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Venturin, Gabriela Lovizutto. "Efeito regulador da PGE2 na produção de TNF-α e IL-17 na atividade microbicida na leishmaniose canina. /". Araçatuba, 2019. http://hdl.handle.net/11449/183297.
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Orientador: Valéria Marçal Felix de Lima<br>Resumo: A leishmaniose canina (CanL) é causada pelo parasito intracelular Leishmania infantum. Devido ao alto parasitismo na pele o cão é considerado o principal reservatório urbano da L. Infantum. A prostaglandina-E2 (PGE2) possui propriedades reguladoras potentes do sistema imunológico e pode se ligar aos receptores EP1, EP2 e EP4 que geram ativação celular ou EP3 que gera inibição de resposta celular. Na CanL o papel regulador da PGE2 ainda não foi estudado, por isso, os parâmetros foram avaliados em cultura de leucócitos esplênicos de cães com CanL. Avaliando o nível de PGE2, seus receptores, e seu efeito modulador sobre a PGE2 na atividade da arginase, NO2, citocinas IL-10, IL-17 e TNF-α e carga. Para isso utilizamos seus agonistas, antagonista e inibidor. Nossos resultados mostraram que a expressão do receptor EP2 diminuiu nos leucócitos esplênicos dos cães com CanL quando comparado aos cães saudáveis. Observamos que o NO2 diminuiu quando tratados com os agonistas dos receptores de PGE2 (EP1/EP2/EP3), antagonista dos receptores de PGE2 (AH-6809) e inibidor de COX-2 (NS-398). A concentração das citocinas TNF-α e a IL-17 diminuíram quando tratadas com agonista do receptor de PGE2 (EP2), e quando estimuladas com a PGE2. A carga parasitária diminuiu na cultura de leucócitos esplênicos de cães com CanL estimulados com PGE2. Concluímos que a infecção por Leishmania modula os receptores de PGE2 em cães, e que a ligação da PGE2 aos receptores pode ativar a capacidade microbicida das cé... (Resumo completo, clicar acesso eletrônico abaixo)<br>Doutor
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Javed, T. "Synthesis of prostaglandins and prostaglandin analogues from norbornadiene." Thesis, University of Salford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356170.
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Nielsch, A. S. "Effects of prostaglandins and prostaglandin synthetase inhibitors on liver toxicity." Thesis, University of Aberdeen, 1987. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU499301.
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A total of 22 non-steroidal anti-inflammatory drugs and derivatives were added to microsomes to study the denaturation of cytochrome P-450 to cytochrome P-420 in the absence of an NADPH-generating system. There was a highly significant correlation among the different compounds between the extent of denaturation of cytochrome P-450 and their surfactant potency. Endotoxin administration to rats caused a maximum decrease in hepatic microsomal enzymes after 24 hours. Significant decreases in cytochrome P-450 (40%), cytochrome b5 levels (22%), aminopyrine N-demethylase (31%) and biphenyl 4-hydroxylase (54%) activities were obtained. Concomitant intravenous injection of 16,16-DMPG F2 and 16,16-DMPG E2 prevented some of the endotoxin-induced changes in hepatic microsomal enzymes. Three days treatment with cocaine was required to obtain hepatic damage in mice. Decreases in cytochrome P-450 content (41%), aminopyrine N-demethylase (31%) and FAD-monooxygenase (35%) activities were obtained, when compared to saline treated mice. The serum enzyme activities were markedly increased (SGOT 13-fold and SOCT 44-fold). Histological changes in form of centrilobular necrosis and fatty changes were present. Repeated subcutaneous administration of iloprost or synthetic prostaglandins just before cocaine prevented some of the hepatic lesions. Iloprost was found to be a better hepatoprotective agent than synthetic prostaglandins against the cocaine mediated liver toxicity. Carbon tetrachloride administration to mice produced similar lesions to those obtained with cocaine. Administration of iloprost prevented some of the lesions caused by carbon tetrachloride, giving a partial protection to the carbon tetrachloride-induced decrease in cytochrome P-450 and the increase in SGOT. Iloprost also partially prevented the carbon tetrachloride mediated centrilobular necrosis.
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Ujjan, Safdar Ali. "Prostaglandin D2 (PGD2) signalling and male germ cell : differentiation in the mouse embryonic testis." Thesis, Montpellier 2, 2014. http://www.theses.fr/2014MON20099.
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La détermination du sexe et la différenciation des cellules germinales est un processus très organisé qui commence au stade embryonnaire et se termine à la vie adulte. Dans les gonades embryonnaires l'expression de Sry suivie par l'expression de Sox9 initie le développement testiculaire tandis que, en l'absence de l'expression de Sry, les gènes associés au sexe féminin initient le développement des ovaires. Les cellules germinales qui ont migré vers les gonades nouvellement formées continuent leur prolifération intense jusqu'à ce qu'ils s'engagent dans la voie le mâle ou femelle. La décision de devenir des cellules germinales mâle ou femelle ne dépend pas seulement du chromosome sexuel des cellules germinales, mais aussi du microenvironnement des gonades. Si les cellules germinales entrent dans la gonade femelle, ils doivent arrêter la prolifération, dépasser l'arrêt mitotique et entrer en méiose et alors s'arrêter en prophase I. Alors que si les cellules germinales entrent dans la gonade mâle, ils doivent arrêter la prolifération et entrer en arrêt de la mitose. Ici, nous montrons que, lors de la détermination du sexe embryonnaire, la prostaglandine D2 (PGD2) produite par chacune des deux enzymes: la L-PGDS et H-PGDS dans les cellules somatiques et les cellules germinales du testicule mâle participe au programme de différenciation des cellules germinales. La voie de signalisation PGD2 entraine l'arrêt de la mitose par l'activation de l'expression et de la localisation nucléaire de l'inhibiteur du cycle cellulaire p21Cip1 et en réprimant les marqueurs de pluripotence et aussi Stra8. En outre, PGD2 est responsable de l'activation du gène spécifique au mâle Nanos2. Par conséquent, ces données suggèrent que la signalisation par le récepteur de PGD2 DP2 est requise pour la différenciation correcte de la cellule germinale mâle<br>The sex determination and subsequent germ cell differentiation is highly ordered process that starts at embryonic stage and completes at adult life. In the embryonic gonads Sry expression followed by Sox9 expression initiates testis development while in the absence of Sry expression, genes associated to female fate initiate ovary development. The germ cells that migrated towards newly formed gonads continue extensive proliferation until they commit to the male or female pathway. The fate decision of germ cells as male or female does not depend only on germ cell chromosomal sex but also on gonadal micro-environment. If germ cells enter into female gonad, they have to stop proliferation, pass through mitotic arrest and enter into meiosis; then arrest into prophase I. While if germ cells enter into male gonad, they have to stop proliferation and enter into mitotic arrest. Here we show that during embryonic sex determination, Prostaglandin D2 (PGD2) produced by each of the two enzymes: L-Pgds and H-Pgds in somatic cells and germ cells of testis participates in male germ cell differentiation program. PGD2 signalling supports mitotic arrest by activating the expression and nuclear localization of cell cycle inhibitor P21cip1 and by repressing pluripotency markers and PGD2 has negative effects on Stra8 expression. In addition PGD2 supports activation of male specific gene Nanos2. Hence these data suggest that PGD2 signalling through DP2 receptor is required for proper male germ cell differentiation
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Gagliolo, Jean-Marie. "Rôle de la sénescence des fibroblastes dans la physiopathologie de la bronchopneumopathie chronique obstructive." Thesis, Paris Est, 2013. http://www.theses.fr/2013PEST1065.
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La sénescence, perte irréversible des capacités réplicatives des cellules associée à la sécrétion de médiateurs inflammatoires, pourrait participer au développement de l'atteinte pulmonaire dans la bronchopneumopathie chronique obstructive (BPCO) en initiant, maintenant et propageant un état inflammatoire. L'objectif de ce travail était d'évaluer les mécanismes de la sénescence impliqués dans l'induction et le maintien de l'inflammation au cours de la BPCO. Ainsi, des fibroblastes pulmonaires de témoins et de patients atteints de BPCO ont été mis en culture à long terme. Un phénotype sénescent majoré associée à un sécrétome pro-inflammatoire était détectée dans les fibroblastes de patients avec BPCO par rapport aux témoins. Par ailleurs, ces fibroblastes présentaient une expression accrue des récepteurs à la PGE2 (EP2 /4)au stade non sénescent et une production accrue de PGE2, un médiateur lipidique pro-inflammatoire, au stade sénescent. Dans cette optique, une partie du travail a consisté à déterminer si la PGE2 pouvait induire la sénescence et l'inflammation des fibroblastes pulmonaires de sujets atteints ou non de BPCO. Nous avons pu démontrer que la PGE2 synthétisée par les fibroblastes sénescents induisait, maintenait (effet autocrine) et propageait (effet paracrine) la sénescence et l'inflammation associée via une voie EP2/4 / COX-2 / oxydants / p53. L'implication des oxydants dans l'induction de la sénescence nous a conduit à étudier les effets de l'hème oxygénase (HO)-1, un système anti-oxydant et anti-inflammatoire sur la prévention de la sénescence des fibroblastes pulmonaires. Ainsi, des fibroblastes pulmonaires ont été traités chroniquement avec des substances pharmacologiques modulant l'activité d'HO-1. Des résultats préliminaires nous ont permis d'observer que l'activation de HO-1 prévenait l'induction de la sénescence chez des fibroblastes pulmonaires de témoins et de BPCO. Au total, la modulation des voies de la PGE2 et de l'HO-1 pourrait contribuer à limiter la sénescence des fibroblastes pulmonaires dans la BPCO<br>Cellular senescence, a state of irreversible loss of replicative capacity associated with the secretion of inflammatory mediators, could participate in the development of chronic obstructive pulmonary disease (COPD) by initiating, maintaining and propagating an inflammatory state. The aim of this PhD project was to evaluate the mechanisms involved in senescence induction in COPD lung fibroblasts. COPD fibroblasts exhibited an increased senescent phenotype as compared to control cells. In addition, COPD fibroblasts showed an increased PGE2 receptors (EP2 /4) expression at non senescent stage and PGE2 production, apro-inflammatory lipid mediator at senescent stage. In this context, one part of the study was devoted to determine whether PGE2 could induce senescence of lung fibroblasts of subjects with and without COPD. We have shown that PGE2 synthesized by senescent fibroblasts induced, maintained (autocrine effect) and propagated (paracrine effect) senescence and associated inflammation via EP2 /4 / COX-2 / oxidants / p53 pathway. The essential role of oxidants production in the induction of senescence in COPD led us to study the effects of heme oxygenase (HO)-1, an antioxidant and anti-inflammatory system on the prevention of senescence in COPD fibroblasts. Pharmacological activation of HO-1 by hemin prevented the induction of senescence in lung fibroblasts from COPD patients probably in relation with an anti -oxidant effect. The modulation of PGE2 and HO-1 pathways may contribute to attenuate fibroblasts senescence in COPD
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Pereira, Priscilla Aparecida Tartari. "Efeitos antagônicos da prostaglandina D2 e prostaglandina E2 na resposta imune durante infecção experimental por Histoplasma capsulatum." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-06012014-081806/.
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O Histoplasma capsulatum é um fungo dimórfico, patogênico e responsável por graves lesões pulmonares. A infecção é adquirida pela inalação de conídios e posterior conversão para leveduras nos alvéolos e bronquíolos, onde são fagocitadas por macrófagos alveolares residentes e leucócitos que migram para o local da infecção. Recentemente, demonstramos que animais infectados com H. capsulatum e tratados com inibidor da síntese de prostaglandinas apresentaram diminuição de carga fúngica nos pulmões e baço, aumento da produção de nitrito e da fagocitose de leveduras por macrófagos alveolares, e maior sobrevivência, quando comparados com os animais somente infectados. Porém, neste estudo não foram determinados quais subtipos de prostaglandinas participam na patogênese da histoplasmose. Vários grupos de pesquisa têm demonstrado que PGD2 e PGE2 podem ter ações biológicas distintas quanto à remoção de microrganismos no hospedeiro. Desta maneira, é fundamental o entendimento do papel da PGD2 e da PGE2 nos mecanismos efetores dos macrófagos na defesa do hospedeiro, especialmente na histoplasmose. Portanto, o objetivo deste estudo foi investigar a participação da PGD2 e PGE2 na infecção experimental por H. capsulatum. Assim, demonstramos que a PGD2 aumentou a fagocitose e mecanismos microbicidas de macrófagos alveolares infectados in vitro com H. capsulatum. Observamos ainda que a 15dPGJ2, metabólito da PGD2, aumentou somente a fagocitose, e PGE2 inibiu os mecanismos efetores do macrófago. Mostramos ainda o aumento de BLT1 em macrófagos alveolares após adição de PGD2, e a possível ligação desta ao BLT1, e de LTB4 em DP2. Além disso, caracterizamos micropartículas de PLGA contendo PGD2 (MS-PGD2), e investigamos seus efeitos. O tamanho, carga elétrica e morfologia das micropartículas foram adequados para um tratamento intranasal e para fagocitose por macrófagos alveolares. As MS-PGD2 foram fagocitadas e capazes de ativar NF-B, e consequentemente, influenciar na produção de nitrito, IL-1, TNF-, IL-6 e TGF-. Com base nestes dados, avaliamos os efeitos do tratamento da MS-PGD2 ou da MS-PGE2 em animais infectados com H. capsulatum. Estas foram administradas via intranasal em animais infectados e tratados ou não com celecoxibe. Verificamos a diminuição da carga fúngica nos pulmões e baço, diminuição do infiltrador celular no espaço broncoalveolar e de citocinas inflamatórias no pulmão após tratamento com MS-PGD2. Contrariamente, após tratamento da MS-PGE2 observamos maior carga fúngica nos pulmões e baço, e aumento da inflamação no tecido e maior produção de IL-10. Além disso, demonstramos que no 21° dia após infecção, referente ao 7° dia após o término do tratamento com MS-PGD2, a carga fúngica manteve-se reduzida nos pulmões, comprovando assim a eficácia deste tratamento. Posteriormente, utilizando inibidores específicos, HQL-79 e CAY10526, mostramos respectivamente o papel protetor da PGD2 e o deletério da PGE2 na histoplasmose. Em conjunto, nossos dados contribuíram para o entendimento das funções antagônicas da PGD2 e PGE2 nesta micose.<br>Histoplasma capsulatum is a pathogenic dimorphic fungus and responsible for severe pulmonary lesions. Infection is acquired by inhalation of conidia and posterior conversion to yeasts in the alveoli and bronchioles, in which they are phagocyted by resident alveolar macrophages and leukocytes that migrate to the local infection. Recently, we demonstrate that mice infected by H. capsulatum and treated with inhibitor of prostaglandins synthesis presented a decrease in fungal burden in lungs and spleen, increase in nitrite production and uptake of yeasts by alveolar macrophages, and more survival, when compared with animals only infected. However, in this study, it was not determined what subtypes of prostaglandins participate in pathogenesis of histoplasmosis. Many research groups have demonstrated that PGD2 and PGE2 can have different biological effects regarding to microorganisms elimination in the host. Thus, it is primordial the understanding about the role of PGD2 and PGE2 on effector mechanisms of macrophages in host defense, especially in histoplasmosis. Therefore, the aim of this study was to investigate the role of PGD2 and PGE2 on experimental infection by H. capsulatum. So, we verify that PGD2 increased the uptake and microbicidal mechanisms of alveolar macrophages infected in vitro by H. capsulatum. 15dPGJ2, a PGD2 metabolite, increased only the phagocytosis, and PGE2 inhibited the effector mechanisms of macrophages. Among these results, we showed an increase of BLT1 expression on alveolar macrophages after addition of PGD2, and a possible binding of this mediator to BLT1, and of LTB4 to DP2. Later, as tool of therapeutic investigation, we used PGD2 encapsulation in biodegradable polymer, PLGA, in order to preserve its stability. Size, zeta potential and morphology were adequate for a possible intranasal treatment and uptake by alveolar macrophages. MS-PGD2 were phagocyted and able to activate NF-B, and consequently, to modulate nitrite, IL-1, TNF-, IL-6 and TGF- production. In this context, we purpose a treatment of the infection with MS-PGD2, in comparison to treatment with PGE2. MS-PGD2 were administrated via intranasal in infected mice, treated or not with celecoxib. We verify a decrease of fungal burden in lungs and spleen, less cellular infiltrate and decrease of some inflammatory cytokines. In contrast, after treatment of MS-PGE2, we observed greater fungal burden in the lungs and spleen, and an increase of the tissue inflammation and production of IL-10. Furthermore, we show that on day 21 after infection, referring to the 7th day after the treatment with MS-PGD2, fungal burden remained reduced in the lungs, thus proving the effectiveness of the treatment. Subsequently, using specific inhibitors, HQL-79 and CAY10526, respectively show the protective role of PGD2 and in deleterious to PGE2 in histoplasmosis. Together, our data contribute to the understanding of the antagonistic functions of PGD2 and PGE2 in this mycosis.
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Oliveira, Milena Lopes. "Ação do 17β-estradiol na síntese de PGF2α endometrial em vacas." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-25082017-095013/.
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O 17β-E2 estimula a expressão de receptores endometriais, ER e OXTR. A ativação de OXTR induz a ativação da cadeia de síntese de PGF2α. A hipótese do presente estudo é que as enzimas de síntese de PGF2α são reguladas pelo 17β-E2. Objetivou-se determinar os efeitos do 17β-E2 na expressão gênica e proteica, assim como na localização de proteínas envolvidas na síntese de PGF2α. Vacas Nelore multíparas, solteiras e cíclicas foram sincronizadas por aplicação de BE e inserção de dispositivo de P4. Após 8 dias realizou-se a remoção do dispositivo de P4 e aplicação de PGF2α, seguido por 4 dias de observação de estro (D0=dia do estro). Entre D14 e D27 foram realizadas avaliações diárias da área do CL (cm2), fluxo sanguíneo (%) e concentração plasmática de progesterona (P4). No D15 as vacas foram divididas em três grupos: Controle (C; não tratado;N= 10), Placebo (P; 6mL de etanol 50%; IV; N= 21) e Estradiol (E; 3mg 17β-E2; 6mL de etanol 50%; IV;N=21). Subsequente aos tratamentos, biópsias uterinas foram coletadas nos tempos 0h (C; N=10); 4h (E4h, N=11 e P4h; N=10) ou 7h (E7h, N=10 e P7h, N=11). Amostras de sangue foram obtidas nos tempos 0h a 7h, para mensuração das concentrações PGFM no D15. O grupo E apresentou acentuada diminuição da área do CL, fluxo sanguíneo e concentração de P4 (P<0,05), comparado ao grupo P. Comparado ao grupo P, as vacas do grupo E anteciparam o dia da luteólise funcional e estrutural em 2 e 3 dias, respectivamente. O grupo E apresentou maior concentração de PGFM nos tempos 4h, 6h e 7h (P<0,05), comparado ao grupo P. A quantificação dos transcritos realizada por qPCR (N=6/grupo). Na hora 4, a abundância dos genes ESR1, ESR2, PRKCα, PRKCβ, PLA2G4, AKR1B1 e AKR1C4 foi menor nas amostras E4h, enquanto OXTR foi maior nas mesmas amostras comparando-se com as amostras P4h (P<0,05). A expressão gênica de PTGS2 não diferiu entre os grupos E4h e P4h (P>0,05). Na hora 7, as amostras E7h também apresentaram menor abundância de ESR1, PRKCα, PRKCβ, AKR1B1 e AKR1C4 (P<0,05) e houve tendência para menor expressão de ESR2, comparado às amostras P7h. Contudo, não houve diferença na abundância de OXTR, PLA2G4 e PTGS2 entre as amostras E7h e P7h (P>0,05). A abundância da enzima PKCα analisada por Western Blotting (N=3/grupo) foi diminuída tanto nas amostras E4h como nas E7h, em relação às amostras P4h e P7h, respectivamente. Na avaliação por imunohistoquímica (N=5/grupo), o grupo E4h apresentou maior imunomarcação de PGR no epitélio glandular (P< 0,05) e houve tendência para maior imunomarcação de PKCϒ no epitélio luminal, comparado ao grupo P4h (P=0,08). Houve tendência para menor imunomarcação de ERα no epitélio glandular do grupo E4h comparado ao grupo E7h (P=0,1). Concluí-se que a aplicação do 17β-E2 levou a redução da maioria dos transcritos das moléculas de síntese de PGF2α, assim como da abundância de PKCα. O possível mecanismo para a estimulação de PGFM por 17β-E2 pode incluir o aumento da ativação de enzimas que participam na cascata de síntese de PGF2α.<br>17β-E2 stimulates the expression of endometrial receptors, ER and OXTR. Activation of OXTR induces the activation of the synthesis of PGF2α pathway. The central hypothesis is that the enzymes involved in PGF2 synthesis are reguleted by 17β-E2. The objective of this study was to determine the effects of 17β-E2 on gene and protein expression and localization of the enzymes involved in PGF2α synthesis. Multiparous, non-lactating and cyclic Nelore cows were synchronized by BE application and P4 device insertion. After 8 days the P4 device was removed and a single dose of PGF2α applied, followed by 4 days of estrus detection (D0 = day of estrus). Daily measurements of CL area (cm2), blood flow (%), and plasma progesterone concentration (P4) were performed between D14 and D27. On D15 cows were divided into three groups: Control (C, untreated, N = 10), Placebo (P; 6mL of ethanol 50%, IV; N = 21) and Estradiol (E; 3mg 17β-E2; Ethanol 50%, IR: N = 21). After the treatments administration, uterine biopsies were collected at times 0h (C; N = 10); 4h (E4h, N = 11 and P4h, N = 10) or 7h (E7h, N = 10 and P7h, N = 11). Blood samples were obtained from time 0h to 7h for the measurement of the PGFM concentrations on D15. Group E showed a marked decrease in CL area, blood flow, and P4 concentration (P <0.05) compared to group P. Also, when compared to group P, cows from group E anticipated the day of functional and structural luteolysis in 2 and 3 days, respectively. Group E presented higher concentration of PGFM at 4h, 6h and 7h (P <0.05), compared to group P. The transcripts abundance was performed by qPCR (N = 6 / group). The transcripts abundance of ESR1, ESR2, PRKCα, PRKCβ, PLA2G4, AKR1B1, and AKR1C4 genes was lower in the E4h samples, while OXTR was higher in the same samples compared to the P4h (P <0.05) samples in the time 4h. The gene expression of PTGS2 did not differ between groups E4h and P4h (P> 0.05). At time 7h, samples E7h also had lower abundance of ESR1, PRKCα, PRKCβ, AKR1B1 and AKR1C4 (P <0.05) and there was a tendency for lower ESR2 expression, compared to samples P7h. Nevertheless, there was no difference in the abundance of OXTR, PLA2G4, and PTGS2 between samples E7h and P7h (P> 0.05). The abundance of the PKCα enzyme analyzed by Western Blotting (N = 3 / group) was decreased in both the E4h and E7h samples, relative to the samples P4h and P7h, respectively. In the evaluation by immunohistochemistry (N = 5 / group), the E4h group presented greater PGR immunostaining in the glandular epithelium (P <0.05) and there was a tendency for a greater immunostaining of PKCϒ in the luminal epithelium, compared to the P4h group (P = 0,08). There was a tendency for lower ERα immunostaining in the glandular epithelium of the E4h group compared to the E7h group (P = 0.1). It was concluded that the application of 17β-E2 led to the reduction of most of the transcripts of the PGF2α synthesis molecules, as well as the abundance of PKCα. The possible mechanism for stimulation of PGFM by 17β-E2 may include increased activation of enzymes that participate in the cascade of PGF2α synthesis.
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Feltrin, Isabella Rio. "Efeitos do 17β-estradiol na abundância de transcritos para enzimas envolvidas na síntese de PGF2α endometrial em fêmeas bovinas no final do diestro". Botucatu, 2020. http://hdl.handle.net/11449/192193.
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Orientador: Claudia Maria Bertan Membrive<br>Resumo: Em bovinos, o 17β-estradiol (17β-E2) estimula a expressão de receptores de estradiol (ER) e ocitocina (OXTR) no endométrio. A ativação de OXTR induz a ativação de uma complexa cascata que resulta na síntese de PGF2α. A hipótese é que o tratamento com 17β-E2, 15 dias após o estro (D15), modula a expressão gênica das proteínas quinase (PKC) e fosfolipase A2 (PLA2), ambas envolvidas na síntese de PGF2α e dependentes de cálcio. Objetivou-se neste estudo determinar os efeitos do 17β-E2 na abundância de trancritos (PKCα, PKCβ, PLA2G4, AKR1B1, AKR1C4 e PTGS2) diretamente envolvidos na síntese de PGF2α. Novilhas (N=50), não prenhes, cíclicas, foram sincronizadas pela inserção de um dispositivo de liberação intravaginal contendo 0,558g de progesterona (P4), pela administração de 1 mg de benzoato de estradiol e 0,075 mg de D-Cloprostenol, ambos intramuscular (IM). Após 6 dias, foi injetado 0,075 mg de D-Cloprostenol, IM. Após 48 horas, o dispositivo contendo P4 foi removido e 0,150 mg de D-Cloprostenol foi administrado IM. Nesta ocasião, um adesivo foi inserido na base da cauda para a identificação dos estros (Boviflag Red Estrus Detector - ABS Pecplan) e observações de estro foram realizadas nos próximos 4 dias. Participaram do experimento somente novilhas identificadas em estro (D0 = dia do estro) e que ovularam (N=46). Entre D14 e D23, a área do corpo lúteo (CL; cm2), fluxo sanguíneo (%) e as concentrações plasmáticas de progesterona (P4) foram avaliadas diariamente. No D15, as novi... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: In cattle, 17β-estradiol (17β-E2) stimulates expression of estradiol (ER) and oxytocin receptor (OXTR) in the endometrium. The activation of OXTR leads to the induction of a complex cascade of molecular activation resulting in PGF2α synthesis. The hypothesis was that 17β-E2 treatment on day 15 (D15) after estrus modulates the gene expression of protein kinase (PKC) and phospholipase A2 (PLA2), both directly involved in the synthesis of PGF2α and calcium dependent. The aim of this study was to determine the effects of 17β-E2 on the abundance of key transcripts (PKCα, PKCβ, PLA2G4, AKR1B1, AKR1C4 and PTGS2) involved in PGF2α signaling and synthesis. Nelore heifers (N=50), don't pregnant, cyclic were synchronized by insertion an intravaginal release device containing 0.558g of progesterone (P4), and by the administration of 1 mg of estradiol benzoate and 0.075 mg de D-Cloprostenol, both intramuscularly (IM). After 6 days, 0.075 mg D-Cloprostenol was injected, IM. After 48 hours the P4 device was removed and 0.150 mg D-Cloprostenol was administered IM. On this occasion, an adhesive was inserted at the base of the tail for the identification of estrus (Boviflag Red Estrus Detector - ABS Pecplan) and estrous observation were made in the next 4 days. Participated in the experiment only the heifers identified in estrus (D0 = day of estrus) that ovulated (N=46). Between D14 and D23, corpus luteum (CL) area (cm2), blood flow (%), and progesterone (P4) plasmatic concentrations were eval... (Complete abstract click electronic access below)<br>Mestre
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Gyomorey, Sandor. "Temporal expression of prostaglandin endoperoxide H synthase type 2 and prostaglandin receptors at birth." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0023/MQ40864.pdf.
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Matthews, Jane Simone. "Characterisation of prostaglandin E receptors." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/19997.
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Prostaglandin (PG) E<SUB>2</SUB> has been shown to act on at least three distinct receptor subtypes, designated EP<SUB>1</SUB>, EP<SUB>2</SUB> and EP<SUB>3</SUB>, with recent evidence suggesting the possibility of a fourth EP-receptor subtype. Whilst good antagonists are not available, a range of PGE analogues of differing selectivity for the three receptor subtypes may be used to determine which is effective in a given system. The activity of these analogues has not yet been assessed on the putative EP<SUB>4</SUB>-receptor containing preparation. This research has involved the use of such compounds in an <i>in vivo</i> model of rabbit-skin inflammation, and biochemical studies on both platelets and cultured macrophages, to determine the subtype(s) of PGE receptor mediating the pro-inflammatory, pro-aggregatory, and anti-inflammatory effects, respectively, of PGE<SUB>2</SUB>. Whilst PGE<SUB>2</SUB> alone had little effect on rabbit skin inflammation, potentiation of vascular permeability induced by mediators of inflammation, such as bradykinin (BK) and FMLP was observed. The potentiation has been attributed to the vasodilator activity of PGE<SUB>2</SUB> which is typically mediated via the EP<SUB>2</SUB>-receptor subtype. However the finding that compounds with both EP<SUB>2</SUB>- and EP<SUB>3</SUB>-receptor activity were the most active, suggested that vasodilatation was not the sole mechanism of the potentiation. A comparison of the ability of PGE<SUB>2</SUB> and the stable PGI<SUB>2</SUB> analogue, cicaprost, to induce vasodilatation and potentiate the responses to both BK and FMLP, was consistent with this suggestion. It has since been proposed that there is an initial EP<SUB>3</SUB>-receptor mediated, dilatation-independent component to the potentiation of BK by PGE<SUB>2</SUB>.
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Engblom, David. "Prostaglandin E₂ in immune-to-brain signaling /." Linköping : Univ, 2003. http://www.bibl.liu.se/liupubl/disp/disp2003/med801s.pdf.
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Soontrapa, Kitipong. "Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression." Kyoto University, 2013. http://hdl.handle.net/2433/170077.
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Silva, Felipe Fortino Verdan da. "Prostaglandina E2 inibe a diferenciação de células Th17 no contexto de fagocitose de células apoptóticas infectadas." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-07012016-154146/.
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A fagocitose de células apoptóticas, também denominada eferocitose, é um processo dinâmico e de fundamental importância para homeostase dos tecidos após uma injúria. Estudos demonstraram previamente que a fagocitose de células apoptóticas promove a síntese de mediadores anti-inflamatórios como PGE2, TGF-? e IL-10, podendo resultar num microambiente supressor e aumento da susceptibilidade do hospedeiro contra agentes infecciosos. Entretanto, a fagocitose de células apoptóticas infectadas por células dendríticas promove a geração não apenas de citocinas anti-inflamatórias como TGF-?, mas também de IL-6 e IL-23, levando a um efeito imunoestimulador, a diferenciação de células Th17. A atuação da PGE2 na imunidade adaptativa vem sendo investigada quanto à diferenciação e ativação de linfócitos Th1, Treg e Th17. Nossos resultados demonstram que a fagocitose de células apoptóticas infectadas com E. coli promove a ativação e migração de células dendríticas, assim como a produção de citocinas pró- e anti-inflamatórias e altos níveis de PGE2. No entanto, diferente da hipótese inicial, a presença de altas concentrações de PGE2 inibe drasticamente a diferenciação de células Th17 no contexto de fagocitose de células apoptóticas infectadas com E. coli por células dendríticas, in vitro. O tratamento de linfócitos T CD4+naive com antagonistas e agonistas de EP2/EP4 demonstram que o efeito supressor de PGE2 é mediado primordialmente pelo receptor EP4. Por fim, nossos resultados in vivo comprovam os resultados obtidos in vitro, demonstrando o papel supressor de PGE2 na diferenciação de células Th17 no contexto de fagocitose de células apoptóticas infectadas em modelo de infecção pulmonar.<br>The phagocytosis of apoptotic cells, also called efferocytosis, is a dynamic process critical for tissue homeostasis after injury. We and other groups previously have shown that phagocytosis of apoptotic cells promotes the synthesis of anti-inflammatory mediators such as PGE2, TGF-? and IL-10, that may result in the suppression of host defense against microorganisms. However, an elegant study using infected apoptotic cells showed that phagocytosis of these cells promote not only the generation of anti-inflammatory cytokines such as TGF-? but also IL-6 and IL-23, resulting in an immunostimulatory effect, the differentiation of Th17 cells. The role of PGE2 in adaptive immunity has been investigated regarding differentiation and activation of Th1, Th17 and Treg. Our results demonstrate that engulfment of E.coli infected apoptotic cells promotes the activation and migration of dendritic cells as well as production of pro and anti-inflammatory cytokines together with high levels of PGE2. However, differing from our hypothesis, high levels of PGE2 inhibits drastically the differentiation of Th17 cells on the context of engulfment of E.coli infected apoptotic cells by dendritic cells in vitro. The treatment of T CD4+naive cells with antagonist or agonists of EP2/EP4 receptors demonstrates the suppressor effect is mainly mediated by EP4 receptor. Finally, the instillation of E.coli infected apoptotic cells in E.coli infected animals resulted on modest Th17 increase but treatment with cox inhibitor increased Th17 cell differentiation. Therefore, our in vivo results prove the in vitro results.
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Nascimento, Juliana. "Perfil do RNAm da proteína transportadora de prostaglandina (PGT) no endométrio equino in vivo e sobre influência embrionária in vitro." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-10102012-182843/.
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Nas éguas cíclicas, a luteólise ocorre entre os dias 14 e 16 após ovulação, pela ação da PGF2ά endometrial. Entretanto, durante a gestação, a luteólise deve ser bloqueada, ao mesmo passo que a ação da PGE2 deve ser estimulada. Ambos hormônios possuem baixa difusão pela membrana plasmática, sendo necessária a presença da proteína transportadora de prostaglandina (PGT) para o influxo e efluxo destes hormônios nas células. Os objetivos deste experimento foram identificar e relacionar o RNAm da PGT no endométrio de éguas cíclica e gestante aos 14 dias (experimento 1) e avaliar o perfil do RNAm para PGT no endométrio eqüino em final de diestro sob efeito de secreção embrionária (experimento 2). Para o experimento 1, um ciclo estral de 11 éguas foi acompanhado. Seis éguas não foram inseminadas e somente detectado o tempo de ovulação e cinco foram inseminadas. Biópsias endometriais foram realizadas quando detectado folículo pré-ovulatório (≥35mm de diâmetro) e edema endometrial (E0; n=6), sete (E7; n=6) e quatorze (E14; n=6) dias após ovulação nas fêmeas cíclicas e aos quatorze dias de gestação (EG; n=4) nas fêmeas gestantes. No experimento 2, 5 embriões eqüinos de 13,5 dias de idade foram coletados, cultivados por 24 horas em ambiente com temperatura e CO2 controlados e o meio condicionado embrionário (MCEE) gerado foi armazenado a -80ºC. Em seguida, amostras endometriais de sete éguas cíclicas aos 14 dias pós ovulação foram coletadas por biópsia uterina e cultivadas por 24 horas, em ambiente com temperatura e CO2 controlados, na presença do MCEE. O RNA total foi extraído de todas as amostras endometriais e amplificado pela reação em cadeia da polimerase em tempo real (RT-PCR), de um passo. A abundância relativa média dos transcritos foi submetida a análise de variância e as médias foram separadas pelo teste LSD (P<0,05). No experimento 1, o RNAm da PGT em tecido equino foi identificado, de maneira que as quantidades relativas deste gene foram similares entre E0, E7, E14 e EG. No experimento 2, o MCEE não modificou a quantidade de RNAm para PGT no endométrio em fase final do diestro.<br>In cyclic mares, luteolysis occurs between the 14th and 16th days after ovulation, due to endometrial PGF2ά However, in pregnant mares luteolysis must be blocked, whereas the PGE2 action must be stimulated. Both hormones have low diffusion through the plasma membrane, wherein the Prostaglandin Transporter Protein (PGT) is needed to influx and efflux of these hormones in the cells. The objectives of this experiment are to identify and to relate with the mRNA to PGT in the endometrium of cyclic and pregnant mares (experiment 1) and to evaluate the mRNA profile to PGT in equine endometrium at end of diestrous, under embryonic secretion effect (experiment 2). In the experiment 1, one estrous cycle of 11 mares (5 to 12 years old) was examined. Six mares were not inseminated and only the time of ovulation was recorded, and five mares were inseminated. Endometrial biopsies were performed when pre-ovulatory follicles (diameter ≥ 35mm) and endometrial edema were detected (E0; n=6), seven (E7; n=6) and fourteen days (E14; n=6) after ovulation in cyclic mares, and fourteen days after ovulation in pregnant mares (EG; n=4). In the experiment 2, five embryos of 13,5 days of age were collected, cultured during 24 hours in controlled temperature and CO2 and the embrionic conditioned medium (ECM) was stored at -80ºC. After that, endometrium samples of 7 mares at fourteen days after ovulation were collected by uterine biopsy and they were cultured during 24 hours, in controlled temperature and CO2, with ECM. Total RNA was extracted and submitted to amplification by one step real-time polymerase chain reaction (RT-PCR). The abundance relative average of trancripts was submitted to variance analysis and averages were separated by LSD test (P<0,05). In the experiment 1 the mRNA to equine PGT was identified so that the relative quantities of this gene were equal among E0, E7, E14 e EG. In the experiment 2, the ECM did not modify the mRNA quantity to PGT in the endometrium at end of diestrous.
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Soares, Júlia Gleyci. "Estratégias para aumentar a recuperação de estruturas embrionárias de búfalas superovuladas." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-16092015-111659/.
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Apesar de inúmeros estudos desenvolvidos no Brasil e no mundo, a utilização das biotecnologias de superovulação (SOV) e transferência de embriões (TE) em bubalinos ainda apresenta resultados inconsistentes, associados à principalmente à baixa taxa de recuperação de embriões. Dessa forma, o objetivo do presente estudo foi avaliar o efeito da utilização de dispositivo de P4 (para promover diminuição da contratilidade do trato genital, Capitulo 1) ou da administração de PGF2α (para promover aumento da atividade da fímbria e da frequência do batimento ciliar, Capítulo 2) durante o período periovulatório na captação dos oócitos pelas fímbrias e no aumento da produção de embriões em búfalas superovuladas. No Experimento 1 (Capítulo 1), doadoras bubalinas foram homogeneamente divididas em dois grupos: controle (G-C; n=8) e tratamento com progesterona (P4) durante o período periovulatório (G-P4; n=8). A emergência da onda de crescimento folicular foi sincronizada com um dispositivo intravaginal de P4 e a administração de 2 mg i.m. de benzoato de em dia aleatório do ciclo estral (Dia 0; D0). A partir do D4, todas as búfalas receberam 200 mg i.m. de FSH duas vezes ao dia, em 8 doses decrescentes. Foram administrados 530µg i.m. de PGF2α no D6 e no D7. A P4 foi removida do G-C no D7 e do G-P4 no D10. No D8, todas as búfalas receberam 25 mg i.m. de pLH. As inseminações foram realizadas 12 e 24 h após o tratamento com pLH. Foram realizadas colheitas de sangue a cada 12h do D7 ao D11 para posterior dosagem de progesterona. As estruturas embrionárias (oócitos/embriões) foram coletadas pelo método não cirúrgico de lavagem uterina seis dias após a segunda IA (D14). Avaliações ultrassonográficas dos ovários foram realizadas no D8 e no D14 para aferir respectivamente as respostas superestimulatória e superovulatória. As variáveis foram analisadas pelo procedimento GLIMMIX do SAS®. As búfalas do G-P4 apresentaram menor taxa de ovulação (13,5±4,9 vs. 71,5±16,1%; P=0,002) e, consequentemente, maior taxa de folículos ≥ 8 mm (87,8±10,6 vs. 34,3±9,8 %; P=0,06) e menor número de CLs no D14 (1,1±0,3 vs. 8,0±2,8; P=0,04) que as búfalas do G-C. O número de estruturas embrionárias (1,9±0,7 vs. 0,0±0,0; P=0,03), de embriões transferíveis (1,6±0,7 vs. 0,0±0,0; P=0,04) e congeláveis (1,6±0,7 vs. 0,0±0,0; P=0,04) foram inferiores para o G-P4. A concentração sérica de progesterona foi maior nos animais do G-P4 (1,87±0,13) que nos do G-C (0,48±0,10; P<0,0001). No Experimento 1 (Capítulo 2), as doadoras foram divididas aleatoriamente em 2 grupos: controle (G-C; n=22) e tratamento com prostaglandina F2α durante o período periovulatório (G-PGF; n=22). Os animais do G-C foram submetidos ao protocolo de superovulação descrito no capítulo 1. No G-PGF todas as búfalas receberam protocolo de superovulação semelhante ao G-C e, adicionalmente, receberam quatro doses de PGF2α (0,53 mg i.m. de cloprostenol sódico) do D8 ao D10 com intervalo de 12h. Foi verificado maior número de estruturas embrionárias recuperadas em búfalas superovuladas tratadas com PGF2α durante o período periovulatório (G-PGF=3,5±0,6) comparado ao grupo controle (G-C=2,3±0,5; P=0,02). Além disso, houve aumento no número de embriões transferíveis (G-PGF=2,7±0,6 vs. G-C=1,8±0,5; P=0,05). No Experimento 2 (Capítulo 2), os animais foram divididos aleatoriamente em três grupos experimentais: Grupo Controle (GC; n=22), Grupo PGF injetável (G-PGF-INJ; n=22) e Grupo PGF Bomba Osmótica (G-PGF-BO; n=22). Os animais pertencentes aos grupos: G-C e G-PGF-INJ foram submetidos aos mesmos protocolos descritos para seus grupos correspondentes no Experimento 1 (Capítulo 2). No GPGF- BO, todas as búfalas receberam protocolo de superovulação semelhante ao G-C e, adicionalmente, receberam a partir do D8 a inserção subcutânea de uma mini-bomba osmótica, contendo PGF2α (2,12 mg de Cloprostenol sódico). A bomba osmótica retirada no D10. Não foram verificadas diferenças no número de estruturas totais recuperadas nas búfalas tratadas com PGFα durante o período periovulatório (G-C=2,1±0,8 vs. G-PGF-INJ=2,1±0,6 vs. GPGF- BO=1,4±0,4; P=0,58). Os tratamentos no período periovulatório com dispositivo intravaginal de P4 (Capítulo 1) e com PGF2α (Capítulo 2) não foram eficientes em aumentar a recuperação de estruturas embrionárias de búfalas superovuladas.<br>Despite numerous studies conducted in Brazil and world-wide, the use of superovulation (SOV) and embryo transfer (ET) biotechnologies in buffaloes still shows inconsistent results, particularly in terms of low embryos recovery rate. Thus, the aim of this study was to evaluate the use of a P4 device (to decrease contractility of the genital tract, Chapter 1) or PGF2α administration (to increase activity of the fimbriae and ciliary beat frequency, Chapter 2) during the periovulatory period in the uptake of oocytes by fimbriae and in the increase of embryo production in superovulated buffaloes. In Experiment 1 (Chapter 1), buffalo donors were homogeneously assigned into 2 groups: Control (C-G; n=8) and progesterone (P4) treatment during the periovulatory period (P4-G; n=8). Follicular growth wave emergence was synchronized with an intravaginal P4 device and the injection of 2 mg i.m. of estradiol benzoate at random stage of the estrous cycle (Day 0; D0). From D4 on, all buffaloes received 200 mg i.m. of FSH twice-daily, in 8 decreasing doses. A dose of PGF2α was given on D6 PM and on D7. The P4 was removed from the C-G on D7 and from the P4-G on D10. On D8, all buffaloes received 25 mg i.m. of pLH. Inseminations were done 12 and 24 h after the pLH treatment. Blood samples were collected every 12h from D7 to D11 for further progesterone assay. The embryonic structures (ova/embryos) were collected by nonsurgical uterine flush 6 days after the second timed AI (D14). Ovarian ultrasound examinations were performed on D8 and on D14 to verify respectively the superestimulation and the superovulatory response. Variables were analyzed by GLIMMIX procedure of SAS®. Buffaloes from P4-G showed lower ovulation rate (13.5±4.9 vs. 71.5±16.1%; P=0.002) and, consequently, higher follicles ≥ 8 mm rate (87.8±10.6 vs. 34.3±9.8 %; P=0.06) and lower number of CLs on D14 (1.1±0.3 vs. 8.0±2.8; P=0.04) than buffaloes from C-G. The total number of embryonic structures (1.9±0.7 vs. 0.0±0.0; P=0.03), transferable (1.6±0.7 vs. 0.0±0.0; P=0.04) and freezable embryos (1.6±0.7 vs. 0.0±0.0; P=0.04) were lower for P4-G. The serum progesterone concentration was greater for animals in P4-G (1.87±0.13) than in the C-G (0.48±0.10; P<0.0001). In Experiment 1 (Chapter 2), donors were randomly assigned into two groups: control (C-G; n=22) and prostaglandin F2α treatment during the periovulatory period (G-PGF; n=22). Animals from C-G were subjected to the superovulation protocol described on chapter 1. In G-PGF all buffaloes received similar superovulation protocol from the C-G and, additionally, received four doses of PGF2α (0.53 mg i.m. of sodic cloprostenol) from D8 to D10, 12h apart. A greater number of embryonic structures were recovered from superovulated buffaloes treated with PGF2α during the periovulatory period (PGF-G=3.5±0.6) compared to control group (C-G=2.3±0.5; P=0.02). Furthermore, increased number of transferable embryos were found in treated animals (PGF-G=2.7±0.6 vs. C-G=1.8±0.5; P=0.05). In Experiment 2 (Chapter 2), animals were randomly assigned into three experimental groups: Control group (CG; n=22), Injectable PGF group (INJ-PGF-G; n=22) and Osmotic pump PGF group (BO-PGF-G; n=22). The animals from C-G and INJ-PGF-G group were subjected to the same protocols described for their correspondent groups in Experiment 1 (Chapter 2). In BO-PGF-G, all buffaloes received the superovulation protocol similar to C-G and, additionally, received from D8, a subcutaneous insertion of a mini osmotic pump, containing PGF2α (2.12 mg de sodic cloprostenol). The osmotic pump was removed on D10. No differences were found on the total number of recovered structures in buffaloes treated with PGF2α during the periovulatory period (C-G=2.1±0.8 vs. INJ-PGF-G=2.1±0.6 vs. BO-PGF-G=1.4±0.4; P=0.58). Treatments on the peri- ovulatory period with intravaginal P4 device (Chapter 1) and PGF2α (Chapter 2) were not efficient in increasing the recovery of embryonic structures in superovulated buffalo.
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Fennekohl, Alexandra. "Einschränkung hepatischer Abwehrreaktionen während einer Entzündung durch Prostaglandin E2 über Gs-Protein-gekoppelte Prostaglandin-E2-Rezeptoren." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=96491574X.
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Milling, Smith Oliver Patrick. "Prostaglandin signalling in the human endometrium." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/24983.
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This thesis is based on the hypothesis that menstrual dysfunction, including heavy menstrual blood loss (MBL) is due to (a) up-regulated expression/synthesis of cycloxygenase enzymes and prostaglandin receptors, and (b) initiation of enhanced intracellular signalling pathways in response to prostaglandins. This thesis describes the use of an endometrial epithelial cell line to explore the molecular signalling pathways involved with the activation of a prostaglandin receptor – the prostacyclin receptor. A rapid activation of ERK1/2 signalling is demonstrated with alterations in expression of angiogenic factors via crosstalk with the epidermal growth factor receptor. By using endometrium collected from women with the complaint of heavy menstrual bleeding, the pattern of expression of the various components of the COX-prostaglandin signalling pathways present in the endometrium of women with normal and heavy MBL is elucidated. There is a significant elevation in expression of COX-1 and COX-2 mRNA in endometrium obtained from women with heavy MBL compared with endometrium obtained from women with normal MBL. Significant alterations in expression of downstream prostanoid synthase and prostanoid receptor mRNAs were also detected. Furthermore, enhanced prostaglandin stimulated production of cyclic AMP observed in endometrium of women with heavy MBL compared with normal MBL. By identifying the prostanoid receptors/signalling pathways that are responsible for disturbed endometrial function, this thesis aims to establish information that may result in the development of novel therapeutic targets for menstrual pathology.
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Norwitz, Errol R. "Prostaglandin production by human decidual cells." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314894.
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Alzamil, Hana Abdulrahman. "Localization of terminal prostaglandin synthases and prostaglandin transporter in human intrauterine tissues and the effect of pro-inflammatory cytokines on prostaglandin production at term and preterm labour." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526056.
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Silva, Júlio César Barboza da. "Utilização de FSH durante a sincronização da emergência da onda de crescimento folicular de doadoras submetidas à Ovum Pick Up, visando melhorar a produção in vitro de embriões." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-24032015-094737/.
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Biotecnologias como a Ovum Pick-Up e a Produção In vitro de embriões (OPU-PIVE) tem sido uma importante ferramenta para alcançar o melhoramento genético rápido nos rebanhos, diminuindo o intervalo entre gerações. No Brasil, a PIVE está em fase de crescimento e representa 70,7% de toda a produção in vitro mundial. Contudo a OPU-PIVE é ainda ineficiente em vacas de leite, especialmente devido à sua reduzida população folicular. Muitos estudos têm mostrado um efeito positivo do FSH em gado de leite e corte. Recentemente, a pré-estimulação com FSH mostrou ser capaz de aumentar o diâmetro dos folículos aspirados e a porcentagem de embriões transferíveis. O FSH estimula o recrutamento dos folículos na fase antral, fazendo com que eles possam se desenvolver até o momento em que ocorre a divergência e um ou mais folículos se torne dominante. A hipótese do presente estudo é que o uso de FSH (200 mg), fracionado em 4 ou 6 aplicações, em vacas holandesas não lactantes, com emergência de onda folicular sincronizada, aumenta o número de folículos ovarianos, o número de oócitos viáveis e a quantidade de embriões na produção in vitro. Trinta e seis vacas Holandesas não lactantes foram utilizadas como doadoras de oócitos e distribuídas em três tratamentos: Controle (C), 4 aplicações de FSH (F4) e 6 aplicações de FSH (F6). Todas as vacas foram submetidas ao mesmo protocolo de sincronização de emergência de onda folicular, diferindo apenas pela administração e número de 4 ou 6 doses de FSH, conforme descrito acima. Em dia aleatório do ciclo estral (D0), todas as vacas receberam um dispositivo de P4 (Primer®, Tecnopec-Agener União, São Paulo, SP, Brasil) e 2 mg de benzoato de estradiol (Ric-BE®, Tecnopec-Agener União, São Paulo, SP, Brasil). Três dias após (D3), foi administrado 0,530 mg de Cloprostenol Sódico (Cioprostinn®, Innovare Biotecnologia e Saúde Animal Ltda, Monte Aprazível, SP, Brasil), induzindo a luteólise com a intenção de liberar espaço no estroma ovariano para o crescimento folicular e facilitar a visualização de folículos na OPU. Vacas do grupo C não receberam tratamentos adicionais. Vacas do grupo F4 receberam 200 mg de FSH (Folltropin - Bioniche Anim,al Health, Belleville, ON, Canadá) fracionados em 4 aplicações de equivalentes concentrações em intervalos de 12 h, iniciando no D4 pela manhã. Vacas do grupo F6 receberam 200 mg de FSH fracionados em 6 aplicações de equivalentes concentrações em intervalos aproximados de 12 h, tendo início no D3 pela manhã. No D7, o dispositivo foi removido e a OPU realizada concomitantemente à contagem dos folículos existentes nos ovários. Os oócitos considerados viáveis foram fertilizados in vitro com sêmen sexado de touros da raça Holandesa. Os dados foram analisados pelo PROC GLIMIX do SAS 9.3, utilizando contrastes ortogonais C1 (C x FSH) e C2 (F4 x F6). Não houve efeito de tratamento no número de folículos (C = 53,3 ± 4,9 vs FSH = 51,36 ± 3,1;P = 0,89), número total de oócitos (C = 19,46 ± 1,64 vs FSH = 18,47 ± 1,27; P = 0,55), número de oócitos viáveis (C = 12,57 ± 1,26 vs FSH = 12,70 ± 1,03; P= 0,606), taxa de recuperação de oócitos (C = 36,5% vs FSH = 36,0%; P = 0,48) e produção de embriões in vitro (C = 4,11 ± 0,52 vs FSH = 4,32 ± 0,46; P = 0,79). Apesar de não ter havido efeito no número de folículos, o tratamento com FSH alterou a distribuição dos mesmos, proporcionando o aumento no número de folículos médios (6 a 10 mm). No entanto, não houve efeito do tratamento com FSH no número de oócitos totais e viáveis recuperados, nem na produção de embriões.<br>Reproductive biotechnologies such as Ovum Pick-Up and in vitro Embryo production (OPU-IVEP) have been widely used as important tools to achieve faster genetic improvement in herds, diminishing the intervals between generations. In Brazil, in vitro Embryo Production (IVEP) is growing in popularity and accounts for 70.7% of all in vitro embryo production worldwide. However, the OPU-IVEP is still poorly efficient in high-producing dairy cattle, especially because of their reduced follicular population. Several studies have shown a positive effect of FSH on OPU-IVEP yeld. Recently, FSH pre-stimulation has shown to be able to increase the diameter of aspirated follicles and the percentage of transferable embryos. The hormone FSH stimulates follicle recruitment in the antral phase, in the way that they develop until the moment of divergence and one or more follicles becomes dominant. The hypothesis of this study is that the use of 200mg FSH split into 6 doses in non-lactating Holstein cows with a synchronized follicular wave emergence increases the number of follicles, the recovery rate and the number of embryos produced in vitro. Thirty six Holstein cows used as oocyte donors were homogenously allocated to one of three treatment groups in a 3x3 Latin square design: Control (C); 4 doses of FHS (FSH4); 6 doses of FSH (F6). All cows were synchronized using the same protocol for synchronization of follicular wave emergence, except for the administration and number of doses of FSH as previously described. At random days of the estrous cycle known as D0, all cows received an intravaginal P4 device (Primer®, Tecnopec-Agener União, São Paulo, Brazil) and 2mg estradiol benzoate (Ric-BE®, Tecnopec-Agener União). Three days after (D3), all cows received 0.530 mg D-Cloprostenol (Cioprostinn®, Innovare Biotecnologia e Saúde Animal Ltda, Monte Aprazível, SP, Brasil). Cows from the Control group received no additional treatment. Cows from group FSH4 were treated with 200 mg of FSH split in 4 doses of similar concentration given approximately 12 h apart, starting on D4 AM. Cows form group FSH6 were treated with 200 mg of FSH split in 6 doses of similar concentration given approximately 12 h apart, starting on D3 AM. On D7, the device was removed and OPU was performed concomitant with antral follicle count in each ovary. The oocytes considered as viable were sent to IVEP. Data was analyzed using the Glimmix of SAS 9.3, with orthogonal contrasts C1 (C x Treatment with FSH) and C2 (FSH4 x F6). There was no effect on the number of antral follicle (C = 53.3 ± 4.9 vs FSH = 51.36 ± 3.1;P = 0.89), number of total oocytes (C = 19.46 ± 1.64 vs FSH = 18.47 ± 1.27; P = 0.55), number of viable oocytes (C = 12.57 ± 1.26 vs FSH = 12.70 ± 1.03; P= 0.61), oocyte recovery rate (C = 36.5% vs FSH = 36.0%; P = 0.48) and number of embryos produced in vitro (C = 4.11 ± 0.52 vs FSH = 4.32 ± 0.46; P = 0.79). Although FSH treatment did not affect the number of follicles, it affected the distribution of them, increasing the number of follicles from 6 to 10 mm. However, FSH treatment did not alter the total number of oocytes and number of viable oocytes or embryo production.
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Kowalewski, Mariusz Paweł. "Untersuchungen zur Rolle des Prostaglandin Systems in der Regulation der Corpus Luteum Funktion der Hündin durch Erfassung der Expression von Cyclooxygenase 1 und -2 (Cox1,-2), Prostaglandin F2alpha Synthase (PGFS), Prostaglandin E2 Synthase (PGES) und Prostaglandin F2alpha Rezeptor (PGFR)." Lollar : Rosenbaum, 2007. http://geb.uni-giessen.de/geb/volltexte/2007/4476/index.html.
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Zarroug, Osman Hamza. "The roles of prostaglandin E2, prostaglandin F2α and aldo-keto reductase 1C isoenzymes in endometriosis and breast cancer". Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/the-roles-of-prostaglandin-e2-prostaglandin-f2alpha-and-aldoketo-reductase-1c-isoenzymes-in-endometriosis-and-breast-cancer(08db7cb3-7222-4513-b13b-cc3474c1ca2b).html.
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Endometriosis and breast cancer are sex hormone dependent diseases characterised by the local production of high levels of 17β-oestradiol. The relationship between prostaglandins and sex steroid hormones is one of the focal questions in endometriosis, breast cancer and other sex steroid hormone related disorders. Therefore, the main hypothesis was that the aldo-keto reductase (AKR) 1C isoenzymes are responsible for controlling the availability of 17β-oestradiol, progesterone and prostaglandins in the microenvironment of the endometrium, and surrounding adipose tissues of endometriotic lesions and breast tumours. This was investigated using quantitative real-time polymerase chain reaction (PCR) for measuring the gene expression of AKR1C1-3 enzymes, and prostaglandin E (1-4) and F receptors in the endometrium, and surrounding adipose tissues of endometriotic lesions and breast tumours. This was then followed by investigating the role of one of the AKR1C enzymes - AKR1C3 - by inhibiting its catalysis using bimatoprost, followed by using PGE2 as one of the main candidates acting as a transcription factor for upregulating the expression of AKR1C3 which in turn upregulates the production of the local 17β-oestradiol. The gene expression of AKR1C1 was significantly higher in endometriotic lesions compared to eutopic endometrium of endometriosis patients. However, there was no significant difference in the gene expression of AKR1C (1-3) enzymes in the surrounding adipose tissues of endometriotic lesions between patients with or without endometriosis. Also, there was no significant difference in the gene expression of AKR1C (1-3) enzymes in the breast adipose tissues of patients with breast tumours, regardless of the oestrogen or progesterone receptor status. The gene expression of prostaglandin E (EP) receptor subtype 3 was significantly higher in the endometriotic lesions compared to eutopic endometrium of endometriosis patients. In the omental adipose tissue, there was no significant difference in the gene expression of EP1-4 and FP receptors between endometriosis and non-endometriosis patients. In the breast adipose tissue, there was also no significant difference in the gene expression of EP1-4 and FP receptors in patients with breast cancer regardless of the oestrogen or progesterone receptor status. The inhibitory constant (Ki) of bimatoprost was determined using oestrone as a substrate: Ki = 2.9µM and αKi = 0.7µM. Bimatoprost also significantly inhibited the production of 17β-oestradiol and inhibited the production of 9α,11β PGF2 in a dose dependent manner in the human endometrial cells. The effect of PGE2 on the expression of AKR1C1 and AKR1C3 was assessed in the human endometrial cells. The EP4 receptor agonist, L-902688, increased the gene expression of AKR1C1 and AKR1C3. Despite gene expression elevation, L-902688 did not increase the production of 17β-oestradiol. In conclusion, the results were contradictory and highlighted the need for further investigation into the relationship between prostaglandins and sex steroid hormones in the microenvironment of the endometrium, and surrounding adipose tissues of endometriotic lesions and breast tumours.
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Wangpradit, Orarat. "Prostaglandin H synthase catalyzes the oxidation of 4-chlorobiphenyl metabolites, and the in vivo effects on prostaglandin production." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1101.
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Polychlorinated biphenyls (PCBs) exert a broad range of toxicity via both parent compounds and their metabolites. Our previous study showed that hydroquinone (H2Q) metabolites of PCBs act as cosubstrates for prostaglandin H synthase (PGHS), and are oxidized by this enzyme to corresponding quinones (Q). The goal of this thesis is to illuminate the PGHS-mediated toxicity of lower chlorinated PCBs. It is hypothesized that PGHS catalyzes two sequential one-electron oxidations of PCB-H2Q to semiquinone (SQ), and Q that interact with biomolecules, such as amino acids, glutathione (GSH), protein, and DNA. In addition, the oxidation of H2Q by PGHS results in an elevation of downstream prostaglandin (PG) production in vivo.
Employing 4-chlorobiphenyl-2f,5f-hydroquinone (4-CB-2f,5f-H2Q) as a model compound, I found that PGHS-2 catalyzes the one-electron oxidation of 4-CB-2f,5f-H2Q to SQ. An unusual electronically distorted SQ spectrum was observed as a result of the mixture of two different SQ species, a quartet and a doublet.
Fate of 4-CB-2f,5f-SQ and/or Q in the presence of biomolecules was further investigated in the next study. 4-CB-2f,5f-SQ/Q reacts readily with the thiol-containing molecules, such as cysteine, and GSH. Oligonucleotides, and DNA did not form a covalent adduct with 4-CB-2f,5f-SQ but preferably stabilized 4-CB-2f,5f-SQ by pi-stacking interaction under the assay conditions.
The in vivo study of downstream PG production in rats treated with 4-CB-2f,5f-H2Q revealed that PGE2 was significantly elevated in ratsf kidneys at 24 h post intratracheal instillation. The increased PGE2 production was correlated with an elevation of alveolar macrophages. These findings suggest two possible mechanisms of enhanced PGE2 production: i) 4-CB-2f,5f-H2Q as a cosubstrate for PGHS in kidney, and 2) release of cytokines from macrophages, leading to stimulation of PGE2 production in other tissues but released and accumulated in kidney for excretion.
In summary, the toxicity of lower chlorinated PCBs metabolites is potentially mediated by PGHS. Quinones generated from the PGHS metabolic pathway covalently bind to GSH resulting in GSH depletion, and oxidative stress. The intercalation or pi-stacking of SQ in DNA may be implicated in genotoxicity as a result of the change in DNA structure.
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Elander, Louise. "Prostaglandin E₂ in brain-mediated illness responses /." Linköping : Department of Clinical and Experimental Medicine, Linköping University, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-53701.
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Elander, Louise. "Prostaglandin E2 in Brain-mediated Illness Responses." Doctoral thesis, Linköpings universitet, Cellbiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-53701.
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We are unceasingly exposed to potentially harmful microorganisms. The battle against threatening infectious agents includes activation of both the innate and of the adaptive immune systems. Illness responses are elicited and include inflammation, fever, decreased appetite, lethargy and increased sensitivity to painful stimuli in order to defeat invaders. While many of these signs of disease are controlled by the central nervous system, it has remained an enigma how signals from the peripheral immune system reach the brain through its blood-brain barrier, which precludes macromolecules, including cytokines, from diffusing into the brain parenchyma. Previous findings indicate the existence of a pathway across the blood-brain barrier, which includes binding of the cytokine interleukin-1 (IL-1) to its receptor in the brain vessels, thereby inducing the production of the prostaglandin E2 (PGE2) synthesizing enzymes cyclooxygenase-2 (Cox-2) and microsomal prostaglandin E synthase-1 (mPGES-1), which ultimately synthesize PGE2. PGE2 subsequently binds to any of the four prostaglandin E2 (EP) -receptors. Previous results from our laboratory have suggested that this pathway plays a critical role in the febrile response to infectious stimuli. The present thesis aims at further investigating the molecular events underlying immune-to-brain signalling, with special emphasis on fever, hypothalamic-pituitary-adrenal (HPA) -axis activation and anorexia and their connection to signalling molecules of the cytokine and prostaglandin families, respectively. In paper I, the molecular processes linking the proinflammatory cytokine interleukin-6 (IL-6) and PGE2 in the febrile response were investigated. Both IL-6 and PGE2 have been shown to be critical players in the febrile response, although the molecular connections are not known, i.e. if IL-6 exerts its effects up- or downstream of PGE2. Mice deficient in IL-6 were unable to respond to bacterial lipopolysaccharide (LPS) with a febrile response, but displayed similar induction of Cox-2 and mPGES-1, and similar concentrations of PGE2 in the cerebrospinal fluid as wild-type mice. Paradoxically, the IL-6 deficient mice responded with a dose-dependent elevation of body temperature in response to intracerebroventricularly injected PGE2. Furthermore, IL-6 per se was not pyrogenic when injected peripherally in mice, and did not cause increased levels of PGE2 in cerebrospinal fluid. IL-6 deficient mice were not refractory to the action of PGE2 because of excess production of some hypothermia-producing factor, since administration of a Cox-2 inhibitor in LPS-challenged IL-6 deficient mice did not unmask any hypothermic response, and neutralization of tumor necrosis factor α (TNFα), associated with hypothermia, did not produce fever in LPS-challenged IL-6 deficient mice. These data indicate that IL-6 rather than exerting its effects up- or down-stream of PGE2 affects some process in parallel to PGE2, perhaps by influencing the diffusion and binding of PGE2 onto its target neurons. In papers II and III, we injected the proinflammatory cytokine IL-1β in free-fed wild-type mice, in mice with a deletion of the gene encoding mPGES-1, or in mice deficient in the EP1, EP2 and EP3. Food intake was continuously measured during their active period, revealing that mPGES-1 deficient mice were almost completely resistant to anorexia induced by IL-1β. However, all of the investigated EP receptor deficient mice exhibited a normal profound anorexic response to IL-1β challenge, suggesting that the EP4 is the critical receptor that mediates IL-1β-induced anorexia. We also investigated the role of mPGES-1 in anorexia induced by lipopolysaccharide (LPS) in mPGES-1 deficient mice. The profound anorexic response after LPS-challenge was similar in mPGES-1 deficient and wild-type mice. To further investigate the anorectic behaviour after LPS injection, we pre-starved the animals for 22 hours before injecting them with LPS. In this paradigm, the anorexia was less profound in mPGES-1 knock-out mice. Our results suggest that while the inflammatory anorexia elicited by peripheral IL-1β seems largely to be dependent on mPGES-1-mediated PGE2 synthesis, similar to the febrile response, the LPS-induced anorexia is independent of this mechanism in free-fed mice but not in pre-starved animals. In papers IV and V, the role of prostanoids for the immune-induced HPA-axis response was investigated in mice after genetic deletion or pharmacological inhibition of prostanoid-synthesizing enzymes, including Cox-1, Cox-2, and mPGES-1. The immediate LPS-induced release of ACTH (adrenocorticotropic hormone and corticosteroids was critically dependent on Cox-1 derived prostanoids and occurred independently of Cox-2 and mPGES-1 derived PGE2. In contrast, the delayed HPA-axis response was critically dependent on immune-induced PGE2, synthesized by Cox-2 and mPGES-1, and occurred independently of Cox-1 derived enzymes. In addition, in the mPGES-1 deficient mice, the synthesis of CRH hnRNA and mRNA was decreased in the paraventricular nucleus of the hypothalamus after LPS-challenge, indicating that the delayed hormone secretion was mediated by PGE2-induced gene-transcription of CRH in the hypothalamus. The expression of the c-fos gene and Fos protein, an index of synaptic activation, was maintained in the paraventricular nucleus and its brainstem afferents both after unselective and Cox-2 selective inhibition as well as in Cox-1, Cox-2, and mPGES-1 knock-out mice. This suggests that the immune-induced neuronal activation of autonomic relay nuclei occurs independently of prostanoid synthesis and that it is insufficient for eliciting stress hormone release.
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Karlsson, Sofia. "Studies of prostaglandin E2 formationin human monocytes." Licentiate thesis, Karlstads universitet, Avdelningen för kemi och biomedicinsk vetenskap, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-4638.
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Prostaglandin (PG) E2 is an eicosanoid derived from the polyunsaturated twenty carbon fatty acid arachidonic acid (AA). PGE2 has physiological as well as pathophysiological functions and is known to be a key mediator of inflammatory responses. Formation of PGE2 is dependent upon the activities of three specific enzymes involved in the AA cascade; phospholipase A2 (PLA2), cyclooxygenase (COX) and PGE synthase (PGEs). Although the research within this field has been intense for decades, the regulatory mechanisms concerning the PGE2 synthesising enzymes are not completely established. PGE2 was investigated in human monocytes with or without lipopolysaccharide (LPS) pre-treatment followed by stimulation with calcium ionophore, opsonised zymosan or phorbol myristate acetate (PMA). Cytosolic PLA2a (cPLA2a) was shown to be pivotal for the mobilization of AA and subsequent formation of PGE2. Although COX-1 was constitutively expressed, monocytes required expression of COX-2 protein in order to convert the mobilized AA into PGH2. The conversion of PGH2 to the final product PGE2 was to a large extent due to the action of microsomal PGEs-1 (mPGEs-1). In addition, experiments with inhibitors of extracellular signal regulated kinase and p38 activation, indicated that phosphorylation of cPLA2α was markedly advantageous for the formation of PGE2. Ellagic acid, a natural polyphenolic compound found in fruits and nuts, was shown to inhibit stimuli induced release of PGE2 in human monocytes. The effect of ellagic acid was not due to a direct effect on the activities of the enzymes but rather to inhibition of the LPS-induced protein expression of COX-2, mPGEs-1 and cPLA2a.
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Li, Ding-You. "Ontogeny and regulation of cerebral prostaglandin receptors." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39944.
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The objective of this thesis was to test the hypothesis that the decreased effects of PGE$ sb2$ and PGF$ sb{2 alpha}$ on cerebral metabolism and vasculature in the newborn might result from a deficiency of brain EP and FP receptors, which may be downregulated by the relatively high brain levels of PGE$ sb2$ and PGF$ sb{2 alpha}.$<br>This study revealed that the densities of EP and FP receptors and receptor-coupled second messengers in brain synaptosomes and microvessels were much lower in the newborn than in the adult pigs, also the relative distribution of EP receptor subtypes in brain synaptosomes and microvessels differed. For example, in brain synaptosomes, only EP$ sb3$ subtype was present in the newborn, and both EP$ sb2$ and EP$ sb3$ subtypes existed in the adult; EP$ sb1$ subtype was not found in the brain synaptosomes. In contrast, in brain microvessels, more than 80% of EP receptors were of EP$ sb1$ subtype with small amount of EP$ sb3$ subtype. No EP$ sb2$ subtype was detected in the brain microvessels.<br>In order to determine whether high levels of prostaglandin in the newborn downregulate EP and FP receptors, newborn pigs were treated with cyclooxygenase inhibitors, ibuprofen or indomethacin. The inhibition of prostaglandin synthesis in the newborn pigs significantly increased EP and FP receptor densities as well as receptor-coupled IP$ sb3$ and cAMP production in brain synaptosomes and microvessels of the newborn to levels found in the adult; this effect could be prevented by co-treatment of membranes with stable PG analogs. Vasoconstrictor effects of PGE$ sb2$ and PGF$ sb{2 alpha}$ on cerebral microvessels of the newborn were also increased.<br>These findings suggest that the relatively low EP and FP receptor densities in the newborn brain are caused by the high levels of prostaglandins and that these receptors and their functions can be upregulated by reducing prostagladin levels.
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Guyot, Thierry. "Stereoselective syntheses of allenes and prostaglandin derivatives." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367140.
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Haupt, Hayley Claire. "Strategies towards the synthesis of prostaglandin analogues." Doctoral thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/6312.
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Includes bibliographical references (leaves 173-179).<br>Different strategies for the synthesis of cyclopentenone prostaglandins and their analogues have been explored. The key transformation critical to the success of each of the described routes involves a Lewis-acid mediated retro Diels-Alder (rDA) reaction as the final step in liberating a 4, 5 disubstituted cyclopent-2-ene-1- one under extremely mild conditions. The first approach involves installation of the a-chain followed by base-mediated methodology to affect regiospecific enolate generation. Effective trapping of the enolate generates the requisite target. Within the context of this strategy both 2- and 3-component coupling protocols have been elaborated. Having demonstrated that the a- and p- sidechains could be installed, the key rDA reaction has been used to generate target analogues. The second approach utilizes a Diels-Alder cycloaddition reaction as the key step. The thermal and Lewis-acid catalysed Diels-Alder reactions between tricyclo[5.2.1.0 2,6]dec-8-en-3-one and 3-hydroxytricyclo[5.2.1.0 2,6]dec-8-ene with butadiene and butadiene sulfone have been investigated. While reaction between the enone and the dienophiles proved to be low yielding, the reaction between the allylic alcohol and butadiene sulfone proceeded readily and in high yield. The derived cycloadduct represents a late-stage intermediate for the synthesis of isoprostanes. Methodologies to perform cis-hydroxylation followed by oxidative cleavage of the cyclohexene moiety have been successfully implemented. Finally, a synthesis was designed for generating oxygen analogues of the prostaglandin targets.
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Inazumi, Tomoaki. "Roles of Prostaglandin EP4 Receptor in Adipocytes." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188727.
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Millard, Lindsey Highstrom. "Prostaglandin Involvement in the Conventional Outflow Pathway." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/145367.
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Prostaglandins (PG) play a major role in many endogenous processes including inflammation, labor, reproduction, and blood clotting. In the last two decades, these lipid signaling molecules have shown great potential as ocular hypotensive agents. Intraocular pressure (IOP) is a major risk factor in primary open-angled glaucoma (POAG), the second leading cause of blindness world-wide. Currently, prostaglandin F(2α) analogues are the most widely prescribed medications used to treat ocular hypertension. Studies have identified that almost all prostaglandin analogues exhibit anti-hypertensive effects in the eye, although they are not clinically available. Initial studies attributed the decrease in IOP observed to changes in hydraulic conductivity across the pressure-independent or uveoscleral pathway. More recent studies have shown that prostaglandin F(2α) analogues also lower IOP by affecting the pressure-dependent or trabecular pathway--the diseased tissue in POAG. Little is currently known about PG endogenous function, or the etiology of POAG. However, these studies suggest prostaglandin involvement in the maintenance of IOP in humans and identify the potential of PG analogues to treatment ocular hypertension. The research and findings presented in this dissertation address three specific aims designed to test the hypothesis that Endogenous prostaglandins, prostaglandin enzymes and prostaglandin receptors are involved in regulating conventional outflow facility. Specific aim 1 characterizes the distribution and activity of prostamide/prostaglandin F synthase (PM/PGFS) in the mouse and human eye using immunohistochemistry, western blot analysis and thin layer chromatography. Using techniques in biochemistry, molecular biology and physiology, specific aim 2, identifies the presence of the PG-EP₄ receptor within the outflow pathways, and the efficacy of a selective PG-EP₄ agonist, 3,7-dithiPGE₁, is also determined. Finally, specific aim 3 identifies PG-EP4 receptor coupling and downstream signaling using in vitro assays of transfected and primary cell lines to measure cAMP accumulation after treatment with a PG-EP₄ agonist. Collectively, these studies reveal the importance of PGE₂ synthesis and signaling to the conventional outflow pathway. They identify the PG-EP₄ receptor as a regulator of aqueous outflow and provide more specific therapeutic targets for the treatment of POAG.
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Fong, Yew Su. "Cardiac contractile actions of prostaglandin F₂α". Thesis, University of Bath, 1998. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242532.
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Khidhir, Karzan Ghafur. "Regulation of hair growth : prostaglandins and prostamides : studies confirming the growth stimulating effects of prostanoids and prostamides on human hair follicles in organ culture and locating their receptors using lipidomics, molecular biological and immunohistological approaches." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/5372.
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Hair growth disorders cause significant psychological distress, but are poorly controlled. Since prostaglandin F₂α (PGF₂α) and prostamide F₂α analogue glaucoma treatments cause eyelash growth as side-effects, they may be useful for alopecia. How they function is unknown; possibilities include direct action on hair follicles or stimulating follicular blood flow. It is important to clarify whether scalp follicles can also respond as human follicle response to androgens differ with body site. Therefore, human scalp follicles were grown in vitro in organ culture with PGF₂α, latanoprost, a PGF₂α analogue, and bimatoprost, a prostamide F₂α analogue, with, or without, appropriate antagonists, and the presence of PGF₂α (FP) and prostamide F₂α receptors were investigated using molecular biological and immunohiostochemical methods. Each treatment significantly stimulated follicle growth rate, the percentage of growing follicles, and the amount of hair produced in a dose-responsive manner (10nM-1μM); the receptor antagonists blocked these effects. Immunohistochemistry of frozen scalp sections demonstrated FP protein only in dermal papillae and connective tissue sheaths. RT-PCR identified FP and various prostamide F₂α receptors in anagen follicles and isolated dermal papillae and bulbar connective tissue sheath, but not in bulb matrix or other epithelial tissues. Therefore, isolated human scalp hair follicles can respond biologically to PGF₂α and related pharmaceuticals in organ culture via follicular receptors and express the genes and protein for FP and prostamide F₂α receptors. PGF₂α-related drugs appear to act directly on follicles via receptors in the regulatory dermal papilla. They offer an exciting, novel approach for treating alopecia and merit clinical investigation.
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Carty, Elizabeth. "Thromboxanes and platelets in inflammatory bowel disease : pathogenic and therapeutic implications." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248411.
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Soares, Elyara Maria. "Avaliação da participação de mediadores lipídicos nas infecções experimentais induzidas por diferentes isolados de Mycobacterium tuberculosis de humanos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-21102013-115021/.
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Os mecanismos que conferem resistência do Mycobacterium tuberculosis (Mtb) à destruição pelo hospedeiro, além da sua capacidade em permanecer e/ou multiplicar-se no interior das células fagocitárias são ainda pouco compreendidos. Nosso grupo de pesquisa tem contribuído para o entendimento do papel dos mediadores lipídicos, que incluem prostaglandinas (PGs) e leucotrienos (LTs) na tuberculose. PGs inibem a resposta imune celular TH1, a produção de citocinas e a fagocitose, e assim facilita a infecção. LTs estão envolvidos no recrutamento de leucócitos, e na modulação da síntese de citocinas, no aumento da fagocitose e dos mecanismos microbicidas, e assim contribui para a eliminação da micobactéria. Neste projeto, avaliamos in vivo e in vitro a produção dos mediadores lipídicos induzidos por cepas de Mtb isolados de pacientes com tuberculose ativa. Demonstramos neste trabalho que macrófagos alveolares infectados com os bacilos da cepa SV009 levam a maior produção de TNF- e nitrito, do que aqueles infectados com a cepa SV068. Em contraste, macrófagos alveolares infectados com os bacilos da cepa SV068 induzem a produção de muito mais LTB4, quando comparado aos bacilos da cepa SV009. Obtivemos maior recuperação de unidades formadoras de colônia (UFC) de macrófagos alveolares tratados com MK886 e infectados com bacilos da cepa SV068; enquanto que mais UFCs foram recuperadas após o tratamento com ácido caféico e infecção com a cepa SV009. Com relação a formação de corpúsculos lipídicos (CLs), observamos um maior número destes quando macrófagos alveolares foram infectados com bacilos da cepa SV068. Ainda, observamos diminuição de CLs quando tratados com MK886 ou ácido caféico. Os bacilos da cepa SV068 foram mais fagocitados, mas os macrófagos não foram muito eficazes na atividade microbicida dos mesmos. Nos experimentos in vivo vimos que camundongos balb/c infectados com a cepa SV068 morrem mais e o tratamento com MK886 parcialmente os protege e a mortalidade não está relacionada com a maior carga bacilar no pulmão ou baço. Houve aumento no recrutamento de neutrófilos induzido pela infecção especialmente após infecção com os bacilos da cepa SV068, sendo que o tratamento com MK886 inibe significativamente o recrutamento quando comparado à infecção com os bacilos da cepa SV009. Células mononucleares também foram recrutadas e permaneceram aumentadas até o final do período observado, sem muitas diferenças significativas quando comparamos a infecção com os isolados SV009 e SV068. A produção de nitrito também encontrou-se elevada em animais infectados com bacilos da cepa SV068. A análise histopatológica dos pulmões dos animais infectados mostrou intensa reação inflamatória com maior comprometimento do parênquima pulmonar dos camundongos infectados bacilos da cepa SV068, com intensa deposição de colágeno e multiplicação bacilar. Encontramos diferenças significativas em relação à producão de citocinas IL-6, IL-10, IL-1, IFN-, TNF- and IL-12 após infecção de 30 e 60 dias com as cepas SV009 e SV068. Também mostramos que há diferenças na produção de LTB4 e PGE2 após 30 e 60 dias de infecção com as cepas SV009 e SV068 em células do camundongos balb/c. Experimentos com animais 129 e 5LO-/- infectados com as duas cepas também foram realizados, e vimos que os animais 5LO-/- são mais suscetíveis à infecção especialmente quando infectados com a cepa SV068. Sugerimos que as cepas são diferentes, mas dependentes de um conjunto de fatores, e nossos dados sugerem que dentre estes mecanismos a produção de TNF- e também de mediadores lipídicos (LTB4 e PGE2) estão envolvidos.<br>The mechanisms that confer resistance to Mycobacterium tuberculosis (Mtb) for destruction by the host, in addition to its ability to retain and/or multiply within phagocytic cells are still poorly understood. Our research group has contributed to the understanding of the role of lipid mediators, including prostaglandins (PGs) and leukotrienes (LTs) in tuberculosis. PGs inhibit Th1 cell immune response, cytokine production and phagocytosis, thus facilitating the infection. LTs are involved in the leukocytes recruitment, and modulation of cytokine synthesis, phagocytosis and microbicidal mechanisms enhancement, and contribute to the elimination of the mycobacteria. In this project, we evaluated in vivo and in vitro the lipid mediators production induced by Mtb strains isolated from patients with active tuberculosis. We demonstrated in this study that alveolar macrophages infected with bacilli from SV009 strain lead to an increase of TNF- production and nitrite, than those infected with the strain SV068. In contrast, alveolar macrophages infected with bacilli from SV068 strain induced more LTB4 production when compared to SV009 infection. We obtained higher recovery colony forming units (CFU) of alveolar macrophages treated with MK886 and infected with bacilli from SV068 strain; while more CFUs were recovered after treatment with caffeic acid and infection with bacilli from SV009 strain. Regarding the lipid bodies (LBs) formation, we observed a greater number of these structures, when alveolar macrophages were infected with bacilli from SV068 strain. Still, we observed a decrease of LBs when the macrophages were treated with MK886 and caffeic acid. Bacilli from SV068 strain were more phagocytosed, but macrophages were not very effective in the microbicidal activity. In the in vivo experiments we found that mice infected with SV068 strain die more than the other and MK886 treatment partially protects the mice, besides, the mortality is not related to the higher bacterial load in the lung or spleen. There was an increase in neutrophil recruitment induced after infection, especially after infection with SV068 strain, and treatment with MK886 significantly inhibits recruitment when compared to infection with SV009 strain. Mononuclear cells were also recruited and remained increased until the end of the observed period, without many significant differences when comparing infection with SV009 and SV068 strains. The nitrite production was also found greater in animals infected with bacilli from SV068 strain. Histopathological analysis of the infected mice lungs showed an intense inflammatory reaction with greater impairment of the mice lungs when infected with bacilli from SV068 strain with an intense collagen deposition and multiplication of bacilli. We suggest that the SV068 strain is more virulent and participates of the immune response by lipid mediators dependent mechanisms.
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Plant, Matthew Hilton. "Characterization of a novel prostaglandin endoperoxide H synthase-1 transcript and examination of prostaglandin endoperoxide H synthase-1 expression." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0004/MQ46601.pdf.
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Simm, Björn [Verfasser]. "Zelluläre Wirkungen von Prostaglandin E2 und Prostaglandin D2 auf periphere und zentralnervöse Strukturen des Thermoregulationssystems der Ratte / Björn Simm." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1125345276/34.
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Kobayashi, Takuya. "Amino acid residues conferring ligand binding properties of prostaglandin I and prostaglandin D receptorsに関する研究". Kyoto University, 2000. http://hdl.handle.net/2433/151431.
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Grahl, Katrin. "Der Einfluss von Glykosaminoglykanen auf die Bildung und Freisetzung von Prostaglandin E2." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-187924.
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Diese Arbeit verdeutlicht die Wirkung von Chondroitinsulfat auf die Synthese von Prostaglandin E2 in humanen mesenchymalen Stromazellen in Abhängigkeit ihres Sulfatierungsgrades. MSC zeichnen sich durch ihre antiinflammatorischen Eigenschaften aus und haben damit einen modulierenden Effekt auf Wundheilungsprozesse. Als Vorläuferzellen von Osteoblasten sind sie direkt an der Knochenneubildung beteiligt. Eine persistierende Entzündung hat eine kontinuierliche Freisetzung von Zytokinen, wie IL-1 zur Folge. Es konnte gezeigt werden, dass IL-1 in hMSC zu einer Freisetzung von PGE2 führt. Unter kurzzeitiger Wirkung stimuliert PGE2 die Knochenneubildung. Eine langanhaltende Präsenz leitet dagegen die Bildung des Faktors RANKL, einen die Osteoklastogenese stimulierenden Faktor, ein. Seit langem ist der positive Effekt von Chondroitinsulfat in chronischen Entzündungsprozessen, wie Rheumatoider Arthritis, bekannt. Zudem werden sie in aktuellen Studien als Beschichtungsbestandteile von Knochenimplantaten verwendet. Sie führten hier zu einer besseren Bioinduktivität und Biokonduktivität. Bisher ist dennoch der molekulare Wirkmechanismus nicht genau beschrieben. Die Schwierigkeit besteht darin, dass die molekularen Signalkaskaden für die einzelnen Kulturmoldelle Unterschiede aufweisen und kein ubiquitärer Mechanismus dargestellt wird.
In hMSC führte die Stimulation mit IL-1 unter vorheriger Zugabe von Chondroitinsulfat zu einer Reduktion der PGE2 Freisetzung. Der Effekt des hochsulfatierten sCS3 war gegenüber dem nativen C4S verstärkt. Die reduzierende Wirkung von C4S setzte verzögert ein. Es ist bereits bekannt, dass die negative Ladung der CS zu einer Bindung von Zytokinen führt. Dadurch wird eventuell die Konzentration der Zytokine, wie IL-1 im Bereich der Zellrezeptoren erniedrigt und führt zu einer verringerten Stimulation der Zelle. Denkbar ist auch die Beeinflussung der intrazellulären Signaltransduktionskaskade durch die Bindung der CS an einen speziellen, bisher unbekannten, Membranrezeptor. Die entscheidenden Enzyme der PGE2 Synthese sind die Cyclooxygenase-2 (Cox-2) und die mikrosomale Prostaglandin E Synthase 1 (mPGES1). Die mRNA beider Enzyme war unabhängig vom Sulfatierungsgrad der CS reduziert. Dieser Effekt konnte auf Protein-ebene nicht belegt werden. Die produzierte Proteinmenge an mPGES1 wird durch IL-1 induziert, bleibt aber auch durch Zugabe von CS unverändert. Somit kann von einer erhöhten Translationseffizient und mRNA Stabilität der mPGES1 RNA ausgegangen werden. MAPK Kinasen sind entscheidende Schnittstellen bei der Regulation der mRNA Stabilität als auch der Aktivität von Transkriptionsfaktoren. In dieser Studie konnte die MAPK p38 als entscheidendes Enzym bei der Wirkung von CS auf die PGE2 Synthese ermittelt werden. Dabei führten sowohl das natürliche C4S als auch das hochsulfatierte sCS3 zu einer verringerten Aktivierung.
Der Transkriptionsfaktor NfkB ist einer von mehreren, die an den Promotorbereichen der beiden induzierbaren PGE2 Enzyme, Cox-2 und mPGES1, binden. Es ist anzunehmen, dass die hier aufgezeigte verringerte Aktivität von NfkB als auch die verhinderte Translokation in den Zellkern eine reduzierte Transkription der jeweiligen mRNA bedingten. Abhängig vom untersuchten Modell und den verwendeten Kulturbedingungen können diese Prozesse moduliert sein.
Die Erkenntnisse dieser experimentellen Arbeit liefern einen weiteren wichtigen Baustein zum Verständnis der molekularbiologischen Abläufe während entzündlicher Prozesse. Die Verwendung von Chondroitinsulfat, insbesondere hochsulfatiertes CS, in Kombination mit hMSC kann gezielt zu einer Verringerung der Entzündungsreaktion während der Implantateinheilung führen. Die durch PGE2 hervorgerufenen Symptome, wie erhöhte Gefäßpermeabilität, Schwellung und verstärktes Schmerzempfinden begründen diese positiven Effekte.
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Pereira, Priscilla Aparecida Tartari. "Papel das prostaglandinas na infecção experimental por Histoplasma capsulatum." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-28112013-100514/.
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histoplasmose é uma doença granulomatosa crônica, cujo agente etiológico é o fungo dimórfico Histoplasma capsulatum. A infecção ocorre pela inalação de conídios ou pequenos fragmentos de micélio que alcançam os alvéolos, onde se transformam em leveduras que é responsável pela patogenia da doença. A imunidade celular do hospedeiro determina o grau das manifestações clínicas na histoplasmose, sendo a interação entre células T e macrófagos, fundamental para o controle da infecção e erradicação do H. capsulatum. Recentemente, nosso grupo de pesquisa demonstrou a participação de leucotrienos nos mecanismos de defesa do hospedeiro durante a histoplasmose. Neste trabalho descrevemos o papel das prostaglandinas, demonstramos que este mediador lipídico contribui para a patogênese da doença, pois sua inibição, com celecoxibe, resultou na sobrevivência de até 80% dos animais infectados com o inóculo letal de H. capsulatum, em contraste com 100% de mortalidade dos animais somente infectados. Além disso, a inibição das prostaglandinas resultou na diminuição (i) da síntese de citocinas pró-inflamatórias e da resposta imune celular e (ii) do recrutamento de neutrófilos e macrófagos para o espaço bronco-alveolar. Por outro lado, resultou no aumento (iii) de células TCD4+ no pulmão, (iv) na síntese de óxido nítrico por células do parênquima pulmonar, (v) na fagocitose de leveduras de H. capsulatum por macrófagos alveolares e (vi) da síntese de LTB4. Nossos resultados sugerem que prostaglandinas têm papel importante na patogênese na infecção por H. capsulatum, modulando a resposta imune do hospedeiro.<br>The Histoplasmosis is a chronic granulomatosas disease whose etiologic agent is pathogenic dimorphic fungus Histoplasma capsulatum. Infection occurs mainly by fungal inhalation that reaches the alveoli, where if transforms into leavenings that are responsible for pathogenic diseases. The cellular immunity of the host determines the degree of the clinical manifestations in histoplasmosis, being the interaction between cells T and macrophages, basic for the control of the infection and eradication of the H. capsulatum. Recently, our group of research demonstrated the participation of leukotrienes in the mechanisms of defense of the host during the Histoplasmosis. Beyond this important lipid mediator who participates in the immune reply against H. capsulatum. In this work, we describe another involved mediator, the prostaglandin. In the present work, we demonstrate that the prostaglandins contribute for pathogenic of the disease, being that during its inhibition with celecoxib it resulted in the survival of up to 80% of the infection-mice with inoculum lethal of H. capsulatum, in contrast with 100% of mortality infection-mice. Moreover, the inhibition of prostaglandins resulted in the reduction (i) of the synthesis of pro-inflammatory cytokines and the cellular immune response and (ii) in the migration of neutrophils and macrophages. For other hand, increased (iii) of cells TCD4+ in the lung, (iv) of the nitric oxide synthesis, (v) of phagocytosis of yeast of H. capsulatum for alveolar macrophages and (vi) of the synthesis of LTB4. Our results suggest that prostaglandins have important role in pathogenic in the infection for H. capsulatum, modulating the host immune response.
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Strohm, Daniela. "Modulation der Insulinsignalgebung durch Prostaglandin E2 und Endocannabinoide." Phd thesis, Universität Potsdam, 2010. http://opus.kobv.de/ubp/volltexte/2011/4967/.
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Die adipositasbedingte Insulinresistenz geht mit einer unterschwelligen Entzündungsreaktion einher. Als Antwort auf dieses Entzündungsgeschehen wird PGE2 unter anderem von Kupffer Zellen der Leber freigesetzt und kann seine Wirkung über vier PGE2-Rezeptorsubtypen (EP1-EP4) vermitteln. In vorangegangenen Arbeiten konnte gezeigt werden, dass PGE2 in Rattenhepatozyten über den EP3 R ERK1/2-abhängig die intrazelluläre Weiterleitung des Insulinsignals hemmt. Über die Modulation der Insulinrezeptorsignalkette durch andere EP-Rezeptoren war bisher nichts bekannt. Daher sollte in stabil transfizierten Zelllinien, die jeweils nur einen der vier EP-Rezeptorsubtypen exprimierten, der Einfluss von PGE2 auf die Insulinrezeptorsignalkette untersucht werden. Es wurden HepG2-Zellen, die keinen funktionalen EP-Rezeptor aufwiesen, sowie HepG2-Zellen, die stabil den EP1-R (HepG2-EP1), den EP3β-R (HepG2 EP3β) oder den EP4-R (HepG2 EP4) exprimierten, sowie die humane fötale Hepatozytenzelllinie, Fh hTert, die den EP2- und den EP4-R exprimierte, für die Untersuchungen verwendet. Die Zellen wurden für 330 min mit PGE2 (10 µM) vorinkubiert, um die pathophysiologische Situation nachzustellen und anschließend mit Insulin (10 nM) für 15 min stimuliert. Die insulinabhängige Akt- und ERK1/2-Phosphorylierung wurde im Western-Blot bestimmt.
In allen Hepatomzelllinien die EP-R exprimierten, nicht aber in der Zelllinie, die keinen EP R exprimierte, hemmte PGE2 die insulinstimulierte Akt-Phosphorylierung. In allen drei stabil transfizierten Zelllinien, nicht jedoch in den Fh-hTert-Zellen, steigerte PGE2 die basale und insulinstimulierte Phosphorylierung der Serin/Threoninkinase ERK1/2. In den HepG2 EP1- und den HepG2-EP3β-Zellen steigerte PGE2 mutmaßlich über die ERK1/2-Aktivierung die Serinphosphorylierung des IRS, welche die Weiterleitung des Insulinsignals blockiert. Die Hemmung der Aktivierung von ERK1/2 hob in EP3 R-exprimierenden Zellen die Abschwächung der Insulinsignalübertragung teilweise auf. In diesen Zellen scheint die ERK1/2-Aktivierung die größte Bedeutung für die Hemmung der insulinstimulierten Akt-Phosphorylierung zu haben. Da durch die Hemmstoffe die PGE2-abhängige Modulation nicht vollständig aufgehoben wurde, scheinen darüber hinaus aber noch andere Mechanismen zur Modulation beizutragen. In den Fh hTert-Zellen wurde die Insulinrezeptorsignalkette offensichtlich über einen ERK1/2-unabhängigen, bisher nicht identifizierten Weg unterbrochen.
Eine gesteigerte PGE2-Bildung im Rahmen der Adipositas ist nicht auf die peripheren Gewebe beschränkt. Auch im Hypothalamus können bei Adipositas Zeichen einer Entzündung nachgewiesen werden, die mit einer gesteigerten PGE2-Bildung einhergehen. Daher wurde das EP R-Profil von primären hypothalamischen Neuronen und neuronalen Modellzelllinien charakterisiert, um zu prüfen, ob PGE2 in hypothalamischen Neuronen die Insulinsignalkette in ähnlicher Weise unterbricht wie in Hepatozyten. In allen neuronalen Zellen hemmte die Vorinkubation mit PGE2 die insulinstimulierte Akt-Phosphorylierung nicht. In der neuronalen hypothalamischen Zelllinie N 41 wirkte PGE2 eher synergistisch mit Insulin. In durch Retinsäure ausdifferenzierten SH SY5Y-Zellen waren die Ergebnisse allerdings widersprüchlich. Dies könnte darauf zurückzuführen sein, dass die Expression der EP Rezeptoren im Verlauf der Kultur stark schwankte und somit die EP R-Ausstattung der Zellen zwischen den Zellversuchen variierte. Auch in den primären hypothalamischen Neuronen variierte die EP R-Expression abhängig vom Differenzierungszustand und PGE2 beeinflusste die insulinstimulierte Akt-Phosphorylierung nicht. Obwohl in allen neuronalen Zellen die Akt-Phosphorylierung durch Insulin gesteigert wurde, konnte in keiner der Zellen eine insulinabhängige Regulation der Expression von Insulinzielgenen (POMC und AgRP) nachgewiesen werden. Das liegt wahrscheinlich an dem niedrigen Differenzierungsgrad der untersuchten Zellen.
Im Rahmen der Adipositas kommt es zu einer Überaktivierung des Endocannabinoidsystems. Endocannabinoidrezeptoren sind mit den EP Rezeptoren verwandt. Daher wurde geprüft, ob Endocannabinoide die Insulinsignalweiterleitung in ähnlicher Weise beeinflussen können wie PGE2. Die Vorinkubation der N 41-Zellen für 330 min mit einem Endocannabinoidrezeptoragonisten steigerte die insulinstimulierte Akt-Phosphorylierung, was auf einen insulinsensitiven Effekt von Endocannabinoiden hindeutet. Dies steht im Widerspruch zu der in der Literatur beschriebenen endocannabinoidabhängigen Insulinresistenz, die aber auf indirekte, durch Endocannabinoide ausgelöste Veränderungen zurückzuführen sein könnte.<br>The obesity related insulin resistance is accompanied by a low grade inflammation. In response to inflammatory stimuli, PGE2 is released from Kupffer cells and signals through four G-Protein coupled PGE2-receptors (EP1-EP4). Previous work showed that PGE2 attenuated insulin signaling in rat hepatocytes through an EP3ß- and ERK1/2-dependent mechanism. Since EP-receptor expression on hepatocytes varies between species and physiological conditions, the effect of the individual EP receptor subtypes on insulin signaling was studied in hepatoma cell lines expressing individual EP receptor subtypes. HepG2 cells lacking functional EP-receptors, and derivatives stably expressing either EP1 receptor (HepG2-EP1), EP3ß receptor (HepG2-EP3ß) or EP4 receptor (HepG2-EP4) and Fh-hTert cells expressing EP2- and EP4-receptor were pre-incubated with PGE2 for 330 min to mimic the sub-acute inflammation. The cells were subsequently stimulated with insulin for 15 min. Akt and ERK1/2 activation was determined by Western Blotting with phospho-specific antibodies.
PGE2 inhibited insulin stimulated Akt phosphorylation in all cell lines expressing EP receptors, except in HepG2 cells which are lacking functional EP receptors. PGE2 increased insulin stimulated phosphorylation of the serine/threonine kinase ERK1/2 in all EP R expressing HepG2 cell lines except in Fh-hTert cells. In HepG2-EP1 and HepG2 EP3ß cells PGE2 increased the serine phosphorylation of the insulin receptor substrate, presumably through an ERK1/2 activation. This IRS-serine phosphorylation leads to attenuation of insulin signal transduction. Inhibiting ERK1/2 activation with a specific inhibitor attenuated the PGE2-dependent inhibition of insulin signal transmission in HepG2 EP3ß cells to some extent. ERK1/2 activation in these cells seems to be of major importance for the observed attenuation of insulin stimulated Akt phosphorylation. Application of inhibitors in the other cell lines stably expressing EP receptors provided evidence that other mechanisms contributed to the attenuation of insulin signaling. Insulin signal transduction in Fh-hTert cells by PGE2 was apparently blocked by an ERK1/2-independent mechanism.
Increased PGE2 production during obesity is not limited to the periphery. Signs of inflammation have been detected in the hypothalamus, which might be associated with an increased PGE2 production. Therefore, the EP receptor profile of primary neurons as well as neuronal cell models was characterised in order to investigate, whether PGE2 attenuates insulin signal transduction in neuronal cells similar to what was observed in hepatocytes. Pre-incubation with PGE2 did not attenuate insulin stimulated Akt phosphorylation in all neuronal cells. The EP receptor profile in SH SY5Y cells and in primary neurons varied depending on the differentiation status of the cells. Although Akt-kinase was phosphorylated in response to insulin stimulation in all neuronal cells studied, gene expression of insulin target genes (POMC, AgRP) was not modulated by insulin. This might be due to the low level of differentiation of the investigated cells.
In the course of obesity, an over-activation of the endocannabinoid system is detected. Since endocannabinoid receptors are related to EP receptors, it was investigated whether endocannabinoids can interfere with insulin signaling in a similar way as PGE2. Pre-incubation of the neuronal cell line N 41 for 330 min with an endocannabinoid receptor agonist, increased insulin stimulated Akt phosphorylation. This implies an insulin sensitising effect of endocannabinoids. This is contradictory to the endocannabinoid-dependent insulin resistance described in the literature and might be caused by indirect endocannabinoid-triggered mechanisms.
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Martin, Rebecca Louise. "Regulation of prostaglandin production in the ovine placenta." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ63196.pdf.
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Kwok, Ho-yan Amy, and 郭可茵. "Molecular cloning and characterization of chicken prostaglandin receptors." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508336.
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Matsuoka, Toshiyuki. "Prostaglandin D_2 as a mediator of allergic asthma." Kyoto University, 2000. http://hdl.handle.net/2433/180888.
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Kwok, Ho-yan Amy. "Molecular cloning and characterization of chicken prostaglandin receptors." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41508336.
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Krause, Petra. "Effects of Prostaglandin E2 on Dendritic Cell functions." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-54682.
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Karlsson, Sofia. "Studies of prostaglandin E2 formation in human monocytes." Karlstad : Faculty of Technology and Science, Biomedical Sciences, Karlstads universitet, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-4638.
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Vijay, Rahul. "Prostaglandin regulation of immune responses against coronavirus infections." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/3209.
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Prostaglandins (PG) are ubiquitous lipid mediators that play key roles in pathophysiological responses to infections. They are considered to have both pro and anti-inflammatory roles depending upon the time of inflammation, the receptors that they bind to and the tissues that they act upon. Hence given their pleiotropic effects, a perfect balance between the pro and anti-inflammatory functions of PGs are required to ensure that a controlled timely immune response is elicited to mediate protection and to avoid immunopathology.
PGD2 is one such PG that was reported to increase with age in the lungs of mice and to mediate an anti-inflammatory effect thereby blunting the immune response following Severe Acute Respiratory Syndrome – Coronavirus (SARS-CoV). Increase in PGD2 with age incapacitates respiratory dendritic cells (rDC) to migrate from lungs to the draining lymph node following SARS-CoV infection due to down regulation of CCR7 (a receptor for chemokines CCL19/21). Migration of rDCs to draining lymph nodes requires high expression of CCR7 and it's binding to CCL19/21, a chemokine that mediates migration of dendritic cells along its gradient. Although increase in levels of PGD2 might prove beneficial in high inflammatory conditions, it should be noted that high levels of such a potent anti-inflammatory mediator during the initiation of an immune response could prove detrimental. In chapter II of this thesis I show that age-related increases in oxidative stress result in the upregulation of a single phospholipase (PLA2) group II D (G2D) (PLA2G2D) with anti-inflammatory roles. PLA2G2D functions by releasing Arachidonic acid (AA) from the lipid membrane, which will be further metabolized to other pro-resolving/ anti-inflammatory lipid mediators including PGD2. I show that inducing oxidative stress in young mice as well as in human peripheral blood macrophages, results in the upregulation of PLA2G2D (probably as a counter mechanism against oxidative stress). Also increase in the expression levels of this gene during the course of SARS-CoV infection results in the upregulation of PGD2, which is completely abrogated in Pla2g2d-/- mice. I also show Pla2g2d/- middle-aged mice have low levels of PGD2 and that they are capable of mounting a strong immune response and survive the otherwise lethal SARS-CoV infection.
PGD2 is also a major PG in the brain and its role has been investigated in many non-infectious setting such as stroke and Alzheimer' disease. The PGD2 binding to one of its receptors DP1 has been shown to have primarily a neuro-protective role. In chapter III, I show that PGD2/DP1 signaling has beneficial effects in the brain of mice infected with a neurotropic strain of murine hepatitis virus (MHV) (rj2.2). In agreement with the neuro-protective role of PGD2, at least 60% of DP1-/- mice succumb to a sublethal dose of rj2.2. rj2.2 infection in these mice is characterized by a delay in the induction of IFN I response and lower activation status of microglia and macrophages in the brain. I also show that abrogation of DP1 signaling results in global defects in the immune system response to infection. Notably, a genome wide expression analysis using microarray, shows that a gene, Pydc3 with putative inflammasome inhibiting function is upregulated in WT mice compared to DP1-/- mice in the CD11b population of cells which primarily comprises microglia and macrophages. In line with the predicted function of Pydc3, DP1-/- mice have higher frequency and number of IL-1β+ producing microglia in the brain. Studies are underway to determine the exact role of DP1 signaling in Pydc3 expression as well as the role of this gene in inflammasome function.
Overall these studies emphasize the immuno-modulatory roles of PGs in the context of a viral infection. Thus, altering the levels of these lipid mediators at appropriate times during the course of infection might prove useful as an effective therapeutic strategy to decide the fate of an infection.
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Rizzoni, Leandro Becalete. "Aplicação do Cloprostenol Sódico em cabras leiteiras no puerpério." Universidade Jose do Rosario Vellano, 2012. http://tede2.unifenas.br:8080/jspui/handle/jspui/148.
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Previous issue date: 2012-04-18<br>This study assessed the of effects the application of cloprostenol in postpartum dairy goats. Twenty-nine Anglonubian goats were used, evenly divided into two groups. The control group received 0.5 ml of saline (0.9%) and group PGF2 0.133 mg cloprostenol in two intramuscular applications on day 1 (D1) and four (D4) PP. The reproductive tract of the animals was assessed by transrectal ultrasound with a linear, 5.0 MHz on days 1, 4, 10, 16, 22, 28, 34, 40 and 46 postpartum. The uterine diameter, cervical diameter, volume of the intrauterine contents and uterine position were measured. In four animals from each treatment the endometrial thickness and diameter of the two larger follicles present in the ovary were evaluated, and vaginoscopy revealed the presence and aspect of the cervical mucus. The data were tested using the ANOVA analysis of variance and the averages (uterine diameter and endometrial thickness), by the Tukey test. The position of the uterus was assessed by the X2 test (chi-square). The body condition score and volume of intrauterine contents were evaluated with the nonparametric Wilcoxon test. All parameters were considered significant at 5% probability level. The uterine diameter behaved differently between the groups. In the PGF2 group there was a marked reduction in uterine diameter until day 22 PP (3.5 ± 0.6 cm) and the control group until day 28 PP (3.6 ± 0.8 cm). The expulsion of uterine contents was earlier in PGF2 group (D40), and on D46 in the control group. Likewise, the presence of cervical mucus was earlier in PGF2 group (D34) compared to control group (D40). The follicular growth did not differ between the groups, the maximum average diameters were 5.1 ± 0.3 mm at 28 dpp for the PGF2 group and 5.2 ± 0.4 mm at 22 dpp for the control group. The results suggest that cloprostenol acts beneficially in the process of uterine involution and expulsion of uterine contents.
Key-words: Goats, Uterine involution, Prostaglandin.<br>Objetivou-se verificar os efeitos da aplicação do cloprostenol sódico no puerpério de cabras leiteiras. Utilizaram-se vinte e nove cabras Anglonubianas, divididas uniformemente em dois grupos. O grupo controle recebeu 0,5 mL de solução salina (0,9%) e o grupo PGF2 0,133 mg de cloprostenol sódico em duas aplicações, nos dias 1 (D1) e 4 (D4) PP, pela via intramuscular. O aparelho reprodutivo dos animais foi avaliado através de ultrassonografia transretal, com transdutor linear de 5.0 MHz nos dias 1, 4, 10, 16, 22, 28, 34, 40 e 46 pós-parto. Aferiu-se o diâmetro uterino, diâmetro cervical, posição uterina e volume do conteúdo intrauterino. Em quatro animais de cada tratamento avaliou-se a espessura do endométrio e diâmetro dos dois maiores folículos presentes nos ovários e, através da vaginoscopia, observou-se a presença e aspecto do muco cervical. Os dados foram submetidos ao teste de analise de variância ANOVA e as médias (diâmetro uterino e espessura do endométrio) ao teste de Tukey. Para a posição uterina, utilizou-se o teste X2 (Qui-quadrado). Para o escore de condição corporal e volume de conteúdo intrauterino procedeu-se ao teste não paramétrico de Wilcoxon. Todas as variáveis foram consideradas significativas a 5% de probabilidade. O diâmetro uterino se comportou de maneira diferente entre os grupos. No grupo PGF2houve uma acentuada redução do diâmetro uterino até o dia 22 PP (3,5 ± 0,6 cm) e no grupo controle, até o dia 28 PP (3,6 ± 0,8 cm). A expulsão do conteúdo uterino foi anterior no grupo PGF2 (D40), enquanto para o grupo controle a expulsão completou-se no D46. Da mesma forma, a presença de muco cervical foi anterior no grupo PGF2(D34) quando comparado ao grupo controle (D40). O crescimento folicular não diferiu entre os grupos. Os diâmetros médios máximos observados foram de 5,1 ± 0,3 mm aos 28 dpp, para o grupo PGF2 e 5,2 ± 0,4 mm aos 22 dpp, para o grupo controle. Os resultados sugerem que o cloprostenol sódico atua beneficamente no processo de involução uterina e expulsão do conteúdo uterino.
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Koeberle, Andreas. "Identification and characterization of microsomal prostaglandin E₂ synthase-1 inhibitors = Identifizierung und Charakterisierung von Hemmstoffen der mikrosomalen Prostaglandin E₂ Synthase-1 /." Tübingen, 2009. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000278394.
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