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Biomedical subjects

D Jandrić

Publications and source records attributed to D Jandrić.

14 recordsLinked to original sources

Effect of Helicobacter pylori eradication on extent of duodenal gastric metaplasia and grade of gastritis.

The extent of the regression of duodenal gastric metaplasia (DGM) after the eradication of Helicobacter pylori infection is controversial. Therefore, we decided to assess the degree of DGM before, sex weeks and one year after H. pylori eradication. 105 consecutive Helicobacter pylori positive patients with endoscopically proven duodenal ulcer, with DGM and Helicobacter pylori infection were recruited for this study. The diagnosis of Helicobacter pylori infection was based on CLO-test and histology, and DGM was assessed on four bulb biopsies taken before, sex weeks and one year after Helicobacter pylori eradication. Histological assessment of Helicobacter pylori associated gastritis was performed according to the Sydney classification. Follow up study on 98 patients before, six weeks and one year after the eradication of Helicobacter pylori showed that the mean extent of DGM did not change significantly after eradication and did not differ when compared with 14 patients with persisting infection. Our results show that the inflammatory process related to Helicobacter pylori does not play the main role in the development of DGM.

Duodenal Ulcer↗

Modulatory effect of 7-thia-8-oxoguanosine on proliferation of rat thymocytes in vitro stimulated with concanavalin A.

7-thia-8-oxoguanosine (immunosine) is a guanosine analogue showing immunostimulatory activity on different components of the immune system, including B lymphocytes, natural killer cells and macrophages. However, little is known about its effect on T-cell functions. In this work it was demonstrated that immunosine at concentrations between 10 microM and 1 mM stimulated proliferation of rat thymocytes in vitro triggered by suboptimal concentrations of concanavalin A (Con A). The effect correlated with increased interleukin 2 (IL-2) production, upregulation of the IL-2 receptor alpha (IL-2Ralpha) expression and decreased apoptosis of thymocytes in comparison to the effect of Con A alone.

Adjuvants, Immunologic↗

A nucleoside analogue, 7-thia-8-oxoguanosine stimulates proliferation of thymocytes in vitro.

7-thia-8-oxoguanosine (immunosine) is a nucleoside analogue with immunoenhancing activity. In this work, its effects on proliferation of thymocytes in vitro were studied. It was found that immunosine stimulated proliferation of thymocytes both of mice and rats. The stimulatory effect depended on antigen presenting cells (APC), since thymocytes depleted of accessory cells did not proliferate to immunosine. In addition, pretreatment of APC with immunosine for 24 h significantly increased proliferation of thymocytes. Immunosine stimulated interleukin 2 (IL-2) production and the expression of activation markers (CD25 and CD71). The upregulation of CD25 (alpha subunit of IL-2R) was detected both on thymocytes and thymic dendritic cells. Proliferation of thymocytes in the presence of immunosine was predominantly mediated by IL-2 since blocking IL-2Ralpha by specific monoclonal antibodies inhibited cell proliferation by 65-85%.

Animals↗

Effect of PAM-2 Cl, HI-6, and HGG-12 in poisoning by tabun and its thiocholine-like analog in the rat.

It has been shown that HI-6 was the most potent oxime so far known in poisoning by sarin, VX , and soman, but its protective effect in tabun poisoning, allegedly due to poor reactivation of inhibited ChE, was much less pronounced. We have found that the thiocholine-like analog of tabun , O-ethyl, N-N- dimethyamino -S-(2-diethylaminoethyl)- thiophosphatemethylsul fomethylate (Ta-S-N+), was very useful in resolving this problem and established the relationship between reactivating and protective effects of PAM-2 Cl, HI-6, and HGG-12 in rats. PAM-2 Cl (protective ratio (PR) = 22.1) and HI-6 (PR = 24.8), combined with atropine, were very effective against Ta-S-N+ poisoning and reactivating inhibited RBC AChE in vitro and rat blood ChE in vivo. The inefficiency of PAM-2 Cl (PR = 1.6) and HI-6 (PR = 2) in tabun poisoning was due to their inadequacy to reactive tabun -inhibited ChEs . The protective effects of HGG-12 in tabun (PR = 2.8) and Ta-S-N+ poisoning (PR = 2.6) were low, and in the absence of any reactivation of inhibited ChEs , have been attributed to its direct pharmacological effects, which were much more potent in the comparison with PAM-2 Cl or HI-6. It is concluded that the reactivation of inhibited ChE is of decisive importance in the efficient protection in poisoning by tabun and other known chemical warfare nerve agents, whereas their direct pharmacological effects are of limited value, allowing survival of animals only against a few LD50s .

Animals↗

Immunosine (7-thia-8-oxoguanosine) acts as a cofactor for proliferation of T cells.

Immunosine (7-thia-8-oxoguanosine) is a novel guanosine analogue showing immunostimulatory activity both in vivo and in vitro. This compound acts on different components of the immune system including B cells, natural killer (NK) cells and antigen-presenting cells (APC). However, its influence on functions of T cells is poorly understood. In this work we studied the effect of immunosine on proliferation of total rat splenocytes and purified T cells triggered by different mitogens and the mechanisms involved. The results demonstrate that immunosine significantly stimulates proliferation of T cells. The effect was dose-dependent and also depended on concentrations of specific stimulators. Maximal stimulation was seen using 250 microM immunosine. The stimulatory effect of immunosine on lymphocyte proliferation triggered by Concanavalin A (Con A) correlated with increased interleukin 2 (IL-2) production and upregulation of the IL-2 receptor alpha (IL-2Ralpha) expression. The dependency of T-cell proliferation on IL-2/IL-2R was confirmed using neutralizing anti-IL-2Ralpha monoclonal antibodies (mAbs). Higher concentrations of immunosine in the presence of optimal concentrations of Con A (5 microg/mL) inhibited proliferation of T cells. A similar stimulatory effect of immunosine on proliferation of purified T cells and IL-2 production was observed using an anti-T-cell receptor (TCR) mAb and a combination of anti-TCR mAb and IL-2. However, the guanosine analogue did not significantly modulate proliferation of T cells triggered by IL-2 alone. When the combination of phorbol myristate acetate (PMA) and ionomycin was used for T-cell stimulation different results were obtained. Under lower cell stimulation immunosine significantly potentiated T-cell proliferation, expression of IL-2Ralpha and IL-2 production. In the presence of suboptimal stimulation the compound stimulated T-cell proliferation and IL-2Ralpha expression, whereas under maximal stimulation an enhancing effect on IL-2 production was seen. Since direct stimulatory effect of immunosine on T-cell growth in culture was rather weak it can be postulated that the compound acts as a cofactor for T-lymphocyte proliferation.

Animals↗

Xylazine, an alpha 2-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro.

In our previous experiments, we demonstrated that xylazine, an alpha 2-adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 microM and 500 microM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 microM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a selective alpha-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor, z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker, partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells.

Adrenergic alpha-2 Receptor Agonists↗