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Jelena Jordovic, Ksenija Bojovic, Jasmina Simonovic-Babic, Vladimir Gasic, Nikola Kotur, Branka Zukic, Marija Vukovic, Sonja Pavlovic, Ivana Lazarevic, Ivana Bekic, Natasa Nikolic, Aleksandar Uroševic, Nikola Mitrovic and Dragan Delic

List of abbreviations UGT1A1 , uridine diphosphate-glucuronosyl transferase 1A1 GS , Gilbert syndrome TA repeats , thymine-adenine repeats CHC , chronic hepatitis C SVR , sustained virologic responce HIV , human immunodeficiency virus PCR HCV RNA , polymerase chain reaction hepatitis C virus ribonucleic acid DNA , deoxyribonucleic acid ALT , alanine aminotransferase AST , aspartate aminotransferase GGT , gamma-glutamyl transpeptidase AFP , alpha-fetoprotein EOT , end of treatment HCC , hepatocellular carcinoma References

Open access

Jelena Jordovic, Ksenija Bojovic, Jasmina Simonovic-Babic, Vladimir Gasic, Nikola Kotur, Branka Zukic, Marija Vukovic, Sonja Pavlovic, Ivana Lazarevic, Ivana Bekic, Natasa Nikolic, Aleksandar Uroševic, Nikola Mitrovic and Dragan Delic

List of abbreviations UGT1A1, uridine diphosphate-glucuronosyl transferase 1A1 GS, Gilbert syndrome TA repeats, thymine-adenine repeats CHC, chronic hepatitis C SVR, sustained virologic responce HIV, human immunodeficiency virus PCR HCV RNA, polymerase chain reaction hepatitis C virus ribonucleic acid DNA, deoxyribonucleic acid ALT, alanine aminotransferase AST, aspartate aminotransferase GGT, gamma-glutamyl transpeptidase AFP, alpha-fetoprotein EOT, end of treatment HCC, hepatocellular carcinoma References

Open access

Blanka Borowiec, Małgorzata Popis and Maurycy Jankowski

Abstract

A large amount of complex hormone associated processes occurring continuously in the human organism is necessary to maintain homeostasis in response to various internal and external conditions. In the same time, as the hormones use the bloodstream as their transmission medium, it is essential that their expression is strictly controlled to maintain their activity only when it is required. Because of that, the endocrine system evolved complex, self-regulating machinery that allows for precise signalling to the glands to initiate hormone expression, as well as equally quick negative feedback in the moment of reaching the optimal blood hormone concentration. The pituitary gland serves as the true endocrine part of that system, expressing a range of hormones that mostly serve as regulators of sub-systems serving different functions, scattered around organisms. The hypothalamus is the neuroendocrine part of the hypothalamic-pituitary axis, meaning it integrates the neuronal and hormonal signals, effectively linking the nervous and endocrine systems. The processes of hypothalamus and pituitary development share some significant similarities, which is unsurprising considering their close association and anatomical proximity at the base of the brain. Arising in highly overlapping developmental timeframes, they are both initially patterned by the gradients of extrinsic signalling molecules. After the initial lineage commitment, in both of those structures, intrinsic factors expressed by the distinct cell populations sustain the morphogenesis to result in a final complexly patterned structure. In this short review, the processes of the pituitary and hypothalamus development are described, with the most important factors driving them discussed.

Open access

Mirjana Đukić, Milica Ninković and Marina Jovanović

Oxidative Stress - Clinical Diagnostic Significance

Elevated free radical production and/or insufficient antioxidative defense results in cellular oxidant stress responses. Sustained and/or intense oxidative insults can overcome cell defenses resulting in accumulated damage to macromolecules, leading to loss of cell function, membrane damage, and ultimately to cell death. Oxidative stress (OS) can result from conditions including excessive physical stress, exposure to environmental pollution and xenobiotics, and smoking. Oxidative stress, as a pathophysiological mechanism, has been linked to numerous pathologies, poisonings, and the ageing process. Reactive oxygen species and reactive nitrogen species, endogenously or exogenously produced, can readily attack all classes of macromolecules (proteins, DNA, unsaturated fatty acid). The disrupted oxidative-reductive milieu proceeds via lipid peroxidation, altered antioxidative enzyme activities and depletion of non-enzymatic endogenous antioxidants, several of which can de detected in the pre-symptomatic phase of many diseases. Therefore, they could represent markers of altered metabolic and physiological homeostasis. Accordingly, from the point of view of routine clinical-diagnostic practice, it would be valuable to routinely analyze OS status parameters to earlier recognize potential disease states and provide the basis for preventative advance treatment with appropriate medicines.

Open access

Aleksandra Nikolić-Kokić, Duško Blagojević and Mihajlo Spasić

Complexity of free radical Metabolism in human Erythrocytes

The auto-oxidation of oxyhaemoglobin to methaemoglobin generating superoxide anion radical (O2 .-) represents the main source of free radicals in the erythro-cytes. Hydrogen peroxide is produced by O2 .- dismutation or originates from the circulation. Human erythrocytes are also exposed to the prooxidative actions of nitric oxide (NO) from circulation. Free radicals that may induce reactions with direct dangerous consequences to erythrocytes are also preceded by the reaction of O2 .- and NO producing peroxynitrite. In physiological settings, erythrocytes show a self-sustaining activity of antioxidative defence (AD) enzymes, such as: superoxide dismutase (SOD, EC 1.11.16), catalase (CAT, EC 1.11.1.6), glutathione peroxidase (GSHPx, EC 1.11.1.9) and glutathione reductase (GR, EC 1.6.4.2), as well as low molecular weight antioxidants: glutathione and vitamins E and C. Their coordinate actions protect the erythrocyte's bio-macromolecules from free radical-mediated damage. Since there is no de novo synthesis of AD enzymes in mature erythrocytes, their defence capacity is limited. Free radicals influence antioxidative enzymes capacities and relative share of particular components in the whole antioxidative system. Therefore, by measuring changes in the activity of individual AD components, as well as their interrelations by statistical canonical discriminant methods, valuable data about the complexity, overall relations and coordinated actions in the AD system in erythrocytes and its relevance for systemic effects can be acquired.

Open access

Dongyan Liu, Si Wang, Teng Jiang and Peng Ding

enhances the gene expression of human polymeric immunoglobulin receptor (pIgR) by TNF-a. Clin Exp Immunol 2004; 135: 448-54. 13. Schneeman TA, Bruno MEC, Schjerven H, Johansen FE, Chady L, Kaetzel CS. Regulation of the polymeric Ig receptor by signaling through TLRs3 and 4: linking innate and adaptive immune response. J Immunol 2005; 175: 376-84. 14. Bruno MEC, Kaetzel CS. Long-term exposure of the HT-29 human intestinal epithelial cell line to TNF-a causes sustained up-regulation of the polymeric Ig receptor and proinflammatory genes

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Mirjana Bećarević, Jelena Seferović, Svetlana Ignjatović, Sandra Singh and Nada Majkić-Singh

acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51: 7-18. Lemieux I. Energy partitioning in gluteal-femoral fat: does the metabolic fate of triglycerides affect coronary heart disease risk? Arterioscler Thromb Vasc Boil 2004; 24: 795-7. Lloyd EE, Gaubatz JW, Burns AR, Pownall HJ. Sustained elevations in NEFA induce cyclooxygenase-2 activity and potentiate THP-1 macrophage foam cell formation. Atherosclerosis 2007; 192: 49-55. Bećarević M, Seferović S, Ignjatović S, Singh

Open access

Anna Besedina

, blood flow and hypoxic nitric oxide homeostasis. Nat Chem Biol 2005; 1: 308-14. 11. Suvorava T, Stegbauer J, Thieme M, Pick S, Friedrich S, Rump LC, et al. Sustained hypertension despite endothelial-specific eNOS rescue in eNOS-deficient mice. Bio chem Biophys Res Commun 2015; 458: 576-83. 12. Oliveira-Paula GH, Lacchini R, Tanus-Santos JE. In du - cible nitric oxide synthase as a possible target in hypertension. Curr Drug Targets 2014; 15: 164-74. 13. Guevara I, Iwanejko J, Dembin´ska-Kie} A, Pankiewicz

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Anđelo Beletić, Aleksandra Dudvarski-Ilić, Branislava Milenković, Ljudmila Nagorni-Obradović, Mila Ljujić, Valentina Đorđević, Dragica Radojković and Nada Majkić-Singh

-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Hum Gene Ther 2006; 17: 1177-86. 27. Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci 2009; 106: 16363-8. 28. Chulay JD, Ye GJ, Thomas DL, Knop DR, Benson JM, Hutt JA, et al. Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes

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Vidosav Majstorović and Valentina Marinković

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