Прегледај по Аутор "Miletic, Natasa"
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- СтавкаDistribution of EGFR SNPs -191C/A and 181946G/A in patients with lung cancer depending on smoking status in the Republic of Srpska, Bosnia and Herzegovina(Balkan Union of Oncology, 2018) Elez-Burnjakovic, Nikolina; Ugrin, Milena; Obradovic, Jasmina; Miletic, Natasa; Racic, Maja; Kulic, Milan; Pavlovic, Sonja; Jurisic, VladimirPurpose: To analyze the frequencies of two single nucleotide polymorphisms (SNPs) of EGFR gene, -191C/A and 181946G/A, among lung cancer patients from the Republic of Srpska, Bosnia and Hercegovina, as well as to assess the association of SNP genotypes with the cancer type and other demographic characteristics of patients, particularly with the smoking status. Methods: This study enrolled 41 lung cancer patients from the territory of Republic Srpska, Bosnia and Herzegovina. Detection EGFR SNPs was performed using PCR-RFLP methodology. PCR was performed on 2720 Thermal Cycler (Applied Biosystems, United States). PCR, as well as RFLP products, were detected by gel electrophoresis. SPSS-17 software (SPSS, Inc.) was used for statistical analyses. Results: There was significantly more male than female smokers in our cohort (p=0.006). In addition, the proportion of smokers was higher among patients with adenocarcinoma in comparison to patients with other lung cancer types (p=0.044). Adenocarcinoma was less common in patients older than 64 years (p=0.035). The wild type homozygous genotype of both SNPs was the most frequent genotype in all the tested demographic groups. Using dominant genetic model for -191C/A SNP, we observed statistically significant association of -191CC genotype and adenocarcinoma (p=0.043) in the subgroup of patients younger than 64 years. Namely, patients younger than 64 years and carriers of -191CC genotype had higher risk (odds ratio/OR=9.6; 95% confidence interval/CI= 0.8477 to 108.7214) for adenocarcinoma than the ones carrying -191CA or -191AA genotype. Conclusions: Patients younger than 64 years and carriers of -191CC genotype have significantly higher risk for adenocarcinoma than carriers of -191CA or -191AA genotype. Further studies on larger cohorts are necessary to evaluate -191C/A SNP as a potential biomarker.
- СтавкаMECHANISM AND CLINICAL IMPORTANCE OF RESPIRATORY FAILURE INDUCED BY ANTICHOLINESTERASES(University of Kragujevac, Faculty of Medical Sciences, Kragujevac, 2017) Ivosevic, Anita; Miletic, Natasa; Vulovic, Maja; Vujkovic, Zoran; Novakovic Bursac, Snjezana; Cetkovic, Slavko S.; Skrbic, Ranko; Stojiljkovic, Milos P.Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. Th ey impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Th eir doses needed for cessation of central respiratory drive are signifi cantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and eff ectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes
- СтавкаTHE IMPORTANCE OF POTASSIUM CHANNELS IN THE MECHANISM OF THE RELAXING EFFECT OF PENTOXIFYLLINE ON ISOLATED RAT UTERI(University of Kragujevac, Faculty of Science, 2013) Milovanovic, Slobodan R.; Kordic-Bojinovic, Jelena; Djordjevic, Stevanka; Drakul, Dragana; Sokolovic, Dragana; Miletic, Natasa; Blagojevic, DuskoBackground. Pentoxifylline is a methylxanthine derivative that is used to treat peripheral vascular disease. One of the mechanisms of action of pentoxifylline is the vasodilatation of blood vessels. Th is study examined the eff ect of increasing pentoxifylline concentrations on the contractility of isolated rat uteri in the presence of a potassium channel antagonist. Methods. Th e uteri were isolated from virgin Wistar rats (180-220 g) and suspended in an isolated organ bath chamber containing De Jalon’s solution and aerated with 95% O2 and 5% CO2. Th e temperature was maintained at 37ºC. Isometric contractions were recorded using an isometric force transducer (Ugo Basile). The preload of the preparation was approximately 1 g. Th e uteri were allowed to contract spontaneously or in the presence of Ca2+ (0.018 and 0.36 mM) and acetylcholine (ACh) and were treated with pentoxifylline. Results. Pentoxifylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity caused by calcium Ca2+ (0.018 mM and 0,36 mM). We showed that the inhibitory eff ects of pentoxifylline depend on the type of muscle contractions activated and that the inhibitory eff ect is signifi cantly stronger for spontaneous rhythmic activity and forin Ca2 -induced contractions of isolated rat uteri+. Th e relaxing eff ect of pentoxifylline depends on the calcium concentration in the medium. Pentoxifylline exerted the weakest relaxant eff ects on contractions induced by acetylcholine. In contrast to methylene blue, tetraethylammonium, or 4-aminopyridine, glibenclamide did not antagonise the relaxing eff ect of pentoxifylline on isolated rat uteri.. Conclusion. Th e results obtained suggest that the mechanism of action of pentoxifylline does not lead to the opening of KATP channels. However, the opening of BKCa and voltage-dependent Ca2+ channels had some role, but to varying degrees, in the mechanism of the relaxing eff ect of pentoxifylline on the spontaneous rhythmic activity and calcium-induced tractions of isolated rat uteri. Our results provide additional confi rmation of the dominance of the NO/cGMP signalling pathway in the mechanism of the relaxing eff ect of pentoxifylline (because the presence of methylene blue signifi cantly antagonised this eff ect) in relation to the opening of potassium channels, especially KATP channels. Th ese results indicate that pentoxifylline could be a potential tocolytic drug.