is cytostatic rather than cytotoxic.

Animals↗
PubMed1983

Antitumor activity of platinum complexes.

Contemporary ideas about the mechanism of antitumor activity of platinum complexes are reviewed and discussed. The induction of SOS functions in bacteria is emphasized and an analogous mechanism in animal cells is suggested. The fate of the leaving ligand in the body is not known. Therefore the complex which reaches the target DNA may be very different from the applied compound. Even the amino ligand may be detached in the body, probably as part of the detoxication by binding to proteins. In the case of fast or medium-speed reactive complexes most of the platinum is inactivated by binding to proteins, whereas slow-reacting drugs are mostly excreted unchanged in the urine. Thus, the quantity of the complex which reaches the target is also difficult to assess. Due to peculiar pharmacokinetics, the results obtained with poorly soluble compounds administered in the solid form cannot be compared with those obtained in true solutions. There are many reasons for believing that the study of a coordination anticancer drug may contribute to our understanding of cancer growth and its reversal.

Animals↗
PubMed1983

Evaluation of infusion sets by biological and chemical testing.

Some of the biological and chemical tests used in toxicological evaluation of synthetic polymers were correlated. The individual tests (sperm cell motility, tissue culture inhibition, intracutaneous test, optical absorption at 220-360 nm, reducing impurities) did not mutually correspond. The final estimation of the tested device is assessed as a sum of these units. Therefore, it is necessary to evaluate the results of the individual tests in arbitrary units.

Animals↗