Marko Ercegovac

GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study

PURPOSE Oxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients. METHODS GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined. RESULTS The frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1-null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype. CONCLUSIONS GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients.

Parallel micropetrographic and chemical studies of the solid degradation products from stepwise alkaline permanganate oxidation of a kerogen concentrate

Abstract The usefulness of parallel micropetrographic and chemical investigations to illustrate the nature of kerogen is demonstrated from data obtained in the study of the Aleksinac shale (Yugoslavia). To obtain more information about the chemical nature of kerogen, the stepwise oxidation with alkaline permanganate reported earlier has been modified and supplemented with micropetrographic and chemical investigations of partially degraded kerogen concentrates isolated from each degradation step. Five different types of particles were observed in kerogen concentrates. The results both of micropetrographic and of chemical investigations indicate a heterogeneity of the Aleksinac shale kerogen and a different reactivity of the particles observed.

Recurrent ischemic stroke associated with sildenafil and tadalafil use in a young adult.

Sildenafil and tadalafil are the most frequently prescribed drugs or male impotence function. Frequent adverse effects, such are eadache, flushing, dyspepsia, nasal congestion, or visual disturances, are the main symptoms of vasodilatation [1]. Clinical trials ave not shown an increased risk of cardiovascular diseases among ildenafil users [2]. However, sildenafil should be prescribed with aution to patients with history of hypotension, arrhythmia, preious myocardial infarction, or stroke [1]. Also, several reports of ransient ischemic attacks (TIA), ischemic and hemorrhagic strokes ave been reported after sildenafil/tadalafil ingestion, followed or ot by sexual exertion [3,4]. We describe a 47-year-old male who experienced recurrent schemic strokes in a 2-year period, both in close temporal assoiation with sildenafil and tadalafil ingestion.

Long-Term Prognosis in Ischemic Stroke Patients Treated with Intravenous Thrombolytic Therapy

BACKGROUND AND PURPOSE It remains unclear if intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator has an impact on the survival and maintenance of a favorable effect on functional recovery over a long follow-up period. The aim of this study was to assess whether or not IVT treatment has a favorable effect on functional recovery and survival less than 1 year after a stroke. METHODS This matched cohort study included 259 patients with acute ischemic stroke (IS) who were treated with IVT and standard care and 259 patients treated with standard care alone in the stroke unit between February 2006 and January 2013. RESULTS After a median follow-up period of 3 years (range, 1-7 years), survival did not differ significantly between the groups; specifically, 56 patients (21.6%) in the thrombolysed group died versus 62 patients (23.94%) in the nonthrombolysed group (log-rank, .240, P = .624). Based on a multivariate Cox proportional hazards regression model, older age (>70 years), stroke severity (National Institutes of Health Stroke Scale score ≥ 15), diabetes mellitus, and a history of atrial fibrillation were independent predictors of long-term mortality after stroke. After the follow-up period, 144 patients (55.6%) in the IVT-treated group versus 112 patients (43.2%) in the control group had an excellent outcome, with a modified Rankin Scale score of 0-1 (hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.16-2.32). Based on a multivariate Cox proportional hazards regression model, an excellent 3-month functional recovery was a strong predictor of favorable outcome (HR = 11.27, 95% CI = 6.45-19.63). CONCLUSION The results suggest that IVT for acute IS has a favorable effect on functional recovery more than 1 year after stroke.

A Shared Haplotype Indicates a Founder Event in Unverricht–Lundborg Disease Patients from Serbia

Unverricht–Lundborg disease (ULD) is an autosomal recessive disorder caused by dodecamer repeat expansion in the promoter region of the cystatin B (CSTB) gene in approximately 90% of the disease alleles worldwide. This study presents results of genetic findings in four Serbian unrelated patients with clinical and molecular diagnosis of ULD. Using newly established PCR protocol with betaine, we detected a homozygous expansion of dodecamer repeats in the CSTB gene in four patients with clinical diagnosis of ULD. Our results are in agreement with previous studies showing that dodecamer repeats expansion is the most common mutation associated with ULD. Haplotype analysis of eight unrelated ULD chromosomes was performed using seven markers flanking CSTB gene and one intragenic variant. We demonstrated the existence of a founder effect, strongly supported by LD calculations. Size of the minimal common haplotype implies that the most recent common ancestor of the Serbian ULD patients lived about 110 generations ago. We showed that Serbian ULD patients share the same common ancestor with patients from Baltic countries and North Africa. In the light of our data, we proposed extended minimal common haplotype, which could be considered as initial haplotype of the founder event common for Serbian, Baltic, and North African ULD patients.

Direct hydroliquefaction of a low rank soft brown coal

Abstract The behaviour of the soft brown coal from the Kostolac Mine (Serbia, Yugoslavia) was investigated during hydroliquefaction carried out in a batch reactor by direct catalytic hydrogenation of the pulverized coal (−160 μm) dispersed in tetralin. The effects of temperature (ranging from 365 to 440°C), pressure (13.5 to 15.0 MPa) and residence time (1 to 8 h) on the yield of individual liquefaction products as well as the petrographic composition of the coal residues were closely followed by separation and analysis of the products. These consisted of liquid products soluble in n -heptane (light oils), n -heptane insoluble products (asphaltenes), the solid coal residue and gaseous products. A good reactivity of this soft brown coal was observed. The yield of liquid products varied from 23 to 64 wt.% (based on dry ash-free coal). A total coal conversion of 80 to 86% was achieved. Petrographic composition and optical properties of the solid coal residues were analyzed microscopically in order to establish the character and intensity of the coal changes. The solid residues were found to consist of 12 various grain categories. The low proportions of unreacted or partly reacted coal grains confirmed the good reactivity of the Kostolac soft brown coal in the applied liquefaction process.

Evidence of stable kerogen composition during bacterial depyritization of an oil shale

Abstract A twofold experimental approach was used to answer the question of the stability of kerogen during the Thiobacillus ferrooxidans depyritization of an oil shale. The direct approach involved a detailed investigation of the kerogen, prior to and after the bacterial depyritization of the substrate, by ultimate-, i.r.-, micropetrographic, P-GC- and P-GC-MS-analyses. An indirect approach was based on a comparison of the bacterially demineralized kerogen with the kerogen in samples obtained by elimination of pyrite with different chemical reagents from the same initial substrate. Based on the experimental evidence of the combined approaches, the Aleksinac shale kerogen seems to remain unchanged during bacterial depyritization, demonstrating the advantages of bacterial vs chemical depyritization processes.

Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study

OBJECTIVE To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. METHODS We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews. RESULTS Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. CONCLUSION The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.

Antiepileptic Drugs Affect Protein, Lipid and DNA Oxidative Damage and Antioxidant Defense in Patients with Epilepsy

Summary Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the prooxidant/ antioxidant balance in epilepsy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with lamotrigine, 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-PGF2a) 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-PGF2a 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-PGF2a 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 epilepsy. Kratak sadržaj Uvod: U pokušaju da se razjasne mehanizmi kojima naj cesce korisceni antiepilepticki lekovi (AEL) uticu na ravnotezu izmedu pro- i antioksidanasa u epilepsiji, u ovom radu je izvedena uporedna analiza pokazatelja oksidativnog o{te}enja i anti oksidantnih mehanizama za{tite kod bolesnika sa epilepsijom na terapiji lamotriginom, karbamazepinom ili valproi~ - nom kiselinom. Metode: Pokazatelji oksidativnog o{te}enja proteina (sa dr`aj karbonilnih grupa, RCD i koncentracija proteinskih tiol grupa plaz me, P-SH), lipida (urinarni izoprostani, 8-epi-PGF2a) i DNK (urinarni deoksiguanozin, 8-OHdG), kao i aktivnost anti oksidantnih enzima, superoksid dizmutaze (SOD) i glutation peroksidaze (GPX) odre|ivani su kod 60 bolesnika sa novo dijagnostikovanom epilepsijom (nakon prvog napada i posle 6 meseci, na terapiji lamotriginom, karbamazepinom ili valproi~nom kiselinom) i kod 20 zdravih osoba. Rezultati: Kod bolesnika sa epilepsijom, koncentracija RCD, 8-epi-PGF2a i 8-OHdG, kao i aktivnosti SOD i GPX su zna~ajno pove}ane, dok je koncentracija P-SH umereno smanjena. Nakon {estomese~ne terapije AEL, uo~eno je smanjenje koncentracije RCD, 8-epi-PGF2a i 8-OHdG do vrednosti sli~nih onim u kontrolnoj grupi, dok je koncentracija P-SH ostala neizmenjena. Zna~ajno smanjenje je uo~eno i u aktiv nosti SOD i GPX, mada vrednosti ostaju zna~ajno pove}ane u odnosu na kontrolu. Zaključak: Terapija lamotriginom, karbamazepinom i valproicnom kiselinom uti~e na ravnote`u izme|u prooksidanasa i antioksidanasa kod bolesnika sa epilepsijom.

Liquefaction behaviour of Kolubara soft brown coal

Abstract The behaviour of Kolubara soft brown coal during direct liquefaction by catalytic hydrogenation was studied and was compared with the Banovici brown coal investigated previously. A sample of washed and dried coal was ground dry, or was ground in the presence of different liquids. Addition of water during grinding resulted in a somewhat coarser granular composition, while n -heptane did not have a noticeable effect. High reactivity of the soft brown coal, which initially was indicated by thermal analysis, was confirmed by high yields of liquid products, particularly of oils soluble in n -heptane. The solid liquefaction residues did not contain pyrolytic carbon and cenospheres, and contained a low proportion of humoplasts indicating the high liquefaction efficiency of the coal in spite of its high content of xylite.