Tatjana Jevtovic Stoimenov

The Effects of Melatonin on Oxidative Stress Parameters and DNA Fragmentation in Testicular Tissue of Rats Exposed to Microwave Radiation

BACKGROUND Microwaves from mobile phones are one of the environmental toxicants that are capable of compromising male fertility by inducing oxidative stress and apoptosis in the testes. Melatonin is a lipophilic tryptophan indole amine and a potent antioxidant. OBJECTIVES The aim of the study was to evaluate the effect of melatonin treatment on oxidative stress parameters and DNA fragmentation in the testicular tissue of rats exposed to microwave radiation (4 h/day). MATERIAL AND METHODS Adult Wistar rats were divided in 4 groups: I--treated with saline; II--treated with melatonin; III--exposed to microwaves; IV--exposed to microwaves and treated with melatonin. The melatonin (2 mg/kg ip) was administered daily. The animals were sacrificed after 20, 40 and 60 days. RESULTS Melatonin treatment prevented previously registered increases in malondialdehyde after only 20 days. Furthermore, it reversed the effects of microwave exposure on xanthine oxidase (after 40 days) and acid-DNase activity (after 20 days). However, neither protein carbonyl content nor catalase and alkaline Dnase activity were changed due to melatonin treatment. CONCLUSIONS Melatonin exerts potent antioxidant effects in the testes of rats exposed to microwaves by decreasing the intensity of oxidative stress; it also reduces DNA fragmentation.

Global and specific histone acetylation pattern in patients with Balkan endemic nephropathy, a worldwide disease

Abstract Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy present in the Danube river regions in several Balkan countries. There appears to be a polygenic susceptibility to the disease in interaction with multiple environmental factors (aristolochic acid, ochratoxin A). In a previous study SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs of BEN patients from Serbia and Bulgaria. Emerging connections between DNA methylation and histone acetylation prompted the present study on histone acetylation in patients with BEN. Methods: The study involved 39 patients with BEN, and 39 controls collected from non-endemic regions in Serbia. The EpiSeeker Histone H3 and H4 Total Acetylation Detection colorimetric Kits and specific acetylated at lysine 18 H3K18 and H3K36 acetylated at lysine 36 detection kits were used. Results: It was documented that total H4 histone acetylation level was increased significantly, while total H3 histone acetylation did not differ significantly. Specific histone structure and functional properties may be affected by the observed derangement of H3 histone acetylation pattern, since H3K36 site was significantly more acetylated, while H3K18 tended to be less acetylated than in control subjects. Multiple regression analysis revealed a statistically significant relationship between H4, H3T and H3K36 in BEN patients. Conclusion: This preliminary study suggests that the acetylation of histone lysine residues was detectable and found increased at specific sites of H3 and total H4 histones isolated from urothelial cells of patients with BEN. Having in mind a possible mechanism and biological role of epigenetic chromatin modification in urothelial tumor development they obtained results may open opportunity for selective therapeutic interventions in patients with BEN.

Vitamin D Receptor Gene Polymorphisms in Serbian Patients With Bronchial Asthma: A Case-Control Study

Vitamin D and single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) gene are potentially involved in the pathogenesis of bronchial asthma (BA); however, precise mechanisms by which vitamin D reduces the inflammation and the role of VDR SNPs in BA are not completely understood. The aim of this study was to examine the possible associations of FokI, BsmI, ApaI, and TaqI SNPs with BA. A total of 168 subjects were screened for VDR SNPs using polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) method. The obtained results showed statistically significant differences in the distribution of FokI genotypes (df = 2; P = 0.008) and alleles (P = 0.002; OR = 0.446; 95%CI = 0.264–0.752) between patients and controls. Distributions of BsmI, ApaI, and TaqI genotypes and alleles did not show statistical differences. BsmI, ApaI, and TaqI SNPs are in linkage disequilibrium (LD) in the whole studied group, as well as in BA patients and controls. The strongest LD was observed between BsmI and TaqI (r2 = 0.69 for all subjects in the study; r2 = 0.75 in BA; r2 = 0.64 in controls), while lower values of LD were observed for BsmI and ApaI, and ApaI and TaqI SNPs. This is the first study that examined the association of VDR SNPs (FokI, BsmI, ApaI, and TaqI) in Serbian patients with BA indicating protective effect of FF genotype and F allele of FokI SNP on BA development. J. Cell. Biochem. 118: 3986–3992, 2017.

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

BACKGROUND Bronchial asthma is an inflammatory disease resulting from a combination of genetic and environmental factors. Single nucleotide polymorphisms in the regulatory regions of cytokine and antioxidant enzyme genes may affect cytokine production and enzyme activity, and thus play a contributory role in asthma pathogenesis. OBJECTIVES The aim of this study was to examine the association of manganese superoxide dismutase (MnSOD) Ala16Val, catalase (CAT) A-21T and tumor necrosis factor alpha (TNF-α) G-308A polymorphisms with bronchial asthma. MATERIAL AND METHODS A total of 79 patients with asthma and 95 healthy controls were screened for MnSOD Ala16Val, CAT A-21T and TNF-α G-308A polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS The results obtained showed significantly higher prevalence of the MnSOD ValVal genotype (χ2=14.463, df=2, p=0.001) and MnSOD 16Val allele (χ2=12.862, p=0.026, OR=0.451, 95% CI=0.291-0.699) in patients with asthma compared to controls. The genotype and allele frequencies distribution of CAT A-21T and TNF-α G-308A gene polymorphisms did not show differences between patients and controls. CONCLUSIONS Our results show an association of MnSOD Ala16Val genetic polymorphism with asthma in a Serbian population and suggest a protective role of the MnSOD 16Ala allele.

Boerhaave syndrome - case report

CONTEXT: Boerhaave syndrome consists of spontaneous longitudinal transmural rupture of the esophagus, usually in its distal part. It generally develops during or after persistent vomiting as a consequence of a sudden increase in intraluminal pressure in the esophagus. It is extremely rare in clinical practice. In 50% of the cases, it is manifested by Macklers triad: vomiting, lower thoracic pain and subcutaneous emphysema. Hematemesis is an uncommon yet challenging presentation of Boerhaaves syndrome. Compared with ruptures of other parts of the digestive tract, spontaneous rupture is characterized by a higher mortality rate. CASE REPORT: This paper presents a 64-year-old female patient whose vomit was black four days before examination and became bloody on the day of the examination. Her symptoms included epigastric pain and suffocation. Physical examination showed hypotension, tachycardia, dyspnea and a swollen and painful abdomen. Auscultation showed lateral crackling sounds on inspiration. Ultrasound examination showed a distended stomach filled with fluid. Over 1000 ml of fresh blood was extracted by means of nasogastric suction. Esophagogastroduodenoscopy was discontinued immediately upon entering the proximal esophagus, where a large amount of fresh blood was observed. The patient was sent for emergency abdominal surgery, during which she died. An autopsy established a diagnosis of Boerhaave syndrome and ulceration in the duodenal bulb. CONCLUSION: Boerhaave syndrome should be considered in all cases with a combination of gastrointestinal symptoms (especially epigastric pain and vomiting) and pulmonary signs and symptoms (especially suffocation).

Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes

Abstract Hyperglycemia mediated oxidative stress and pro‐angiogenic molecules such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) are considered important for diabetic retinopathy onset and progression. Melatonin is a pineal hormone that regulates circadian and seasonal rhythms and most likely is involved in regulating glucose metabolism. We aimed to evaluate the potential benefit of melatonin supplementation to the pre‐diabetic retina by assessing melatonin effects on lipid peroxidation (thiobarbituric acid reactive substances, TBARS), protein oxidation (advanced oxidation protein products, AOPP) and concentrations of inducible nitric oxide synthase (iNOS), VEGF and MMP9 in the retina of rats with pre‐diabetes. Pre‐diabetes was induced by streptozotocin (45 mg/kg, i.p.) following nicotinamide injection (110 mg/kg, i.p.). Beside mild hyperglycemia, lower serum insulin, increased fructosamine and lower HDL cholesterol, the present study demonstrated decreased serum melatonin in pre‐diabetic rats, as well as, increased concentration of retinal TBARS, AOPP, iNOS, VEGF, and MMP9. Oral supplementation with melatonin (85 &mgr;g/animal/day) caused melatonin and HDL cholesterol levels to rise in treated rats and reduced levels of fasting serum glucose and fructosamine. It also affected serum insulin and quantitative insulin sensitivity check index (QUICKI) in treated groups but had no significant effect on non‐fasting glucose. Finally, supplementation with melatonin reduced concentrations of TBARS, AOPP, iNOS, VEGF, and MMP9 in significant level, thereby exerting an overall positive effect on oxidative stress and pro‐angiogenic signaling in the pre‐diabetic retina. Thus, oral melatonin might be considered in an early treatment or in the prevention of retinal changes associated with pre‐diabetes. Graphical abstract Figure. No Caption available.

Expression of prolactin receptors in the duodenum, kidneys and skeletal system during physiological and sulpiride-induced hyperprolactinaemia

Introduction and aimHyperprolactinaemia in pregnancy leads to mild and reversible changes in the maternal skeletal system, and medicamentous hyperprolactinemia causes more detrimental effects. We conducted an experimental study to evaluate differences between Prlr gene expression in the duodenum, vertebrae and kidneys during physiological and medicamentous hyperprolactinaemia, which could influence calcium homeostasis.MethodsExperimental animals (18 weeks old, Wistar female rats) were divided as follows: group P (nine rats that were 3 weeks pregnant), group M (ten rats that were intramuscularly administrated sulpiride (10 mg/kg) twice daily for 3 weeks), and the control group (C, ten age-matched nulliparous rats, 18-week-old). Laboratory investigations included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorus excretion, osteocalcin (OC), serum procollagen type 1 N-terminal propeptide (P1NP), vitamin D, parathyroid hormone (PTH) and prolactin (PRL). Relative quantification of gene expression for prolactin receptors in the duodenum, vertebrae and kidneys was determined using real-time PCR.ResultsExpression of the Prlr gene was significantly higher in the duodenum (p < 0.001) and lower in vertebrae (p < 0.001) and kidneys (p < 0.01) in rats with physiological hyperprolactinaemia (PHP) than in the control group. Significantly lower Prlr expression in the duodenum was verified (p < 0.001), along with increased Prlr gene expression in vertebrae (p < 0.001) and kidneys (p < 0.01), in rats with medicamentous hyperprolactinaemia (MHP) than in the C group.ConclusionsDownregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.

Interactive Map Visualization System Based on Integrated Semi-structured and Structured Healthcare Data

Data in the healthcare industry is overwhelming, not only because of its volume but also because of its variety. In order to use such data, it needs to be pre-processed and integrated first. An additional problem is the visualization of such big data and making it valuable, readable and easier to come to the conclusions. This paper presents a system that uses interactive maps for presenting data and services for integrating healthcare data and combining it with other external sources. The purpose of this system is to show a presence of some disease in the country, how many patients with that diagnosis had to travel to some other location in order to get the medical examination and how far they had to go. Such information can be valuable in process of organizing and optimizing healthcare resources and creating models for cheaper and more optimal healthcare both from system’s and patient’s perspective.

Boerhaave syndrome and black esophagus

They describe a rare case of spontaneous esophageal perforation in the setting of hematemesis in association with duodenal ulcer and black esophagus.Boerhaave syndrome is an unusual entity in clinical medicine that was historically described by classical physical examination findings of the Mackler triad (vomiting, chest pain and sub-cutaneous emphysema), Hamman’s mediastinal crepitus with heartbeat and pneumomediasti-num on X-ray imaging. Computed tomography scans showing Gastrografin extravasation are diagnostic on call to the operating room.

Catalase C-262T Gene Variant in Patients with Bronchial Asthma

Summary Bronchial asthma (BA) is a chronic inflammatory disease of the airways in the pathogenesis of which oxidative stress has a very important role. Single nucleotide polymorphisms (SNPs) in catalase gene may result in decreased antioxidative defense capacity, and thus a higher risk for BA development. Since oxidative stress has an important role in the pathogenesis of BA and catalase has a key role in antioxidant defense, the aim of this study was to examine the association of CAT C-262T polymorphism with BA in Serbian patients with BA. A total of 170 subjects (79 patients with BA and 91 controls) were screened for CAT C-262T SNP using PCR-RFLP method. The analysis of genotype distribution did not show statistically significant differences between BA patients and controls (p > 0.05). Moreover, no differences were detected when comparison was performed based on dominant or recessive model. The distribution of CAT-262C and CAT-262T alleles did not show differences between patients and healthy controls (p = 0.715; OR = 1.091; 95% CI = 0.684–1.741). Further analysis of genotype and allele distributions, based on stratification by sex, did not show significant differences between BA patients and controls (p > 0.05). This is the first study that examined CAT C-262T (rs1001179) SNP in Serbian patients with BA. The results obtained in this study showed that biallelic SNP at the position-262 in the catalase gene is not associated with BA in the Serbian population.