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Adrenal incidentalomas are unexpectedly identified adrenal masses without prior suspicion of the existence of adrenal disease. The majority of adrenal incidentalomas are benign adrenal adenomas (80–90%), and they are non-functioning adrenocortical adenomas in more than 70% of cases. Mild hypercortisolemia is the most common finding in hormonally active adrenal incidentalomas. It is defined as autonomous cortisol secretion in up to 15% of patients. Despite a lot of research that anticipated higher cardiometabolic risk in patients with autonomous cortisol secretion, there is still no clear consensus on biochemical criteria for an autonomous cortisol secretion diagnosis in patients with adrenal incidentalomas. This review delineates the advantages and limitations of different laboratory tests recommended for the diagnosis of autonomous cortisol secretion in adrenal incidentalomas. Adrenalni incidentalomi predstavljaju vizuelizacionim tehnikama slučajno otkrivene tumore nadbubrežne žlezde, bez prethodne sumnje na postojanje poremećaja funkcije ili bolesti nadbubrega. 80-90% adrenalnih incidentaloma predstavljaju benigne tumore, koji su u preko 70% slučaja nefunkcionalni, dok je kod oko 15% pacijenata sa benignim adrenalnim incidentalomima dokazana autonomna sekrecija kortizola. Iako su rezultati većeg broja istraživanja ukazali na veći kardiometabolički rizik kod pacijenata sa autonomnom sekrecijom kortizola, još uvek ne postoji jasan konsenzus o biohemijskim kriterijumima za postavljanje dijagnoze autonomne sekrecije kortizola kod pacijenata sa adrenalnim incidentalomima. U ovom radu su opisane osnovne prednosti i nedostaci različitih laboratorijskih testova koji se koriste za postavljanje dijagnoze autonomne sekrecije kortizola.

Cilj ove doktorske disertacije je bio da se ispita uticaj upotrebe antiektoparazitika na sprečavanje nastanka hroničnog stresa, kroz određivanje koncentracije kortizola i kortikosterona u krvi, dlaci i mleku, kao i na proizvodne sposobnosti životinja, kroz određivanje količine proizvedenog mleka, sastava mleka i broja somatskih ćelija u mleku. Pre izvođenja samog ogleda utvrđene su bazalne vrednosti kortizola u krvi, dlaci i mleku kod holštajn rase goveda, uz ispitivanje uticaja laktacije i rase na koncentracije ovog hormona. Za utvrđivanje bazalnih vrednosti kortizola u krvi i dlaci odabrano je 25 jedinki holštajn rase (13 krava i 12 junica) i 24 jedinke buša rase (13 krava i 11 junica). Kod istih krava određena je i bazalna vrednost kortizola u mleku, dok je kod junica određena i razlika u koncentraciji kortizola u opranoj i neopranoj dlaci. Kod dodatnih 12 krava holštajn rase i istih junica holštajn rase utvrđena je razlika između konentracije kortizola u beloj i crnoj dlaci. Za ispitivanje vrednosti indikatora stresa u uslovima tretmana antiektoparaziticima odabrano je 26 krava holštajn rase. Ogled je izveden tokom letnjeg perioda 2014. godine. Krave su na početku ogleda podeljene u dve grupe, netretirana (n=13) i tretirana (n=13), ali su zbog pojave mastitisa iz tretirane grupe isključene 3 krave, a iz netretirane 1 krava. Pre izvođenja ogleda posmatranjem i daljom identifikacijom je utvrđeno značajno prisustvo ektoparazita, štalske muve (Stomoxys calcitrans), na kravama. Odabrana grupa krava je tretirana antiektoparazitikom na bazi ciflutrina 0., 28. i 56. dana ogleda. Od svih krava su tokom trajanja ogleda uzimani uzorci krvi, mleka i dlake 0., 21., 42., 63. i 84. dana ogleda (periodi P0, P1, P2, P3 i P4), za određivanje koncentracije kortizola i kortikosterona kao i uzorci mleka za određivanje hemijskog sastava i broja somatskih ćelija u mleku. Takođe, u uzorcima krvi određena je koncentracija glukoze, ukupnih proteina, albumina, globulina, uree, ukupnog bilirubina i aktivnost enzima kreatin kinaze i alkalne fosfataze. Pre određivanja koncentracije kortizola i kortikosterona izvršena je validacija ELISA metode za određivanje ovih parametara u dlaci... The aim of this doctoral dissertation was to examine impact of antie-ctoparasitic drugs usage on chronic stress prevention, by determining of blood, hair and milk cortisol and corticosterone concentrations, as well as on productive capability of animals, by determining milk yield, milk composition and somatic cell count in milk. Before the beginning of the experiment, the basal values of blood, hair and milk cortisol concentrations were established for Holstein breed, including examination of effects of lactation and breed on concentration of this hormone. Twenty five Holstein breed animals (13 cows and 12 heifers) and 24 Busha breed animals (13 cows and 11 heifers) were chosen for determination of blood and hair basal cortisol concentrations. The same cows were used for determination of milk basal cortisol concentrations, while differences in cortisol concentrations between washed and unwashed hair were determined using same heifers. Additional 12 Holstein cows and same heifers were used for estimation of cortisol concentrations difference between white and black hair. Twenty six Holstein cows were included in study for examination of impact of anti-ectoparasitic grugs usage on stress indicators values. Study was obtained during summer season of year 2014. Initially, cows were divided in two groups, non-treated (N=13) and treated (N=13), but due to mastitis, 3 cows from treated and 1 cow from non-treated group were excluded. Before treatment, significant presence of Stable fly ectoparasitic (Stomoxys calcitrans) was obtained on cows, by observation and identification. Treated group of cows was treated with anti-ectoparasitic ciflutrin on days 0., 28. and 56. of experiment. Blood, hair and milk samples were taken from all cows in experiment at days 0., 21., 42., 63. and 84. of experiment (periods P0, P1, P2, P3 and P4), for determining cortisol and corticosterone concentrations, as well as milk samples for determination of milk chemical composition and somatic cell counts. Glucose, total protein, albumin, globulin, urea, total bilirubin concentrations and creatine kinase and alkaline phosphatase activity were also determined in blood samples...

The aim of this doctoral dissertation was to examine impact of antie-ctoparasitic drugs usage on chronic stress prevention, by determining of blood, hair and milk cortisol and corticosterone concentrations, as well as on productive capability of animals, by determining milk yield, milk composition and somatic cell count in milk. Before the beginning of the experiment, the basal values of blood, hair and milk cortisol concentrations were established for Holstein breed, including examination of effects of lactation and breed on concentration of this hormone. Twenty five Holstein breed animals (13 cows and 12 heifers) and 24 Busha breed animals (13 cows and 11 heifers) were chosen for determination of blood and hair basal cortisol concentrations. The same cows were used for determination of milk basal cortisol concentrations, while differences in cortisol concentrations between washed and unwashed hair were determined using same heifers. Additional 12 Holstein cows and same heifers were used for estimation of cortisol concentrations difference between white and black hair. Twenty six Holstein cows were included in study for examination of impact of anti-ectoparasitic grugs usage on stress indicators values. Study was obtained during summer season of year 2014. Initially, cows were divided in two groups, non-treated (N=13) and treated (N=13), but due to mastitis, 3 cows from treated and 1 cow from non-treated group were excluded. Before treatment, significant presence of Stable fly ectoparasitic (Stomoxys calcitrans) was obtained on cows, by observation and identification. Treated group of cows was treated with anti-ectoparasitic ciflutrin on days 0., 28. and 56. of experiment. Blood, hair and milk samples were taken from all cows in experiment at days 0., 21., 42., 63. and 84. of experiment (periods P0, P1, P2, P3 and P4), for determining cortisol and corticosterone concentrations, as well as milk samples for determination of milk chemical composition and somatic cell counts. Glucose, total protein, albumin, globulin, urea, total bilirubin concentrations and creatine kinase and alkaline phosphatase activity were also determined in blood samples... Cilj ove doktorske disertacije je bio da se ispita uticaj upotrebe antiektoparazitika na sprečavanje nastanka hroničnog stresa, kroz određivanje koncentracije kortizola i kortikosterona u krvi, dlaci i mleku, kao i na proizvodne sposobnosti životinja, kroz određivanje količine proizvedenog mleka, sastava mleka i broja somatskih ćelija u mleku. Pre izvođenja samog ogleda utvrđene su bazalne vrednosti kortizola u krvi, dlaci i mleku kod holštajn rase goveda, uz ispitivanje uticaja laktacije i rase na koncentracije ovog hormona. Za utvrđivanje bazalnih vrednosti kortizola u krvi i dlaci odabrano je 25 jedinki holštajn rase (13 krava i 12 junica) i 24 jedinke buša rase (13 krava i 11 junica). Kod istih krava određena je i bazalna vrednost kortizola u mleku, dok je kod junica određena i razlika u koncentraciji kortizola u opranoj i neopranoj dlaci. Kod dodatnih 12 krava holštajn rase i istih junica holštajn rase utvrđena je razlika između konentracije kortizola u beloj i crnoj dlaci. Za ispitivanje vrednosti indikatora stresa u uslovima tretmana antiektoparaziticima odabrano je 26 krava holštajn rase. Ogled je izveden tokom letnjeg perioda 2014. godine. Krave su na početku ogleda podeljene u dve grupe, netretirana (n=13) i tretirana (n=13), ali su zbog pojave mastitisa iz tretirane grupe isključene 3 krave, a iz netretirane 1 krava. Pre izvođenja ogleda posmatranjem i daljom identifikacijom je utvrđeno značajno prisustvo ektoparazita, štalske muve (Stomoxys calcitrans), na kravama. Odabrana grupa krava je tretirana antiektoparazitikom na bazi ciflutrina 0., 28. i 56. dana ogleda. Od svih krava su tokom trajanja ogleda uzimani uzorci krvi, mleka i dlake 0., 21., 42., 63. i 84. dana ogleda (periodi P0, P1, P2, P3 i P4), za određivanje koncentracije kortizola i kortikosterona kao i uzorci mleka za određivanje hemijskog sastava i broja somatskih ćelija u mleku. Takođe, u uzorcima krvi određena je koncentracija glukoze, ukupnih proteina, albumina, globulina, uree, ukupnog bilirubina i aktivnost enzima kreatin kinaze i alkalne fosfataze. Pre određivanja koncentracije kortizola i kortikosterona izvršena je validacija ELISA metode za određivanje ovih parametara u dlaci...

Uvod. Jedna nedelja blage restrikcije spavanja ima negativne efekte na pospanost, performansu i proinflamatorne citokine i dovodi do povecanja energetskog unosa. Mnogi pojedinci pokušavaju da prevaziu navedene štetne efekte spavajuci duže preko vikenda. Meutim, efekti produženog spavanja posle blage restrikcije spavanja na sekreciju hormona stresa i hormona koji regulišu apetit, kao i na stepen gladi i energetski unos, nisu bili predmet dosadašnjih studija. Ciljevi istraživanja. Proceniti efekte produženog (“vikend”) spavanja posle “jedne radne nedelje” blage restrikcije spavanja na pospanost/budnost, inflamaciju i hormon stresa, kortizol, kao i na energetski unos, stepen gladi, i na dvadesetcetvorocasovnu sekreciju cirkulišuceg leptina. Materijal i metode. Trideset zdravih, mladih muškaraca i žena (prosecne godine starosti ± SD, 24.7 ±3.5, prosecna vrednost ITM ± SD, 23.6 ±2.4 kg/m2) ucestvovali su u eksperimentalnoj studiji laboratorije za istraživanje spavanja. Studija je trajala 13 dana [4 bazalne noci (8h/noc), posle kojih su usledile 6 noci restrikcije spavanja (6h/noc) i 3 noci produženog spavanja (10h/noc)]. Dvadesetcetvorocasovni profili cirkulišuceg interleukina-6 (IL-6), kortizola i leptina; objektivne i subjektivne dnevne pospanosti (Test višestrukog uspavljivanja i Stendfordska skala pospanosti), neurobihejvioralne performanse (Test psihomotorne vigilnosti), raspoloženja (Profili stanja raspoloženja), energetski unos i stepen gladi evaluirani su cetvrtog (bazalni period), desetog (posle jedne nedelje restrikcije spavanja) i trineastog dana (posle 2 noci produženog spavanja). Rezultati. Dvadesetcetvorocasovni serijski nivoi IL-6 u plazmi su znacajno porasli u toku restrikcije spavanja, dok su se posle produženog spavanja vratili na bazalne nivoe. Dvadesetcetvorocasovni serijski nivoi kortizola ostali su nepromenjeni tokom restrikcije spavanja u poreenju sa bazalnim nivoima, ali su bili znacajno niži posle produženog spavanja... Introduction. One workweek of mild sleep restriction adversely impacts sleepiness, performance and pro-inflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. Furthermore, energy intake increases after sleep restriction, however, the effects of extended recovery sleep following prolonged sleep curtailment on hunger, food consumption, and appetite- and stress-regulating hormones have not been studied. Aims. To assess the effects of extended “weekend” recovery sleep after “one workweek” of mild sleep restriction on sleepiness/alertness, inflammation and stress hormones, as well as on energy intake, hunger, and 24-hour circulating leptin. Material and methods. Thirty healthy, young men and women (mean age ±SD, 24.7 ± 3.5; mean body mass index ±SD, 23.6 ± 2.4 kg/m2) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8h/night), followed by 6 sleep restriction nights (6h/night) and 3 recovery nights (10h /night)]. Twentyfour- hour profiles of circulating interleukin-6 (IL-6), cortisol, and leptin; objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), performance (Psychomotor Vigilance Task), mood (Profile of Mood States), energy intake, and hunger were assessed on days 4 (baseline), 10 (after one week of sleep restriction) and 13 (after 2 nights of recovery sleep). Results. Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared to baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Furthermore, feelings of hunger did not change during either sleep restriction or recovery, while, energy intake increased significantly during sleep restriction and did not return to baseline after recovery...

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 podaci o međusobnoj interakciji ove dve osovine. U ispitivanju su bile uključene dve grupe ispitanika, zdravih muškaraca uzrasta 18 do 25 godina: 1) sedentarna grupa studenata (n=15), koji se nisu bavili nikakvom fizičkom aktivnošću najmanje 6 meseci; 2) grupa aktivnih sportista – amaterskih ragbi igrača (n=23), koji su nakon uzimanja uzoraka za određivanje bazalnih vrednosti, podeljeni u dve grupe: kontrolnu (n=10) i interventnu grupu (n=13). Sedentarna grupa i interventna grupa ragbista uzimali su preparat magnezijuma tokom 28 dana (u ukupnoj d ozi o d 5 00 m g n a d an). Za procenu razlike uticaja magnezijuma na bazalne vrednosti parametara aktivnosti HPA i HPG osovine kod ragbista i fizički neaktivnih osoba, svi parametri su određivani kod obe grupe isitanika pre početka suplementacije i 29. dana od početka eksperimenta... 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 two groups of healthy male participants, aged 18-25 years: 1) sedentary group of students (n=15) who had not been involved in any regular exercise for at least six months; 2) the group of active athletes – amateur rugby players (n=23) who were, after basal sampling, randomly assigned to control (N=10) and intervention (N=13) group. The sedentary group and intervention group of rugby players received magnesium supplement during 28 days (total amount 500 mg Mg/day). In order to examine the difference in magnesium effect on basal HPA and HPG axes activity parameters between rugby players and physically non-active persons, all parameters were determined in both groups, before supplementation and on the 29th day of the experiment. The evaluation of magnesium influence on the dynamics of the change of HPA and HPG axes parameters’ activity was done based on the measurement of all parameters on the day of the competition, as well on the first, third and sixth day after the game...

Uvod: Sindrom sistemskog inflamatornog odgovora (SIRS) predstavlja inflamatorno stanje uzrokovano infekcijom ili sepsom i koje se širi na ceo organizam. SIRS se smatra delom „citokinske oluje“ i manifestuje se disregulacijom različiutih citokina. Ozbiljnost bolesti se najbolje prediktuje korišćenjem APACHE II skora (Acute Physiology and Chronic Health Evaluation II) dok se ishod kod pacijenta, odnosno organska disfunkcija ili insuficijencija prediktuje pomoću SOFA skora (Sequential Organ Failure Assessment). SIRS dovodi do značajnih promena u dinamici kortizola ukazujući na disocijaciju između adrenalnog korteksa i hipotalamo-hipofizne jedinice. Navedena promena se manifestuje visokim koncentracijama kortizola i ACTH odmah nakon početka SIRS-a. Međutim, nekoliko dana kasnije, ACTH se spušta do veoma niskih koncentracija dok koncentracije kortizola ostaju visoke. Navedeno se objašnjava direktnim efektom citokina, kao što je interleukin 6 (IL-6), na koru nadbubrega koji stimulišu oslobađanje glukokortikoida. Odgovor kortizola na stimulaciju sa ACTH predstavlja važan prediktor ishoda kod kritično bolesnih. Bolesnici sa neadekvatnim odgovorom kortizola na stimulaciju sa ACTH imaju visoku stopu mortaliteta. Stimulacija sa 250 μg ACTH se smatra zlatnim standardom u proceni adrenalne funkcije. Međutim, niskodozni test sa 1 μg ACTH (NDT) predstavlja senzitivniji test u detekciji specifičnih formi adrenalne insuficijencije kao što je hipotalamo-hipofizna disfunkcija. Upotreba NDT u kritično obolelih nije jasno definisana jer postoji mali broj podataka za formiranje jasne preporuke... Introduction: Systemic inflammatory response syndrome (SIRS) represens inflamatory condition caused bz infection or sepsis that spreads all over the body. SIRS is considered a part of the „cytokine storm“ and is manifested by dysregulation of different cytokines. The severity of the disease is best predicted using Acute Physiology and Chronic Health Evaluation II (APACHE II) score while the patient’s outcome, namely organ dysfunction/failure during Intensive Care Unit (ICU) monitoring is predicted using Sequential Organ Failure Assessment (SOFA) score. SIRS leads to significant changes in cortisol dynamics indicating on the disociation between adrenal cortex and the hypothalamo-pituitary unit. This is manifested by the very high concentrations of cortisol and ACTH immediatly after commencement of SIRS. However, a few days later ACTH falls to the very low concentration while the concentrations of cortisol remains high. This is explained by direct effect of cytokines, as it is interleukin 6 (IL-6), on the adrenal cortex that is simulating glucocorticoid realease. Cortisol response on the stimulation with ACTH was shown to be important predictor of the outcome in critically ill patients. Patients with inadequate cortisol response on stimulation with ACTH had high mortality rate. Stimulation with 250 μg of ACTH is considered to be gold standard test for the assessment of adrenal function. However, the low-dose (1 μg) test (LDT) represents a more sensitive test for detecting specific forms of adrenal insufficiency as it is hypothalamo-pituitary disfunction. The use of LDT in critically ill patients is not clearly defined as the data on LDT are limited and not sufficient for the clear recommendation...

Cilj ove doktorske je bio da se ispita efekat hipotireoze majke indukovane tokom kasnog graviditeta na endokrini i metabolički status novorođenih teladi tokom prvih sedam dana neonatalnog života. Hipotireoza majke je indukovana davanjem PTU u dozi od 4mg/kg telesne mase tokom poslednjih 20 dana graviditeta. Nakon rađanje, telad koja potiču od majki tretiranih sa PTU (n=10) je svrstano u oglednu grupu, dok je 10 teadi koja su poticala od majki koje nisu tretirane sa PTU svrstano u kontroln grupu. Sva telad su bila odmah po rođenju odvojena od majki i napajana kolostrumu i mlekom tokom ispitivanog perioda. Svakodnevno, tokom prvih sedam dana neonatalnog života teladima je uzimana krv punkcijom v. jugularis. Odmah nakon rođenja teladi uzimani su uzorci tkiva placente majke i tkiva tireoidee teladi. Koncentracija tireoidnih hormona i koncentracija TSH ispitivana je u svim uzetim uzorcima krvi. U uzorcima krvi uzetih 0., 1., 2., 3., 4. i 7. dana nakon rođenja određene su koncentracije glukoze, insulina, kortizola, IGF-I i relativna zastupljenost IGFBP-2 i IGFBP-3. U svim uzorcima krvi uzetih tokom sedam dana ispitivanja, ispitane su koncentracije ukupnih proteina, albumina i globulina, kao i koncentracije holesterola i triglicerida. U uzorcima tkiva placente majki i tkiva tireoidee teladi, ispitivana je ekspresija iRNK za pojedine tipove dejodinaze, dok su u uzorcima tkiva tireoidee određivane i histološke promene. Telad ogledne grupe rađala su se sa značajno nižim koncentracijama tireoidnih hormona (T3 i T4) i značajno višim koncentracijama TSH u odnosu na telad kontrolne grupe. Ova razlika je bila značajna tokom prva dva dana neonatalnog života. Počevši od 3. dana, koncentracije tireoidnih hormona su se kod ogledne grupe povećavale, a TSH snižavale, tako da su koncentracije tireoidnih hormona u periodu od 4. do 6. dana bile značajno više a koncentracije TSH značajno niže kod ogledne nego kod kontrolne grupe. Koncentracije insulina su u momentu rođenja bile značajno niže kod teladi ogledne grupe u odnosu na telad kontrolne grupe. Vrednosti insulinemije su se kod ogledne grupe povećavale tako da je vrednost bila veća nego kod kontrolne grupe već 4. dana, iako ne statistički značajno... The aim of this PhD thesis was to was to examine the effect of induced hypothyroidism in Holstein heifers in the latest stage of pregnancy on endocrine end metabolic status of newborn calves during the first seven days of neonatal life. The study was conducted by inducing hypothyroid state in the dams by oral treatment with 4mg PTU/kg body weight, during a period of 20 days prior to expected calving. After birth, calves originating from dams treated with PTU (n = 10) were classified as experimental group, while 10 calves that originated from dams not treated with PTU were classified as the control group. All calves were separated immediately after birth from their dams and fed colostrum and milk during the test period. During this period, calves body weight was also determined. Blood samples were taken daily by puncture of v. jugularis from each calf for the first seven days of life. Immediately after parturition placental samples and calves thyroid tissue samples were obtained. Concentrations of thyroid hormones and TSH were determined in all blood samples. Concentration of IGF-I and relative presence of IGFBP-2 and IGFBP-3 were determined in samples taken on days 1, 2, 3, 4 and 7 after birth. Concentrations of glucose, insulin and cortisol were determined in samples taken on days 1, 2, 3, 4, 7. Concentrations of total protein, albumin, globulin, triglyceride and cholesterol were determined in samples obtained during the all seven days of study period. On placental and thyroid tissue samples, expression of iRNA for DIO1, DIO2 and DIO3 were determined. Determination of histological changes was done on thyroid tissue samples taken from calves with established macroscopic changes on thyroid gland. Calves in experimental group were born with significantly lower thyroid hormone concentrations and significantly higher TSH concentrations compared to control group. Hypothyroid state was significant within the first two days after birth. After day 3, concentrations of thyroid hormones increased, so in the period of days 4, 5 and 6 they were higher compared to the control group, while the TSH concentrations decreased until day 4 after which the TSH concentrations were lower compared to the control group...

periodu kod krava čiji je porođaj indukovan preparatima prostaglandina F2α. Cilj je bio da se utvrdi efekat Se na učestalost zaostale posteljice (RP), oksidativni/antioksidativni status, stepen opšteg stresa, uticaj na koncentraciju tireoidnih i steroidnih hormona, kao i da se uporede vrednosti istih parametara kod životinja sa i bez zaostale posteljice, nezavisno od tretmana. Ogled je izveden na trideset tri (33) krave Holštajn-Frizijske rase koje su metodom slučajnog izbora podeljene u tri grupe kojima je jednokratno, intramuskulurno, apliciran suplement natrijum selenita (NaSe) i tokoferol acetata (TAc) na sledeći način: kontrolna grupa (n=9) nije dobijala suplement i služila je kao negativna kontrola; grupa 1 (n=11) je dobila 10 mg NaSe + 400 mg TAc; grupa 2 (n=13) je dobila 20 mg NaSe + 800 mg TAc, 21 dan pre očekivanog porođaja. Porođaj kod svih krava je indukovan sa PGF2α, ali ne pre 275-og dana graviditeta. Heparinizirana krv je sakupljana za određivanje aktivnosti glutation peroksidaze (GPx), koncentracije Se, malondialdehida (MDA), tiroksina (T4), trijodtironina (T3), kortizola, estradiola, progesterona, β-hidroksibutirata (BHBA) i aktivnosti glutamat dehidrogenaze (GLDH). Procenat zastupljenosti RP kod krava u grupi 1 opao je na 38,2%, a u grupi 2 na 30,8%, u odnosu na kontrolu (66,7%), kao posledica dodavanja Se. Koncentracija Se i aktivnost GPx u krvi suplementiranih grupa bile su više u odnosu na kontrolu, ali se nisu međusobno razlikovale, dok je koncentracija MDA kod suplementiranih krava bila značajno niža u poređenju sa kontrolom. Plazmatska koncentracija T4 bila je značajno viša u grupi 1 u poređenju sa kontrolom, dok se koncentracija T3 nije razlikovala između grupa. Koncentracija kortizola u grupi 2 bila je značajno niža u odnosu na kontrolu i grupu 1. Pritom, kod nesuplementiranih životinja nivo kortizola je neprekidno rastao u periodu od 12h pre do 12h posle porođaja, dok se kod suplementiranih grupa nivoi nisu menjali. Koncentracije progesterona i estradiola nisu reagovale na dodatak Se. Plotkinje koje nisu razvile RP imale su značajno višu koncentraciju Se i aktivnost GPx u punoj krvi i, kao posledicu, značajno niže koncentracije MDA u krvnoj plazmi u odnosu na krave kod kojih je dijagnostikovana RP. Krave sa RP imale su značajno višu koncentraciju progesterona u poređenju sa životinjama bez RP, dok se nivoi ostalih steroidnih hormona nisu razlikovali. Plazmatska aktivnost GLDH i koncentracija BHBA kretale su se u fiziološkim granicama. This study analyzes the effects of pre-partal application of selenium (Se) to cows whose parturition was induced using prostaglandine F2α. The goal was to determine the effects of Se on the incidence of retained placenta (RP), oxidative/anti-oxidative status, level of general stress, thyroid and steroid hormones, as well as to compare the above parameters between cows with and without RP, independently of treatment. The experiment was carried out on 33 Holstein-Friesian cows divided randomly into 3 groups. The treatment consisted of a single term i/m injection of sodium selenite (NaSe) and tocopherol acetate (TAc), as follows: the untreated group (n=9) served as a negative control; group 1 (n=11) recieved 10 mg NaSe + 400 mg TAc; group 2 (n=13) recieved 20 mg NaSe + 800 mg TAc, 21 days before the expected parturition. In all cows parturition was induced using PGF2α, never before the 275th day of gestation. Heparinized blood was collected to determine GPx activity, concentrations of Se, malondialdehyde (MDA), thyroxine (T4), triiodothyronine (T3), cortisol, 17β-estradiol, progesterone, β-hydroxybutyrate (BHBA) and glutamate dehydrogenase (GLDH) activity. Percent of RP in group 1 was reduced to 38,2% and in group 2 to 30,2% compared to control (66,7%) as a consequence of Se supplementation. Blood Se concentration and GPx activity were higher in supplemented groups compared to the control, but did not differ between groups 1 and 2; plasma MDA content was significantly lower in supplemented groups compared to the control. Plasma T4 was significantly higher in group 1 compared to the control, while T3 did not differ between groups. Plasma cortisol content was significantly lower in group 2 compared to the control and group 1. In unsupplemented animals plasma cortisol level constantly raised from 12h before to 12h after parturition, while in the supplemented group it was unchanged. Plasma progesterone and estradiol levels were unaffected by Se treatment. Cows without RP had significantly higher blood Se concentration and GPx activity and as a consequence lower plasma MDA content compared to cows with RP. Plasma progesterone was higher in non-RP animals, while the concentration of other hormones did not differ. Plasma GLDH activity and BHBA concentrations were within physiological limits

Posttraumatski stresni poremećaj (PTSP) je psihijatrijska bolest koja se može razviti posle izlaganja traumatskom događaju. PTSP predstavlja veliko medicinsko i ekonomsko opterećenje za društvo, zbog relativno velike učestalosti i komorbiditeta sa mnogim drugim psihijatrijskim i somatskim bolestima. Smatra se da se najbolji rezultati u razumevanju patogeneze PTSP-a i njegovoj dijagnostici i terapiji mogu postići integrisanjem psiholoških, bioloških i farmakoterapeutskih pristupa. Aktuelna istraživanja sugerišu da je PTSP povezan sa neuroendokrinim poremećajima i promenama imunskih funkcija. Smatra se da je hiperosetljivost hipotalamo-hipofizno-adrenokortikalne (HHA) ose na kortizol neuroendokrini „pečat“ PTSP-a, dok je priroda imunskih poremećaja povezanih sa PTSP-om još uvek nejasna. Većina studija pokazala je da je PTSP povezan sa pojačanom inflamacijom, ali su objavljeni i podaci o nepromenjenom inflamatornom statusu, pa čak i smanjenom nivou inflamatornih markera u cirkulaciji PTSP pacijenata. Pretpostavlja se da pojačana inflamacija kod osoba obolelih od PTSP-a može biti posledica nedovoljne imunosupresije kortizolom. Međutim, podaci o nivou kortizola i funkcionisanju kortizolskih receptora kod pacijenata sa PTSP-om nisu konzistentni. Izlaganje različitim stresorima indukuje sintezu unutarćelijskih proteina toplotnog stresa (HSP) čije funkcije potpomažu preživljavanje ćelija. Tokom mnogo godina HSP su posmatrani kao unutarćelijski proteini, ali sada se zna da ih mnoge sisarske ćelije oslobađaju u cirkulaciju, gde mogu da aktiviraju pro-inflamatorne odgovore. Uzimajući da pojačana inflamacija koja je povezana sa PTSP-om verovatno nije posledica umanjenog anti-inflamatornog delovanja kortizola, mi smo pretpostavili da ona može biti posledica indukcije i oslobađanja Hsp60 i Hsp70 psihološkom traumom. Cilj ove studije bio je da se povežu parametri inflamatornog statusa sa nivoima kortizola i HSP u cirkulaciji, kao i da se otkriju moguće veze između inflamatornih markera i vanćelijskih HSP sa izlaganjem traumi, simptomima PTSP-a, osetljivošću i otpornošću na PTSP... Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder that may develop following exposure to life-threatening traumatic event. PTSD represents a serious medical and economic burden for the society due to its relatively high life-time prevalence rate and comorbidity with variety of other mental disorders and somatic illnesses. General opinion is that the best results in understanding of PTSD pathogenesis, diagnosis and treatment could be achieved by integrating psychological, biological and pharmacotherapeutical approaches. Current research has suggested that PTSD is associated with neuroendocrinological disturbances and immune function alterations. The hypersensitivity of hypothalamic-pituitary- adrenocortical (HPA) axis to cortisol feedback inhibition is considered the neuroendocrine hallmark of PTSD, while the nature of PTSD-related immune alterations is not well understood. Most studies report that PTSD is associated with excessive inflammation, but unaltered inflammatory state and even decreased circulatory levels of inflammatory markers were also reported. It has been hypothesized that excessive inflammation in individuals with PTSD might be a consequence of insufficient immunosuppression by cortisol. However, the data on cortisol levels and cortisol receptor functioning in PTSD patients are inconsistent. Exposure to a variety of stressors will induce intracellular heat shock proteins (HSPs) with cellular functions beneficial for cell survival. For many years HSPs have been viewed as intracellular proteins, but it is now known that they can be released from various mammalian cells into the peripheral circulation, where they are capable of activating pro-inflammatory responses. Taking that PTSD-associated excessive inflammation is not likely to be caused by impaired anti-inflammatory action of cortisol, we hypothesize that it might be a consequence of Hsp60 and Hsp70 induction and release by psychological trauma...

Cilj ovog rada bijo je da se ispita uticaj toplotnog stresa na metabolički i endokrini status krava. Ogled je izveden na 20 krava Holštajn – frizijske rase od 18. do 45. dana laktacije tokom letnjeg perioda u trajanju od 37 dana. Tokom perioda izvođenja ogleda određivana je vrednost „satnih“ toplotnih indeksa (THI) a zatim izračunata vrednost prosečnih jutarnjih (od 22 h prethodnog do 9 h tekućeg dana), popodnevnih (od 10 h do 21 h tekućeg dana) i celodnevnih THI. Uzorkovanje krvi i određivanje trijasa izvršeno je 1., 2., 8., 11., 14., 18., 25., 29. i 37. dana ogleda, u jutarnjem i popodnevnom periodu. Na osnovu vrednosti satnih THI ceo ogledni period je podeljen na tri perioda: period A u kome su krave bile izložene izrazitom toplotnom stresu (THI ≥ 78) najmanje 7 sati u toku 24 sata (1., 8., 14., i 37. dan ogleda); period B u kome su krave bile izložene umerenom toplotnom stresu (72 ≥ THI ≤ 78) najmanje 7 sati u toku 24 sata (2., 18., i 29. dan ogleda); period C u kome krave nisu bile izložene toplotnom stresu (THI ≤ 72) u toku 24 sata (11. i 25. dana ogleda). Prosečni dnevni THI u periodu A (73,25 ± 0,89) je bio značajno veći (p

physical chemistry / biophysical chemistry and dynamics of non-equilibrium processes U ovom doktorskom radu razmatrano je modelovanje hipotalamo-hipofiznoadrenalnog (HPA) sistema, veoma složenog i važnog neuroendokrinog sistema, bitnog za održavanje svakodnevnih fizioloških funkcija organizma, i presudnog za odgovor organizma na dejstvo različitih stresora, odnosno u reakciji „bori se ili beži“. Cilj rada je modelovanje uticaja stresa na dinamiku HPA sistema. U tu svrhu postavljen je stehiometrijski model koji opisuje dnevni ritam sekrecije hormona ovog sistema, analizirana stabilnost sistema diferencijalnih jednačina koje slede iz njega i ispitivana simulacija rada ovog sistema pri dejstvu stresora. U složenom biološkom sistemu, kao što je HPA sistem, gde nisu još u potpunosti razjašnjeni svi procesi i mehanizmi funkcionisanja, a ni sve nije merljivo, matematičko modelovanje je korisno, posebno ako bi pomoglo da se izdvoje i definišu individualne karakteristike na osnovu kojih bismo mogli predvideti kako bi pojedinac reagovao u različitim situacijama. U poglavlju 1, izložen je opis hipotalamo-hipofizno-adrenalnog sistema. Krajnji proizvod ovog sistema, hormon kortizol (kod čoveka) i kortikosteron (kod glodara), pozitivnim i negativnim povratnim spregama reguliše sopstveno stvaranje, odnosno aktivnost čitavog sistema. U poglavlju 2, dat je kratak prikaz nekoliko do sada u stručnoj literaturi objavljenih modela ovog sistema i istaknuta razlika izmedju stehiometrijskih i nestehiometrijskih modela. U poglavlju 3, izložen je model razmatran u ovom radu, koji opisuje ritam rada hipotalamo-hipofizno-adrenalnog sistema i analizirana je stabilnost datog modela primenom metode stehiometrijske mrežne analize. U poglavlju 4 prikazani su rezultati numeričkih simulacija rada HPA sistema pri akutnom i hroničnom dejstvu stresora, dobijeni na osnovu razmatranog modela. Svrha ovog rada nije bila da se formuliše matematički model HPA sistema koji bi opisivao sve procese prisutne u ovom složenom sistemu, jer čak i kada bi to bilo moguće uraditi, dobijeni model bi bio preobiman i davao bi malo značajnih odnosa u sistemu. Umesto toga, cilj nam je bio formulisanje minimalnog modela koji bi dovoljno verno prikazao suštinski bitne interakcije i predvideo ponašanje sistema pri zadatim uslovima In this doctoral dissertation modelling of the hypothalamic-pituitary-adrenal (HPA) system, a very complex and important neuroendocrine system, relevant for maintenance of everyday physiological functions of an organism, and crucial in response to different stressors, i.e. in “fight or flight’ reaction, is considered. The aim of this work is modelling of the influence of stressors on the HPA system dynamics. With this intention, a stoichiometric model was made, to describe the daily rhythm of hormonal secretion,stability of corresponding differential equations system was analyzed, and functioning of this system under stress was simulated In complex biological systems, such as the HPA system, where all underlying processes and mechanisms are not fully understood jet, and not everything could be measured, mathematical modelling is useful, especially if it could lead to, and define individual personal characteristics, based on which we could estimate how would a person react in different situations. In chapter 1, description of the HPA system is given. Final products of this system, hormones cortisol (in humans), and corticosterone (in rats), through different positive and negative feedback actions regulate their own production, i.e. activity of this system. In chapter 2, a short description of several models of this system published in the literature so far, and a difference between stoichiometric and non-stoichiometric models is specified. In chapter 3, the model of the HPA system functioning considered in this work is described, and stability of this model is analyzed using stoichiometric network analysis. In chapter 4, results of numerical simulations of the HPA system functioning, under acute and chronic stress conditions, obtained based on the model considered, are given. The aim of this work wasn’t to formulate a mathematical model that could describe all processes present in this complex system, because even if that could be possible, resulting model would be too large and it would not give enough important relations in the system. Instead of that, our aim was to formulate a minimal model that could describe crucial interactions in the system, and predict the behaviour of the system in given conditions