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Bilberry (Vaccinium myrtillus L., Ericaceae) is a rich source of different mineral elements that are important as essential trace elements, or that can be potentially toxic, depending on their concentration. The contents of sixteen elements: the major (Al, Ca, Fe, K and Mg) and trace elements (As, Ba, Cd, Co, Cu, Cr, Mn, Ni, Pb, Sr and Zn) in roots, stems, leaves and fruits of bilberry and the corresponding soil substrate were determined in order to investigate element mobility and availability in soil. Soil was subjected to sequential extraction procedure as proposed by the Community Bureau of Reference in order to fractionate acid-soluble/exchangeable, reducible, oxidizable and residual fractions. Analysis of water and ethanol extracts of bilberry aerial parts revealed a significant transfer of elements during the extraction procedure, with corresponding extraction coefficient values of up to 95.12%. Results showed that bilberry fruits could serve as a good dietary source of essential elements for humans, especially Mn and Cu.

The emergence of rapid-acting antidepressants such as ketamine has motivated studies aiming to reveal the molecular mechanism of the ketamine antidepressant effect and to enable the clinical application of rapid-acting antidepressants. Here, we provide an overview of studies addressing the antidepressant effects of ketamine in depressed patients and animal models of depression and we compare the reduction of depressive symptoms in humans with the reduction in immobility time in the forced swim test in rodents after acute ketamine treatment. We also discuss different theories and potential biochemical pathways involved in the rapid antidepressant response to ketamine including the modulation of glutamatergic neurotransmission and intracellular hub-kinase activation. Finally, we summarize recent brain-region specific studies and we suggest that the activation of the ventral hippocampusmedial prefrontal cortexdorsal raphae nuclei (vHC-mPFC-DRN) neuronal pathway may mediate the antidepressant effect of ketamine. Although substantial progress has been made, further brain-region specific animal studies and longitudinal clinical trials are necessary for the understanding and successful application of novel rapid-acting antidepressants. Drug Dev Res 77 : 414-422, 2016.

Propofol je često korišćeni anestetik u modernoj medicini. Adiktivni potencijal propofola je uočen, kao i uticaj na memorijski proces. Međutim, oba fenomena su još uvek nedovoljno istražena. Imajući u vidu da je adolescencija period izuzetne osetljivosti na dejstvo adiktivnih supstanci i intenzivne maturacije mnemoničkog potencijala, cilj ovog rada je bio da se ispita uticaj jednokratnog izlaganja propofolskoj anesteziji, što je tipičan način kliničke primene anestetika, na dopaminsku signalizaciju, sinaptičku i neuronsku aktivnost u različitim regionima mozga i ponašanje juvenilnih/peripubertetskih pacova, kao model sistema humanog periadolescentnog razvoja. Efekti su analizirani 4, 24 i 48 sati nakon tretamana, kod mužjaka Wistar pacova starih 35 dana. Dobijeni rezultati su po prvi put ukazali da izlaganje propofolskoj anesteziji izaziva promene u ekspresiji/fosforilaciji signalnih molekula koji su već prepoznati kao značajni za dejstvo adiktivnih supstanci. Od svih analiziranih dopaminoceptivnih moždanih regiona (medijalni prefrontalni korteks, strijatum i talamus) jedino su u talamusu uočene značajne promene u ekspresiji fosforilisane/aktivirane forme DARPP-32 proteina, pokazatelja postsinaptičke dopaminske signalizacije, 4 i 24 sata nakon tretmana, i bile su praćene povećanom ekspresijom FosB/ΔFosB proteina, biohemijskog pokazatelja neuronske aktivnosti. Promene su lokalizovane u paraventrikularnom talamičkom jedru i mediodorzalnom talamusu. U strijatumu i medijalnom prefrontalnom korteksu je uočen porast u ekspresiji fosforilisane forme CaMKIIα, biohemijskog senzora sinaptičke aktivnosti koji ima važnu ulogu u pamćenju prethodnog izlaganja adiktivnim supstancama. Smanjenje u intenzitetu anksioznosti (procenjeno na osnovu rezultata dobijenih u testu svetlo/tamne kutije i uzdignutog krstastog lavirinta) je zabeleženo 24 sata nakon tretmana, kada je uočen i pad u ekspresiji FosB proteina u strijatumu, što se može tumačiti kao traženje senzacija usled smanjene akt, Propofol is a commonly used anesthetic in modern medicine. Addictive potential of propofol is observed, as well as the impact on the memory process. However, both phenomena are still insufficiently explored. Bearing in mind that adolescence is a period of extreme sensitivity to addictive substances and intense maturation of the mnemonic potential, the aim of this study was to examine the effect of a single exposure to propofol anesthesia, which is a typical method of its clinical application, on dopaminergic signaling, synaptic and neuronal activity in different brain regions and behavior of juvenile/peripubertal rats, as a model system of human periadolescencent development. The effects were analyzed 4, 24 and 48 hours after the treatment, in male Wistar rats aged 35 days. The obtained findings for the first time showed that exposure to propofol anesthesia caused changes in the expression/phosphorylation of signal molecules that are already recognized as significant for the action of the addictive substances. Of all the analyzed dopaminoceptive brain regions (medial prefrontal cortex, striatum and thalamus), significant changes in the expression of the phosphorylated/activated form of DARPP-32 protein, indicator of postsynaptic dopaminergic signalling, were observed only in the thalamus, 4 and 24 hours after the treatment, and were accompanied by increased expression of FosB/ΔFosB protein, a biochemical indicator of neuronal activity. The alterations were localized in the paraventricular thalamic nucleus and the mid-dorsal thalamus. An increase in the expression of the phosphorylated form of CaMKIIα, a biochemical sensor of synaptic activity that has an important role in memory on addictive substances exposure, was detected in striatum and medial prefrontal cortex. Reduction in the intensity of anxiety (estimated in accordence to the data obtained in the light/dark box and elevated plus maze tests) was observed 24 hours after the treatment, along with the decrease

The aim of this study was to establish correlation of chemical composition and antioxidant activity of bilberry plants from Montenegro. Total phenolic, tannin, flavonoid, procyanidin and anthocyanin contents were determined in fruits and leaves extracts using spectrophotometric methods, while the measurements of metal content was carried out in an Inductively Coupled Atomic Emission Spectrometer. Qualitative and quantitative analyses of major phenolics were achieved by HPLC. In the investigated extracts, the most abundant phenolic was chlorogenic acid, followed by protocatechuic acid, while resveratrol, isoquercetin, quecetin and hyperoside were also present in significant quantities. Antioxidant potential was evaluated using two in vitro assays-FRAP and DPPH-being in the accordance with the cyclic voltammetry tests, performed as well. The results revealed that all the investigated extracts were rich in phenolic and essential mineral constituents, with significant antioxidant activity, depending on the polyphenolic and mineral contents, which was confirmed by principal component analysis.

The athlete's heart is a set of morphological and functional characteristics that develop over time due to sports training. These adaptive changes result in increase in cardiac work efficiency and economy. They are manidested as cardiac muscle hypertrophy and dilation, with accompanying angiogenesis and slower heart rate, that are influenced by variable regulatory systems and genetic predisposition. The problem of sudden cardiac death in athletes, which persists despite numerous activities aimed at prevention, creates the need for a better definition of the athlete's heart, especially in terms of its differentiation from certain pathological conditions. This is of particular importance in the context of cardiac electrical activity. Right heart adaptations, hormonal regulatory mechanisms and the effects of nonphysiological adaptations during training, that may lead to pathologic alterations direction, are all relevant in the investigation of adverse cardiac events in athletes. In order to prevent sudden cardiac death in athletes, it is necessary to examine competitive athletes as well as apparently health individuals who recreationally exercise at a high volume. There are guidelines for mass screening and individual examinations, for all age groups and both genders, as well as for public service staff who require intense physical activity during their occupation. Both American and European recommendations require a detailed anamnesis and physical examination, whereas European, apart from that, require initial electrocardiography. The implementation of additional tests is necessary if the existence of any underlying pathophysiologic process is suspected. Checks should be performed before engaging in sports activities, as well as during training and competition periods., Sportsko srce predstavlja efekat morfoloških i funkcionalnih adaptacija srca koje se razvijaju tokom vremena, pod uticajem sportskog treninga. Promene na srcu kod sportista za posledicu imaju promenu efikasnosti i ekonomičnosti srčanog rada. Manifestuju se hipertrofijom i dilatacijom srca, sa pratećom angiogenezom i usporenim srčanim radom, procesima koji su pod kontrolom različitih regulatornih sistema i genetske predispozicije. Problem iznenadne srčane smrti u sportu, čija se incidenca ne smanjuje uprkos brojnim aktivnostima koje se sprovode u cilju njene prevencije, nameće potrebu boljeg definisanja sportskog srca, naročito u smislu njegovog razlikovanja od pojedinih patoloških stanja. Kod izvesnog broja sportista uočavaju se promene električne aktivnosti, te je i u tom smislu potrebno razlikovati zdravo od bolesnog srca. Poslednjih godina posebno je u fokusu definisanje adaptivnih promena desnog srca. Dodatno, postoje nova saznanja o hormonskoj regulaciji adaptivnih promena srca sportista, a istražuju se i efekti nefizioloških manipulacija u trenažnom procesu koji mogu 'skrenuti' fiziološke procese u patološkom pravcu. U cilju prevencije iznenadne srčane smrti, neophodno je redovno pregledanje kako sportista, tako i fizički aktivnog dela populacije. Aktuelne preporuke daju smernice za masovne skrininge i individualne preglede sportista, za sve starosne grupe oba pola, kao i pripadnike javnih službi koje u opisu posla imaju intenzivne fizičke napore. Dok američke preporuke zahtevaju samo detaljnu anamnezu i fizikalni pregled, evropske preporuke zahtevaju i inicijalnu elektrokardiografiju. I evropske i američke preporuke zahtevaju sprovođenje dodatnih ispitivanja kod sumnje na postojanje bilo kakvog oboljenja. Ove preglede bi trebalo obavljati pre početka trenažnog procesa, kao i tokom perioda treniranja i takmičenja.

Although a magnesium-mediated attenuation of memory deficits was reported in animal models of ageing and traumatic brain injury, a possible memory enhancement in healthy subjects has not been investigated yet. We used novel object recognition test (NORT) to examine the effects of acute (30 mg/kg) and chronic (50 mg/kg, 28 days) Mg-sulfate treatment on the long-term memory (LTM) in healthy adult male rats, and to test the sustainability of magnesium effects in the models of acute and chronic (21 days) ACTH administration (10 mu g/animal), mimicking the stress- and depression-like conditions. A single dose of Mg-sulfate enhanced the LTM retrieval in the 24 h inter-trial NORT protocol, in healthy, as well as in rats acutely treated with ACTH. Memory enhancement was also detected after 4-week long Mg-sulfate intake, in both healthy and rats chronically treated with ACTH. While the present findings on procognitive effects of chronic Mg-sulfate treatment corroborate with those from studies on the therapeutic potential of Mg-threonate, the current study is the first to report on memory enhancement induced by a single dose of magnesium.

Poremećaji raspoloženja, uključujući i depresiju, predstavljaju ozbiljne zdravstvene probleme i prema podacima Svetske zdravstvene organizacije do 2020. godine postaće vodeći uzrok radnog onesposobljavanja na globalnom nivou. Poznato je da je hiperaktivnost osovine hipotalamus-hipofiza-nadbubreg (HPA) čest pratilac depresivnih poremećaja, kao i da je hronična izloženost stresu vodeći faktor rizika u razvoju ovih bolesti. Jedan od najvećih problema farmakoterapije depresije predstavlja prilično veliki procenat neadekvatnog odgovora pacijenata na terapiju selektivnim inhibitorima preuzimanja serotonina (SSRI), koji predstavljaju lekove prvog izbora. Stoga, identifikacija biomarkera povoljnog odgovora na terapiju atnidepresivima, kao i pronalaženje eventualnog dodatnog tretmana koji bi povećao verovatnoću dobrog odgovora na terapiju od velikog je kliničkog značaja. Poslednjih godina pokazano je da hormon oksitocin učestvuje u modulaciji ponašanja i raspoloženja kao i da ima ulogu u adaptaciji organizma na hronični stres. Cilj istraživanja obuhvaćenih ovom doktorskom disertacijom bio je da se ispita uticaj oksitocina na ponašanje i parametre aktivnosti HPA osovine u modelu hroničnog stresa/depresije indukovane dugotrajnom primenom kortikosterona kod pacova Wistar soja. Takođe, cilj je bio i da se u navedenom modelu ispita efekat dodatnog tretmana oksitocinom uz antidepresiv citalopram, lek iz grupe SSRI. Da bi se realizovali postavljeni ciljevi, istraživanja su podeljena u tri faze. U prvoj fazi, ispitivan je uticaj različite dužine tretmana kao i različitih doza oksitocina na ponašanje i nivo biogenih amina u plazmi pacova. U drugoj eksperimentalnoj fazi, ispitivan je uticaj tretmana oksitocinom u dozi 10 IU/400 μL, s.c., tokom 14 dana na ponašanje i parametre aktivnosti HPA osovine u modelu hroničnog stresa/depresije izazvane primenom kortikosterona u dozi 100 mg/L, per os, tokom 21. dana..., Mood disorders, with depression leading the way, are severe health problems and according to the World Health Organization, depression is becoming the leading cause of disability worldwide. It is known that depressive disorders are frequently accompanied with hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis, as well as that the chronic stress is one of the most important risk-factors for its development. One of the most important problems of depressive disorders pharmacotherapy is that fairly large percentage of patients does not respond adequately to the therapy with selective serotonin reuptake inhibitors (SSRI), which are the first-line treatment drugs. Therefore, the identification of biomarkers of favorable response to antidepressant therapy, as well as discoveries of potential additional treatments, which would increase the probability of favorable response to the primary therapy is of the major clinical importance. In recent years, it has been shown that the hormone oxytocin modulates mood and behavior, and mediates adaptation feedback-response against chronic stress. The aim of the doctoral dissertation research was to evaluate the influence of oxytocin on the behavior and parameters of HPA axis activity, in the model of the long-term corticosterone administration-induced depression-like symptoms in adult male Wistar rats. Furthermore, the aim was to examine the potential beneficial effect of administering oxytocin alongside citalopram, an antidepressant from SSRI group, in this animal model. In order to fulfil these aims, the experimental work has been conducted in three phases. In the first phase, the effects of different treatment durations and dosages of oxytocin on behavior and plasma levels of biogenic amines were evaluated. In the second experimental phase, the effects of 14-day long oxytocin treatment (10 IU/400 μL, s.c.) on behavior and HPA axis activity in the model of chronic stress/depression induced by 21-day long corticosterone ad

In this paper we described the homeostasis of elementary iron: its absorption, utilization, storage and elimination. Special attention was paid to new insights into the regulatory mechanisams involved in its homestasis, especially the role of recently discovered hormone hepcidin, which is synthesized in the liver. Since it is reckoned that hepcidin has a central role in the systemic regulation of iron metabolism, the influences of various factors and conditions on the hepatic synthesis of hepcidin were delineated. Furthermore, we briefly described the most common disorders of iron homeostasis and their possible involvement in the pathogenesis of some diseases., U radu je opisan promet gvožđa u organizmu: unošenje, iskorišćavanje, deponovanje i eliminacija. Posebna pažnja posvećena je novim saznanjima o regulaciji prometa tog elementa neophodnog za život. U tom smislu je istaknut, relativno skoro otkriven, hormon hepcidin koji sintetišu hepatociti. Smatra se da hepcidin zauzima centralno mesto u sistemskoj regulaciji metabolizma gvožđa i prikazan je uticaj različitih faktora i stanja na sintezu hepcidina u jetri. Ukratko su opisani i najčešći poremećaji homeostaze gvožđa i njegova eventualna uloga u patogenezi nekih oboljenja.

The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCR alpha beta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCR alpha beta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCR alpha beta(high) high thymocytes. In urapidil-administered rats the percentage of CD4+CD8-SP TCR alpha beta(high) thymocytes was increased, while that of the CD4-CD8+ TCR alpha beta(high) was reduced. compared with controls. In addition, proportions of CD4+CD25+ RT6.1- and CD161+TCR alpha beta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development.

Uravnotežena ishrana, kojom se obezbeđuje unos svih neophodnih hranjivih sastojaka, od posebnog je značaja za sportiste. Zbog savremenog načina ishrane oni često unose nedovoljne količine magnezijuma i veoma su osetljivi na deficijenciju ovog jona koji ima ključne uloge u mnogim ćelijskim reakcijama u organizmu. Savremeno psihosocijalno okruženje postavlja kompleksne zadatke pred mlade ljude koji često vode stresan način života. Osim toga, mlade osobe koje redovno treniraju i učestvuju u takmičenjima, izložene su dodatnom psihofizičkom stresu. S obzirom da je magnezijum jon izuzetno važan za normalno odvijanje energetskog metabolizma, kao i da je pokazan njegov uticaj na aktivnost hipotalamo-hipofizno-nadbubrežne (HPA) osovine, koja j e u u skoj s prezi s a aktivnošću hipotalamo-hipofizno-gonadne (HPG) osovine, može se pretpostaviti da dodatak suplemenata magnezijuma ishrani ragbista, može imati višestruk uticaj na fiziološki odgovor koji se javlja kao posledica psiho-fizičkog stresa kojem su ragbisti izloženi tokom takmičenja. Hormonski sistem je veoma kompleksan i da bi se dobila jasna slika na koji način funkcioniše potrebno je simultano ispitati više sistema odjednom. Cilj rada bio je da se ispita da li magnezijum utiče na parametre aktivnosti HPA i HPG osovine, kao i na njihov međusobni odnos, i da li je taj uticaj različit kod ragbista u odnosu na efekte kod muškaraca istog uzrasta koji se ne bave sportom. Takođe, cilj je bio da se utvrdi da li i na koji način magnezijum menja dinamiku promene parametara aktivnosti HPA i HPG osovine nakon utakmice kod ragbista. U cilju procene aktivnosti HPA osovine vršeno je određivanje nivoa ACTH, kortizola, IL-6 kao i određivanje ukupnog broja leukocita, njihove diferencijalne formule i stepena oštećenja DNK perifernih limfocita. Procena aktivnosti HPG osovine izvršena je određivanjem nivoa FSH, LH i testosterona, kao i koncentracije eritrocita i hemoglobina. Praćenjem testosteron/kortizol (T/C) odnosa dobijeni su značajni, Balanced diet, with proper dietary intake of all necessary nutrients, is of particular importance for athletes. Due to contemporary dietary habits and suboptimal magnesium intake, athletes are very sensitive to deficiency of this ion involved in key intracellular reactions in human body. Contemporary psychosocial environment puts complex tasks in front of young people who often lead stressful way of life. Furthermore, young athletes, who are involved in trainings and competitions on a regular basis, are exposed to additional psycho-physical stress. Since, magnesium ion is extremely important for normal energy metabolism and its effect on activity of hypothalamic-pituitary-adrenal (HPA) axis, which is in tight conjunction with activity of hypothalamic-pituitary-gonadal (HPG) axis, is well proven, it could be presumed that addition of magnesium supplement to the rugby players diet, might have multiple effects on physiological response on psychophysical stress during rugby competition. In order to get a clear picture of how hormonal system functions, simultaneous examinations of several systems are needed. The aim of this study was to examine whether magnesium has an effect on parameters of HPA and HPG axis activity, as well on their interaction, and are these effects different in rugby players compared to the age-matched sedentary individuals. Another goal was to examine if magnesium might have an influence on the dynamics of the change of parameters of HPA and HPG axis activity. In order to evaluate HPA axis activity, the levels of ACTH, cortisol, IL-6, total/differential leucocytes counts, as well the degree of peripheral blood lymphocyte (PLB) DNA oxidative damage, were determined. The evaluation of HPG axis activity was done through determination of FSH, LH and testosterone levels, the number of erythrocytes and hemoglobin concentration. Testosterone/cortisol (T/C) ratio gave us important information on reciprocal interaction of these two axes. The study included

Istraživanja u ovom radu su obuhvatila primenu koncepta analize značaja pritisaka i uticaja i metoda za identifikaciju i klasifikaciju izvora pritisaka; karakterizaciju i analizu pritisaka; procenu statusa vodnih tela i procenu uticaja/rizika da se ne dostigne njihov dobar ekološki status/potencijal. Ukupan broj registrovanih zagađivača na teritoriji AP Vojvodine iznosi 185, trenutno radi njih 130. Najviše zagađivača svoje otpadne vode ispušta u Tisu, DTD Vrbas-Bezdan i Begej, koji su recipijenti 61% od ukupne količine otpadnih voda. Skoro 70% od ukupnog broja zagađivača pripada sektoru prerađivačke industrije, a među njima je najzastupljenija proizvodnja prehrambenih proizvoda i pića. Prosečna dnevna količina ispuštenih otpadnih voda iznosi oko 140.000 m3/dan. Ukupno organsko zagađenje koje se emituje u vodotoke na području AP Vojvodine, a potiče od otpadnih voda iznosi 33 tHPK/dan i 15 tBPK/dan. Polovina zagađivača svoje otpadne vode ispuštaju bez ikakvog tretmana, četvrtina njih poseduje primarni tretman prečišćavanja, dok tercijarni tretman primenjuje svega 3% zagađivača. Veoma je mali broj zagađivača kod kojih su emitovane konecentracije usklađene sa propisanim graničnim vrednostima emisije, za nutrijente je to oko 50%, dok je za organske materije samo četvrtina od ukupnog broja zagađivača. Od 37 vodotoka, samo tri se klasifikuju u klasu 2, što odgovara dobrom kvalitetu voda. Kvalitet najvećeg broja vodotoka odgovara slabom ili lošem statusu/potencijalu (tj. klasama 4 ili 5). Najveća odstupanja od dobrog statusa/ potencijala su u sadržaju nutrijenata i parametara kiseoničnog režima. Rezultati su pokazali da su polutanti visokog rizika najčešće nutrijenti i parametri kiseoničnog režima, što najverovatnije predstavlja negativan uticaj ispuštanja otpadnih voda. Ukupno opterećenje zagađujućih materija a time i broj vodotoka na kojima je premašeno ciljano opterećenje znatno raste sa porastom emitovanog opterećenja iz koncentrisanih izvora, ali i sa s, Research in this study included the concept of pressure and influence significance analysis as well as the methods for identification and classification of the pressure sources: characterisation and analysis of pressures; assessment of the water bodies’ status and assessment of impacts/risks thattheir good ecological status/potential is not achieved. Total number of registered polluters in Vojvodina is 185, 130 of them currently working. Most polluters discharge their waste water into the Tisa River, DTD Vrbas-Bezdan and Begej River, who are the recipients of 61% of the total volume of wastewater. Almost 70% of the total number of contaminants belongs to the processing industry, and among them the most common is food and beverage production. The average daily amount of discharged wastewater is approximately 140 000 m3/day. Total organic pollution emitted into the watercourses in the areaof AP Vojvodina originates from the waste water is 33 tCOD/day and 15 tBOD/day. Half of the polluters discharge their waste water without any treatment; a quarter of them haveprimary wastewater treatment, while tertiary treatment is applied by only 3% of polluters. A very small number of polluters have their emitted pollutant concentration compatible with the prescribed emission limit values: for nutrients it is about 50%, while for the organic matter, it is only a quarter of the total number of polluters. From 37 watercourses, only three are classified as class 2, which corresponds to good quality water. Quality of the greatest number of watercourses corresponds to poor or bad status/potential (ie. classes 4 or 5). The biggest deviation from good status/potential is due to nutrients content and oxygen regime parameters. Results showed that high-risk pollutants are commonly nutrients and oxygen regime parameters, which probably represents the negative impact of waste water discharges. The total load of pollutants, and therefore the number of watercourses where the target load it exc

Contemporary lifestyle is commonly associated with chronic stress, an environmental factor contributing to development of various psychological and somatic disorders. Increased levels of glucocorticoids, observed in the chronic stress, induce the production of reactive oxygen species leading to genotoxicity. The aim of this study was to investigate whether chronic administration of oxytocin (OXY) 10 IU/400 mu L/day, s.c., for 14 days, a hormone presumed to exert antioxidant effect, may prevent DNA damage in the comet assay of peripheral blood lymphocytes of Wistar rats treated chronically with corticosterone (CORT) 100 mg/L ad libitum, per os, for 21 days, as well as, to influence some plasma oxidative stress parameters, i.e. levels of total lipid hydroperoxide (LOOH), and malondialdehyde (MDA), and the activity of antioxidative enzyme superoxide dismutase (SOD). Even though there was no reduction in overall number of damaged cells after oxytocin treatment only, the marked increase in total comet score (TCS) after incubation with H2O2 in CORT group compared to controls, was absent in the CORT + OXY experimental group. Furthermore, significant decrease of highly damaged cells compared to corticosterone group was noted. Chronic oxytocin administration thus protected lymphocytes from high intensity damage that leads to cellular death. In addition, treatment with OXY along with CORT, significantly decreased concentration of LOOH in plasma, and increased SOD compared to CORT treatment only. This finding corresponds well with current reports on beneficial effects of OXY in conditions of HPA axis hyperactivity, and supports the hypothesis of OXY-mediated antioxidant action.

Background: Physical exercise activates the hypothalamopituitary-adrenal (HPA) axis and induces the body's inflammatory response. Due to contemporary dietary habits and increased energy expenditure, athletes are susceptible to depletion of magnesium ions. The aim of our study was to investigate, through assessment of plasma ACTH, serum IL-6, and salivary/serum cortisol levels, if chronic magnesium supplementation might reduce damaging stress effects in amateur rugby players. Methods: Rugby players (N=23) were randomly assigned to intervention and control group. Basal samples were collected before intervention group started a 4-week-long supplementation with magnesium (500 mg Mg/d). Blood and saliva sampling were done a day before the match (Day-1), on the morning of competition (Game), and during a six-day-long recovery period (Day1, Day3 and Day6). ACTH, serum/salivary cortisol, IL-6 and total/differential leukocytes counts were determined at each time point. Results: There was a statistically significant increase in ACTH concentration in intervention group compared to control group, while reductions in cortisol concentrations between the two groups were the greatest at Day-1 (p lt 0.01) and at the day of competition (Game) (p lt 0.01). Our results revealed that magnesium completely abolished the increase in IL-6 level noted in control group on Day1 and Day3 vs. Day-1 (p lt 0.01) and also diminished the rise in neutrophil/lymphocyte ratio in intervention group vs. control group (p lt 0.01). Conclusions: These results suggest the possibly important influence magnesium supplementation might have on the change of parameters of HPA axis activity and reduction of immune response activation following strenuous physical exercise such as a rugby game.

Depression contributes substantially to disease burden worldwide; however despite of this, the progress in understanding its pathophysiology has been extremely slow and the discovery of new therapeutic mechanisms is at a near standstill. The molecular targets of current major classes of antidepressants were all reverse engineered from drugs previously discovered by serendipitous clinical observations. Since the existence of adult-born neurons was unequivocally documented, adult neurogenesis became a very promising, but also very hyped target for antidepressant drugs. Introduction of corticotrophin releasing hormone inhibitors aimed to exploit a prospective reduction of glucocorticoid-mediated inhibition of adult neurogenesis with the aim to produce antidepressant effect. Although these drugs failed to demonstrate efficiency in phase three clinical trials, they provided the following valuable lesions for the future: (1) Inter-species differences between animals and humans should be considered very carefully, (2) Animal model phenotypes mimicking depression should be more robust, preferably shown by multiple behavioral paradigms, and (3) variability between different subgroups of depression should be taken into consideration because of the pronounced heterogeneity of the disease., Iako depresija značajno doprinosi morbiditetu na globalnom nivou, napredak u razumevanju patofiziologije ove bolesti je izuzetno spor, pa su posledično, otkrića novih terapeutskih mehanizama praktično u zastoju. Ciljni molekuli preko kojih deluju antidepresivi koji su danas u upotrebi identifikovani su reverznim inženjeringom lekova otkrivenih empirijski, kliničkim zapažanjima. Otkad je jasno pokazano postojanje novonastalih neurona, adultna neurogeneza je postala izuzetno atraktivna potencijalna meta delovanja kandidata za antidepresivne lekove. Uvođenje inhibitora kortikotropin-oslobađajućeg hormona imalo je za cilj da se iskoristi činjenica da glukokortikoidni hormoni inhibiraju adultnu neurogenezu i time doprinose antisdepresivnom efektu. Iako su se ovi lekovi pokazali kao neefikasni u trećoj fazi kliničkih studija, naučene su sledeće važne lekcije za budućnost: (1) razlike u funkcionisanju mozga ljudi i životinja moraju biti pažljivo razmotrene, (2) da bi se zaključilo da animalni model ima depresivni fenotip, isti je potrebno ubedljivo demonstrirati, po mogućstvu korišćenjem većeg broja bihejvioralnih testova i (3) varijacije u simptomima između različitih podklasa depresije treba uzeti u obzir imajući u vidu heterogenost oboljenja.

Sedentary lifestyle is highly associated with increased risk of cardiovascular disease, obesity, and type 2 diabetes. It is known that regular physical activity has positive effects on health; however several studies have shown that acute and strenuous exercise can induce oxidative stress and lead to DNA damage. As magnesium is essential in maintaining DNA integrity, the aim of this study was to determine whether four-week-long magnesium supplementation in students with sedentary lifestyle and rugby players could prevent or diminish impairment of DNA. By using the comet assay, our study demonstrated that the number of peripheral blood lymphocytes (PBL) with basal endogenous DNA damage is significantly higher in rugby players compared to students with sedentary lifestyle. On the other hand, magnesium supplementation significantly decreased the number of cells with high DNA damage, in the presence of exogenous H2O2, in PBL from both students and rugby players, and markedly reduced the number of cells with medium DNA damage in rugby players compared to corresponding control nonsupplemented group. Accordingly, the results of our study suggest that four-week-long magnesium supplementation has marked effects in protecting the DNA from oxidative damage in both rugby players and in young men with sedentary lifestyle.

The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00 +/- 0.00 to 1.25 +/- 0.54 parts per thousand (P lt 0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2=3008 +/- 638 vs. 2900 +/- 543ml/min, ns; peak workload=269 +/- 53 vs. 249 +/- 40W, ns; test duration 13.7 +/- 2.2 vs. 13.3 +/- 1.7min, ns; VE/VCO2 22.1 +/- 1.4 vs. 23.3 +/- 2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28 +/- 2.5 vs. 30.4 +/- 3.2, P=0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17 +/- 0.02 vs. 1.14 +/- 0.04, P=0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism.