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I Karner

Publications and source records attributed to I Karner.

23 records · Page 2Linked to original sources

In vitro cytotoxicity of three 4,9-diazapyrenium hydrogensulfate derivatives on different human tumor cell lines.

DNA intercalating agents interfere with DNA's role as a template in replication and transcription by inserting an intercalator molecule between adjacent base pairs. We synthesized three potential novel intercalators, 4,9-diazapyrenium hydrogensulfate derivatives: 5, 10-diphenyl-4,9-dimethyl-4,9-diazapyrenium hydrogensulfate (FDAP), 4, 9-dimethyl-4,9-diazapyrenium hydrogensulfate (GDAP) and 2,4,7, 9-tetramethyl-4,9-diazapyrenium hydrogensulfate (MDAP) and tested their biological effects in vitro on four human tumor cell lines (SKBr3: breast carcinoma, HeLa: cervical carcinoma, CaCo2: colon carcinoma and SW620: poorly differentiated cells from lymph node metastasis of colon carcinoma). Cytotoxic effects on cell growth and viability were determined using tetrazolium dye (MTT) assay. DNA synthesis and proliferation of treated cells were studied by the [(3)H]-thymidine incorporation test. DNA fragmentation was analyzed by agarose gel electrophoresis. The growth inhibitory effect was cell-specific and dose-dependent. The most pronounced antiproliferative effect was observed on SKBr3 cells for FDAP (10(-5) M) 91.8%, for MDAP (10(-5) M) 85.3% and on SW620 cells for GDAP (10(-5) M) 65.3%. The DNA ladder fragmentation of treated HeLa and SKBr3 cells, as a hallmark of apoptosis, was observed. Based on specific DNA fragmentation, morphological changes (reduced cell volume, round cell shape, condensed chromatin) and growth inhibition of treated human tumor cells we conclude that tested substances induced apoptotic cell death.

Antineoplastic Agents↗

The influence of Helicobacter pylori infection on gastrin and somatostatin values present in serum.

BACKGROUND/AIMS: Recent studies on the role of Helicobacter pylori in pathogenesis of duodenal ulcers have focused on the mechanism by which H. pylori infections causes exaggerated gastrin release. METHODOLOGY: We compared the gastrin and somatostatin serum values between two groups of patients; 37 H. pylori-positive ones and 29 H. pylori-negative ones. We applied radioimmunoassay technique to determine the gastrin and somatostatin values in serum. H. pylori was confirmed by urease test and by histopathological color according to Giemsa. RESULTS: The level of gastrin in the serum of Helicobacter pylori-positive patients with chronic gastritis were significantly higher in relation to H. pylori-negative patients. The somatostatin concentration in the sera of H. pylori-positive patients with duodenal ulcer (16.27 +/- 9.49 pg/mL) were less in comparison with those without duodenal ulcer (23.25 +/- 13.59 pg/mL). CONCLUSIONS: The results suggest that H. pylori infection suppresses the somatostatin secretion.

Adult↗

Antineoplastic activity of novel N-1-sulfonypyrimidine derivatives.

We evaluated the potential activity of novel N-1-sulfonyl derivatives of pyrimidine bases uracil and cytosine on pancreatic carcinoma cells (MIAPaCa2), colon carcinomas cells (HT-29, CaCo2), cervical carcinoma cells (HeLa) and poorly-differentiated cells from lymph node metastasis of colon carcinoma (SW-620). The cytotoxicity of N-1-sulfonylpyrimidine derivatives was analyzed with the MTT cell survival assay and their antiproliferative activity was measured via radioactive precursors incorporation assay. The N-1-sulfonylpyrimidine derivatives affected the growth of all examined cell lines at concentrations of 10(-8)-10(-5) M, by 25-70%. Growth inhibition depended on the tumor cell line type and the concentration of investigated compounds. The compounds 2, 4, 7, 8 and 9 inhibited DNA, RNA and protein synthesis in CaCo2, MIAPaCa2 and HeLa cells. The exposure of tumor cells in vitro to compounds 2, 4, 7, 8, 9, 10 and 11, at the 10(-6) M concentration, caused both morphological (condensation of chromatin, cell shrinkage), as well as biochemical changes (ladder pattern of DNA fragmentation and exposure of phosphatidylserine on outer lipid bilayer plasma membrane) characteristic of apoptosis. After 24 hours of the N-1-sulfonylpyrimidine derivative application, the p53 oncoprotein expression could not be detected by immunocytochemical analysis. On the basis of present results it can be concluded that novel N-1-sulfonylpyrimidine derivatives are promising antitumor agents with a strong antiproliferative activity and an ability to induce apoptosis in treated tumor cells.

Antineoplastic Agents↗

[Endemic goiter in Croatia].

In the early nineties, 40 years after the introduction of iodine prophylaxis in Croatia (10 mg KI/kg salt), a nationwide study was initiated with the aim to determine the real prevalence of goiter in the country. A total of 2436 schoolchildren of both sexes, aged 7-15 years, were included in the study. Investigations were designed in a way to cover most of geographical regions in Croatia and subjects were randomly selected. The prevalence of goiter in schoolchildren was assessed by palpation and in part by ultrasonography of the neck. At the same time urinary iodine excretion was measured and potassium iodide content in salt samples was determined. The results revealed the persistence of mild endemic goiter in the inland parts of Croatia with the prevalence of 6-29% in the age group 7-11 years and 10-43% among the age group 12-15 years. The overall goiter prevalence in schoolchildren in Croatia fluctuates from 8% to 35%. The urinary iodine excretion in Zagreb varied from 1.6 to 24.4 micrograms/dL with a median of 9.0, while in 14% it was below 5 micrograms/dL. The urinary iodine excretion in Samobor varied between 0.5 and 19 micrograms/dL with a median of 7.4 micrograms/dL, while in 30% it was below 5 micrograms/dL. Examination of salt from all three salt plants in Croatia showed iodine contents between 0.0 and 12.73 mg/kg with the average value of 5.39 mg/kg. Such prevalence, most probably due to less than optimum iodine intake, is unlikely to change until potassium iodide content of salt is increased from its present level of 10 mg of KI per kg of salt, with concomitant stricter observance of legal regulations.

Adolescent↗

4,9-diazapyrenium dications induce apoptosis in human tumor cells.

We investigated the antiproliferative effects of two planar 4,9-diazapyrenium hydrogenasulphates against human malignant MiaPaCa 2 (pancreatic carcinoma), Hep 2 (laryngeal carcinoma) and human normal fibroblasts (WI 38) cell lines. The tested compounds were very potent in inhibiting the growth of the treated cell lines. Treatment with molar concentrations of the substances (10(-4)-10(-7) M) caused growth inhibition by more than 50%. The morphological changes of treated cells were also observed. Cells became smaller, with condensed chromatin and fragmented nuclei, the characteristics of dying cells. The identification of DNA-fragmentation and the appearance of chromatin aggregation leads us to assume the tested substances induced apoptosis of the investigated tumor cell lines.

Apoptosis↗