Irena Kostic

Early Cytokine Profile Changes In Interstitial And Necrotic Forms Of Acute Pancreatitis

ABSTRACT Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes. The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1st and 3rd day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP. In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.

Inhibitory effects of selected antiepileptics on spontaneous motility of isolated human oviducts.

ObjectiveSpontaneous motility of the human oviduct is an important factor in the regulation of fertility that can be influenced by a variety of substances. In this study we examined the effects of several antiepileptic drugs on spontaneous contractions of isolated human oviducts.Methods The isolated ampullar and isthmic segments of Fallopian tubes, taken from 34 patients with extensive uterine fibroids, were exposed to carbamazepine, lamotrigine, valproic acid, phenobarbital, diazepam and lorazepam.ResultsCarbamazepine and lamotrigine produced concentration-dependent inhibition of spontaneous contractions of both ampullar and isthmic isolated preparations, while the other investigated substances did not exhibit any effect. The effective concentrations of carbamazepine and lamotrigine fall within the range of their therapeutic serum concentrations.ConclusionWhen choosing antiepileptics for women of reproductive age, the effects of the drug on motility of the Fallopian tubes should also be considered.

Clinical and laboratory parameters associated with death in acute pancreatitis

Introduction. Acute pancreatitis is an inflammatory condition having the significant mortality rate in the case of severe forms of disease. The aim of this study was to investigate putative factors of increased mortality with contradictory prior evidence, and to reveal factors that were insufficiently explored previously. Methods. A prospective cohort study with nested case/control design included all adult patients treated for acute pancreatitis in Clinical Center of Kragujevac, Serbia, during the 3-year period (from October 2011 to December 2014). The cases (n=19) were patients who died, while the controls (n=113) were patients who survived. The associations between putative risk factors and the study outcomes were tested by univariate and multivariate logistic regressions, and expressed as crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). Results. Significant association with the lethal outcome in acute pancreatitis was found for advanced age (adjusted OR 1.12, 95%CI 1.02-1.23), presence of significant comorbidities (adjusted OR 10.62, 95%CI 1.01-111.39), higher interleukin-8 (IL-8) value on third day from onset of symptoms (adjusted OR 1.05, 95%CI 1.02-1.08), use of tramadol and/or morphine (adjusted OR 47.34, 95%CI 3.21-699.08), BISAP score ≥ 3 in the first 24 hours (adjusted OR 48.11, 95%CI 3.14-736.29), and prophylactic use of antibiotics (adjusted OR 0.07, 95%CI 0.01-0.85). Conclusion. Advanced age, significant comorbidities, use of tramadol and/or morphine and more severe disease as assessed by BISAP score can increase the risk for death in acute pancreatitis, while prophylactic use of antibiotics may have a protective role. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Effects of Divalent Cations on Outward Potassium Currents in Leech Retzius Nerve Cells

Abstract The present study examines the effects of divalent metals, cadmium (Cd2+) and manganese (Mn2+), on the outward potassium currents of Retzius cells in the hirudinid leeches Haemopis sanguisuga using conventional two-microelectrode voltageclamp techniques. The outward potassium current is activated by depolarization and plays an important role in determining both the neuronal excitability and action potential duration. A strong inhibition of the fast current and a clear reduction in the late currents of the outward current with 1 mM Cd2+ were obtained, which indicated that both components are sensitive to this metal. Complete blockage of the fast and partial reduction of the slow outward currents was observed after adding 1 mM Mn2+ to the extracellular fluid. These data show that the outward K+ current in leech Retzius nerve cells comprises at least two components: a voltage-dependent K+ current and a Ca2+- activated K+ current. These observations also indicate that Cd2+ is more eff ective than Mn2+ in blocking ion fl ow through these channels and that suppressing Ca2+-activated K+ outward currents can prolong the action potential in nerve cells.

Blood cells in thyroid cancer patients: a possible influence of apoptosis

Abstract The side effects of radioactive iodine (131-I) treatment of differentiated thyroid cancer (DTC) patients include reduction of peripheral blood cell counts. The aim of this study was to analyze some potential changes in blood cell counts of DTC patients after 131-I therapy, especially CD3-positive, CD19-positive, and CD56-positive peripheral blood lymphocytes (PBL), as well as the possible role of apoptosis in selected lymphocyte populations. The study group included 24 thyroid cancer patients and 24 control subjects. Peripheral blood samples from patients and controls were analyzed using 5-color flow cytometry. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. There was a statistically significant decrease of all blood cells after the 131-I therapy. The CD19+ B lymphocyte population was the most affected (5.82 ± 3.21% before therapy vs. 3.93 ± 2.60% after therapy, p = 0.008). This decrease was correlated with the degree of apoptosis of peripheral blood lymphocytes (Spearman’s r = 0.563, p =0.013). We concluded that 131-I therapy of DTC patients led to a decrease of all peripheral blood cells, especially CD19+ B lymphocytes. This directly correlated with apoptosis of PBLs, indicating that radiation damage to B cells leads to subsequent elimination by apoptosis.

Analysis of Treatment-Related Factors Affecting Mortality in Patients with Severe Necrotizing Acute Pancreatitis

Summary The aim of the paper was to determine the factors related to the initial therapy that may contribute to death from severe necrotizing acute pancreatitis and to analyze their clinical importance as well as possible additive effects. A retrospective case-control study included all adult patients treated for severe necrotizing acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the five-year period (2006-2010.). The cases (n = 41) were patients who died, while the controls (n = 69) were participants who survived. In order to estimate the relationship between potential risk factors and observed outcome, crude and adjusted odds ratios (OR) with 95 % confidence intervals (CI) were calculated in logistic regression models. Significant association with observed outcome was shown for the use of gelatin and/or hydroxyethyl starch (adjusted OR 12.555; 95 % CI 1.150-137.005), use of albumin (adjusted OR 27.973; 95 % CI 1.741-449.373), use of octreotide (adjusted OR 16.069; 95 % CI 1.072-240.821) and avoiding of enteral feeding (adjusted OR 3.933; 95 % CI 1.118-13.829), while the use of nonsteroidal anti-inflammatory drugs had protective role (adjusted OR 0.057; 95 % CI 0.004-0.805). The risk of death in patients with predicted severe necrotizing acute pancreatitis could be reduced with avoidance of treatment with colloid solutions, albumin and octreotide, as well as with an early introduction of oral/enteral nutrition and use of nonsteroidal anti-inflammatory drugs.

Protein and Lipid Concentrations in Patients with Differentiated Thyroid Cancer Treated with Radioactive Iodine-131 / Koncentracija Proteina I Lipida Kod Pacijenata Sa Diferentovanim Karcinomom Štitaste Žlezde Koji Su Lečeni Radioaktivnim Jodom-131

ABSTRACT Short-term, overt hypothyroidism in patients with differentiated thyroid cancer (DTC) before radioiodine (131-I) therapy might be accompanied by a number of metabolic changes, including altered protein and lipid metabolism. Protein concentrations and their relationship to lipids in the serum of DTC patients have not been fully elucidated. The aim of our study was to evaluate the protein and lipid concentrations in 24 DTC patients before and 3 and 7 days after 131-I therapy compared with those of 20 healthy control subjects. After radioiodine therapy, the mean protein concentration (78.71 ± 6.71 g/L vs. 87.16 ± 6.04 g/L; p = 0.003) and cholesterol level (8.12 ± 2.13 mmol/L vs. 8.84 ± 2.09 mmol/L; p = 0.001) were lower 3 days after therapy; this persisted up to 7 days after therapy, whereas triglyceride concentrations were higher 3 days after therapy (2.44 ± 1.07 mmol/L vs. 2.26 ± 1.08 mmol/L; p = 0.041) and returned towards the pretreatment values at 7 days after 131-I therapy. There was an indirect correlation between the protein and triglyceride concentrations 3 days after 131-I therapy in patients over 50 years old (Spearman’s r = - 0.583, p = 0.048) but not in patients under 50 years old (Pearson’s r = - 0.277, p = 0.384). Radioiodine therapy of DTC patients led to decreased serum protein and cholesterol concentrations, accompanied by increased triglyceride levels; these changes were especially evident in older subjects with metastases. SAŽETAK Prolazna, manifestna hipotireoza koja se javlja kod pacijenata sa diferentovanim karcinomom štitaste žlezde (DTC) pre terapije radioaktivnim jodom (131-I) može biti udružena sa brojnim metaboličkim promenama, uključujući i promene u metabolizmu proteina i lipida. Koncentracija proteina i njihov odnos sa lipidima u serumu pacijenata sa DTC nakon terapije 131-I nedovoljno su ispitani. Cilj našeg istraživanja bio je da se ispita serumska koncentracija proteina i lipida kod pacijenata sa DTC pre, kao i tri i sedam dana posle terapije 131-I. Studijom je obuhvaćeno 24 DTC pacijenata i 20 zdravih ispitanika. Pokazano je značajno, progresivno smanjenje koncentracije proteina (78.71±6.71 g/L vs. 87.16±6.04 g/L; p=0.003) i holesterola (8.12±2.13 mmol/L vs. 8.84±2.09 mmol/L; p=0.001) tri dana nakon terapije 131-I, uz statistički značajno povećanje koncentracije triglicerida tri dana nakon terapije (2.44±1.07 mmol/L vs. 2.26±1.08 mmol/L; p=0.041) i povratkom na preterapijske vrednosti 7 dana posle terapije. Pri tom, indirektna korelacija između koncentracije proteina i triglicerida tri dana posle 131-I pokazana je u grupi pacijenata starijih od 50 godina (Spearman r=- 0.583, p=0.048), što nije bio slučaj sa ispitanicima mlađim od 50 godina (Pearson r=- 0.277, p=0.384). U zaključku, terapija radioaktivnim jodom prouzrokuje smanjenje koncentracije serumskih proteina i holesterola, koje je udruženo sa povećanjem koncentracije triglicerida i posebno je izraženo kod starijih pacijenata sa metastazama.

10.5937/mckg48-2741 = New pharmacological strategies in the treatment of non-small cell lung cancer

According to the number of deaths lung cancer is the leading cancer type, and non-small cell lung carcinoma (NSCLC) is the most frequent subtype. Because of high NSCLC morbidity the aim of this paper is to discuss the appearance of new pharmacological possibilities in the lung cancer therapy. In the research field of new drugs there are two approaches that differ from the standard chemotherapy. According to one approach targeted therapy against specific molecules in the cancer cells is considered, like inhibitors of growth factors, or inhibitors of cell signalling (e.g. tyrosine kinase inhibitors, serine-threonine inhibitors), while on the other hand, drugs that could induce immune system in order to destroy lung cancer (like inhibitors of programmed death receptors, their ligands, or MAGE-A3 antagonists) are on the way to be discovered. Some of these drugs are approved by the U.S. Food and Drug Administration, while the others are in the first phases of clinical trials.