Tryptophanis anaminoacidwhichhasmanyfunctionsinthebody. Besidesitsparticipationin theproductionofproteins,itactsasasubstrateforthekynurenineandmethoxyindolemetabolic pathways. The kynurenine pathway ends with the production of nikotinamid e adenin dinukleotide ( NAD + ) ,whichisneededfortheproductionofcellularenergy. Thus,withincreased energy demand during immune system activation, the activity of the kynurenine pathway is increased. Dueto increasedactivity,itproduces more immunoactiveandneuroactivemetab olites suchaskynurenicacidandquinolinicacid.Thesemetabolitesareinvolvedinmanyprocessesin the body and affect the pathology of many diseases. Studies show that regulation of these metabolites could be a key innovation in the treatment of cance r, cardiovascular or neurodegenerative diseases. The methoxyindole pathway is another important tryptophan processingpathway.Itsbest - knownmetabolitesareserotonin,whichactsasaneurotransmitter, andmelatonin,ahormonewithimmunomodulatoryeffect sregulatedby thecircadianclock . This workdeals with thecircadian rhythmicityofenzymeexpressionofthesetwo metabolic pathways.Italsodescribestheeffectofsystemicadministrationoflipopolysaccharideendotoxin ontheexpressionofgenesoft heseenzymes.OurexperimentsusedWistarratsat30daysofage. The lipopolysaccharide was administered...

JAK/STAT signaling pathway is one of the most studied intracellular cascades transmitting signals from the extracellular environment to the cell nucleus in order to affect expression of target genes. Circadian clocks localized in the suprachiasmatic nuclei (SCN) of the hypothalamus are sensitive especially to light but they can respond to non-photic stimuli such as growth factors, opioids, leptin and cytokines that have been demonstrated to perform its function via the JAK/STAT signaling pathway. The recent findings of our laboratory demonstrated that STAT3 protein is highly produced by SCN of rat. Primary aim of our experiments was to test the circadian regulation of STAT3 production in SCN and describe the effect of exogenously administered leptin on STAT3 phosphorylation in the SCN, pineal gland and hypothalamic structures responsible for regulated feeding behavior and energy metabolism. Because activation of leptin receptors may stimulate a number of other signaling cascades, we chose phosphorylated forms of kinase ERK1/2 and GSK-3β as other markers of intracellular changes after administration of leptin in the studied structures. Our results proved rhythmic production of STAT3 protein in SCN of rat and indicated circadian regulation of sensitivity to leptin in hypothalamic structures. The data...

Includes bibliographical references (leaves 166-195) Addresses the nature of the central mechanisms involved in the regulation of the circadian pattern of secretion of the pineal hormone melatonin in the highly seasonal Suffolk breed of sheep. Provides new information on the behaviour of the onset and offset of melatonin secretion under different photoperiodic conditions.

Includes bibliographical references (leaves 166-195) / xxi, 195 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Addresses the nature of the central mechanisms involved in the regulation of the circadian pattern of secretion of the pineal hormone melatonin in the highly seasonal Suffolk breed of sheep. Provides new information on the behaviour of the onset and offset of melatonin secretion under different photoperiodic conditions. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1991?

Dehydroepiandrosterone, a C-19 steroid, is found endogenously with the highest circulating serum levels. It is converted to important steroids such as the sex hormones oestrogen and testosterone. DHEA has come under the spotlight as a purported “fountain of youth” due to its well-characterised age-related decline. The supplementation of DHEA in both the elderly and those with a pathophysiological deficiency has been shown to be of benefit, particularly with regard to wellbeing and depression. The role of DHEA in the periphery has not been elucidated beyond its role as a precursor hormone in sex steroid biosynthesis, though it has been established as a neuroactive neurosteroid, capable of exerting neuroprotective effects in the brain. Since the importance of free radicals in aging and neurodegeneration is well established, investigations were conducted on the ability of DHEA to inhibit free radical generation or scavenge existing free radicals. DHEA was able to significantly inhibit quinolinic acid-induced lipid peroxidation, a measure of membrane damage, over a range of concentrations, although the reduction did not appear to be dose-dependent. This was observed in both in vitro and in vivo studies. Thus, the ability of a compound to reduce the degree of lipid peroxidation may indicate its value as a neuroprotectant. However, DHEA did not significantly reduce cyanide induced generation of the superoxide free radical, suggesting that DHEA is not an effective free radical scavenger of the superoxide anion and that the reduction in lipid peroxidation does not occur through a scavenging mechanism. Apoptosis is a physiological process which is necessary for development and homeostasis. However, this form of programmed cell death can be initiated through various mechanisms and too much apoptotic cell death results in deleterious effects in the body. DHEA was shown not to induce apoptosis. Even the lowest concentration of DHEA investigated in this thesis shows a remarkable decrease in the degree of apoptosis caused by intrahippocampal chemical insult by the neurotoxin quinolinic acid. Cresyl violet was used to visualise tissue for histological examination which revealed that DHEA is able to preserve the normal healthy morphology of hippocampal cells which have been exposed to quinolinic acid. Cells maintained their integrity and showed little evidence of swelling associated with necrosis. Organ culture studies were performed by assessing the impact of DHEA on several pineal metabolites. The study revealed that DHEA exerted an effect on the metabolism of indoleamines in the pineal gland. Melatonin, the chief pineal hormone, did not appear to be affected while the concentrations of N-acetylserotonin, serotonin and methoxytryptamine showed significant alterations. Thus, the neuroprotective mechanism of DHEA does not appear to be mediated by an increase in the presence of melatonin. The biological importance of metal ions in neurodegeneration is also well established and thus the potential interaction between DHEA and metal ions was considered as a mechanism of action. Spectroscopic and electrochemical analyses were performed to determine whether DHEA is able to interact with metal ions as a ligand. These reveal that DHEA does not form a strong bond with the metals investigated, namely copper (II) and iron (III), but that a weak interaction is evident. These investigations were conducted in a rodent model, which has neither large amounts of endogenous DHEA, nor the enzymatic infrastructure present in humans. Thus, the theory that DHEA exerts its effects through downstream metabolic products is unlikely. However, these investigations reveal that there is merit in the statement that DHEA itself is a neuroprotective molecule, and confirm that the further investigation of DHEA is an advisable strategy in the war against neurodegeneration and aging.

No description available.

No description available.

Este estudo foi realizado para testar técnicas de ressonância magnética funcional (RMf) para investigar aspectos funcionais da pineal humana. Foram coletadas imagens funcionais e amostras de sangue total para a dosagem da melatonina plasmática antes, durante e após a apresentação de estímulo com luz azul quase monocromática em indivíduos saudáveis. Os participantes realizaram o exame de tomografia computadorizada do crânio sem o uso de contraste endovenoso (TC), para a avaliação qualitativa do grau de calcificação pineal. As conclusões foram: a) não houve ativação da pineal em resposta à aplicação da luz; b) não houve diferenças estatisticamente significativas entre as condições pré-estímulo, durante o estímulo ou pós-estímulo usando diferentes métodos de análise dos dados de RMf, porém, observou-se tendência de maior poder espectral na pineal durante a aplicação do estímulo luminoso do que nas condições pré e pós-estímulo; c) foi identificada a conectividade funcional da pineal, que poderá ser melhor avaliada em estudo futuro. / This study aimed to test the functional magnetic resonance imaging (fMRI) techniques in order to investigate the functional aspects of human pineal gland. Some functional images and total blood samples for dosing the plasmatic melatonin concentration were collected before, during and after the presentation of a monochromatic blue light stimulation in healthy individuals. All subjects were examined by a brain CT scan, with no the administration of endovenous contrast, for the qualitative assessment of the pineal calcification level. The conclusions were the following: a) there was no pineal activation in response to the application of light; b) there were no statistically significant differences between the pre-, during and poststimulation conditions with different analysis methods of fMRI data, however, there was a trend of greater spectral power in the pineal gland during the luminous stimulation application than under the other conditions; c) the functional connectivity of the pineal could be identified, which should be better assessed in a future study.

Este estudo foi realizado para testar técnicas de ressonância magnética funcional (RMf) para investigar aspectos funcionais da pineal humana. Foram coletadas imagens funcionais e amostras de sangue total para a dosagem da melatonina plasmática antes, durante e após a apresentação de estímulo com luz azul quase monocromática em indivíduos saudáveis. Os participantes realizaram o exame de tomografia computadorizada do crânio sem o uso de contraste endovenoso (TC), para a avaliação qualitativa do grau de calcificação pineal. As conclusões foram: a) não houve ativação da pineal em resposta à aplicação da luz; b) não houve diferenças estatisticamente significativas entre as condições pré-estímulo, durante o estímulo ou pós-estímulo usando diferentes métodos de análise dos dados de RMf, porém, observou-se tendência de maior poder espectral na pineal durante a aplicação do estímulo luminoso do que nas condições pré e pós-estímulo; c) foi identificada a conectividade funcional da pineal, que poderá ser melhor avaliada em estudo futuro. / This study aimed to test the functional magnetic resonance imaging (fMRI) techniques in order to investigate the functional aspects of human pineal gland. Some functional images and total blood samples for dosing the plasmatic melatonin concentration were collected before, during and after the presentation of a monochromatic blue light stimulation in healthy individuals. All subjects were examined by a brain CT scan, with no the administration of endovenous contrast, for the qualitative assessment of the pineal calcification level. The conclusions were the following: a) there was no pineal activation in response to the application of light; b) there were no statistically significant differences between the pre-, during and poststimulation conditions with different analysis methods of fMRI data, however, there was a trend of greater spectral power in the pineal gland during the luminous stimulation application than under the other conditions; c) the functional connectivity of the pineal could be identified, which should be better assessed in a future study.

<p>Увод: Пинеална жлезда је неуроендокрини, циркумвентрикуларни орган филогенетски пореклом органа вида. Калцификације пинеалне жлезде су чест налаз приликом радиолошких претрага, без још увек довољно доказа да ли су оне нормалан налаз. Магнетна резонанца описује три морфолошка типа пинеалне жлезде. Циљеви: Утврдити степен корелације морфолошких типова пинеалне жлезде утврђених патохистолошким налазом са налазом компјутеризоване томографије, као и степен корелације присуства калцификација у пинеалној жлезди утврђених патохистолошким налазом и налазом компјутеризоване томографије. Утврдити степен калцификације пинеалне жлезде патохистолошким налазом у зависности од старости. Материјал и методе: Макроскопском морфолошком и микроскопском, хистолошком анализом обухваћено је 111 изолованих пинеалних жлезди осoба оба пола, не млађих од 18 година од којих је 27 снимљено апаратом Somatom Sensation 64 са дебљинама реконструисаних пресека 5 и 1mm, а још 9 апаратом Somatom Emotion 16. Резултати: Постоји статистички значајна разлика у одређивању сва три дијаметра епифизе петомилиметарским реконструкцијама, и при утврђивању два дијаметра једномилиметарским реконструкцијама. Постоји статистички значајна разлика у утврђивању морфолошких типова хистолошком и методом компјутеризоване томографије. Присутна је позитивна корелација калцификованости жлезде одређене мерењем њене густине у Хаунсфилдовим јединицама и утврђене микроскопски. Калцификованост пинеалног паренхима не корелира старости. Закључак: Наша студија је показала да су једномилиметарске реконструкције тачније у одређивању дијаметара жлезде. Макроскопским и микроскопским мерењем утврђена су сва три типа пинеалне жлезде описана магнетнорезонантним осликавањем. Утврђена је статистички значајна повезаност густине пинеалне жлезде измерене у Хаунсфилдовим јединицама на једномилиметарским реконструкцијама и степена калцификованости израженог у процентима. Није утврђена повезаност калцификованости епифизе мерене микроскопски и старости.</p> / <p>Uvod: Pinealna žlezda je neuroendokrini, cirkumventrikularni organ filogenetski poreklom organa vida. Kalcifikacije pinealne žlezde su čest nalaz prilikom radioloških pretraga, bez još uvek dovoljno dokaza da li su one normalan nalaz. Magnetna rezonanca opisuje tri morfološka tipa pinealne žlezde. Ciljevi: Utvrditi stepen korelacije morfoloških tipova pinealne žlezde utvrđenih patohistološkim nalazom sa nalazom kompjuterizovane tomografije, kao i stepen korelacije prisustva kalcifikacija u pinealnoj žlezdi utvrđenih patohistološkim nalazom i nalazom kompjuterizovane tomografije. Utvrditi stepen kalcifikacije pinealne žlezde patohistološkim nalazom u zavisnosti od starosti. Materijal i metode: Makroskopskom morfološkom i mikroskopskom, histološkom analizom obuhvaćeno je 111 izolovanih pinealnih žlezdi osoba oba pola, ne mlađih od 18 godina od kojih je 27 snimljeno aparatom Somatom Sensation 64 sa debljinama rekonstruisanih preseka 5 i 1mm, a još 9 aparatom Somatom Emotion 16. Rezultati: Postoji statistički značajna razlika u određivanju sva tri dijametra epifize petomilimetarskim rekonstrukcijama, i pri utvrđivanju dva dijametra jednomilimetarskim rekonstrukcijama. Postoji statistički značajna razlika u utvrđivanju morfoloških tipova histološkom i metodom kompjuterizovane tomografije. Prisutna je pozitivna korelacija kalcifikovanosti žlezde određene merenjem njene gustine u Haunsfildovim jedinicama i utvrđene mikroskopski. Kalcifikovanost pinealnog parenhima ne korelira starosti. Zaključak: Naša studija je pokazala da su jednomilimetarske rekonstrukcije tačnije u određivanju dijametara žlezde. Makroskopskim i mikroskopskim merenjem utvrđena su sva tri tipa pinealne žlezde opisana magnetnorezonantnim oslikavanjem. Utvrđena je statistički značajna povezanost gustine pinealne žlezde izmerene u Haunsfildovim jedinicama na jednomilimetarskim rekonstrukcijama i stepena kalcifikovanosti izraženog u procentima. Nije utvrđena povezanost kalcifikovanosti epifize merene mikroskopski i starosti.</p> / <p>Introduction: Pineal gland is a small neuroendocrine, circumventricular organ wich evolved from the eye. Calcifications were incidentally discovered and frequently without a proof whether they were normal or abnormal. Magnetic resonance imaging describes three morphological types. Aim: To determine if there is a correlation between pineal gland morphology types and calcifications established with histology and with computed tomography (CT) and if there is the correlation between calcifications and age. Method of work and material: Macroscopic and mycroscopic analysis encounted 111 isolated pineal glands of both sexes, no younger than 18, from wich 27 was examed with Somatom Sensation 64 and 9 with Somatom Emotion 16 with 5mm and 1mm reformated pictures. Results: All three diameters measured on 5mm reformated pictures and two measured on 1mm reformated pictures differed statistically compared to diameters measured macroscopically. There was siginificant difference between morphological types established on computed tomography and macroscopically. Pineal gland calcifications measured microscopically and with CT correlated positivelly. Pineal gland calcifications were not dependant on the patients age. Conclusion: Allthough 1mm reformated pictures are more accurate than 5mm, the pineal gland morpholgy types determined macroscopically and with CT are not correlated. However, calcification measurement with CT correlates with the microscopic measurement. Calcifications measured microscopically are not correlated with age.</p>