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tom 57
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nr 12
15-24
EN
Expression of cyclooxygenase-2 (COX-2) is involved in the chronic inflammation-related development of Barrett’s adenocarcinoma and the use of selective COX-2 inhibitors (coxibs) might provide new chemoprevention strategy for Barrett’s adenocarcinoma (BA). Despite an excellent gastrointestinal (GI) safety profile of coxibs, their use is limited because of the possible cardiovascular complications. The coupling of NSAIDs with a NO-donating moiety has led to the birth of a new class of anti-inflammatory drugs, called the COX-inhibiting nitric oxide donators (CINODs). The member of this group, NO-aspirin (NO-ASA) retains the anti-inflammatory properties of traditional aspirin (ASA), but the release of NO accounts for anti-thromboembolic effect and better GI safety profile. The role of NO-ASA in the prevention of Barrett’s adenocarcinoma (BA) has not been studied so far. Therefore, the aim of the present study was: 1) to analyse the expression of COX-2 in the biopsies obtained from BE; 2) to compare the effect of NO-ASA with that of ASA on proliferation rate in Barrett’s adenocarcinoma cell line (OE-33 cells); 3) to determine the effect of both compounds on the apoptosis rate using FACS analysis and expression of 32-kDa procaspase-3 and active proapoptotic 20-kDa caspase-3 in OE-33 cell line. The expression of COX-2 was assessed in biopsies obtained from the Barrett’s mucosa and normal squamous epithelial esophageal mucosa from 20 BE patients by RT-PCR and Western blot analysis, respectively. The BA cell line (OE-33) was incubated with NO-ASA or ASA (10-1000µM). The cell proliferation and apoptosis rate was measured by BrdU and FACS-analysis, respectively. The expression of caspase-3 (active and inactive form) was analyzed by Western blot. In Barrett’s mucosa a significant up-regulation of COX-2 was observed. Compared with traditional ASA, NO-ASA caused a significantly stronger induction of apoptosis (dose-dependently). Inhibition of cell proliferation in OE-33 cells observed under NO-ASA treatment was due to the apoptosis induction. The increase in apoptotic rate was accompanied by the upregulation of active 20-kDa caspase-3. At the highest concentration (1000µM), a necrotic death of OE-33 cells was observed under NO-ASA treatment. We conclude that: NO-ASA caused induction of apoptosis in BA cell line and slight growth inhibition. These results indicate that this compound may represent a promising chemopreventive agent for Barrett’s adenocarcinoma.
EN
The aim of the study was to determine whether treatment with recommended doses of meloxicam or flunixin had an effect on the apoptosis of peripheral blood T lymphocytes in calves. The study was carried out on 4-5 months old calves (n = 24, 8 per group). Experimental animals were injected subcutaneously with a single dose of 0.5 mg . kg-1 of meloxicam or intravenously with 3 doses of 2.2 mg . kg-1 day-1 of flunixin. The non-treatment animals served as control. Blood samples were taken at day 0 and at days 1, 2, 3, 5, 7 and 14 after the first NSAIDs injection. Apoptosis was determined by flow cytometry using Annexin V-PE/7-AAD staining. The kinetic analysis of apoptosis in the total lymphocyte population, as well as in the CD4+ and CD8+ subsets did not reveal significant differences in the frequency of early apoptotic cells between control and experimental groups throughout the period studied. Although, 24 h after administration of the first dose of NSAIDs, late-stage apoptosis/necrosis was significantly increased in the total lymphocyte population (the meloxicam group), as well as in the CD4+ (the meloxicam group and the flunixin group) and CD8+ (the flunixin group) subsets of T cells. However, this disturbance was transient, relatively poorly expressed and, thus, unlikely to be of clinical significance. Our results indicate that the use of meloxicam or flunixin in accordance with the recommended dosage regimen in cattle do not have a clinically significant influence on apoptosis of peripheral blood T cells.
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tom 13
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nr 3
353-365
EN
The ubiquitin-proteasome system is responsible for the degradation of most intracellular proteins, including those that control cell cycle progression, apoptosis, signal transduction and the NF-κB transcriptional pathway. Aberrations in the ubiquitin-proteasome system underlie the pathogenesis of many human diseases, so both the ubiquitin-conjugating system and the 20S proteasome are important targets for drug discovery. This article presents a few of the most important examples of the small molecule inhibitors and modulators targeting the ubiquitin-proteasome system, their mode of action, and their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases.
EN
Rhodiola kirilowii (RK) roots and rhizomes are traditionally used in China as a tonic, adaptogen, antimicrobial and anti-inflammatory drug. The aim of this work was to study the in vivo and in vitro effects of aqueous and 50% hydro-alcoholic extracts of RK rhizomes on some parameters of cellular immunity in H-2d mice and rats. We show for the first time that in vitro both extracts stimulated granulocyte activity and increased lymphocyte response to mitogens, and in vivo they enhanced the ability of lymphocytes derived from parental strain mice fed R. kirilowii aqueous and hydro-alcoholic extracts, to induce local cutaneous graft-versus-host reaction (GVH) in F1 hybrids. Conclusion: Rhodiola kirilowii extracts are cellular immunity enhancers.
EN
Rhodiola quadrifida (Rq) roots and rhizomes are traditionally used in Asia as a tonic, adaptogen, antidepressant and anti-inflammatory drug. The aim of this work was to study the in vivo effect of aqueous and 50% hydro-alcoholic extracts of Rq rhizomes on some parameters of cellular immunity in mice and rats. The metabolic activity of blood phagocyting cells was determined based on the measurement of intracellular respiratory burst after stimulation by PMA in RBA test. Potential bactericidal activity of phagocyting cells was determined in isolated blood leukocytes stimulated with killed microorganisms, according to the PKA test. Proliferative response of lymphocytes stimulated by mitogen concanavaline A (ConA) or lipopolysaccharide (LPS) were determined by MTT assay. Both extracts stimulated granulocytes activity in vitro and increased lymphocyte response to mitogens. The ability of parental strain mice lymphocytes to induce local cutaneous graft-ver- sus-host reaction (GVH) in F1 hybrids was stimulated by 50% hydro-alcoholic extract only.
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Content available Paracetamol-inhibitable COX-2
58%
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tom 51
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nr 4,1
EN
Phagocytosis and the release of oxidative products generated by the respira­tory burst have been studied in vitro under the influence of non-steroidal anti-inflammatory drugs: naproxen and ibuprofen, using.phagocytes of periph­eral blood from healthy human donors. Phagocytosis wis monitored by flow cytometry in order to investigate the uptake of propvdium iodide-labelled bacteria (Staphylococcus aureus) by polymorphonuclear leucocytes. In addi­tion, the phagocytic capacity and percentage of killed bacteria was measured in isolated neutrophils using the Pantazis & Kniker method. It was found that naproxen and ibuprofen affect the phagocytic function and hydrogen peroxide production in the examined granulocytes.
EN
Constitutive (COX-1) and inducible (COX-2) cyclooxygenase isoforms have been detected in various mammalian tissues. Their activity is blocked by non-steroidal anti-inflammatory drugs that may induce various side reactions. The aim of the study was to evaluate the effects of DFU, a selective COX-2 inhibitor, on exocrine and endocrine pancreatic function and the immunoexpression of both COX isoforms in maternal and foetal rat pancreases. The compound was administered to pregnant Wistar rats once daily from the 8th to the 21st day of gestation. Glucose level and amylase activity were determined in the maternal sera. Maternal and foetal pancreases were examined histologically. Immunoexpression of COX-1 and COX-2 was also evaluated. Both biochemical parameters, as well as the histological structure of the pancreas were undisturbed in the dams and their foetuses. The maternal glucose level was found to be an important factor for foetal growth. Strong cytoplasmic COX-1 immunostaining was observed in acinar secretory cells, whereas in islets the immune reaction was weak. Endocrine cells also revealed strong cytoplasmic COX-2 staining in the maternal and foetal pancreases. Acinar cells exhibited nuclear reaction, which was strong in the foetal but weak in the maternal pancreases. No differences in COX immunoexpression were found between the DFU-exposed and the control groups in either mothers or foetuses. It should be stressed that DFU administered throughout mid and late pregnancy in rats did not change maternal or foetal pancreatic morphology or immunoexpression of either of the main COX isoforms in the organ.
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