Papers by Dusica Pavlovic
Physiological Research, 2011
Pneumatic tourniquets are widely used in pediatric extremity surgery to provide a bloodless field... more Pneumatic tourniquets are widely used in pediatric extremity surgery to provide a bloodless field and facilitate dissection. This prospective study was carried out to examine possible effect of different anesthesia techniques on oxidative stress and endothelial dysfunction connected with ischemia-reperfusion injury during extremity operations at children's age. Patients were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples for determination of the malondialdehyde in plasma and erythrocytes, protein carbonyl groups concentration as well as plasma nitrites and nitrates level and xanthine oxidase activity were obtained at four time points: before peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release, 5 and 20 min after tourniquet release. This study demonstrates that...
Acta Facultatis Medicae Naissensis, 2018
Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymo... more Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with erosive arthritis and rapid radiological progression of the disease. The examined group included 131 patients with early RA. Using the PCR-RFLP method, the TNF-Alpha-308 G/A gene polymorphism was determined for all patients. In relation to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). Based on the presence of the destructive changes in joints found in the initial radiographs, the findings were classified as erosive and non-erosive RA. Radiological progression was assessed on the basis of the annual change in the Larsen score – LS (0-200). Group A comprised 62 (47.33%) patients, while group G comprised 69 (52.67%) patients. The presence of cysts and erosions in subgroups A and G was compared before the start of the methotrexate therapy. It ...
Medicina, 2019
Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the mo... more Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter meth...
Medicina, 2019
Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the mo... more Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter meth...
Bratislava Medical Journal, 2012
Diazepam, a peripheral-type benzodiazepine receptor ligand, is widely used as a therapeutic agent... more Diazepam, a peripheral-type benzodiazepine receptor ligand, is widely used as a therapeutic agent. On the other hand, peripheral-type benzodiazepines have been shown to induce apoptosis in different immune cell types. In this study, we examined the possible protective role of vitamin C in diazepam-induced apoptosis and evaluated the cellular content of glutathione during this process. Rat thymocytes were incubated for 24 hours with diazepam and increasing concentrations of vitamin C or with diazepam alone. The exposure to diazepam resulted in an increase in apoptotic cell death and decrease in glutathione content in rat thymocytes. Vitamin C was effective in ameliorating the effect of diazepam in rat thymocytes by decreasing the proportion of apoptotic cells and increasing the cellular content of glutathione. These results suggest that vitamin C reduced the diazepam-induced apoptosis in rat thymocytes by restoring the cellular content of glutathione, which may be useful in preventing the diazepam-induced immunosupression (Tab. 1, Fig. 1, Ref. 31).
Renal Failure, 2012
Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the mammalian kidney ... more Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the mammalian kidney is a major target of Cd-induced toxicity. We analyzed the effects of cadmium exposure on the model system of experimental animals, the thiobarbituric acid (TBA)-reactive substance (TBARS) level, and the activity of xanthine oxidase (XO) and catalase in kidney of rats, with and without glutathione and lipoic acid (LA). The experimental animals were classified into six groups, regarding cadmium, glutathione, and LA intake. The concentration of TBARSs in the homogenate was determined by spectrophotometric method according to Nabavi et al. The specific activity of XO was determined spectrophotometrically by the method of Aygul et al. Catalase activity in tissues was determined by spectrophotometric method according to Nabavi et al. The increased level of TBARS and the increased activity of XO in kidney tissue in cadmium poisoning are statistically significant compared to control (p < 0.001). Glutathione and LA applied along with cadmium lowered TBARS concentration and reduced XO activity (p < 0.001). Catalase activity in the kidney tissue was increased in the group, which was administered cadmium (p < 0.001). In conclusion, glutathione and LA, as physiological antioxidants applied with cadmium, have reduced the level of lipid peroxide and the activity of XO, and can be used as protectors in conditions of cadmium poisoning.
Journal of Medical Biochemistry, 2012
Summary Nitric oxide (NO) is an important signalling molecule in a variety of physiological proce... more Summary Nitric oxide (NO) is an important signalling molecule in a variety of physiological processes. NO, a gas, is produced from L-arginine by different isoforms of the nitric oxide synthase and serves as mediator in important physiological functions, such as promoting vasodilation of blood vessels and mediating communication between nervous system cells. Contradictory to its physiologic actions, free radical activity of NO can cause cellular damage by the induction of nitrosative stress with significant implications on nervous system diseases. Although the mechanism of NOmediated neurodegeneration still remains unclear, numerous studies suggest its crucial role in modification of protein functions by nitrosylation and nitro-tyrosination. NO contributes to glutamate excitotoxicity, participates in organelle fragmentation, inhibits mitochondrial respiratory complexes and mobilizes zinc from the internal stores. Recently, NO has been emerged as a mediator of epigenetic gene expressi...
facta.junis.ni.ac.rs
Enzymes catalyze virtually every biochemical process in the cell. The usefulness of the most impo... more Enzymes catalyze virtually every biochemical process in the cell. The usefulness of the most important pharmaceutical agents, antimetabolites, is based on the concept of competitive enzyme inhibition. The antimetabolites are structural analogues of normal biochemical compounds. As competitive inhibitors they compete with the naturally substrate for the active site of enzyme and block the formation of undesirable metabolic products in the body. Antibacterial, antiviral and anticancer pharmaceutical agents are among numerous examples of antimetabolites. Sulfa drags, sulfanilamide, structural analogs of amino acids (cycloserine, L-fluoroalanine), folic acid antagonists (4amino-10-methyl folic acid=methotrexate), analogues of purine and pyrimidine (6-mercaptopurine, allopurinol, 5fluorouracil, 5-azacytidine), inhibitors of polyamine biosynthesis (difluoromethyl ornithine, methylglyoxal-bis (guanyl hydrazone)) are the most used in modern chemotherapy The use of enzyme inhibitors, antimetabolites, beside the therapeutic significance has also provided valuable informations about enzyme mechanisms and has helped to define some metabolic pathways.
Rheumatology International, Jan 24, 2019
Oxidative stress is believed to be of great importance for both the etiology and the persistence ... more Oxidative stress is believed to be of great importance for both the etiology and the persistence of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the association of-262C/T polymorphism of the catalase (CAT) gene with JIA, as well as to evaluate whether this polymorphism can influence plasma CAT activity and outcome in JIA patients treated with etanercept. A total of 154 subjects (60 JIA patients and 94 healthy volunteers) were screened for CAT-262C/T gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma CAT activity was determined using the spectrophotometric method according to Goth, prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA ACR (American College of Rheumatology) response criteria. The genotype and allele frequency distributions of CAT-262C/T polymorphism in the patients were significantly different from those of the controls (p = 0.014, p = 0.006). The TT genotype (polymorphic homozygous) was associated with a 4.36-fold higher likelihood of having JIA (95% CI 1.545-12.323, p = 0.005) as compared to the CC genotype (wildtype). At month 12 of treatment, JIA patients, carriers of the CC genotype, showed significantly higher plasma CAT activity (p = 0.004) and achieved the JIA ACR 70 response more often (p = 0.003) than the patients, carriers of the CT/TT genotype. This is the first study implying the possible association of CAT-262C/T polymorphism with JIA. The results suggest the potential protective effect of the CC genotype, with regard to CAT activity and treatment outcome.
Journal of Hepatology, Apr 1, 2001
Journal of the Neurological Sciences, Oct 1, 2013
Acta Medica Medianae, 2018
Although there is a disturbance of oxidative stress markers in acute ischemic stroke (AIS), genet... more Although there is a disturbance of oxidative stress markers in acute ischemic stroke (AIS), genetic contribution of-262C/T polymorphism of catalase (CAT) gene on plasma CAT activity in this disease is not yet established. The aim of this study was to investigate the distribution of CAT-262C/T polymorphism in AIS patients compared to controls, as well as to evaluate whether this polymorphism can influence plasma CAT activity. A total of 34 patients with AIS and 32 healthy volunteers were screened for the CAT-262C/T gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Plasma CAT activity was determined using spectrophotometric method according to Goth. Although the patients with the diagnosis of AIS had a higher frequency of polymorphic-262T allele in comparison to the group of healthy subjects, the difference was not statistically significant (p = 0.117). CAT activity was significantly lower in the patients (12.95 ± 2.86 kU/L) compared to the controls (25.58 ± 13.50 kU/L, p < 0.001). The patients carriers of the-262T allele, showed significant decrease of plasma CAT activity (11.93 ± 2.82 kU/L) compared to the patients with genotype-262CC (13.99 ± 2.59 kU/L, p = 0.039). This is the first study examining the CAT-262C/T polymorphism and its influence on plasma CAT activity in AIS. Bearing in mind that the presence of-262T allele in AIS patients significantly decreased plasma catalase activity compared to CC genotype carriers, further studies should be focused on the testing of the potential protective role of the-262CC genotype in ischemic stroke.
Annals of the Rheumatic Diseases, 2015
Table 1 Global disease activity GDA according to physician and according to parent by VAS Biomark... more Table 1 Global disease activity GDA according to physician and according to parent by VAS Biomarkers ESR, CRP, Hemoglobin Raynaud phenomenon and Digital ulcers Raynaud activity score, Raynaud severity, Number of ulcers, New ulcers, Digital ulcer severity Skin mRSS, Newly occurred calcinosis, Newly occurred teleangiectasia, Presence of scleroderma-related edema Pulmonary FVC, DLCO, 6 minute walk test, Borg index Cardiac Left Ventricular and Right Ventricular ejection fraction, Newly occurred carditis, Newly occurred arrythmia, Pro-BNP level New onset or worsening of PAH Gastrointestinal New onset of swallowing difficulties, Change in stool frequency, New sign of reflux Renal Newly occurred hypertension, Newly occurred renal crisis, Proteinuria, Creatinine clearence, Change in GFR Health related quality of life and function PEDSQL, CHAQ Pain VAS, Fatigue VAS Essential paediatric data to collect: Weight, Height, Growth velocity, Tanner stage.
Journal of Basic and Clinical Physiology and Pharmacology, 2007
Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, includ... more Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.
Journal of Basic and Clinical Physiology and Pharmacology, 2009
Under physiological conditions insulin controls the metabolism of carbohydrates, lipids and prote... more Under physiological conditions insulin controls the metabolism of carbohydrates, lipids and proteins. Diabetes mellitus is a metabolic disease characterized by a disturbance in the intermediary metabolism of glucose and glucose-induced insulin release. Arginase (L-arginine amidinohydrolase, EC 3.5.3.1) modulates nitric oxide synthase activity by regulating intracellular Larginine availability. In diabetes mellitus, a decrease in nitric oxide bioavailability is a central mechanism for endothelial dysfunction. The aim of our study was to assess arginase activity in the blood of children with diabetes mellitus. Blood arginase activity, serum glucose (14.155± 4.197 mmol/L; p < .001) and blood HbA, c (11.222±3.186 %; p < .001), were significantly higher in diabetic children than in healthy controls, whereas the magnesium (Mg 2+) level, a cofactor of many enzymes, was significantly lower (0.681 ±0.104 μηιοί; ρ < .001). In diabetic children, arginase activity, hyperglycemia (r = 0.143), and the HbAi c level (r = 0.381) showed a positive correlation between but a negative correlation between Mg 2 * and arginase activity (r=-0.206). The higher arginase activity and the lower Mg 2+> levels in diabetic children could be a consequence of reduced insulin action and increased protein catabolic processes in these pathophysiological conditions. The inverse directions of arginase activity and serum Mg 2+ levels are in agreement with this concept.
Nephron Experimental Nephrology, 1998
Progression of some renal diseases is characterized by generation of reactive oxygen metabolites ... more Progression of some renal diseases is characterized by generation of reactive oxygen metabolites that are also involved in the pathophysiology of obstructive nephropathy. Catalase activity and lipid peroxidation were investigated in rats with unilaterally (UUL) and bilaterally ligated ureters (BUL). Forty-eight hours after ligation, the animals were sacrificed, and enzyme activity as well as the malondialdehyde (MDA) concentration were measured in the plasma, kidneys and livers. The activity of catalase was significantly reduced in the plasma of the BUL rats and in the kidneys of both investigated groups. In the liver, catalase activity was decreased only in the BUL group. The MDA concentration in the plasma and kidneys of the BUL rats was significantly increased while in the liver it remained unchanged. These results suggest that lipid peroxidation in the induced uremic state could be responsible for catalase inactivation.
Journal of Hepatology, 1998
Journal of Hepatology, 1998
Journal of Hepatology, 2006
Background and Aims: Hereditary Haemochromatosis (HH) is the most common autosomal recessive diso... more Background and Aims: Hereditary Haemochromatosis (HH) is the most common autosomal recessive disorder, with approximately 1 in 300 Caucasians having HH. The majority of HH patients are homozygous for a Cys-282 ~ Tyr (C282Y) mutation in HFE gene. The C282Y HFE mutant protein is retained in the endoplasmic reticulum and fails to undergo late Golgi processing, and is therefore subject to accelerated degradation. The resulting block in intracellular transport, accelerated turnover, and failure of C282Y protein presentation on the cell surface may provide a basis for impaired function of this mutant protein in HH. We have previously demonstrated in a model system that ER stress responses are induced by C282Y HFE protein expression. We sought to relieve these ER stress reponses, in particular ER stress apoptosis signals such as CHOP/GADD153, Bcl-2, caspase 3 and the novel caspase 4. Methods: Vector constructs of Normal HFE and Mutant HFE were made and transfected into HEK293 cell lines. Using this in vitro cell model system we preformed inhibitions studies using tauroursodeoxycholic acid (TUDCA). The effect of various doses of TUDCA were studied on these novel ER stress signals which were found only in association with C282Y HFE compared to wild-type HFE protein expression. Protein extracts were separated by electrophoresis on standard SDS-polyacrylamide gels and probed for specific proteins of interest. Reporter gene assays were also preformed in co-transfected cells measuing, CHOP/GADD153, Bcl-2 activation and caspase 3. Results: We demonstrated the activation and inhibition of novel molecular ER stress events in association with the mutant C282Y HFE protein. Whereby CHOP/GADD153, Bcl-2, caspase 3 and the novel ER specific caspase 4 are activated. We show TUDCA's ability to inhibit CHOP/GADD153, Bcl-2 activation, caspase 3 and caspase 4 induced by C282Y HFE protein expression. Conclusion: Our findings identify the activation of caspase 3 and the novel ER specific caspase 4 by the C282Y HFE protein. We also implicate TUDCA as a potential inhibitor of these novel ER stress molecular events associated with HH. These results indicate further the previously suggested potential of TUDCA to protect the liver, for example during ischemic and toxic insults.
Journal of Hepatology, 2000
Uploads
Papers by Dusica Pavlovic