Thesis (Ph. D.)--University of Virginia, 2008. / Includes bibliographical references. Also available in electronic form as viewed 2/16/2009.

Thesis (M.S.)--University of North Carolina at Wilmington, 2004. / Includes bibliographical references (leaves : [89]-95).

Thesis (MSc)--University of Stellenbosch, 2008. / Bibliography. Also available via the Internet.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 80-97).

Thesis (Ph.D. (Psychiatry))--University of Pretoria, 2003. / Summary in English and Afrikaans. Includes bibliographical references.

H ιδιοπαθής θρομβοπενική πορφύρα είναι ένα αυτοάνοσο νόσημα που χαρακτηρίζεται από χαμηλό αριθμό αιμοπεταλίων και αιμορραγίες. Επιπλέον αυτή η ασθένεια κατηγοριοποιείται σε οξεία (όταν διαρκεί λιγότερο από έξι μήνες) και χρόνια μορφή. Η λεπτίνη είναι μια ορμόνη/κυτταροκίνη που παράγεται από τα αδιποκύτταρα και ρυθμίζει την όρεξη και τον μεταβολισμό. Ως κυτταροκίνη η λεπτίνη προάγει την Th1 απόκριση και παίζει πολύ σημαντικό ρόλο στα αυτοάνοσα νοσήματα όπως έχει παρατηρηθεί σε πολλά μοντέλα ζώων. Στην εργασία αυτή μελετήσαμε τον ρόλο της λεπτίνης στην παιδική ιδιοπαθή θρομβοπενική πορφύρα (ΙΘΠ). Από τα πειράματά μας διαπιστώσαμε ότι τα επίπεδα της λεπτίνης συσχετίζονται αρνητικά με τον αριθμό των αιμοπεταλίων των ασθενών. Επιπλέον αποδείξαμε ότι στην ασθένεια που μελετήσαμε η λεπτίνη έχει αντί-φλεγμονώδη ρόλο αφού επάγει την έκφραση της IL-10 από το μονοκύτταρα Το μόριο της εκλυτικής ορμόνης της κορτικοτροπίνης (CRH) εκφράζεται κυρίως στον υποθάλαμο και ενεργοποιεί μέσω του άξονα υποθάλαμος-υπόφυση-επινεφρίδια τα γλυκοκορτικοειδή τα οποία έχουν ανοσοκατασταλτική δράση. Η CRH που εντοπίζεται στην περιφέρεια έχει αντιθέτως προ-φλεγμονώδη δράση. Εμείς μετρήσαμε τα επίπεδα της CRH στο πλάσμα υγιώς και ασθενών δοτών και παρατηρήσαμε ότι στους υγιείς δότες η CRH έχει την ικανότητα να ρυθμίζει αρνητικά την έκφραση της λεπτίνης. Ο έλεγχος όμως αυτός χάνεται στους ασθενείς με αποτέλεσμα τα επίπεδα τα λεπτίνης αυξάνονται στον ορό τους / Ιdiopathic thrombocytopenic purpura is an autoimmune disease characterized by a low platelet count and bleeding. Moreover this disorder is classified as acute (of six month or less duration) or chronic. Leptin is an adipocyte-derived hormone/cytokine that regulates food intake and basal metabolism. As a cytokine leptin promotes T helper 1 (TH1)-cell differentiation and can modulate the onset and progression of autoimmune responses in several animal models of disease. Here, we review the role of leptin in childhood idiopathic thrombopenic purpura (ITP). We found that leptin levels negatively correlated with platelet numbersand also that it plays an active anti-inflammatory role by promoting IL-10 secretion by monocytes. Corticotropin-Releasing Hormone (CRH) CRH, the hypothalamic component of the hypothalamic-pituitary,adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. We measured CRH levels in the plasma of children suffering from ITP and in the plasma of the paediatric controls, and we found that in controls CRH down-regulates leptin’s expression but not in patients.

Made available in DSpace on 2016-02-05T18:29:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-29. Added 1 bitstream(s) on 2016-02-05T18:33:27Z : No. of bitstreams: 1 000854973_20161205.pdf: 410109 bytes, checksum: 5ceaa1852fc805e9d99744c37a96f7bb (MD5) Bitstreams deleted on 2016-12-06T15:11:22Z: 000854973_20161205.pdf,. Added 1 bitstream(s) on 2016-12-06T15:12:04Z : No. of bitstreams: 1 000854973.pdf: 2773395 bytes, checksum: daf1de70009034e8b87b75a4cc4b7610 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O hormônio liberador de gonadotropina (GnRH) é um dos fatores chaves na regulação neuroendócrina da reprodução dos vertebrados. Alguns peixes apresentam três variantes do GnRH: o GnRH1 envolvido na secreção de gonadotropinas, o GnRH2 que regula o comportamento alimentar e sexual e o GnRH3 expresso no bulbo olfatório e o nervo terminal cujas fibras nervosas inervam a retina e o epitélio olfatório. O zebrafish possui duas variantes do GnRH (GnRH2 e GnRH3), sendo o GnRH3 a variante hipofisiotrófica. Estudos mostram possível envolvimento do GnRH no sistema olfato-retinal. No sistema olfatório o GnRH regula a sensibilidade na detecção de alimento, o reconhecimento intra e interespecífico, entre outros. Na retina, o GnRH3 pode estar envolvido na acuidade visual e do processamento de informação da retina. Existem estudos que reportam a presença de receptores de GnRH em diferentes camadas da retina, no entanto ainda não é clara a presença de receptores no epitélio olfatório. Neste contexto, no presente estudo analisamos a localização do gnrh2, gnrh3 e seus receptores (gnrhr1,2,3 e 4) e do gnih (hormônio inibidor de gonadotropinas) no epitélio olfatório, a retina e o bulbo olfatório de machos e fêmeas adultos e comparamos a expressão destes genes em fêmeas em diferentes estágios de maturação gonadal. Para tanto, o RNA total do epitélio olfatório, retina, bulbo olfatório, cérebro e gônadas foi extraído. Com base na sequência dos genes gnrh2, gnrh3, gnrhr1, gnrhr2, gnrhr3 e gnrhr4, primers forward e reverse foram desenhados para RT-PCR e qPCR. Sondas para a hibridização in situ também foram construídas para verificar os sítios de expressão destas moléculas no epitélio olfatório, retina e gônadas. Imunohistoquímica com os anticorpos anti-GnRH3 (BB8 e GF6) foram realizadas para localizar a proteína do GnRH3 nos tecidos analisados. O presente estudo apresenta um panorama da expressão do sistema... / The gonadotropin releasing hormone (GnRH) is one of the key factors involved in the neuroendocrine regulation of vertebrate reproduction. Some fish species have three GnRH variants: GnRH1 involved in gonadotropin secretion, GnRH2 regulating food and sexual behaviors and the GnRH3 which is expressed in the olfactory bulb and terminal nerve whose fibers innervate the retina and the olfactory epithelium. Two GnRH variants (GnRH2 and GnRH3) are present in the zebrafish, in which GnRH3 acts as the hypophisiotrophic variant. Recent studies have been showing the role of GnRH in the olfactory-retinal system. In the olfactory system, GnRH regulates food detection, and intra and interspecific recognition. In retina, GnRH3 may be involved in visual acuity modulation and retinal processing information. Moreover, studies have reported the presence of GnRH receptors in the retina, but not yet in the zebrafish olfactory epithelium. Therefore, the current study analyzed the presence of GnRH2, GnRH3 and its receptors (GnRH-R1,2,3 and 4) and GnIH (gonadotropin inhibitory hormone) in the olfactory epithelium, olfactory bulb, retina and in gonads of adult zebrafish. We also compared the expression of these genes during the different stages of ovarian maturation in zebrafish. For that, total RNA of the olfactory epithelium, olfactory bulb, retina and gonads was extracted with the PureLink® RNA Mini Kit(Ambion®). RT-PCR and qPCR analysis were performed using forward and reverse primers for gnrh2, gnrh3, gnrhr1, gnrhr2, gnrhr3, gnrhr4 for . Probes for in situ hybridization were constructed to verify the expression sites of these molecules in the olfactory epithelium, retina, and gonads. Immunohistochemistry usinganti-GnRH3 antibodies (BB8 and GF6) were performed to identify the GnRH3 protein in these tissues. The current study presents a general expression view of GnRH/GnIH and their receptors in the olfactory epithelium-olfactory bulb-retinal axis during ... / FAPESP: 2014/02481-9

Orientador: Laura Satiko Okada Nakaghi / Coorientador: Rafael Henrique Nóbrega / Banca: Elisabeth Criscuolo Urbinati / Banca: Matias Pandolfi / Resumo: O hormônio liberador de gonadotropina (GnRH) é um dos fatores chaves na regulação neuroendócrina da reprodução dos vertebrados. Alguns peixes apresentam três variantes do GnRH: o GnRH1 envolvido na secreção de gonadotropinas, o GnRH2 que regula o comportamento alimentar e sexual e o GnRH3 expresso no bulbo olfatório e o nervo terminal cujas fibras nervosas inervam a retina e o epitélio olfatório. O zebrafish possui duas variantes do GnRH (GnRH2 e GnRH3), sendo o GnRH3 a variante hipofisiotrófica. Estudos mostram possível envolvimento do GnRH no sistema olfato-retinal. No sistema olfatório o GnRH regula a sensibilidade na detecção de alimento, o reconhecimento intra e interespecífico, entre outros. Na retina, o GnRH3 pode estar envolvido na acuidade visual e do processamento de informação da retina. Existem estudos que reportam a presença de receptores de GnRH em diferentes camadas da retina, no entanto ainda não é clara a presença de receptores no epitélio olfatório. Neste contexto, no presente estudo analisamos a localização do gnrh2, gnrh3 e seus receptores (gnrhr1,2,3 e 4) e do gnih (hormônio inibidor de gonadotropinas) no epitélio olfatório, a retina e o bulbo olfatório de machos e fêmeas adultos e comparamos a expressão destes genes em fêmeas em diferentes estágios de maturação gonadal. Para tanto, o RNA total do epitélio olfatório, retina, bulbo olfatório, cérebro e gônadas foi extraído. Com base na sequência dos genes gnrh2, gnrh3, gnrhr1, gnrhr2, gnrhr3 e gnrhr4, primers forward e reverse foram desenhados para RT-PCR e qPCR. Sondas para a hibridização in situ também foram construídas para verificar os sítios de expressão destas moléculas no epitélio olfatório, retina e gônadas. Imunohistoquímica com os anticorpos anti-GnRH3 (BB8 e GF6) foram realizadas para localizar a proteína do GnRH3 nos tecidos analisados. O presente estudo apresenta um panorama da expressão do sistema... / Abstract: The gonadotropin releasing hormone (GnRH) is one of the key factors involved in the neuroendocrine regulation of vertebrate reproduction. Some fish species have three GnRH variants: GnRH1 involved in gonadotropin secretion, GnRH2 regulating food and sexual behaviors and the GnRH3 which is expressed in the olfactory bulb and terminal nerve whose fibers innervate the retina and the olfactory epithelium. Two GnRH variants (GnRH2 and GnRH3) are present in the zebrafish, in which GnRH3 acts as the hypophisiotrophic variant. Recent studies have been showing the role of GnRH in the olfactory-retinal system. In the olfactory system, GnRH regulates food detection, and intra and interspecific recognition. In retina, GnRH3 may be involved in visual acuity modulation and retinal processing information. Moreover, studies have reported the presence of GnRH receptors in the retina, but not yet in the zebrafish olfactory epithelium. Therefore, the current study analyzed the presence of GnRH2, GnRH3 and its receptors (GnRH-R1,2,3 and 4) and GnIH (gonadotropin inhibitory hormone) in the olfactory epithelium, olfactory bulb, retina and in gonads of adult zebrafish. We also compared the expression of these genes during the different stages of ovarian maturation in zebrafish. For that, total RNA of the olfactory epithelium, olfactory bulb, retina and gonads was extracted with the PureLink® RNA Mini Kit(Ambion®). RT-PCR and qPCR analysis were performed using forward and reverse primers for gnrh2, gnrh3, gnrhr1, gnrhr2, gnrhr3, gnrhr4 for . Probes for in situ hybridization were constructed to verify the expression sites of these molecules in the olfactory epithelium, retina, and gonads. Immunohistochemistry usinganti-GnRH3 antibodies (BB8 and GF6) were performed to identify the GnRH3 protein in these tissues. The current study presents a general expression view of GnRH/GnIH and their receptors in the olfactory epithelium-olfactory bulb-retinal axis during ... / Mestre

Orientador: Maria Emilia Franco Oliveira / Coorientador: Pedro Paulo Maia Teixeira / Coorientador: Fábio Morato Monteiro / Banca: Pietro Sampaio Baruselli / Banca: Lindsay Unno Gimenes / Resumo: Devido a comum ocorrência de regressão prematura (RP) do corpo lúteo (CL) em novilhas após primeira ovulação (OV), os objetivos do estudo foram: 1) acompanhar a dinâmica lútea após indução da OV em novilhas Nelore pré-púberes e 2) determinar diferenças relacionáveis a funcionalidade dessa estrutura. Cinquenta e sete fêmeas (289,61±32,28 kg, ECC de 5,66±0,65 e 17,47±0,81 meses de idade) foram divididas em dois grupos de tratamento para indução da OV. No grupo GP4+GnRH foi utilizado dispositivo intravaginal de progesterona (P4) de 3º uso por 10 dias e, 48 horas após remoção, aplicado 0,02mg de acetato de buserelina (GnRH), e no grupo GGnRH foi utilizado somente o GnRH. Os CLs formados foram acompanhados pela ultrassonografia a cada dois dias até a sua regressão funcional (diminuição do sinal vascular do Doppler colorido e concentrações de P4 abaixo de 1 ng/mL), sendo determinado para cada dia o diâmetro, área, valores numéricos (VPN) e heterogeneidade dos pixels e percentual (%) de vascularização. A velocidade do pico sistólico, velocidade diastólica final, índice de resistência e o índice de pulsatilidade (IP) da artéria ovariana também foram determinados para cada avaliação, além da concentração sérica de P4. Essas características foram comparadas entre os tratamentos, funções dos CLs (duração normal ou regredido prematuramente), dias das avaliações e suas interações, utilizando o procedimento MIXED do programa SAS (p≤0,05). Três animais de cada tratamento não responderam ao ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Due to the common occurrence of premature regression (PR) of the corpus luteum (CL) in heifers after the first ovulation (OV), the aims of this study were to: 1) monitor the luteal dynamics after OV induction in prepubertal Nellore heifers, and 2) determine differences related to the functionality of this structure. Fifty-seven females (BW 289.61±32.28 kg, BCS 5.66±0.65 and 17.47±0.81 months old) were divided into two treatment groups for OV induction. In the group GP4+GnRH, an intravaginal progesterone (P4) device of 3rd use was used for 10 days and, 48 hours after its removal 0.02 mg of buserelin acetate (GnRH) was applied, and in the GGnRH group only GnRH was used. Formed CLs were monitored via ultrasonography every two days until functional regression (decrease of the vascular signal of color Doppler and serum P4 concentrations below 1 ng/mL), being determined for each day the diameter, area, numerical values (NV) and heterogeneity of the pixels, and vascularization percentage (%). The systolic and diastolic peak velocity, resistance and pulsatility index (PI) of the ovarian artery were also determined for each day in addition to the serum P4 concentration. These characteristics were compared between treatments, CLs functions (normal duration or prematurely regressed), days of evaluations and their interactions, using the MIXED procedure of SAS program (p≤0.05). Three animals from each treatment did not respond to the OV inductor (6/57=11%), which determined an ovulation ... (Complete abstract click electronic access below) / Mestre

The plasma membrane electrical activities of neurons that secrete gonadotropin releasing hormone (GnRH), referred to as GnRH neurons hereafter, have been studied extensively. A couple of mathematical models have been developed previously to explain different aspects of these activities including spontaneous spiking and responses to stimuli such as current injections, GnRH, thapsigargin (Tg) and apamin. The goal of this paper is to develop one single, minimal model that accounts for the experimental results reproduced by previously existing models and results that were not accounted for by these models. The latter includes two types of membrane potential bursting mechanisms and the associated calcium oscillations in the cytosol. One of them has not been reported in experimental literatures on GnRH neurons and is thus regarded as a model prediction. Other improvements achieved in this model include the incorporation of a more detailed description of calcium dynamics in a three dimensional cell body with the ion channels evenly distributed on the cell surface. Although the model is mainly based on data collected in cultured GnRH cell lines, we show that it is capable of explaining some properties of GnRH neurons observed in several of other preparations including mature GnRH neurons in hypothalamic slices. One potential explanation is suggested. A phenomenological reduction of this model into a simplified form is presented. The simplified model will facilitate the study of the roles of plasma membrane electrical activities on the pulsatile release of GnRH by these neurons when it is coupled with a model of pulsatile GnRH release based on the autoregulation mechanism. / Science, Faculty of / Mathematics, Department of / Graduate