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Radiotherapy affects not only malignant, but also a healthy tissue adjacent to tumor by increasing reactive oxygen species generation, with consequent damage to biomolecules, such as the oxidation of membrane lipids, known as lipid peroxidation. The end product of lipid peroxidation is malondialdehyde. Radioprotectors are compounds that could significantly protect normal cells from radiation, without changing the tumor cell radiosensitivity. Synthetic radioprotectors usually have side effects and are toxic. Natural radioprotectors exert protection without adverse effects. In this study, we examined the radioprotective ability of linden honey in rat blood, by detecting alterations in the activities of antioxidant enzymes catalase and glutathione peroxidase and malondialdehyde concentration after the exposure to a therapeutic dose of gamma rays. Sixteen rats were randomly divided into Control and Honey groups. Honey group received honey (1.5 mL(kgd-1)) orally for four weeks, while at the same time Control group were given distilled water. After four weeks, blood was sampled from all animals. Samples were halved, and one series of samples were gamma irradiated (2 Gy). Radiation induced decreased glutathione peroxidase activity and increased malondialdehyde level, while honey treatment attenuated those alterations, keeping glutathione peroxidase and malondialdehyde at physiological levels. These findings confirm radioprotective properties of linden honey.

Linden honey represents a unique honey variety valued for its nutritional benefits, distinctive taste and aroma. Phenols, polyphenols, flavonoids, ascorbic acid and phenolic acids in honey have antioxidant activities. This study aimed to investigate the effects of linden honey on the activities of antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPx), as well as on the concentration of malondialdehyde (MDA) in individually housed animals. The investigated parameters were quantified using spectrophotometric method for determination of enzyme activities and MDA concentration in the blood. We found that treatment with linden honey in the socially isolated animals significantly increased the enzyme activities of CAT and GPx, and significantly decreased the concentration of MDA. The modulation of CAT and GPx activities in socially isolated animals treated with linden honey may be very important for understanding the role of honey in the capacity of antioxidant defense system to increase and maintain its stability in psychosocial stress conditions. Our results may be important in biomedical research for understanding the role of honey in the amelioration of oxidative stress.

This study aimed to investigate the effects of chronic restraint stress (CRS) on the protein levels of dopamine-β-hydroxylase (DBH), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and brain-derived neurotrophic factor (BDNF), as well as the concentration of noradrenaline (NA) in the rat hippocampus. The investigated parameters were quantified by Western blot analyses and ELISA kits. We found that CRS increased the protein levels of DBH by 30 %, VMAT2 by 11 %, BDNF by 11 % and the concentration of NA by 104 %, but decreased the protein levels of NET by 16 % in the hippocampus of chronically stressed rats. The molecular mechanisms by which CRS increased the hippocampal NA level are an important adaptive phenomenon of the noradrenergic system in the stress condition. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine whether there are differences in adrenomedullary function in respect to the left and right sides in chronic stress conditions. We investigated how chronic stress isolation (CSI 12 weeks) affected the protein levels of key enzymes involved in adrenaline (A) synthesis (phenyl ethanolamine N-methyltransferase -PNMT), storage (vesicular monoamine transporters 2 - VMAT2) and degradation (catechol-O-methyltransferase - COMT), as well as the concentrations of A as an index for adrenomedullary function in the left and right adrenal medulla. Also, we examined the concentrations of malondialdehyde (MDA), protein levels of nuclear factor κB (NF-κB), and activity of catalase (CAT) in the left and right adrenal medulla. The investigated parameters were quantified by Western blot analysis, assay of enzymatic activity, and CAT Research ELISA kits. We found that CSI pro duced significantly increased levels of PNMT protein, and VMAT2 protein, as well as increased concentrations of A in the right adrenal medulla. However, we recorded that CSI increased protein levels of COMT and NF-κB, as well as the concentrations of MDA in the left adrenal medulla. Also, CSI decreased the activity of CAT only in the left adrenal medulla. Based on these results, it may be concluded that adrenomedullary function is different in respect to the left and right sides in chronic stress conditions.

This study examined the effects of chronic restraint stress (CRS: 2 hours × 14 days) on gene expression of three antioxidant enzymes, copper, zinc superoxide dismutase (SOD 1), manganese superoxide dismutase (SOD 2) and catalase (CAT) in the rat hippocampus. Also, we examined changes in the activities of SOD 1, SOD 2 and CAT in the hippocampus of chronically stressed rats. Investigated parameters were quantifi ed by using real-time RT-PCR, Western blot analysis and assay of enzymatic activity. We found that CRS did not change mRNA and protein levels of SOD 1 and CAT, but increased mRNA and protein levels of SOD 2. However, CRS treatment increased the enzyme activities of SOD 1, SOD 2 and CAT. Our fi ndings indicate that the increased activity of antioxidant enzymes (SOD 1, SOD 2 and CAT) in the hippocampus may be an important adaptive phenomenon of the antioxidant defense system in chronically stressed rats.

The paper considers the basic concepts of perceiving the city, first and foremost its polarization against the country or the village and (much later) polarization between the old "solidary" and contemporary anomic cities. Aside from this, the paper considers the basic premises and practice of the application of the Convention for the Safeguarding of Intangible Cultural Heritage, which are mostly based on safeguarding/protecting premodern cultural elements and - mostly essentialist - group identities, in order to highlight the possibilities of reworking the conceptual framework for the application of the Convention to - heretofore unknown - urban heritages which originated on completely different premises, as well as the issues and dilemmas which can arise from such attempts. The paper considers the relationship between the Convention and the Modern age, the perception/perceptions of the city, the city as palimpsest, and, ultimately the relationship of the Convention with the city and (potential/possible) intangible urban heritage. Attempts to safeguard specific forms of urban intangible heritage have, heretofore, been faced with a slew of problems, stemming first and foremost from the insistence on "backwardness" as authenticity (Hafstein 2013, 45), but also the insistence on exoticism: that which is safeguarded is completely different from contemporary western civilization, completely in line with the definition of the exotic as aestheticization which makes pain (of contemporary poverty as opposed to colonial conquest of yore) into spectacle, and into culture (of global society as opposed to the former colonial empire) (Arac and Ritvo 1991, 3). Every city ever was and always is a crossroads of cultures - in space (those with exist simultaneously), as well as in time (past and future). Of course, the reading of such complex heritage, which constantly changes meaning even if it retains the same or similar appearance, is a daunting task, while its "safeguarding", whatever that may entail in the bureaucratic sense, is almost unfeasible. Culture, definitely cannot be copyrighted (Brown 1998), so neither can "tradition" - not even its material remnants - it cannot stay unchanged whatever we may try. But this does not mean that we should not attempt and keep discovering new ways in which heritage can be built into our everyday lives - safeguarded in spirit, however much the form may vary.

The aim of this study was to examine how acute immobilization stress affects the concentrations of catecholamines in the plasma and the expression of the splenic catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-Я-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in chronically socially isolated rats. We found that acute immobilization increases the plasma catecholamine levels and splenic PNMT protein levels in chronically socially isolated rats. These results show that acute stress of chronically stressed animals activates the sympatho-adrenomedullary system and increases synthesis of splenic PNMT by 37%, both of which can modulate the immune function. [Projekat Ministarstva nauke Republike Srbije, br. III 41027, br. III 41022 and br. ON 173044]

In this study we examined how chronic forced running (CFR) affects the expression of catecholamine biosynthetic enzymes and cAMP response element-binding (CREB) in the adrenal medulla and the weight of adrenal glands of rats. Also, we examined how CFR and additional acute immobilization stress affect the expression of catecholamine biosynthetic enzymes in the adrenal medulla and the concentration of catecholamines and corticosterone (CORT) in the blood plasma. In this experiment we used as a model forced exercise in rats (treadmill running). We used the most advanced method for determining the level of gene expression, Real-time PCR with TaqMan probes, as well as Western blot analysis (ECL). We found that CFR decreases tyrosine hydroxylase (TH), and dopamine-β-hydroxylase (DBH) mRNA and protein levels in the adrenal medulla. The decreased TH and DBH mRNA levels coincide with the reduced expression of CREB in the adrenal medulla and with the reduced plasma CORT level. Additionally, CFR reduces the level of phenylethanolamine N-methyltransferase (PNMT) mRNA, but elevates its protein level in the adrenal medulla and increases the concentration of adrenaline (A) in the plasma. Reduced level of PNMT mRNA in the adrenal medulla coincides with reduced plasma CORT level. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. The increased synthesis of PNMT enzyme in the adrenal medulla may result in an increased biosynthesis of A under chronic stress conditions. Additionally, increased level of catecholamines in the plasma after chronic physical stress is the allostatic load that may induce numerous diseases and pathological conditions.

This paper analyzes climate change and its impact on river discharge. This issue is very well studied worldwide, but in Serbia so far has been poorly studied. The first part of the paper presents the views of two different opinions, those who favored anthropogenic impact on the increasing greenhouse effect, and those who say that this is due to natural factors. Most attention is paid to changes in temperature and precipitation patterns. Classification by the group of those who favor the promotion of natural phenomena is demonstrated through the analysis of river flow fluctuations in the hydrological gauge Beli brod located on Kolubara River.

Protection of hydrological heritage sites, water protection segment, is an integral part of nature conservation. Today it is the basic theme of the hydrological heritage, the new field of hydrology and geo-heritage, which, by exploring and evaluating hydrological diversity of a particular area and identifying representative water phenomena, sets their preservation and protection as one of the utmost objectives. Two main problems in the protection of water phenomena in Serbia are: inadequate attitude of the individual and society, as a result of poor knowledge of the characteristics and values of waters, and the ever-present need for men to use them (as resources). Lack of understanding, in the professional sphere, the value and importance of water phenomena in the natural system - as a result of a firmly based biocentrism in nature conservation, lack of hydrologic group within the geo-heritage and a small number of interested professionals are some of the associated problems that limit the activities in this field. Specific problems - from the lack of organized and synchronized scientific research to the lack of a database on the hydrological heritage sites, are somewhat common to other segments of the nature conservation of Serbia. There are three possible directions of the future actions on the protection of hydrological heritage sites of Serbia: complete protection, protection with utilization for the needs of tourism and protection with utilization for the needs of water management. The most complex task of hydrological heritage will just be to combine the preservation and protection with tourism and water management, because it is diverse and often conflicting industries about. A possible solution to this problem is illustrated through the idea of water reserves.

Incomplete definitions of geodiversity and geoheritage caused the domination of clearly geological approach to these scientific problems. That is the reason why some of the integral elements of geographical environment were neglected. Wrong theoretical assumptions reflected negatively the determination and advancement of this scientific discipline. The reasons for such condition are mentioned in the paper, as well as the necessity of different and more comprehensive perspective of geodiversity and geoheritage, by which the directions of the future development are implied. .

Until recently hydrological heritage has practically existed in science neither as an idea nor a subject. Definitions of the main terms, general classification of hydrological heritage, as well as expanded classification of hydrological heritage of Serbia are presented in the paper which is the starting point needed for further determination of new direction in hydrology and geoheritage. The paper has also pointed to the key reasons for the previous unfavourable status of hydrological heritage and its scientific and national significance, as well as the necessity of its existence and complex development.

This paper discusses continuous influence of the Romanticism' ideas all until the present time. The ideas about the golden age in the past, on an ideal society based on class, gender, and generational hierarchy were dominant in the children' education until the second part of the 20th century. This was influenced, in turn, by fairy tales created in the 19th century, which are taken even today, to be the most appropriate children' literature. The flow-literary production of novels with fairy tales content, where the plot is taken place in some fictional, fairy-like world during the second part of the 20th century, corresponds hence to the need of adult audience/readers: a basic need for dream fulfillment about the roles of romantic heroes who do not exist in a real life. At the same time, the existing negation of modernization and introduction of new technologies corresponds nicely with the fears generated by accelerated changes, as one of the key attributes of the contemporary world. Deconstruction of the romanticized narratives begins in the framework of the postmodern fantasy literature, since the 1980's. This perspective reflects new possibilities for perceiving and estimation of the objective social reality of the Western civilization.

The examples from Kosovo and Metohia attempted to point to some problems in the domain of hydrogeographic regionalization. The river water regime, especially the phase of high flows which marks this regime, has been the topic of almost all researches which treat water resources of drainage basins. However, the thing that has not been achieved till now is the unique solution by which the classification of rivers would be made according to this feature. On this example it has been shown that even some older methods, based on genetic analysis of hydrograms and of global type, as well as some recent ones, with lot of quantitative entry and regional approaches, cannot with certainty answer all the challenges which river regimes bring with themselves. This work shows that apart from climate, orographic and physiognomic features of drainage basins, the periods of data processing and the analysis of individual intra-annual series of discharges are very important as well. Discretization on time periods shorter than one month, as well as elimination of the extreme values of discharges in the longtime series is recommended for the future research.

The paper raises a discussion about the relation of museums and (national) politics, primarily about the concept of 'apolitcism' of museum work, the idea that is spread among many museum workers as reality. I analyze the process of appearing of big museums in Europe and Serbia, as well as the aims of their work, in order to show that museums - from the very beginning of their appearing - function as means for consolidating national borders (outer and inner), teaching about patriotism. I also analyze the influence of German romanticism, that created the illusion of 'apoliticism' of the culture in general, as well as of museums. The change of attitude towards the state-as-nation in contemporary European community means also the change of museologic activities that should take part in the constitution of Europeism/European identity as meta-nation. That change has not still come to museums in Serbia, which points to the fact that society has not changed yet in the direction of appropriating of European values.

This paper discusses an application of new readings of classical anthropological texts, using as an example the Levi-Strauss' book Tristes Tropiques and the book's impact, reception and application in the local (Serbian) anthropological practice. The messages of the classical works even they are published half a century ago, could still be considered significant especially so for the local anthropological practice. Tristes Tropiques were published in 1960 in Serbo-Croatian language (published by Zora, Zagreb) only 5 years after the first edition in French and more than a decade before the book was translated completely into English. At the time, the book was not classified as ethnography/anthropology - it was published in the edition of 'foreign writers', hence, it was considered to be a literary work/fiction. It is possible that the categorization of the book was due to the fact that Tristes Tropiques was very different than the contemporary works at the time in the local (than Yugoslavian) ethnological/ethnographical production. The difference appears too profound so no parallel could be drawn or discover any common ground. Susan Sontag argues that Tristes Tropiques is one of the great books of the 20th century, and Gertz claim that in the whole body of anthropology, there is not a text so self-referential and liberating as Tristes Tropiques. However, the book was not so widely read in Serbia especially not so as an anthropological literature, therefore, many educational points remained until this day outside of the framework of the local ethnographic production. Even though the book was published in XX century, it deserves to be read today for many reasons. We should read the book not because it represents a great ethnographic account, or because the author is a creator of a new paradigm in anthropology, but because the book even today, shed a light on the same thing: it is possible, even necessary to get out from the closed circle of the known way of thinking and because the book inspires many dilemmas and questions that could provide new unexpected answers, to be told in totally novel ways.

Serotonin and noradrenaline are involved in the mechanisms of action of most antidepressant drugs. We examined the effects of chronic treatment with maprotiline, a selective inhibitor of noradrenaline reuptake, and fluxilan, a selective inhibitor of serotonin reuptake, on the behavior of unstressed controls and chronic unpredictable mild stress (CUMS) model rats in the forced swim test (FST) and elevated plus maze test. Both selective reuptake inhibitors resulted in a significant reduction of time spent in immobility. Climbing was significantly increased in maprotiline- and swimming was exclusively elicited in the fluxilan-treated unstressed control and CUMS rats. Maprotiline-treated ani­mals displayed decreased anxiety and fluxilan-treated rats enhanced anxiety. The obtained results suggest that central noradrenergic and serotonergic systems might be affected differently during FST. The results also demonstrate that the anxiogenic effects of chronic fluxilan treatment are similar to those reported by many other studies. These differences observed for the effects of fluxilan in relation to those reported for maprotiline and probably due to the different phar­macological profiles of these drugs.

This work discusses creationism as a new form of religious fundamentalism, which is attacking not only modern science but also the foundations of secularism in Europe, America and almost the whole world, as well as how creationism is using the mechanisms of secular society/state, first of all museums and science in order to strengthen its influence. At the same time a question is posed how much literally understood principles of general tolerance and democracy can subvert the existence of secular and multicultural society in which they arose.

Chronic stress induces changes in the neuroendocrine and neuronal system, including elevation of catecholamines and corticosterone (CORT) levels, and could be an important factor in initial depression. Antidepressants affect monoaminergic neurotransmission and modulate central neuropeptides involved in the coordination of stress response and the control of HPA axis activity. We studied the effects of chronic treatment with fluxilan, a selective inhibitor of serotonin reuptake, in unstressed controls and chronic unpredictable mild stress (CUMS) rats, on behaviour and plasma noradrenaline (NA), adrenaline (A), corticosterone (CORT) and adrenocorticotropic hormone (ACTH). CUMS did not affect plasma NA, A and ACTH, but elevated plasma CORT content. Plasma concentration of catecholamines after fluxilan administration was significantly increased in control and CUMS group. On the other hand, fluxilan expressed no effect on plasma ACTH and CORT concentrations in control animals, but decreased ACTH and CORT levels in CUMS animals. behaviorally, fluxilan treated animals displayed enhanced anxiety. The results demonstrate that the anxiogenic effects of chronic fluxilan administration are similar to those reported by many other studies. The findings described here suggest that elevated plasma catecholamines may contribute to an adverse effect of this drug on cardiovascular parameters during antidepressant therapy.

The present study analyzed the effects of chronic treatment with low doses of diazepam on body weight, defecations and urinations, vertical rears, the elevated platform test, and self-grooming in male rats exposed for 21 days to social isolation. The rats were treated for 21 days with diazepam (0.2 mg/kg, i.p) or its vehicle. Social isolation led to decreased body weight and vertical rears, more defecations and urinations, increased reluctance to step down from the test platform, shorter duration of grooming, and longer reluctance to start grooming. Chronic diazepam in individually housed rats produced increase in body weight and vertical rears, decrease in the number of defecations and urinations, and shortening of the time of reluctance to step down from the platform. The number of grooming bouts, their duration, and reluctance to start grooming were not altered by diazepam, but it decreased the percentage of incorrect transitions. The obtained data indicate that chronic diazepam treatment of socially isolated rats changes non-grooming behavior and some grooming behavior parameters. .

The second half of the 20th century, especially the last thirty or so years witnessed an increase in interest related to subjects dealing with the roots of Christianity, which came about as a consequence of the general identity crisis of the contemporary world. Dan Brown’s novel "Da Vinci Code" published in the USA in 2003, and in 2004 in Serbia, has achieved worldly success in sales has become very popular literature among other works that deal with central characters or norms based on Christian thought. In Serbia and Monte Negro, as well as in other Christian countries, "Da Vinci Code" is the best seller for 2005. This great popularity of the novel tells us that the readership worldwide Christina civilization, including in Serbia, has recognized certain questions relevant to their own respectable lives and identities. Among the Serbian readership, it is not so much the question of the basic norms of the general Christian civilization, but in effect, much more - the reality of living in transition. Dan Brown’s "Da Vinci Code" has thus became, a true trial-step-stone of identification, pointing out that the images of our everyday reality are not after all only those of the past and isolation, perhaps them being not even the dominant any more. At the same time, the novel shows how a text could be interpreted in many various ways becoming so a foundation for opposed identifications.

The paper discuses the relationship between an ideal and real model of a family organization in patriarchal communities, the position of an individual within his family structure, and possibilities of creation and realization of an individual identity. The main assumption is that the creation of an individual identity within patriarchal relationships is encouraged only in stable socio-economic conditions, while crisis situations bring about the return of family/group identity, defined by an ideal model of a family organization. This assumption is confirmed on the example of refugees: in a crisis situation the principle of cooperation and disregard of interpersonal tensions become dominant over display of individual ambitions - and this is proven to be the only modus of survival. Such periods were frequent, and last until this day, so the model of cooperation as a basis of functioning of a Balkans patriarchal family reinvents itself in almost every generation. Some ideal images of the past still live, but they refer to better, wealthier and more stable life, while interfamily relations remain the same.

This paper discusses possible application of ethnographic research in the realm of virtual reality, especially in the relationship between cultures in virtual communities. This represents an entirely new area of ethnographic research and therefore many adjustments in the research design are needed for example, a development of a specific method of data gathering and tools for their verification. A virtual, cyber space is a version of social space more or less synchronous with it, but without the, "real", that is, physical presence of the people who create it. This virtual reality, defined and bounded by virtual space, is in fact real - and though we are not able to observe real, physical parameters of its existence, we can perceive its consequences. In sum, an innovative ethnographic research method is fully applicable for exploring the realm of virtual reality; in order to do so we need to expand, in addition to the new research design and methods, the field of science itself.

Although physical geography has a long tradition, its faster development started since the establishing of Geography Institute in 1893. At first geomorphology was developed, then climatology, mathematical geography and hydrology and much later biogeography and paleogeography. In the past period, the schedule of physically geographical subjects didn't change much but as for scientific development, physical geography is in constant ascent. Through basic and graduate studies, it trains young geography staff for scientific research, but also for practical work in various fields of social life.

(1) Background: Physical activity may cause an imbalance in the major functions of the human body. This study aimed to investigate the effects of endurance running training on the parameters of the antioxidant defense system (SOD, CAT, GPx, GR, GSH), LPO (malondialdehyde, MDA), and stress hormones (A, NA) in young healthy, previously untrained men. (2) Methods: The training program was as follows: 8 weeks of running, three times per week; the duration of a single session was 30-70 min, the intensity was twice a week in the so-called extensive endurance zone, and once a week in the anaerobic threshold zone. Blood samples were collected from the subjects, before and after the running program. (3) Results: The training program resulted in a significant increase in maximal oxygen consumption ( p < 0.001). The activities of SOD, GPx, and GR also increased significantly ( p < 0.05, p < 0.01, and p < 0.05, respectively), while CAT activity and GSH and MDA concentrations remained unchanged. The concentration of A decreased ( p < 0.05), while the NA concentration increased significantly ( p < 0.05). SOD, GPx, GR, and NA positively correlated with VO 2 max ( p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively), while a negative correlation was detected between A and VO 2 max ( p < 0.05). (4) Conclusions: These results indicate that there is no persistent oxidative stress in response to the applied 8-week running program, probably due to exercise-induced protective alterations in the antioxidant defense system. Furthermore, adaptations occurred at the hormonal level, making the organism more ready for a new challenge.

Background: This study aimed to investigate the effects of lithium treatment on gene expression and activity of the prefrontal antioxidant enzymes: copper, zinc superoxide dismutase (SOD1), manganes superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPx) in animals exposed to chronic restraint stress (CRS)., Methods: The investigated parameters were quantified using real-time RT-PCR, Western blot analyses, and assays of enzyme activities., Results: We found that lithium treatment decreased gene expression of SOD2, as well as the activities of SOD1 and SOD2 in chronically stressed rats to the levels found in unstressed animals. However, lithium treatment in animals exposed to CRS increased prefrontal GPx activity to the levels found in unstressed animals., Conclusions: These findings confirm that treatment with lithium induced the modulation of prefrontal antioxidant status in chronically stressed rats. Our results may be very important in biomedical research for understanding the role of lithium in maintaining the stability of prefrontal antioxidant defense system in neuropsychiatric disorders caused by chronic stress., Competing Interests: The authors declare that they have no competing interests., (© 2022 Gavrilović et al.)

Introduction: The oxidative stress contributes to all three phases of carcinogenesis and represents a concomitant condition in renal cell carcinoma (RCC). RCC is the most common type of neoplasm of the kidney, and despite numerous studies the set of predictive and prognostic markers of survival are still unknown. The aim of our study was to examine the relation between antioxidant (AO) status and overall survival (OS) in RCC patients., Material and Methods: Our study included 95 patients with RCC, who underwent radical nephrectomy. We analysed the prognostic role of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glutathione, and malondialdehyde) and other clinicopathological factors (size, grade, stage, and histological subtype) on the OS of RCC patients., Results: The 5-year OS was 54.6%. The survival analysis related to AO parameters showed no significant difference in survival of RCC patients. The concentration of malondialdehyde, an indicator of lipid peroxidation, also had no significant effect on the survival rate of RCC patients. Univariate and multivariate analysis confirmed the significance of clinicopathological parameters (size, p < 0.001; Fuhrman grade, p = 0.001, and stage, p < 0.001) for patients' survival., Conclusions: In our cohort of patients, different antioxidant parameters were not found to be predictors for OS of patients with RCC, who underwent radical nephrectomy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

We previously found that compared to patients with benign uterine diseases (polyps, myomas), patients with premalignant (hyperplasia simplex and complex) and malignant (adenocarcinoma) lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme (AOE) activities. To further elucidate the mechanism of the observed changes, we examined protein and mRNA levels of copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and transcription factor Nrf2. We also examined correlations of AOE expression with AOE activity, lipid hydroperoxides (LOOH) level, and level of Nrf2. Our results showed decreased CuZnSOD, CAT, and Nrf2 levels, and increased GPx and GR levels in hyperplasias, while in patients with adenocarcinoma, the level of CAT was decreased and GR was increased, compared to benign groups. Similar changes in mRNA levels were also detected, indicating predominantly translational control of the AOE expression. The positive correlation of enzyme expression/activity was recorded for CuZnSOD, GPx, and GR, but only among groups with benign diseases. Only GR and GPx expressions were positively correlated with LOOH. Nrf2 protein was positively correlated with mRNA levels of CuZnSOD and GR. Observed results indicate involvement of diverse redox mechanisms in etiopathogenesis of different gynecological diseases, and may improve redox-based approaches in current clinical practice.

This study examined the effects of lithium on gene expression and activity of the antioxidant enzymes copper zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in the hippocampus of chronically stressed rats. In addition, we examined the effects of lithium on anxiety behaviors, hippocampal concentrations of dopamine (DA) and malondialdehyde (MDA), protein levels of brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT), as well as activity of monoamine oxidase (MAO) in chronically stressed rats. The investigated parameters were quantified by real-time RT-PCR, Western blot analyses, and assays of enzyme activities. We found that lithium did not change gene expression of SOD1, CAT, GPx, and GR but decreased gene expression of SOD2 in chronically stressed rats. A very important result in this study was that lithium treatment decreased the enzyme activities of SOD1 and SOD2 but increased the enzyme activities of GPx and GR in stress condition, which indicates the control of redox balance. The reduced concentration of MDA confirms this. In addition, we found that lithium treatment decreased high protein levels of BDNF and DAT in chronically stressed rats to the level found in unstressed animals. Also, lithium treatment increased the expression of TH but decreased the enzyme activity of MAO B, which contributed to the increase of hippocampal concentration of DA in chronically stressed rats to the level of unstressed animals. Finally, lithium treatment in animals exposed to chronic stress increased the time spent in open arms. Lithium-induced modulation of hippocampal antioxidant status and attenuation of oxidative stress stabilized behavior in animals with high anxiety index. In addition, reduced oxidative stress was followed by the changes of both turnover of DA and levels of BDNF protein in chronically stressed rats treated with lithium. These findings may be important in preclinical research of the effects of lithium on oxidative stress level in pathological conditions.

Endometrial tissue is under a strong influence of sex hormones. These hormones are considered as developmental factors of endometrial hyperplasia and endometrial cancer. We examined the influence of gonadotropins (follicle-stimulating and luteinizing hormone) and sex hormones (estradiol, progesterone) on oxidant/antioxidant parameters in blood and endometrial tissue of women with complex endometrial hyperplasia. In blood, superoxide dismutase activity was significantly higher in luteal phase and postmenopause compared to the follicular phase. A significant phase-related difference of glutathione peroxidase and glutathione reductase activity was recorded in the endometrium. Both enzymes had lower activity in luteal phase and postmenopause compared to the follicular phase. The linear regression analysis of individual hormonal variables against antioxidant parameters showed negative correlation between glutathione peroxidase activity and gonadotropin concentrations in the endometrium. The regression of hyperplastic to normal endometrium is the purpose of conservative treatment based on administration of progestogens or gonadotropin-releasing hormone analogues. Our findings indicate that gonadotropins influence the antioxidant enzymes activity in women with complex endometrial hyperplasia, which may affect disease development. Further studies are needed to clarify the molecular basis of hormone action on antioxidant system that may potentially initiate a development of treatments based on redox-dependent mechanism.

Purpose: Previously, we examined manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), and catalase (CAT) activities in rat brain irradiated with 2 or 3 Gy of γ-rays. The results indicated that lower MnSOD activity and inducibility found in hippocampus might explain higher radiosensitivity of this brain region. Thus, in this study, we wanted to determine changes of MnSOD, CuZnSOD, and CAT activities after dose of 5 Gy and to find out if differences in MnSOD activity are caused by changes in its expression., Methods: Heads of 4-day-old female rats were irradiated with γ-rays, using (60)Co. Animals were sacrificed 1/24 h after exposure. Hippocampus and cortex tissues were prepared for enzyme activity measurements and Western blot analysis., Results: One hour after exposure, γ-rays significantly decreased MnSOD activity in both examined brain regions. Twenty-four hours later, MnSOD recovery showed dose and regional dependence. It was weaker at higher doses and in hippocampal region. MnSOD expression changed in the similar manner as MnSOD activity only at lower doses of γ-rays. In both examined brain regions, gamma radiation significantly decreased CuZnSOD activity and did not change activity of CAT., Conclusions: Our results confirmed that MnSOD plays an important role in different regional radiosensitivity but also showed that depending on dose, radiation affects MnSOD level by utterly different mechanisms. Postradiation changes of CuZnSOD and CAT are not regionally specific and therefore, cannot account for the different radiosensitivity of the hippocampus and cortex.

Uterine leiomyomas are benign soft-tissues tumors that arise from uterine smooth muscle tissue. Etiopathogenesis of leiomyomas is not well understood. We aimed to examine whether antioxidant enzyme activities and lipid hydroperoxides level in patients with leiomyoma are influenced by changes in sex hormones and gonadotropins (estradiol (E2), progesterone, FSH, and LH) during menstrual cycle and in postmenopause. The material consisted of blood and uterine tissue specimens. Hormone concentrations were determined and assays for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and lipid hydroperoxides concentration were performed. In blood of examined women, a significant difference in catalase, glutathione peroxidase and glutathione reductase activity was recorded among the phases. There was also a positive correlation between the estradiol/progesterone concentration and the catalase activity. Progesterone negatively correlated with lipid hydroperoxides level. In myoma tissue, we recorded a phase-related difference in lipid hydroperoxides level and activities of superoxide dismutase, glutathione peroxidase activities, and glutathione reductase. Negative correlation was observed between FSH and glutathione peroxidase. The results suggest that antioxidant status in patients with uterine leiomyoma is influenced by the changes in sex hormones during the menstrual cycle and in postmenopause, indicating a role of the observed relationship in the leiomyoma etiology.

Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

Treadmill training produces modulation of neuro-endocrine and immune functions. This study examined the effects of chronic forced running (CFR) on the plasma concentration of catecholamines and the expression of splenic catecholamine biosynthetic enzymes in rats by using real-time RT-PCR and Western blot analyses. We found that CFR increases the plasma catecholamine levels, decreases splenic tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels and increases splenic PNMT protein levels. This shows that CFR is a very strong stressor which activates the sympatho-adrenomedullary system and increases synthesis of splenic PNMT by 20%, which both can modulate the immune function., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro- and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSH-related antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.

Reactive oxygen species (ROS) are independently recognized to play a significant role in radiation-induced damage on healthy tissue and in aging process. However, an age-related alteration of antioxidant (AO) system in radiation response in humans is poorly investigated. The aim of this paper was to evaluate the irradiation effects on the activities and expression of AO system in the blood of healthy women during aging. Blood samples were irradiated with curative and palliative doses of 2 Gy or 9 Gy γ-rays. AO capacity for detoxification of O(2)•(-) and H(2)O(2) in response to 2 Gy γ-irradiation decreases in women above 58 years, while in response to 9 Gy shows signs of weakening after 45 years of age. Due to reduction of AO capacity during aging, cytotoxic effects of curative and palliative doses of irradiation, mediated by ROS, may significantly increase in older subjects, while removal of H(2)O(2) excess could reduce them.

Sensitivity of target cells to glucocorticoids is regulated by the expression of intracellular glucocorticoid receptor (GR), which mediates the effects of glucocorticoids. The level of GR and of its nuclear transporter protein 70 (Hsp70) were followed in hippocampus and brain cortex of adult Wistar rat males exposed to acute (immobilization, cold) and chronic (social isolation, isolation, and 15 min daily swimming) stress or their combinations. Changes in plasma levels of adenocorticotropic hormone and corticosterone were also studied. A significant decrease in cytosol GR and Hsp70 was observed after acute stress. Opposite to that, chronic stress led to negligible changes in both cytosol GR and Hsp70 levels. Isolation, as chronic psychosocial stressor, caused reduced responsiveness to novel acute stressors, judged by the cytosol GR and Hsp70 levels. This was not observed if chronic isolation was combined with 15 min daily swimming prior to acute exposure to immobilization. The data suggest that repeated physical exercise may, at least in some cases, diminish detrimental effects of chronic social isolation on limbic-hypothalamic-pituitary-adrenocortical axis, as judged by the levels of GR and Hsp70 in the Wistar rat brain.

The pattern and intensity of glucocorticoid receptor (GR) and heat shock 70 protein (Hsp 70) changes in the hippocampus and brain cortex of adult Wistar rat males exposed to acute (immobilization, cold) and chronic (social isolation, crowding, daily swimming) stress or their combinations were followed by Western immunoblotting. Plasma ACTH and CORT were measured by chemiluminescent method and RIA. A significant decrease in cytosol GR and Hsp 70 was observed after acute stress, while chronic stresses led to negligible changes in both these proteins and caused a reduced responsiveness to a novel acute stress. This was valid irrespective of the type of chronic or acute stress combinations for both hippocampal and cortical GR and Hsp 70. The results support the hypothesis that chronic stress-induced deregulation of the LHPA axis may be caused, at least in part, by partial disruption of intracelullar negative feedback control in the higher centers of the brain., (Copyright 2005 S. Karger AG, Basel.)

Changes in plasma levels of noradrenaline (NA), adrenaline (A), adrenocorticotropic hormone (ACTH) and corticosterone (CORT), as well as in cytosol glucocorticoid receptor (GR) and heat shock protein 70 (Hsp 70) in hippocampus of adult rat males exposed to two long-term types of psychosocial stress, both under basal conditions and in response to immobilization and cold as heterotypic additional stressor were studied. Long-term isolation produced a significant elevation of basal plasma ACTH and CORT levels, but did not affect that of NA and A, while long-term crowding conditions did not elevate the basal plasma levels of these hormones. Long-term isolation of rats exposed to 2 h of immobilization or cold led to a significant elevation of plasma NA, A and CORT in comparison with the controls. Long-term crowding conditions and exposure of animals to immobilization or cold also resulted in an increased plasma NA, A and CORT levels, but to a lesser extent in comparison with the long-term isolation. At the same time, plasma ACTH was significantly more elevated in long-term crowded than in long-term isolated rats. Both kinds of long-term psychosocial stresses (isolation and crowding) had similar but less pronounced effects on cytosol GR and Hsp 70 concentrations in hippocampus comparing to acute immobilization and cold stress. It seems that long-term psychosocial stresses attenuate the effects of an additional stress on hippocampal GR and Hsp 70 concentrations. These data suggest that individual housing of rats appear to act as a stronger stressor than crowding conditions. When the animals suffering a long-term isolation were exposed to either acute immobilization or cold, a stronger activation of the sympatho-adrenomedullary system (SAS) was recorded in comparison with that found in the long-term crowded group subjected to short-term immobilization or cold. No significant differences in the activity of hypotalamo-pituitary-adrenal (HPA) axis were observed between long-term isolated and long-term crowded rats.