Browsing by Author "Simić, Tatjana (6602094386)"

Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the pro oxi dant/ antioxidant balance in epi lep sy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with la mo trigine, carbamazepine and valproic acid. Methods: Byproducts of oxidative damage to proteins (reactive carbonyl derivatives, RCD and protein thiol groups, PSH), lipids (urinary isoprostanes, 8-epi-PGF2α) and DNA (urinary 8-hydroxy-2'-deoxyguanosine, 8-OHdG), as well as the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in 60 patients with newly diagnosed seizure (at illness onset and after 6 months of treatment with lamotrigine, carbamazepine or valproic acid) and in 20 healthy controls. Results: In patients with epilepsy, RCD, urinary 8-epi-PGF2α and 8-OHdG, together with SOD and GPX activities were significantly increased, while P-SH were only slightly decreased. After 6 months of treatment with AEDs, a decrease was observed in RCD, urinary 8-epi-PGF2α and 8-OHdG to values slightly higher or similar to the control, while P-SH remained unchanged. A decrease was also observed in SOD and GPX activities, although they remained significantly in creased compared to controls. Conclusions: The results of this study have shown that treatments with lamotrigine, carbamazepine and valproic acid affect the prooxidant/antioxidant balance in patients with epi lepsy.

Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the pro oxi dant/ antioxidant balance in epi lep sy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with la mo trigine, carbamazepine and valproic acid. Methods: Byproducts of oxidative damage to proteins (reactive carbonyl derivatives, RCD and protein thiol groups, PSH), lipids (urinary isoprostanes, 8-epi-PGF2α) and DNA (urinary 8-hydroxy-2'-deoxyguanosine, 8-OHdG), as well as the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in 60 patients with newly diagnosed seizure (at illness onset and after 6 months of treatment with lamotrigine, carbamazepine or valproic acid) and in 20 healthy controls. Results: In patients with epilepsy, RCD, urinary 8-epi-PGF2α and 8-OHdG, together with SOD and GPX activities were significantly increased, while P-SH were only slightly decreased. After 6 months of treatment with AEDs, a decrease was observed in RCD, urinary 8-epi-PGF2α and 8-OHdG to values slightly higher or similar to the control, while P-SH remained unchanged. A decrease was also observed in SOD and GPX activities, although they remained significantly in creased compared to controls. Conclusions: The results of this study have shown that treatments with lamotrigine, carbamazepine and valproic acid affect the prooxidant/antioxidant balance in patients with epi lepsy.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a result of interplay between psychological, immune, neurological and genetic factors, manifested by variety of urological, as well as brain-related symptoms. However, its relation with brain excitability has not been addressed. herefore, our aim was to assess susceptibility to seizures in rats with CP/CPPS. We induced CP/CPPS in adult rats by intraprostatic injection of 3% λ-carrageenan. Sham operated rats served as controls (0.9% NaCl, Sham). On day 7 upon injection, rats were treated with lindane (4 mg/kg) and observed for convulsive behavior (seizure incidence, latency and severity) and EEG manifestations (number and duration of ictal periods). Interleukin levels (IL-1β and IL-6) were measured in prostate, hippocampus, thalamus and cerebral cortex. Scrotal skin mechanical pain thresholds were determined and prostates were histologically evaluated. Animals with CP/CPPS showed significantly higher incidence, decreased latency time and augmented severity of lindane-induced seizures compared with Sham group. EEG revealed increased number of ictal periods in CP/CPPS rats. Higher levels of IL-1β and IL-6 were determined in the thalamus and cortex in CP/CPPS animals vs. Sham. IL-1β level was higher and IL-6 was lower in prostates from CP/CPPS animals comparing to Sham. CP/CPPS development was verified by histological findings of nonbacterial inflammation in the prostates, as well as by significantly decreased scrotal pain threshold in CP/CPPS animals. On the basis of this research, we concluded that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with increased level of IL-1β and IL-6 in the cortex and thalamus. © 2019 Elsevier B.V.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a result of interplay between psychological, immune, neurological and genetic factors, manifested by variety of urological, as well as brain-related symptoms. However, its relation with brain excitability has not been addressed. herefore, our aim was to assess susceptibility to seizures in rats with CP/CPPS. We induced CP/CPPS in adult rats by intraprostatic injection of 3% λ-carrageenan. Sham operated rats served as controls (0.9% NaCl, Sham). On day 7 upon injection, rats were treated with lindane (4 mg/kg) and observed for convulsive behavior (seizure incidence, latency and severity) and EEG manifestations (number and duration of ictal periods). Interleukin levels (IL-1β and IL-6) were measured in prostate, hippocampus, thalamus and cerebral cortex. Scrotal skin mechanical pain thresholds were determined and prostates were histologically evaluated. Animals with CP/CPPS showed significantly higher incidence, decreased latency time and augmented severity of lindane-induced seizures compared with Sham group. EEG revealed increased number of ictal periods in CP/CPPS rats. Higher levels of IL-1β and IL-6 were determined in the thalamus and cortex in CP/CPPS animals vs. Sham. IL-1β level was higher and IL-6 was lower in prostates from CP/CPPS animals comparing to Sham. CP/CPPS development was verified by histological findings of nonbacterial inflammation in the prostates, as well as by significantly decreased scrotal pain threshold in CP/CPPS animals. On the basis of this research, we concluded that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with increased level of IL-1β and IL-6 in the cortex and thalamus. © 2019 Elsevier B.V.

Glutathione S-transferase (GST) isoenzyme profiles of non-tumor and tumor renal tissue of patients suffering from renal cell carcinoma (RCC) of the clear cell type were determined and compared to those of normal renal tissue. GST isoenzyme(s) were first separated on the basis of their affinity to glutathione sepharose 4B affinity column. Affinity-bound GSTs were further purified by anionic and cationic chromatofocusing. The results presented in this study show that non-tumor tissue distant from renal tumors and renal tumors have lower specific GST activity and a different isoenzyme profile than normal human kidney. Purification of normal kidney GSTs by affinity chromatography revealed the presence of two GST fractions: flow-through GST without affinity for glutathione affinity resin and GST fraction tightly bound to affinity matrix. In non-tumor kidney tissue of RCC patients, substantially less flow-through GST fraction was found, whereas renal tumors did not express flow-through GST at all. Isoelectric chromato-focusing indicated smaller numbers of GST isoenzymes in non-tumor and tumor kidney regions, with anionic forms dominating. It could be speculated that decreased expression of cationic GST isoenzymes (corresponding to class a) in non-tumor kidney tissue of RCC patients might be responsible for differences in sensitivity to specific carcinogens. The observations that RCCs are devoid of affinity flow-through GST and have small number of isoenzymes are further proof of low-level GST expression in RCC. © Springer-Verlag 2003.

The aim of the study was to evaluate high-sensitivity C-reactive protein (hs-CRP) and fibrinogen in non-obese normoinsulinemic adolescent girls with polycystic ovary syndrome (PCOS) and their relationship with anthropometric and lipid parameters. The study comprised a total of 26 adolescent girls newly diagnosed with PCOS and 12 healthy controls with regular ovulatory menstrual cycles. The concentration of hs-CRP, fibrinogen, anthropometric measurements, and biochemical and hormonal testing were assessed. PCOS adolescent girls had significantly higher levels of hs-CRP and fibrinogen compared to healthy controls. In univariate regression analysis, statistically significant associations of hs-CRP and fibrinogen levels of PCOS patients have been shown with body mass index (BMI), waist circumference (WC), hip circumference (HC) and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio, while hs-CRP levels were also associated with cholesterol and LDL. In the multivariate regression model, we found that hs-CRP levels were predicted by BMI (β=0.541, p<0.001) and LDL (β=0.507, p=0.014), while fibrinogen levels were predicted by BMI (β=0.449, p=0.004). We have shown an association of proinflammatory indices hs-CRP and fibrinogen with anthropometric and lipid parameters of adolescent women with PCOS. The inflammatory markers might be useful in monitoring normal-weight adolescent women with PCOS in an effort to timely prevent unfavorable changes in body mass and lipid profile. © 2018 2018 Walter de Gruyter GmbH, Berlin/Boston.

The aim of the study was to evaluate high-sensitivity C-reactive protein (hs-CRP) and fibrinogen in non-obese normoinsulinemic adolescent girls with polycystic ovary syndrome (PCOS) and their relationship with anthropometric and lipid parameters. The study comprised a total of 26 adolescent girls newly diagnosed with PCOS and 12 healthy controls with regular ovulatory menstrual cycles. The concentration of hs-CRP, fibrinogen, anthropometric measurements, and biochemical and hormonal testing were assessed. PCOS adolescent girls had significantly higher levels of hs-CRP and fibrinogen compared to healthy controls. In univariate regression analysis, statistically significant associations of hs-CRP and fibrinogen levels of PCOS patients have been shown with body mass index (BMI), waist circumference (WC), hip circumference (HC) and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio, while hs-CRP levels were also associated with cholesterol and LDL. In the multivariate regression model, we found that hs-CRP levels were predicted by BMI (β=0.541, p<0.001) and LDL (β=0.507, p=0.014), while fibrinogen levels were predicted by BMI (β=0.449, p=0.004). We have shown an association of proinflammatory indices hs-CRP and fibrinogen with anthropometric and lipid parameters of adolescent women with PCOS. The inflammatory markers might be useful in monitoring normal-weight adolescent women with PCOS in an effort to timely prevent unfavorable changes in body mass and lipid profile. © 2018 2018 Walter de Gruyter GmbH, Berlin/Boston.

Exposure to potential carcinogens is among the etiological factors for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. RCC is very resistant, while TCC exhibits a high recurrence rate and multifocality. Cytosolic glutathione S-transferases (GST) are a superfamily of enzymes which protect normal cells by catalyzing conjugation reactions between electrophylic compounds, including carcinogens, and glutathione. Some GST enzymes posses hydroperoxidase activity. The most well characterized classes have been named Alpha (GSTA), Mu (GSTM), Pi (GSTP) and Theta (GSTT) and each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, among which GSTM1-null and GSTT1-null confer impaired catalytic activity. Individuals with the GSTM1-null genotype carry a substantially higher risk for bladder carcinogenesis. The effects of glutathione S-transferase T1 polymorphism on the increased susceptibility to RCC and TCC of urinary bladder depend on the presence of specific chemical exposures to compounds metabolized via the GSTT1-1 pathway. In the process of kidney cancerisation expression of GST alpha isoenzymes tends to decrease, consequently favoring a prooxidant environment necessary for the growth of RCC. GST pi enzyme activities are generally retained in RCC and might contribute to the chemotherapy resistance of RCC. In the malignant phenotype of TCC of the urinary bladder up regulation of various GST classes occurs. Up regulation of GSTT1-1 and GSTP1-1 might have important consequences on the tumor growth, by providing a reduced environment and inhibition of apoptotic pathways.

Exposure to potential carcinogens is among the etiological factors for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. RCC is very resistant, while TCC exhibits a high recurrence rate and multifocality. Cytosolic glutathione S-transferases (GST) are a superfamily of enzymes which protect normal cells by catalyzing conjugation reactions between electrophylic compounds, including carcinogens, and glutathione. Some GST enzymes posses hydroperoxidase activity. The most well characterized classes have been named Alpha (GSTA), Mu (GSTM), Pi (GSTP) and Theta (GSTT) and each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, among which GSTM1-null and GSTT1-null confer impaired catalytic activity. Individuals with the GSTM1-null genotype carry a substantially higher risk for bladder carcinogenesis. The effects of glutathione S-transferase T1 polymorphism on the increased susceptibility to RCC and TCC of urinary bladder depend on the presence of specific chemical exposures to compounds metabolized via the GSTT1-1 pathway. In the process of kidney cancerisation expression of GST alpha isoenzymes tends to decrease, consequently favoring a prooxidant environment necessary for the growth of RCC. GST pi enzyme activities are generally retained in RCC and might contribute to the chemotherapy resistance of RCC. In the malignant phenotype of TCC of the urinary bladder up regulation of various GST classes occurs. Up regulation of GSTT1-1 and GSTP1-1 might have important consequences on the tumor growth, by providing a reduced environment and inhibition of apoptotic pathways.

Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed subjects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active genotype is protective against RCC, whereas a GSTT1 active genotype increases RCC risk in occupationally exposed subjects.

Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed subjects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active genotype is protective against RCC, whereas a GSTT1 active genotype increases RCC risk in occupationally exposed subjects.

The deleterious effects of free radicals in acute myocardial ischaemia/reperfusion are rather well known. However, the possibility that thrombolysis positively affects the recovery of blood antioxidant capacity in the later postinfarction period, and thus contributes to the better overall outcome of these patients, has not yet been investigated. We followed the time course of erythrocyte antioxidant activity in 45 patients with first acute myocardial infarction (AMI), who were treated with streptokinase. Success of thrombolysis was evaluated by noninvasive clinical signs of reperfusion using continuous vector cardiography. The patients were divided into two groups according to successful or unsuccessful reperfusion. The control group consisted of 24 healthy subjects. Glutathione peroxidase (GPX) and superoxide dismutase (SOD) were determined immediately after admittance to the hospital (0 hours) and after subsequent thrombolytic therapy (1.5, 6, 12, and 24 hours after initiation of infusion of streptokinase), and 2, 4, and 8 days after AMI. Patients with AMI had decreased antioxidant enzyme activity at the time of admittance to the hospital, showing that the oxidative/antioxidative balance is disturbed early during the ischemic phase of AMI. In AMI patients without successful reperfusion, erythrocyte antioxidant enzyme activity remains low during the postinfarction period of 7 days. It can be concluded that prolonged ischemia reduces antioxidant enzyme activity. AMI patients with successful reperfusion have a significant rise in the activity of antioxidant enzymes within the first hours after thrombolysis, followed by a decrease until the third postinfarction day. During the subsequent postinfarction period, erythrocyte antioxidant activity gradually recovered and reached control levels. These beneficial effects of reperfusion on erythrocyte antioxidant status might contribute to the better overall prognosis of these patients. Copyright © 2004 by the Japanese Heart Journal.

Time-dependent alterations in glutathione (GSH) concentration and the activities of several key enzymes of GSH metabolism were studied in a rat model of experimental Fanconi syndrome induced by i.p. injection of sodium maleate (400 mg/kg BW). The changes in the parameters tested were monitored 0, 2, 4, and 12 h after sodium maleate administration. A significant decrease in renal GSH level was observed 2 and 4 h after sodium maleate treatment (27% and 38% of control values, respectively). The renal GSH depletion did not appear to be due to the decreased production rate or to an increased degradation of the tripeptide. This suggestion is based on the findings that the activities of the GSH synthesis (γ-glutamyl cysteine synthetase and glutathione reductase) and those of the catabolic pathways (γ-glutamyl transpeptidase) were unaltered at the same time points. The unchanged activity of γ-glutamyl transpeptidase also suggests preserved luminal membrane integrity in experimental Fanconi syndrome. The decreased activity of glutathione peroxidase, which utilizes GSH as a cosubstrate in the course of inactivation of free radicals, in the first hours after treatment could facilitate lipid peroxidation reactions in this model of acute renal failure. The observed changes in all parameters tested were transient, with recovery to baseline levels in a period of 12 h after sodium maleate administration. At the same time a pronounced functional impairment still existed. The beneficial effect of fast recovery of renal GSH level on the functional and morphological restitution in experimental Fanconi syndrome is suggested.