Pituitary-ovarian axis of rats from fetal to peripubertal period of life after intrauterine exposure to dexamethasone

Tokom fetalnog razvića organizam prolazi kroz “kritične periode”, tokom kojih se dešavaju intenzivne ćelijske deobe, razvijanje i sazrevanje tkiva, organa i organskih sistema. Sredina u kojoj fetus raste i razvija se u velikoj meri odreñuje kvalitet razvojnog procesa, a svaka promena uslova dovodi do čitavog niza poremećaja, koji mogu biti praćeni smanjenjem fetalnog rasta ili IUGR (eng. Intrauterine growth retardation). Posledice IUGR su dugotrajne i ispoljavaju se u vidu različitih metaboličkih i kardiovaskularnih oboljenja u kasnijem životu. Fetalno okruženje na taj način odreñuje adultni fenotip, a njihova povezanost proučava se u okviru koncepta programiranja. Najčešće korišćeni eksperimentalni pristupi u proučavanju programiranja i efekta IUGR su dijeta majke koja vodi pothranjenosti, izazivanje stresne reakcije kod majke ili primena antenatalne terapije glukokortikoidima. Svaki od ovih eksperimentalnih modela različitim mehanizmima dovodi do izlaganja fetusa povećanoj koncentraciji glukokortikoida, koji u velikoj meri mogu da poremete fiziološki tok razvojnog procesa. Cilj ove studije je bio da se ustanovi da li je izlaganje fetusa pacova od 16. do 18.dana gestacije sintetičkom glukokortikoidu deksametazonu programiralo razvoj i funkciju hipofizno-ovarijalnog sistema od fetalnog do peripubertalnog perioda života. Predmet istraživanja u ovoj doktorskoj disertaciji bili su fetusi i ženke pacova koje su od 16. do 18. dana gestacije izloženi deksametazonu. Gravidne ženke pacova su tri uzastopna dana (od 16. do 18. dana gestacije) subkutano tretirane deksametazonom (Dexamethasonis phosphat - Dx, Krka, p.o., Novo Mesto) rastvorenom u fiziološkom rastvoru (0.9% NaCl), u dozi od 1.0, 0.5 i 0.5 mg Dx/kg...During fetal development an organism undergoes “critical periods” of intensive cell division as well as the growth and maturation of tissues, organs and organ systems. The fetal environment principally determines the quality of the developmental process, while variation of conditions may lead to a range of disorders followed by intrauterine growth retardation (IUGR). The consequences of IUGR are long-lasting and manifest through various metabolic and cardiovascular issues in later life. Thus, the fetal environment prejudices the adult phenotype, while their intertwining is elaborated with the programming concept. The most widely exploited experimental approaches in the field of programming and IUGR effects are maternal diet leading to offspring malnutrition, provoking stress to mother and antenatal glucocorticoid therapy. Each of these experimental approaches via different mechanisms leads to fetal exposure to elevated glucocorticoid levels, which may disrupt to a great extent the physiology of the developmental process. The aim of this study was to establish whether the exposure of rat fetuses to synthetic glucocorticoid dexamethasone, during the period between days 16 and 18 of gestation, programmed the development and function of the pituitary-ovarian system, starting from the fetal to the peripubertal period of life. The subject of this doctoral thesis investigation were rat fetuses and females exposed to dexamethasone from the 16th to the 18th gestational day. During three consecutive days (16–18 days of gestation) pregnant rat females were subcutaneously treated with dexamethasone (Dexamethasonis phosphate – Dx, Krka, p.o., Novo Mesto) dissolved in saline (0.9% NaCl), in doses of 1.0, 0.5 and 0.5 mg Dx/kg..

Neonataly applied SRIH-14 has immediate and prolonged inhibitory effect on pituitary GH cells

The immediate and prolonged effects of neonatal SRIH-14 treatment on pituitary somatotrophs (GH) were investigated. Female rats were injected s.c. twice a day with 20 _g of SRIH-14/100g b.w., for five consecutive days (from 3rd to 7th day of life). Animals were sacrificed at different life periods: at neonatal (8th day), juvenile (16th day), peripubertal (38th day) and adult (80th day) period of life. GH cells were studied using the peroxidase-antiperoxidase immunocytochemical procedure. Morphometry and stereology were used to evaluate changes in the number of GH-immunoreactive cells per unit area, their volume and volume density. After SRIH-14 treatment, the most prominent decrease of all measured parameters was observed in the neonatal period. SRIH-14 induced a significant decrease of GH cell volumes and volume densities in the juvenile, peripubertal and adult periods of life. The number of GH-positive cells was significantly decreased when examined immediately after treatment, but significantly increased in adult females. Body weight, absolute or relative pituitary weights were not affected in any of the examined age groups. These findings suggest that neonatal SRIH-14 treatment exerts a significant immediate and prolonged inhibitory effect on GH cells, but does not affect the growth rate in female rats.Ispitivan je neposredan i odložen efekat neonatalnog tretmana somatostatinom (SRIH-14) na somatotropne (GH) ćelije. Ženke pacova su dva puta dnevno s.c. tretirane sa 20 _g SRIH-14/100g t.m. u toku pet dana (od 3. do 7. dana života) i žrtvovane u različitim periodima života: u neonatalnom (8. dan) juvenilnom (16. dan), peripubertalnom (38. dan) i adultnom (80. dan) periodu. GH ćelije su imunocitohemijski obeležene metodom peroksidaza-antiperoksidaza a morfometrijskim i stereološkim metodama određivani su broj GH ćelija po jedinici površine, njihov volumen i volumenska gustina. Nakon somatostatinskog tretmana, najznačajnije smanjenje svih merenih parametara utvrđeno je u neonatalnom periodu. SRIH-14 je izazvao značajno smanjenje volumena i volumenske gustine GH ćelija u juvenilnom, peripubertalnom i adultnom periodu života. Broj GH-pozitivnih ćelija po mm2 je bio značajno smanjen kada je ispitivan neposredno nakon tretmana, ali je bio značajno povećan kod adultnih ženki. Telesna masa, kao i apsolutne i relativne mase hipofiza nisu bile izmenjene ni u jednoj od ispitivanih starosnih grupa. Dobijeni rezultati ukazuju da neonatalni tretman somatostatinom izaziva značajan neposredan i odložen inhibitoran uticaj na GH ćelije, ali ne utiče na stopu rasta kod ženki pacova.nul

Reversal of FLT3 Mutational Status and Sustained Expression of NPM1 Mutation in Paired Presentation, and Relapse Samples in a Patient with Acute Myeloid Leukemia

We report a case of de novo acute myeloid leukemia (AML) with unstable FLT3 gene mutations and stable NPM1 mutation. FLT3/D835 and NPM1 (Type A) mutations were detected upon diagnosis. During the relapse, the FLT3/D835 mutation changed to an FLT3/ITD mutation while the NPM1 (Type A) mutation was retained. Cytogenetic analyses showed the normal karyotype at diagnosis and relapse. Our findings raise interesting questions about the significance of these mutations in the leukemogenic process, about their stability during the evolution of the disease, and regarding the selection of appropriate molecular markers for the monitoring of minimal residual disease

Glycerol acetylation on mesoporous KIL-2 supported sulphated zirconia catalysts

Zirconia nanomaterials were prepared by impregnation of KIL-2 type silica with 4, 8 and 12 wt.% ZrO2 and were modified by sulphate groups in order to vary the type and strength of acidity. Samples were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and N2 physisorption methods. Acidic properties of adsorbed pyridine were investigated by FT-IR spectroscopy. The catalytic performance of ZrKIL-2 and SO4 2−/ZrKIL-2 in glycerol esterification with acetic acid was studied and compared to that of pure zirconia varieties. It was found that silica-supported zirconia samples are more active than pure zirconia ones. With increasing ZrO2 content, KIL-2-supported catalysts showed increasing catalytic activity and selectivity in producing valuable fuel additives, di- and triacetyl glycerols. Sulphated analogues showed even higher activity and selectivity compared to non-sulphated ones due to their strong Brönsted acidity

Schizotypy: Current concepts and future research implications

Shizotipija je konstrukt koji se koristi kako bi se opisala grupa osoba sa simptomima koji ne ispunjavaju kriterijume za postavljanje dijagnoze shizofrenije, ali imaju sličnosti sa ovim kompleksnim i heterogenim psihiajtrijskim oboljenjem. MKB-10 opisuje shizotipiju kao privremeno stanje (shizotipalni poremećaj), dok je DSM-5 opisuje kao trajniji poremećaj (shizotipalni poremećaj ličnosti). S obzirom da se shizotipija prostire kroz normalnu, supkliničku i kliničku populaciju, temeljno teorijsko razumevanje ovog koncepta može biti od pomoći prilikom razvijanja mera procene shizotipije. Do sada, najveći deo psihometrijske evaluacije shizotipije bazirao se na varijetetima individualnih razlika (poremećaja) ličnosti. Ovaj članak se fokusira na evoluciju termina shizotipije, na razumevanje ovog fenomena, mogućnosti psihometrijske procene u skladu sa trenutnim modelima ličnosti i na klinička razmatranja koja bi dovela do poboljšane detekcije i intervencije u ovoj oblasti.Schizotypy is a construct used to describe a group of persons with symptoms which do not fulfill criteria for schizophrenia, but have some similarities with this complex and heterogeneous psychiatric disorder. ICD-10 describes schizotypy as a state (schizotypal disorder), while DSM-5 labels it as a trait marker (schizotypal personality disorder). Considering how schizotypy encompasses through the normal, subclinical and clinical population, a thorough theoretical understanding of this concept could be helpful in developing measures of assessment. So far, most of the tools for psychometric evaluation of schizotypy have focused only on abnormal personality. The present article focuses on the evolution of the term schizotypy, its current understanding, the possibilities of psychometric assessment in relation to contemporary constructs of personality and on clinical considerations for improved detection and intervention in this field

Development of pituitary ACTH and GH cells in near term rat fetuses

This study describes the development of ACTH and GH cells in 19- and 21-day-old rat fetuses using immunohistochemistry and morphometric measurements. Between days 19 and 21 of pregnancy, the total volume of fetal ACTH cells was unchanged, while their volume density and number per unit of area decreased significantly. ACTH-like immunopositivity in the pars intermedia increased during the examined period. The cell volume, volume density and number of GH cells per unit of area all markedly increased in parallel with fetal development, i.e., from gestational days 19 to 21. GH-like immunopositivity is demonstrated in the pars intermedia of 21-day-old fetuses for the first time.Prezentovano istraživanje opisuje razvoj ACTH i GH ćelija hipofize fetusa pacova, neposredno pred rođenje korišćenjem imunohistohemije i morfometrijskih merenja. Od 19. do 21. dana gestacije volumen ACTH ćelija fetusa bio je nepromenjen, dok su volumenska gustina i broj ćelija po jedinici površine značajno smanjeni. Intenzitet ACTH imunopozitivnosti u pars intermedia povećavn je tokom ispitivanog perioda. Volumen GH ćelija, volumenska gustina i brojnost po jedinici površine značajno su povećani tokom završnog perioda fetalnog razvoja, tj. od 19. do 21. dana gestacije. GH imunopozitivnost prvi put je demonstrirana u ćelijama pars intermedia kod fetusa starih 21 dan.nul

Changes of c-myc expression in b16 melanoma cells induced by 8-chloroadenosine-3′, 5′-monophosphate and tiazofurin

The aim of this study was to investigate the in vitro effects of 8- chloroadenosine 3′, 5′-monophosphate (8-Cl-cAMP) and tiazofurin (TR) on the expression of c-myc gene in B16/F10 and B16/C3 mouse melanoma cells. Exponentially growing cells were treated with 8-Cl-cAMP or TR (5µmol - 25µmol) for 6h and 24h. The level of c-myc expression, estimated by RT-PCR, did not significantly change in B16/F10 cells after treatment with 8-Cl-cAMP or TR. Similar results were obtained in B16/C3 cells after treatment with 8-Cl-cAMP. The level of c-myc expression has shown a significant increase in B16/C3 cells after treatment with TR. Further studies of these agents will lead to better understanding of molecular mechanisms of their action.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Characteristics of the pituitary immunopositive ACTH cells in rat females after chronic exposure to constant light

The effects of chronic exposure to light of adult female Wistar rats on growth and function of pituitary adrenocorticotropes (ACTH cells) were examined. The animals were exposed to continuous light of 600 lux for 95 days, starting on day 30 of age. Control rats were kept under a 12:12 h light-dark cycle, at ambient temperature. ACTH-producing cells were studied using the peroxidase-antiperoxidase immunohistochemical procedure and blood samples were collected for hormone analyses. In animals exposed to a chronic light-treatment all morphometric parameters measured throughout the present study i.e.: ACTH cell volume, nuclear volume and relative volume density were increased by 22% and the differences between this group and the controls were statistically significant (p<0.05). The concentration of plasma ACTH was elevated by 13% in light-exposed group in comparison with the control and this difference was statistically significant (p<0.05), as well. These findings suggest that continuous exposure to light is specifically involved in growth and secretory activity of ACTH cells of adenohypophysis of rat females.Ispitivani su efekti dugotrajnog izlaganja ženki Wistar pacova stalnom svetlu, na adrenokortikotropne (ACTH) ćelije. Eksperimentalne životinje stare 30 dana izlagane su konstantnom svetlu (600 luksa) tokom 95 dana. Kontrolne životinje odgovarajuće starosti su držane na normalnom, 12:12 h dnevno-noćnom režimu i sobnoj temperaturi. ACTH ćelije su imunohistohemijski bojene metodom peroksidaza-antiperoksidaza (PAP), a istovremeno je sakupljana krv za određivanje koncentracije ACTH u plazmi. Životinje izložene stalnom svetlu imale su za 22% povećane sve morfometrijske parametre ACTH ćelija merene tokom ovog rada (zapremina ćelija, njihovih jedara i volumenska gustina) u odnosu na kontrole i uočene razlike su bile statistički značajne (p < 0.05). Koncentracija ACTH u plazmi je takođe bila veća za 13% (p < 0.05) u odnosu na kontrolne vrednosti. Ovi rezultati ukazuju da dugotrajno izlaganje stalnom svetlu na specifičan način stimuliše rast i sekretornu aktivnost ne samo ACTH ćelija adenohipofize već i ćelija pars intermedia ženki pacova

Razvoj bolničke apotekarske prakse u Specijalnoj bolnici za bolesti zavisnosti

The Special Hospital for Addiction Diseases (SBBZ) received the status of a secondary level health care institution and reference center for addiction diseases in 2007. The turning points in the development of the pharmacy service in SBBZ in the previous 60 years are presented, by applying the method of historical analysis for the period from 1958 until today. The dispensary for the treatment of alcoholics and the fight against alcoholism was founded in 1958 in Belgrade, and a hospital pharmacy within the Clinical Department for Alcoholism started operating there. For the next four decades, it grew into the Institute for Alcoholism (1968), the Institute for Alcoholism and Drug Addiction in 1973, and in 1980 changed its name to the Institute for Addiction Diseases. This health institution is part of the OOUR Clinic for Psychiatry and Neurology (1987), which was one of the working organizations of the Clinical Hospital Center "Dr Dragisa Misovic-Dedinje". The Institute for Addiction Diseases was founded in 1992, separated from the KBC and has been operating as the SBBZ since 2007 (1). With the independence of the hospital, the hospital pharmacy organizationally belonged to the laboratory and the hospital pharmaceutical activity was performed by only one pharmacist (2). It can be concluded that the transformation of the health institution had little impact on the work of the hospital pharmacy service because at all turning points there was always a pharmacist as the only professional, a holder of a job in a hospital pharmacy.Specijalna bolnica za bolesti zavisnosti (SBBZ) dobija status ustanove sekundarnog nivoa zdravstvene zaštite i referentnog centra za bolesti zavisnosti 2007. godine. Obavlja delatnosti iz oblasti: psihijatrije, neurologije, interne medicine, biohemijsko-toksikološke dijagnostike, farmaceutske delatnosti, psihologije, specijalne pedagogije, socijalne zaštite. Prikazane su prelomne tačke u razvoju apotekarske službe u SBBZ u prethodnih 60 godina, primenom metode istorijske analize za period od 1958.godine do danas. Dispanzer za lečenje alkoholičara i borbu protiv alkoholizma osnovan je 1958. godine u Beogradu i u njemu počinje sa radom bolnička apoteka u sklopu Kliničkog odeljenja za alkoholizam. Narednih četiri decenije prerasta u Institut za alkoholizam (1968. god.), “Institut za alkoholizam i narkomaniju” 1973. godine, a 1980. godine menja naziv u Zavod za bolesti zavisnosti. Ova zdravstvena ustanova ulazi u sastav OOUR-a Klinika za psihijatriju i neurologiju (1987.god.), koja je bila jedna od radnih organizacija Kliničko-bolničkog centra “Dr Dragiša Mišović- Dedinje”. Zavod za bolesti zavisnosti je osnovan 1992. godine, izdvojio se iz KBC i od 2007. godine radi kao SBBZ (1). Osamostaljivanjem bolnice, bolnička apoteka je organizaciono pripala laboratoriji i bolničku farmaceutsku delatnost je obavljao samo jedan farmaceut (2). Broj zaposlenih se menjao ali ne u srazmeri sa obimom poslova u bolničkoj apoteci, da bi mnogo kasnije, 2020. godine bolnička apoteka postala izdvojena, samostalna organizaciona jedinica sa zaposlenim 1 specijalistom farmacije i 1 farmaceutskim tehničarom. Može se zaključiti da je transformacija zdravstvene ustanove imala malog uticaja na rad bolničke apotekarske službe jer je u svim prelomnim tačkama uvek postojao farmaceut kao jedino stručno lice, nosilac poslova u bolničkoj apoteci.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra