Possible role of a hydrogen peroxide-mediated mechanism in glucocorticoid receptor functional alterations associated with moderate asthma

It is well known that pathogenesis and maintenance of chronic asthma is associated with alterations of glucocorticoid receptor (GR) function, and also with persistent pulmonary inflammation, the important mediators of which are reactive oxygen and nitrogen species. In this paper, we tested a hypothesis that GR functional alterations in asthma result from the action of oxidants. To that end, we conducted a series of ex vivo treatments of peripheral blood mononuclear cells (PBMCs) of healthy donors with oxidizing agents (3 morpholinosydnonimine, SIN1; S-nitroso-N-acetyl-penicillamine, SNAP; and hydrogen peroxide, H2O2) and compared the resulting GR modifications with those previously noticed in asthmatic patients. The results show that treatment of PBMCs by H2O2 provoked an increase in the level of GR protein, accompanied by a rise in the number of hormone-binding sites and a decline in the receptor's affinity for the hormone. The H2O2 induced changes, including a characteristic GR isoprotein expression pattern, were found to be very similar to the GR changes previously observed in PBMCs of moderate asthmatic patients, but not in mild asthmatics and healthy subjects. Treatment with the other oxidants applied herein produced different effects or exerted no influence on GR. Thus, this study provides preliminary data suggesting that functional alterations of the GR associated with moderate asthma may be mediated by redox mechanisms that are based on oxidative and regulatory actions of H2O2

Changes of antioxidant enzyme activity and heat shock protein content in lymphocytes of children with asthma

The aim of the present study was to examine whether changes in the antioxidant status and expression of major intracellular stress proteins are associated with pathophysiology of childhood asthma and severity of the disease. The activities of copper/zinc (CuZn) and manganese (Mn) superoxide dismutase (SOD) and catalase (CAT) in peripheral blood mononuclear cells (PBMCs) of 28 stable pediatric patients (11 mild persistent and 17 moderate persistent asthmatics) and 12 healthy children were assessed by native gel assays. The levels of two heat shock proteins (HSPs), Hsp70 and Hsp90, were examined by quantitative Western blot analysis. Moderate asthmatics, in comparison to healthy children, displayed higher activity of CuZnSOD, while differences of MnSOD and CAT activity between the groups of patients were not found. The levels of Hsp90 and the inducible isoform of Hsp70 were increased in moderate asthmatics as compared to mild asthmatics and healthy children. The results demonstrate an imbalance in cellular antioxidant and stress response systems that may contribute to pathogenesis of childhood asthma, but are not necessarily related to severity of the disease.Cilj ove studije bio je da se ispita da li su promene antioksidativnog statusa i ekspresije glavnih unutar ćelijskih stres proteina povezane sa patogenezom astme i težinom ovog oboljenja kod dece. Aktivnost bakar/cink(CuZn)-i mangan (Mn)-superoksid dismutaze (SOD), i katalaze (CAT) u mononuklearnim ćelijama iz periferne krvi 28 dece sa stabilnom astmom (11 sa blagim i 17 sa srednje teškim oblikom bolesti) i 12 zdrave dece ispitana je enzimskim testom u nativnom gelu. Koncentracije dva ispitivana proteina toplotnog stresa, Hsp70 i Hsp90, određene su tehnikom kvantitativnog imunoblota. Pacijenti sa srednje teškom astmom pokazali su povećanu aktivnost CuZn-SOD upoređenju sa zdravom decom, dok razlike u aktivnosti Mn-SOD i CAT između ispitivanih grupa pacijenata nisu zapažene. Nivo Hsp90 i inducibilne izoforme Hsp70 bio je povećan kod srednje teških astmatičara upoređenju sa blagim astmatičarima i zdravom decom. Rezultati ukazuju da disbalans u ćelijskom antioksidativnom i anti-stres sistemu može doprineti patofiziologiji dečje astme, ali ne mora biti povezan sa težinom oboljenja.nul

Differences in engineers' brain activity when CAD modelling from isometric and orthographic projections

A way of presenting information in visual representations of technical systems influences the progress and the outcome of the engineering design process. Consequently, improving the means by and through which information is utilised during the process is one suggested approach to advancing engineering design. Engineers' interaction with visual representations of technical systems is mainly visual and virtual. Although such interactions are cognitively complex, little is known about cognition (mental information processing) underlying the utilisation of design information during engineering design. To narrow the research gap, this study explores how visual representations of technical systems affect engineers' brain activity while generating computer-aided design (CAD) models based on them. More precisely, the brain activity of 20 engineers is captured and analysed using electroencephalography (EEG) during the visuospatially-intensive design tasks of CAD modelling in two conditions; when technical systems are presented with orthographic and isometric projections in technical drawings. The results imply the sensitivity of engineers' brain activity in CAD modelling to the visual representation from which a technical system is interpreted. In particular, significant differences are found in theta, alpha, and beta task-related power (TRP) over the cortex when interpreting the technical drawings and CAD modelling from them. Furthermore, the results reveal significant differences in theta and alpha TRP when considering the individual electrodes, the cortical hemispheres, and the cortical areas. In particular, theta TRP over the right hemisphere and the frontal area seems essential in distinguishing neurocognitive responses to the orthographic and isometric projections. As such, the conducted exploratory study sets the foundations for exploring engineers' brain activity while performing visuospatially-intensive design tasks, whose segments are relatable to the aspects of visuospatial thinking. Future work will explore brain activity in other design activities that are highly visuospatial, with a larger sample size and an EEG device of a higher spatial resolution

Possible role of a hydrogen peroxide-mediated mechanism in glucocorticoid receptor functional alterations associated with moderate asthma

It is well known that pathogenesis and maintenance of chronic asthma is associated with alterations of glucocorticoid receptor (GR) function, and also with persistent pulmonary inflammation, the important mediators of which are reactive oxygen and nitrogen species. In this paper, we tested a hypothesis that GR functional alterations in asthma result from the action of oxidants. To that end, we conducted a series of ex vivo treatments of peripheral blood mononuclear cells (PBMCs) of healthy donors with oxidizing agents (3 morpholinosydnonimine, SIN1; S-nitroso-N-acetyl-penicillamine, SNAP; and hydrogen peroxide, H2O2) and compared the resulting GR modifications with those previously noticed in asthmatic patients. The results show that treatment of PBMCs by H2O2 provoked an increase in the level of GR protein, accompanied by a rise in the number of hormone-binding sites and a decline in the receptor's affinity for the hormone. The H2O2 induced changes, including a characteristic GR isoprotein expression pattern, were found to be very similar to the GR changes previously observed in PBMCs of moderate asthmatic patients, but not in mild asthmatics and healthy subjects. Treatment with the other oxidants applied herein produced different effects or exerted no influence on GR. Thus, this study provides preliminary data suggesting that functional alterations of the GR associated with moderate asthma may be mediated by redox mechanisms that are based on oxidative and regulatory actions of H2O2.Poznato je da su patogeneza i napredovanje hronične astme povezani sa funkcionalnim promenama glukokortikoidnog receptora (GR) i dugotrajnom inflamacijom disajnih puteva, čiji su medijatori reaktivne vrste kiseonika i azota. U ovom radu testirali smo hipotezu da funkcionalne promene GRu astmi nastaju kao posledica delovanja oksidanata. U tom cilju sproveli smo seriju ex vivo tretmana mononuklearnih ćelija periferne krvi zdravih donora oksidujućim agensima (3-morfolinosidnoniminom, SIN-1; S-nitrozo-N-acetil-penicilaminom, SNAP; i vodonik peroksidom, H2O2) i uporedili nastale modifikacije GR sa onima koje su ranije zapažene kod astmatičnih pacijenata. Rezultati su pokazali da je tretman perifernih limfocita vodonik peroksidom izazvao povećanje koncentracije GR proteina, koje je bilo praćeno povećanjem broja mesta vezivanja hormona i smanjenjem afiniteta receptora prema hormonu. Promene indukovane vodonik peroksidom, uključujući i karakterističnu ekspresiju izoformi GR proteina, bile su vrlo slične promenama koje su ranije zapažene u perifernim limfocitima pacijenata obolelih od srednje teškog oblika astme, ali ne i kod blagih astmatičara i zdravih donora. Tretman drugim primenjenim oksidantima proizveo je drugačije efekte, ili nije imao uticaja na GR. Prema tome, ova studija je dala preliminarne podatke koji ukazuju da su funkcionalne promene GR povezane sa srednje teškom astmom verovatno posredovane redoks mehanizmima koji se zasnivaju na oksidativnoj i regulatornoj ulozi vodonikperoksida.Projekat ministarstva br. 14300

Normal and reversed phase high performance liquid chromatography of some new 1, 2, 4-triazole derivatives

The retention behaviour and separation ability of normal and reversed phase HPLC with one non-polar and two polar mobile phases, have been studied by measuring the retention constants of a series of newly synthesized 1,2,4-triazole derivatives. The results are discussed in terms of the nature of the solute, eluent and stationary phase

Geopolitičko ponašanje savremene Turske

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Role of ovarian hormones in thymic involution in rats

Timus je primarni limfoidni organ koji obezbeđuje mikrosredinu neophodnu za diferencijaciju/sazrevanje T-limfocita. Tokom ontogeneze, ovaj organ trpi značajne strukturne i funkcionalne promene koje se zbirno označavaju kao involucija timusa, i manifestuju se kao smanjena efikasnosti timopoeze i posledično, smanjen izlazak novoformiranih T-limfocita na periferiju. Involucija timusa je kod glodara najizraženija u periodu sticanja polne zrelosti. Veliki broj literaturnih podataka ukazuje na to da hormoni hipotalamo-hipofizo-gonadne (H-H-G) osovine, pre svega hormoni gonada, utiču na razvoj i involuciju timusa. Međutim, uprkos brojnim istraživanjima u proteklim decenijama, uloga hormona jajnika u inicijaciji i održavanju/progresiji involucije timusa nije do kraja rasvetljena. Cilj ove doktorske disertacije je bio da se ispita uloga hormona jajnika u inicijaciji i održavanju/progresiji involucije timusa. U tom cilju ispitivan je uticaj jednokratnog davanja testosterona u kritičnom neonatalnom uzrastu, koji dovodi do odlaganja sazrevanja H-H-G osovine i promena u obrascu sekrecije hormona jajnika kod adultnih životinja (neonatalna androgenizacija) i uklanjanja jajnika ženkama pacova u uzrastu od 10 meseci, kada su involutivne promene timusa jasno izražene, na građu timusa i timopoezu u ranom adultnom uzrastu; odnosno u uzrastu od 11 meseci. Posebno je ispitivan, mogući, indirektan uticaj promena u sekreciji hormona jajnika na aktivnost timusnog kateholaminergičkog regulatornog sistema. Neonatalna androgenizacija, delujući na različite stadijume diferencijacije/sazrevanja T-ćelija, od ulaska/diferencijacije progenitorskih ćelija do linijskog usmeravanja timocita, povećala je efikasnost timopoeze (na osnovu većeg broja svežih timusnih emigranata u perifernoj krvi i slezini), uključujući, najverovatnije, i povećano stvaranje ćelija regulatornog fenotipa (CD4+CD25+FoxP3+ i CD161+TCRαβ+ ćelije). Pored toga, kod ovih životinja je uočeno favorizovano stvaranje ćelija CD4-CD8+TCRαβ++ fenotipa (fenotipska defeminizacija/maskulinizacija procesa timopoeze). Uprkos povećanoj efikasnosti timopoeze, nepromenjena relativna zastupljenost timusnih epitelnih ćelija (TEC) kao i nivo iRNK za IL-6, a smanjen nivo iRNK za IL-7 u tkivu timusa, ukazuju, da je kod neonatalno androgenizovanih životinja, u uzrastu od 3 meseca, najverovatnije, došlo do pokretanja mehanizama negativne povratne sprege, koji ograničavaju ekspanziju TEC i timopoezu. Ovarijektomija u uzrastu od 10 meseci, nakon 30. dana, imala je za posledicu povećanje relativne zastupljenosti TEC i efikasnosti timopoeze (uključujući i povećano stvaranje ćelija regulatornog fenotipa), što se manifestovalo povećanim brojem svežih timusnih emigranata CD4+ i CD8+ fenotipa u perifernoj krvi i slezini. Međutim, uprkos regeneraciji epitelne komponente timusa i povećanoj efikasnosti timopoeze, smanjen nivo iRNK za IL-6 i IL-7 u tkivu timusa ovarijektomisani životinja sugeriše da je kod ovih životinja došlo do aktivacije intratimusnih mehanizama negativne povratne sprege koji ograničava ekspanziju TEC koje sintetišu IL-6 i efikasnost timopoeze. U zaključku, nalazi dobijeni u ovoj disertaciji ukazuju da neonatalna androgenizacija menja kinetiku postnatalnog razvoja timusa i polno specifičan obrazac diferencijacije/sazrevanja timocita i odlaže, ali vrlo verovatno ne sprečava involuciju timusa, dok uklanjanje hormona jajnika u uzrastu kada su involutivne promene timusa uznapredovale dovodi do delimične reverzije ovih promena i efikasnije timopoeze, koji su, najverovatnije, vremenski ograničenog trajanja. Pored toga, pokazano je da se uticaj hormona jajnika na ove procese odvija i indirektno, menjanjem efikasnosti modulatornog delovanja noradrenalina na timopoezu.The thymus is a primary lymphoid organ that provides the microenvironment necessary for the differentiation/maturation of T-lymphocytes. During ontogeny, thymus undergoes significant structural and functional changes leading to reduced efficiency of thymopoiesis and, consequently, reduced output of newly generated Tlymphocytes. These changes are collectively referred to as thymic involution. The most profound thymic changes in rodents, occur around puberty. There is an accumulating body of evidence indicating that hormones of the hypothalamic-pituitary-gonadal (H-PG) axis, particularly gonadal hormones, influence thymic development and involution. However, despite extensive research in the past decades, the role of ovarian hormones in the initiation and maintenance/progression of thymic involution is not fully understood. Bearing all aforementioned in mind, this dissertation was aimed to elucidate the role of ovarian hormones in initiation and maintenance/progression of thymic involution. To this end the effects of single injection of testosterone in critical postnatal period, which postpones H-P-G axis maturation and affects the gender-specific pattern of gonadal hormone secretion in adult animals (neonatal androgenization), and ovarian hormone removal in rats with advanced thymic involutive changes (10-month-old), on thymic structure and function, were examined in 3-month-old and 11-month-old female rats, respectively. In addition, the putative indirect, catecholamine-mediated effects of the neonatal androgenization and ovariectomy on thymopoiesis were explored. Neonatal androgenization, affecting distinct stages of thymocyte differentiation/maturation (from progenitor cell entry and differentiation to thymocyte lineage commitment), increased the efficiency of thymopoiesis and consequently thymic output (as evidenced by the increased number of recent thymic emigrants in peripheral blood and spleen), including, most likely, increased output of the cells with regulatory phenotype (CD4+CD25+FoxP3+ and CD161+TCRαβ+ cells). In addition, neonatal treatment with testosterone skewed thymocyte lineage commitment towards CD4-CD8+TCRαβ++ cells (phenotypic defeminization/masculinization of thymopoiesis). Despite the increased efficiency of thymopoiesis, unaltered relative abundance of thymic epithelial cells (TEC) and the thymic level of IL-6 mRNA, and reduced thymic level of IL-7 mRNA, indicated, most likely, activation of intrathymic negative feedback mechanisms limiting TEC proliferation and thymopoiesis in 3- month-old neonatally androgenized rats. Ovariectomy at the age of 10 months led to the expansion of TECs and greater efficiency of thymopoiesis (including generation of cells with regulatory phenotype), increasing the number of both CD4+ and CD8+ recent thymic emigrants in peripheral blood and spleen of 11-month-old rats, compared with age-matched controls. However, despite the regeneration of the thymic epithelial component and increased efficiency of thymopoiesis, reduced thymic levels of mRNA for IL-6 and IL-7 in ovariectomized rats indicated activation of intrathymic negative feedback mechanisms limiting the expansion of IL-6-synthesizing TECs and thymopoietic efficiency in these animals. In conclusion, the data obtained in this dissertation indicate that neonatal androgenization alters the kinetics of postnatal thymic development and sex-specific pattern of thymocyte differentiation/maturation and postpones thymic involution, but, most likely, does not prevent it completely. The removal of ovarian hormones in female rats with advanced thymic involutive changes leads to partial reversion of these changes, and an increase in thymopoietic efficiency of, most likely, limited duration. In addition, these data indicate that ovarian hormones might affect thymic development/involution not only directly, but also indirectly by diminishing the efficiency of noradrenaline-mediated modulation of thymopoiesis

Odgajivačka strategija u malim i zatvorenim populacijama domaćih životinja

This paper reviews the main characteristics of small and/or closed livestock populations. Although the emphasis during the realization of the genetic improvement in animal breeding is put on commercial breeding programmes, autochthonous breeds, races, strains, even herds of domestic animas, at the same time represent a potentially important segment for achieving the maintenance of the overall livestock production. These programmes are particularly important for the improvement of populations of animal genetic resources, as well as for the improvement of production in rural marginal areas. One of the main parameters for determining the size, and also the potential danger of a population is a so called effective size of the population (Ne). This parameter is determined according to the available number of male and female head of breeding stock in the population or in the herd and it varies under the influence of the sexes, changes in the size of the families, changes in the size of the population during time, as well as overlapping of the generations. Apart from the improvement of the economically important traits, the breeding programmes in small populations first of all must provide the increase of the effective size of the population aiming to limit or decrease the inbreeding, as well as the decrease of the variance in the size of the family. This is mainly achieved with so called "circular breeding plans" the sires being replaced by sons in the reproduction, and dams by daughters. The shortage of the generation interval by the change of the presence of some age categories i.e. larger number of young animals and animals that are at the peak of production comparing to a small number of older animals, can additionally influence on the genetic improvement of the traits.U radu su prikazane osnovne karakteristike malih i/ili zatvorenih populacija domaćih i gajenih životinja. Iako se akcenat prilikom realizacije genetskog unapređenja u stočarstvu stavlja na komercijalne odgajivačke programe, autohtone vrste, rase, sojevi, pa i zapati domaćih životinja, takođe predstavljaju potencijalno važan segment za dostizanje održivosti celokupne stočarske proizvodnje. Ovi programi su naročito značajni za unapređenje populacija animalnih genetskih resursa, kao i za unapređenje proizvodnje u ruralnim marginalnim oblastima. Jedan od osnovnih parametara za određivanje veličine, pa samim tim i potencijalne ugroženosti jedne populacije jeste tzv. efektivna veličina populacije (Ne). Ovaj parametar se određuje na osnovu raspoloživog broja priplodnjaka i plotkinja u populaciji ili zapatu i varira pod uticajem odnosa polova, promena u veličini familija, promena u veličini populacije tokom vremena, kao i preklapanja generacija. Pored unapređenja ekonomski važnih osobina, odgajivački programi u malim populacijama na prvom mestu moraju obezbediti povećanje efektivne veličine populacije sa ciljem ograničavanja ili smanjivanja inbreeding-a, kao i smanjivanja varijanse u veličini familije. To se uglavnom postiže tzv. "cirkularnim odgajivačkim planovima" u kojima očeve u reprodukciji zamenjuju sinovi, a majke kćeri. Skraćenje generacijskog intervala promenom zastupljenosti pojedinih starosnih kategorija u smislu veće zastupljenosti mladih grla i grla koja su u vrhu proizvodnje, a na račun starijih grla, može dodatno uticati na genetsko unapređenje osobina

Uticaj veličine farmi na osobine mlečnosti krava

Objective of this study was to analyze the effect of the dairy farm on milk traits of cows in Vojvodina. The research was carried out on small farms with 10 to 20 cows, medium farms with 20 to 50 cows, and large farms with over 50 dairy cows. The study included registered animals of Simmental (SM) and Holstein-Friesian breed (HF; including Red Holstein) in the first lactation for traits of milk yield and yield and content of milk fat. Total of 1323 first lactations were analyzed. The average milk yield (both breeds) in the first lactation of 305 days was 6295 kg of milk with 234,3 kg of milk fat and average milk fat content of 3,74%. Milk performance of cows varied significantly (CV=22,9% and SD=1447,8), as well as milk fat yield (CV=21,6% and SD=50,8). Large farms produced in average 6534 kg of milk, medium farms 6347kg and small farms 4717kg. Size of the farm exhibited significantly high effect on all observed traits, and the tendency was that farms with higher number of animals realize also higher average of production. Farm management and various breeding-zootechnical conditions present on farms had significant effect on milk performance of cows.Cilj rada je da se ispita uticaj veličine govedarske farme na osobine mlečnosti u Vojvodini. U odnosu na veličinu farme, ispitivanje je sprovedeno na malim farmama sa 10 do 20 krava, srednje velikim od 20 do 50 i velikim sa preko 50 krava. Ispitivanje je obuhvatilo umatičena grla simentalske (SM) i holštajnfrizijske rase (HF; uključujući i crveni holštajn) u prvoj laktaciji za osobine prinosa mleka, mlečne masti i sadržaja mlečne masti. Ukupno je analizirano 1323 prvih laktacija. Prosečna mlečnost krava (obe rase) u prvoj laktaciji za 305 dana je iznosila 6295 kg mleka sa 234,3 kg mlečne masti i prosečnim sadržajem masti od 3,74%. Mlečnosti krava je značajno varirala (CV=22,9% i SD=1447,8) kao i prinos mlečne masti (CV=21,6% i SD=50,8). Velike farme su prosečno proizvele 6534 kg, srednje 6347 kg i male 4717 kg. Veličina farme je ispoljila signifikantno visok uticaj na sve posmatrane osobine a tendencija je da se na farmama sa većim brojem grla ostvaruje prosečno veća proizvodnja. Farmski menadžment i različiti odgajivačko zootehnički uslovi na farmama su ostvarili značajan uticaj na mlečnost krava

Simentalska rasa goveda u različitim sistemima proizvodnje

The paper gives the analysis on the state in population of Simmental cattle reared in Europe with a special review on the state in Simmental cattle in our country which makes about 80 % total cattle fund in Serbia, and is characterized by a negative trend in the number of cattle, as well as by a low average milk production per cow. The most important results obtained by both domestic and foreign authors by means of various methods of improving Simmental breed and its raising in different systems have been shown. The directions for improving Simmental cattle according to the productive directions have been analyzed. Possible methods of improving the Simmental cattle in our country have been pointed out, which should be in accordance with already existing genetic potential of each actual population, its purpose (registered breeding stock, production breeding stock), as well as with the market needs for cow milk, milk products and meat (primarily beef meat, for export). A special emphasis has been given to the importance of organizing the production of meat in the cow-calf system in which Simmental breed, following the model of many European countries, should have good performance also in our country, if the same production should be organized in deserted hilly and mountainous regions. In this way we could contribute to more significant increase in overall beef production, and to reactivate unused natural resources as well.Analizirano je stanje u populaciji simentalskih goveda koja se gaje u Evropi, sa posebnim osvrtom na stanje simentalske rase kod nas, koja u poslednje dve decenije čini između 80 i 85 % ukupnog fonda goveda Srbije, a koju prati negativni trend brojnosti (veličini populacije), kao i niska prosečna proizvodnja mleka po kravi. Analizirani su pravci oplemenjivanja simentalskih goveda u skladu sa smerovima proizvodnje. Ukazano je na moguće metode oplemenjivanja simentalske rase kod nas, koje bi morale biti u skladu sa postojećim genetskim potencijalom svake konkretne populacije, njenom namenom (matični zapati, proizvodni zapati), kao i u skladu sa potrebama tržišta za kravljim mlekom i mlečnim proizvodima. Kao metod oplemenjivanja simentalske rase kombinovanog smera proizvodnje do sada je više primenjivan metod selekcije u čistoj rasi. Metod meliorativnog ukrštanja simentalske rase sa crvenim holštajnom je značajno manje u primeni i više ga sprovode odgajivači proizvodnih zapata goveda simentalske rase. Poseban akcenat je dat značaju organizovanja proizvodnje mesa u sistemu krava-tele, gde bi simentalska rasa po uzoru na mnoge evropske zemlje i kod nas dala dobre rezultate, ako bi se ista proizvodnja organizovala u napuštenim brdskim i planinskim područjima. Na ovaj način bi se moglo doprineti značajnijem povećanju ukupne proizvodnje junećeg mesa, kao i aktiviranju neiskorišćenih prirodnih resursa, što bi predstavljalo strateški interes države. U cilju povećanja ekonomičnosti u proizvodnji u sistemu krava-tele, neophodno je postizanje maksimalne plodnosti, iz kog razloga bi trebalo redovno primenjivati indukciju i sinhronizaciju estrusa. Sezonu telenja treba planirati u skladu sa konkretnim klimatskim prilikama na konkretnom području, a sve u cilju maksimalnog korišćenja perioda vegetacije (paše) od strane krava i teladi