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1

Benz, Nathalie. "Stimulation de cellules épithéliales bronchiques humaines par la GnRH : effet sur le transport ionique médié par le CFTR." Phd thesis, Université de Bretagne occidentale - Brest, 2013. http://tel.archives-ouvertes.fr/tel-00952459.

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Introduction : La mucoviscidose est une maladie génétique autosomale récessive causée par des mutations dans le gène CFTR (cystic fibrosis transmembrane conductance regulator). Ce dernier code un canal chlorure AMPc-dépendant localisé dans la membrane apicale des cellules épithéliales, dont l'activité est régulée par de nombreuses interactions protéine-protéine. Dans le cadre de la recherche de nouveaux partenaires du CFTR, une interaction directe entre le canal (sauvage et muté F508del) etl'annexine A5 (AnxA5) a été mise en évidence dans notre laboratoire. Des stratégies de sur et de sousexpression nous ont également permis d'établir un lien fonctionnel entre les deux protéines. En effet, nos travaux montrent que les sécrétions ioniques dépendantes du CFTR sont corrélées au niveau d'expression intracellulaire de l'AnxA5. Par ailleurs, une élévation des courants médiés par le CFTR ainsi qu'une augmentation de la quantité de canaux dans la membrane plasmique sont observées suite à la surexpression de l'AnxA5 dans des cellules exprimant le CFTR muté F508del.But de l'étude : Au vu de ces observations, l'AnxA5 apparaît comme une cible potentielle pour la correction de certains défauts engendrés par la mutation F508del. Une piste thérapeutique pourrait être l'identification de composés capables d'augmenter son expression dans des cellules épithéliales exprimant le mutant F508del de la protéine CFTR. Considérant les informations fournies par la littérature, notre choix s'est porté sur la GnRH (gonadotropin-releasing hormone), molécule utilisée en thérapeutique humaine depuis plus de 25 ans. Ainsi, nous avons évalué l'effet de la GnRH sur la modulation de l'expression de l'AnxA5 et sur le transport ionique dépendant du CFTR dans nos différents modèles d'étude Résultats : Outre la présence du récepteur de la GnRH dans nos modèles cellulaires, nous montrons également que l'expression de l'AnxA5 y est augmentée dès 60 minutes de traitement avec l'hormone (1 nM). De plus, comparativement à des cellules non stimulées, des cellules prétraitées avec la GnRH présentent une hausse significative des sorties actives d'iodure, corrélant avec une augmentation de la quantité de CFTR à la surface cellulaire. Ces observations ont été faites dans les modèles exprimant le CFTR muté F508del ainsi que dans ceux exprimant le CFTR sauvage. Conclusion : Dans nos modèles et selon nos conditions de stimulation, un traitement avec la GnRH augmente l'expression intracellulaire de l'AnxA5 et conduit à une élévation des sécrétions ioniques médiées par le canal CFTR. Néanmoins, au vu de la multitude de voies de signalisation susceptibles d'être activées et de gènes pouvant être régulés suite à la liaison de la GnRH sur son récepteur, l'effet observé sur l'AnxA5 ne représente probablement pas le seul évènement cellulaire à l'origine de l'impact positif enregistré sur l'activité du canal CFTR.
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2

Musafer, Gnai Nishani. "Non-linear univariate and multivariate spatial modelling and optimal design." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/95625/1/Gnai%20Nishani_Musafer_Thesis.pdf.

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This thesis developed a novel adaptive methodology for the optimal design of additional sampling based on a geostatistical model that can preserve both multivariate non-linearity and spatial non-linearity present in spatial variables. This methodology can be applied in mining or any other field that deals with spatial data. The results from the different environment case studies demonstrated the potential of the proposed design methodology.
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3

Ludwig, Carolin. "Downregulation der hypophysären GnRH-Rezeptoren mit einem neuen GnRH-Implantat beim Rüden." Giessen : VVB Laufersweiler, 2008. http://d-nb.info/988308991/04.

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4

GERBER, MONIQUE. "Sterilites feminines par dysovulation : traitement par analogue du gnrh et gnrh micropulse." Toulouse 3, 1990. http://www.theses.fr/1990TOU31027.

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5

Nguyen, Kathryn Alexandra. "GnRH regulation of signaling /." Diss., Connect to a 24 p. preview or request complete full text in PDF formate. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3266839.

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6

Hoo, L. C., and 何麗莊. "Transcriptional regulation of the human gonadotropin-releasing hormone(GnRH) II and GnRH receptor genes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29297011.

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7

Albertson, Asher J. "Extra-pituitary functions for GnRH." Laramie, Wyo. : University of Wyoming, 2007. http://proquest.umi.com/pqdweb?did=1313910061&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.

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8

Ott, Thomas Ruthard. "Receptor activation in GNRH receptors." Doctoral thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/2700.

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9

Ludwig, Carolin [Verfasser]. "Downregulation der hypophysären GnRH-Rezeptoren mit einem neuen GnRH-Implantat beim Rüden / eingereicht von Carolin Ludwig." Giessen : VVB Laufersweiler, 2008. http://d-nb.info/989051080/34.

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10

Shivji, Nadia. "GnRH neuron migration during embryonic development." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611556.

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11

Haywood, S. A. "GnRH network : noradrenaline and sex steroids." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603906.

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The first studies in this thesis use <I>in situ</I> hybridisation to investigate if temporal changes occur in cellular GnRH gene expression during the preovulatory phase of the oestrous cycle and further investigation gene expression in other neurotransmitter systems in the GnRH network within the preoptic area and the brainstem. It is evident from these studies that, during the oestrous cycle, transcriptional changes within GnRH, enkphalin, nitric oxide synthase and noradrenaline containing neural populations, in the preoptic area and brainstem respectively, are small, and are perhaps not pertinent to the imminent LH surge. Nevertheless, it is already established that sex steroid dependent changes in GnRH secretion are associated with an increased in noradrenergic activity. The second study, using immunocytochemical techniques, focuses on this relationship and demonstrates, for the first time, the presence of progesterone receptors (PR) in up to 35% of noradrenaline cells in caudal regions of the nucleus tractus solitarii (A2 cell group). Moreover, this study shows that dynamic fluctuations in sex steroid receptors occur during the oestrous cycle, with the highest percentage of A2 neurones expressing PR and oestrogen receptor (ERα) on proestrous morning with a nadir on dioestrous afternoon. Further studies in steroid-primed female rats provide evidence that this is predominantly an oestrogen-inducing effect on PR expression. Finally, using retrograde tracing techniques combined with dual-labelling immunocytochemistry I show that approximately 5-12% of A cells in the brainstem project to the vicinity of the GnRH perikarya located in the rostral preoptic area (rPOA) and that the majority of these projecting A2 neurones express PR.
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12

曾美好 and May-ho Tsang. "Dopaminergic regulation of gonadotropin-releasing hormone (GnRH) secretion and gene expression in a GnRH neuronal cell line." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1995. http://hub.hku.hk/bib/B31213698.

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13

Tsang, May-ho. "Dopaminergic regulation of gonadotropin-releasing hormone (GnRH) secretion and gene expression in a GnRH neuronal cell line /." Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17095219.

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14

Joseph, Nerine Theresa. "Characterisation of the tissue-specific expression, pharmacology and signalling cascades activated by chicken GnRH receptor subtypes suggested evolutionary specialisation of type III cGnRH receptor function." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4802.

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Variant GnRH ligand and receptor subtypes have been identified in a number of non-mammalian vertebrate species, however research into avian species GnRH systems is lacking. Two isoforms of GnRH are present in the domestic chicken, the evolutionarily conserved GnRH-II and diverged cGnRH-I. The expression of two GnRH ligands parallels the expression of two chicken GnRH receptor subtypes; cGnRH-R-I and the novel cGnRH-R-III. The occurrence of two isoforms of the receptor in the chicken raises questions about their specific biological functions and interactions with the two ligands. Differential roles for these molecules in regulating gonadotrophin secretion or other functions are currently unclear. To investigate this, cGnRH-R-III cDNA was cloned from a broiler chicken anterior pituitary gland and its structure and expression was compared with cGnRH-R-I. Expression profiling of cGnRH-R-III cDNA showed that it is predominantly expressed in the anterior pituitary, approximately 1400 times more abundantly than cGnRH-R-I suggesting that cGnRH-R-III is the predominant regulator of chicken gonadotrophin synthesis and secretion. Additionally, pronounced sex and age differences existed, with higher pituitary cGnRH-R-III mRNA levels in sexually mature females versus juvenile females. In contrast, higher mRNA expression levels occurred in juvenile males compared to sexually mature males. Determination of ligand-binding selectivity and the level of cGnRH-R-III activation in response to the endogenous ligands, cGnRH-I and GnRH-II, was anticipated as facilitating the elucidation of the physiological roles of the receptor subtypes. Additionally, the development of analogs that differentially promote or inhibit activation of the receptor subtypes may be valuable tools for determining the role of receptor types in the regulation of gonadotrophin production. To investigate this, pharmacological profiling of cGnRH-R-III in terms of ligand-binding selectivity and inositol phosphate production in response to GnRH analogs was determined in comparison with the pharmacological profile of cGnRH-R-I. Functional studies in COS-7 cells indicated that cGnRH-R-III has a higher binding affinity for GnRH-II than cGnRH-I (IC50: 0.57 v 19.8 nM) and more potent stimulation of inositol phosphate production (EC50: 0.8 v 4.38 nM). Similar results were found for cGnRH-R-I, (IC50: 0.51 v 10.8 nM) and (EC50: 0.7 v 2.8 nM). Mammalian receptor antagonist 27 distinguished between cGnRH-R-I and cGnRH-R-III (IC50: 2.3 v 351 nM), and application of this synthetic peptide may facilitate delineation of receptor subtype function either in-vitro or in-vivo. The length of the C-terminal tail of cGnRH-R-III is 8 residues longer than that of cGnRH-R-I and this observation stimulated investigation of differences in ligand-induced internalisation between the two receptor subtypes. The initial rate of receptor internalisation was faster for cGnRH-R-III than for cGnRH-R-I (26%.min-1 v 15.8%.min-1). Although proteins encoded by cGnRH-R-III splice variants do not bind GnRH ligands independently and mRNAs were not detectable by Northern blot analysis, cGnRH-R-III_SV2 significantly reduced maximum ligand-binding of cGnRH-R-III, suggesting that it may impair the function of the full-length type III cGnRH receptor. It was anticipated that the two cGnRH-R subtypes may have differential roles in the regulation of luteinising hormone (LH) and follicle stimulating hormone (FSH) gene transcription through the activation of differential second messenger pathways. Three putative Src homology domain 3 (SH3) binding motifs were identified in the type III cGnRH receptor cytoplasmic C-terminal tail domain which are not present in the type I cGnRH-R and suggested the potential for differential coupling to the Mitogen Activated Protein Kinase (MAPK) cascade. To investigate this possibility, activation of the MAPK cascade via cGnRH-R-III and cGnRH-R-I was determined by quantifying elevation of phosphorylated ERK (pERK 1/2) in response to GnRH. Studies performed in COS-7 cells showed a 4-6 fold increase in ERK 1/2 phosphorylation via the type I and type III receptors within 10 minutes of GnRH-I or GnRH-II stimulation, indicating that both receptors signal through the ERK 1/2 pathway in response to cGnRH-I or GnRH-II. The responses were dose-dependent at cGnRH-R-I and cGnRH-R-III. Effects of pre-treatment with PLC and c-Src inhibitors showed that both cGnRH-Rs may activate pERK 1/2 independently of PLC but dependently upon c-Src. However, it must be noted that 100% of the PLC activity was not inhibited by PLC inhibitor as measured by inositol phosphate production at 60 minutes, and the PLC inhibitor has not been shown to inhibit PLC in the same time frame used for the pERK experiments. Mutagenesis of the individual SH3 binding motifs of cGnRH-R-III were performed and the effects on pERK 1/2 levels quantified. The results indicated that the SH3 binding motifs of cGnRH-R-III do not contribute to additional MAPK activation when compared to the native cGnRH-R-III. Both cGnRH-R-I and cGnRH-R-III were HA epitope-tagged (HA-cGnRH-R-I and HA-cGnRH-R-III) and the methodology was optimised for HA-cGnRH-R-III immuno-precipitation. Several size forms of HA-cGnRH-R-III were detectable by immuno-precipitation, facilitating characterisation of the composition of the receptor protein-protein complexes formed using a western blot approach. In summary, the abundance of cGnRH-R-III expression compared to cGnRH-R-I suggests it is probably the major mediator of pituitary gonadotroph function, and that tissue-specific recruitment of cGnRH-R-isoforms has occurred in the avian pituitary during evolution. Pharmacological profiling demonstrated that cGnRH-R-III, like cGnRH-R-I, has a higher ligand-binding selectivity and induction of inositol phosphate production in response to GnRH-II than with cGnRH-I, although cGnRH-I is established as the physiological regulator of gonadotroph function. These results suggest that evolutionary recruitment of ligand-receptor pairing for particular physiological processes does not correlate with in-vitro properties such as highest ligand-binding affinity or efficacy of inositol phosphate production. Therefore evolutionary plasticity has occurred in the tissue-specific adoption of GnRH ligand and receptor subtypes for regulation of particular physiological functions in birds.
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15

Stavrou, Emmanouil. "Regulation of FOXO transcription factors by gonadotropin-releasing hormone." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5686.

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G protein-coupled receptors (GPCRs) are a large family of trans-membrane receptors that transmit signals from extracellular stimuli to target intracellular signal transduction pathways. The gonadotropin-releasing hormone receptor (GnRH-R) is a GPCR which binds the decapeptide GnRH. In the pituitary gonadotrope, GnRH stimulates gonadotropin (LH and FSH) biosynthesis and secretion to regulate reproduction. GnRH and the GnRH-Rs are also present in many extra-pituitary tissues, although their role at these sites remains largely undetermined. GnRH-Rs are known to recruit a diverse array of signalling pathway mediators in different cell-types. These include; Gq/11-PLCβ-IP3/DAG-Ca2+/PKC signalling, monomeric G-proteins and integrins to mediate cell adhesion and migration, the activation of the major members of the mitogen-activated protein kinase (MAPK) super-family (extracellular signal-regulated kinase (ERK), c-Jun N-terminal Kinase (JNK) and p38MAPK), and β-catenin and other mediators of the canonical Wnt signalling pathway. This thesis describes the regulation of Forkhead Box O (FOXO) transcription factors by GnRH. The mammalian FOXO transcription factors, FOXO1, FOXO3a and FOXO4, are emerging as an important family of proteins that modulate the expression of genes involved in cell-cycle regulation, induction of apoptosis, DNA damage repair and response to oxidative stress. In this thesis, emphasis is placed on delineating the novel role of FOXO transcription factors in mediating two important and widely-researched areas of GnRH biology. Firstly, the role of FOXO transcription factors in mediating cell-growth inhibition in response to GnRH treatment is assessed in a heterologous HEK293/GnRH-R expressing cell line. Secondly, the role of transcription factors in regulating luteinising hormone-β (LHβ)-subunit expression is investigated in the LβT2 gonadotrope cell line. Activation of the GnRH-R can inhibit cell proliferation and induce apoptosis in certain tumour-derived cell lines. Several studies have reported that these events can occur as a result of changes in the expression profiles of specific cell-cycle regulatory and apoptotic genes, many of which are FOXO-target genes, including GADD45, FasL, p21Cip1 and p27Kip1. In this thesis, a role for FOXOs in targeting the expression of several of these genes in response to GnRH is assessed, highlighting a specific role for FOXO3a in mediating GADD45 and FasL expression. The signalling mechanisms through which FOXO3a regulates GADD45 expression in response to GnRH is also described. Finally, a stable FOXO3a-knock-down cell line was generated in order to further examine FOXO3a involvement in GnRH-induced cell-growth inhibition. GnRH is an essential regulator of the reproductive process by stimulating the synthesis of LH and FSH in pituitary gonadotropes, thereby regulating gametogenesis and steroidogenesis. Diverse signalling pathways have been reported to regulate LHβ-subunit expression in response to GnRH, including the ERK/JNK/p38MAPK cascades and factors such as Egr1, SF1 and β-catenin. In the second part of this thesis, the role of FOXOs in regulating LHβ-subunit expression in response to GnRH is described. The data presented suggests that GnRH can regulate LHβ-subunit expression through both indirect and direct FOXO3a-mediated mechanisms. Firstly, FOXO3a was found to regulate Egr1 expression to indirectly target LHβ-promoter activity. Secondly, a role for β-catenin as a FOXO3a co-factor to directly regulate LHβ-subunit expression, together with Egr1 and SF1, is also proposed. FOXO3a expression and sub-cellular localisation was assessed and demonstrated in LβT2 cells and in adult human male pituitary sections. The research presented in this thesis adds to the diversity of signalling pathways and mediators that GnRH can target in different cellular backgrounds in order to mediate a variety of cellular processes. The antiproliferative and apoptotic effects of GnRH on tumour-derived cell lines are well-documented, and this research highlights a novel role for FOXO3a in mediating these events. The regulation of gonadotropin synthesis remains an important topic of research, and the novel implication of FOXO3a in mediating LHβ-subunit expression adds further complexity to gonadotrope physiology.
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16

Douthit, Courtney Jacqueline. "Gene expression and protein levels of GnRH isoforms and their cognate receptors in the stallion testis and spermatozoa." Thesis, Kansas State University, 2016. http://hdl.handle.net/2097/27630.

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Master of Science<br>Department of Animal Sciences and Industry<br>Teresa Douthit<br>Joann Kouba<br>Gonadotropin-releasing hormone (GnRH-I), as well as its receptor, GnRHR-I, once thought to be localized solely to the hypothalamus and anterior pituitary, have since been detected in the testis of numerous mammals. Another isoform of GnRH, GnRH-II, has been isolated from the testis of numerous mammals and binds a specific receptor, GnRHR-II. Our objective was to establish whether GnRH-I and GnRH-II, along with their specific receptors, are produced and present in the equine testis. Testicular tissue was collected from colts < 2 yr (n = 5) and stallions ≥ 2 yr (n = 10) of age during routine castrations. Total RNA extracted from testicular tissue was reverse transcribed and cDNA was subjected to conventional PCR using gene specific primers for GnRH-I, GnRHR-I, GnRH-II, and GnRHR-II. Protein was extracted and subjected to dot blot and Western blot using antibodies directed against GnRH-I, GnRH-II, GnRHR-I, or GnRHR-II. Transcripts for both ligands and receptors were detected in all testes. Product identity was confirmed by sequencing, which also clarified that unusual band sizes were the result of alternative splicing of GnRHR-II, and the retention of an intron in the GnRH-II mRNA was discovered. Prepro-GnRH-I and prepro-GnRH-II protein was detected in all stallion testes via dot blot technique. On Western blots, testicular samples from colts (n = 4) had 3-fold greater GnRHR-I levels compared to stallions (n = 7; P < 0.022). Conversely, there was a tendency for GnRHR-II protein to be greater in tissue collected from stallions compared to colts (P < 0.0756). Finally semen was collected from mature stallions (9 to 18 yr; n = 4) and purified using a discontinuous gradient. By utilizing immunocytochemistry, GnRHR-II was localized to the connecting piece of mature stallion spermatozoa. This is the first report identifying GnRH-I and -II and their receptors in the equine testis and GnRHR-II on mature stallion spermatozoa. These decapeptide hormones may act via autocrine and/or paracrine signaling to affect steroidogenesis and spermatogenesis in the stallion testis.
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17

Breuckmann, Andreas. "Untersuchungen am GnRH-System von Xiphophorus helleri." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=971092699.

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18

Pfleger, Kevin D. G. "Structural determinants of GnRH ligand-receptor interactions." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/25079.

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The aim of this thesis was to investigate how the spatial arrangements of amino acids in both the ligand and influence gonadotrophin-releasing hormone (GnRH) ligand-receptor interactions. A number of residues in the receptor extracellular loops (ECLs) have been identified as interacting directly with ligands. Therefore, these regions play a crucial role in ligand binding. Chimeric receptors, consisting of the human receptor containing the three catfish receptor ECLs in all single, double and triple combinations were produced. Certain combinations of ECLs were found to have different effects on the binding of mGnRH, [D-Trp<sup>6</sup>]-GnRH, GnRH II, [D-Lys<sup>6</sup>]-GnRH II and Antagonist 135-18. ECL3 appears to influence the binding of mGnRH, but not [D-Trp<sup>6</sup>]-GnRH, which correlates with previous studies. The difference in the binding affinity of these two ligands could be attributed to the ECLs, as their affinities at the triple-ECL substituted chimeric receptor were not significantly different to those at the wild type catfish receptor. Substitution of the ECLs did not simulate binding at the wild type catfish receptor for GnRH II, [D-Lys<sup>6</sup>]-GnRH II or Antagonist 135-18. This implies that these ligands form different interactions with GnRH receptors compared with those formed by mGnRH and [D-Trp<sup>6</sup>]-GnRH. Potential interactions between ECLs were investigated with additional mutant receptors. ECL interactions may influence ligand binding by altering the spatial arrangement or accessibility of ligand contact sites. Interactions between ECLs 2 and 3 appear to be particularly important: they are partly responsible for differences in the binding of GnRH II at the catfish compared with at the human receptor; a single residue in ECL2, namely Glu<sup>5.35</sup>, is likely to be responsible for the different affinity of GnRH II at the rat receptor compared with at the mouse and human receptors as a result of repulsion between ECLs 2 and 3; and human and chicken GnRH receptors appear to have important differences in ECLs 2 and 3 such that agonist binding at human-chicken chimeric receptors is severely affected.
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19

White, Colin D. "Dissection of GnRH receptor-G protein coupling." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3885.

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Hypothalamic gonadotropin-releasing hormone (GnRH) (GnRH I) is the central regulator of the mammalian reproductive system. Most vertebrates studied also possess a second form of GnRH, GnRH II. GnRH I acts on its cognate G proteincoupled receptor (GPCR) on pituitary gonadotropes and activates Gq/11-mediated signalling pathways to stimulate the biosynthesis and the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH). Both GnRHs have also been suggested to inhibit cellular proliferation, an action which has largely been proposed to be mediated by the coupling of the receptor to Gi/o. However, the range of G proteins activated by the GnRH receptor and the signalling cascades involved in inducing antiproliferation remain controversial. To delineate the G protein coupling selectivity of the mammalian GnRH receptor and to identify the signalling pathways involved in GnRH I-mediated cell growth inhibition, I examined the ability of the receptor to interact with Gq/11, Gi/o and Gs in Gαq/11 knockout MEF cells. My results indicate that the receptor is unable to interact with Gi/o but can signal through Gq/11. Additionally, my data do not support the suggestion of GnRH receptor-Gs interaction. Furthermore, I show that the GnRH Iinduced inhibition of cell growth is dependent on Gq/11, src and extracellular signal regulated kinase (ERK) but is independent of the activity of protein kinase C (PKC), Ca2+, jun-N-terminal kinase (JNK) or P38. Based on these findings and previous research within our group, I propose a mechanism whereby GnRH I may induce antiproliferation. Previous studies from our laboratory suggest that the GnRH receptor can adopt distinct active conformations in response to the binding of GnRH I and GnRH II. These data thus account for our hypothesis of ligand-induced selective signalling (LiSS). Given my previous results, I examined the ability of the GnRH receptor to couple to G12/13. My work indicates that the receptor can directly activate G12/13 and the downstream signalling cascades associated with this G protein family. Indeed, I provide evidence, in several cellular backgrounds, to suggest that GnRH receptor- G12/13-mediated signalling is involved in the regulation of GnRH-induced MAPK activity, SRE-driven gene transcription and cytoskeletal reorganisation. Furthermore, I propose a role for these G proteins in the transcriptional regulation of LHβ and FSHβ. Finally, I confirm previous results from our laboratory indicating that the GnRH receptor may interact with src Tyr kinase and show that GnRH I but not GnRH II may, independently of Gq/11, stimulate the Tyr phosphorylation and thus the activation of this protein. I propose that this differential signalling accounts for the distinct effects of GnRH I and GnRH II on cellular morphology and SREpromoted transcriptional activity. The research presented within this thesis provides evidence to refute published conclusions based on largely circumstantial experimental data, describes novel GnRH receptor signalling pathways and offers support for the concept of LiSS. It may assist in the development of new therapeutic compounds which selectively target one GnRH-mediated signalling pathway while bypassing others.
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20

Karunadasa, Delicia Kumari. "Embryonic development of GnRH and vomeronasal neurons." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615881.

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21

Davidson, L. "Protein-protein interactions in GnRH receptor signalling." Thesis, University of Edinburgh, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649167.

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Human embryonic kidney (HEK) 293 cells, stably expressing the rat GnRH receptor were used to investigate the mechanism of ERK activation by GnRH.  ERK activation was found to be dependent on cell adhesion to the extracellular matrix, and required an intact actin cytoskeleton. Through the use of specific pharmacological inhibitors and expression of dominant negative cDNA constructs, ERK activation was found to be mediated by the Rho family GTPase Rac1, and the non-receptor tyrosine kinases Src and focal adhesion kinase (FAK). FAK was found to function as a tyrosine phosphorylated scaffold upon which components of the ERK cascade assembled. Having established a role for Src in the activation of ERK, a proteomics study was undertaken to identify novel Src binding proteins that may be involved in the regulation of GnRH receptor signalling. Through a combination of immune-precipitation, two-dimensional gel electrophoresis, and matrix assisted laser desorption ionisation – time of flight mass spectrometry, Src was found to associate with the lipid kinase diacylglycerol kinase zeta (DGKζ). This interaction was found to be required for GnRH to stimulate DGKζ enzyme activity. By phosphorylating the second messenger molecule diacylglycerol to produce phosphatidic acid, DGKζ may play an important role in regulating GnRH receptor signalling. In this thesis, a potential mechanism of ERK activation is described for the GnRH receptor, with Src playing a key role in this pathway. In addition, Src was found to be involved in the activation of DGKζ, and is therefore implicated in the regulation of diacylglycerol signalling. This is the first report of an interaction between Src and DGKζ.
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22

Goubillon, Marie-Laure. "Étude dynamique du générateur hypothalamique à GnRH." Lyon 1, 1996. http://www.theses.fr/1996LYO1T156.

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23

McPhie, Christine A. "GnRH binding sites in the human placenta." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20682.

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Binding sites for GnRH in the human placenta differ from the well-characterised pituitary GnRH receptor. The pituitary superagonists Buserelin and Tryptorelin were found by the placenta, as were the salmon and chicken-II isoforms of GnRH, however placental binding of the GnRH agonist analogues was not enhanced compared to the two isoforms, which were not bound by the pituitary receptor. Specific activity of binding of GnRH, GnRH isoforms and GnRH agonist analogues to the human placental binding site varied with stage of gestation. The high levels observed in early trophoblast (6-8 weeks) fell to almost non-detectable levels at 12-18 weeks, before increasing to maximal levels by term. Rebinding data suggested that differential tracer degradation could not account for gestational age-related variations in binding, and decreased binding was not related to contamination of the membrane fraction by non-villous tissue. Although the specific activity of binding to placental binding sites varied with gestation, specificity was unchanged: Tryptorelin, Buserelin, chicken GnRH-II, salmon GnRH > mammalian GnRH π lamprey GnRH, chicken GnRH-I. Buserelin, Tryptorelin and chicken GnRH-II were displaced from the membrane binding site by cytosolic extracts of placenta of all stages of gestation. Cytosol fractions from 12-18 weeks displaced iodinated GnRH tracers from the binding sites of membrane preparations from the same stage of gestation to a greater extent than an excess of non-iodinated Buserelin, but did not displace tracer from term membrane binding sites to the same degree. Membrane binding and the displacement effect of cytosol were reduced in the presence of protease inhibitors, however this was due to the presence of ethanol (as a solvent) in the inhibitor cocktail. The exact nature of this ethanol effect is unknown.
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24

Santos, Marta. "Gestão da comunicação e as relações públicas da GNR: O sítio da GNR." Master's thesis, Academia Militar. Direção de Ensino, 2013. http://hdl.handle.net/10400.26/7689.

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A Internet é a marca cultural da sociedade contemporânea, denominada por Sociedade da Informação, onde a informação e serviços nela disponíveis são objeto de crescente utilização, nomeadamente os sítios. As instituições recorrem a esta ferramenta comunicacional ao serviço das relações públicas, para garantir uma comunicação mais eficiente que as aproxime dos cidadãos. Neste contexto, foi objetivo desta investigação perceber como o sítio da Guarda Nacional Republicana na Internet disponibiliza a informação institucional e os serviços online, tendo em conta as expetativas e necessidades dos cidadãos na área da segurança. Este trabalho apresenta na primeira parte o enquadramento conceptual de suporte à investigação e, na segunda parte versa-se sobre o estudo de caso do sítio da Guarda Nacional Republicana. Numa abordagem qualitativa, realizou-se a análise comparativa dos sítios dos serviços centrais de natureza operacional do Ministério da Administração Interna. Para tal, foi desenvolvida uma Tabela de Análise com cinco indicadores de avaliação, ao nível dos conteúdos, acessibilidade, usabilidade e navegabilidade, privacidade e autenticação, e serviços, onde se incluem, também, os serviços policiais e de segurança. Esta análise foi realizada por cinco especialistas das áreas de comunicação, design de comunicação, marketing, informática e jornalismo. Com os resultados deste procedimento verificou-se que, em relação à qualidade da arquitetura da informação, o sítio da Polícia de Segurança Pública obteve a classificação de nível Muito Bom, distinguindo-se dos restantes sítios analisados que conquistaram apenas a classificação de nível Bom. A Guarda Nacional Republicana destacou-se com a melhor classificação ao nível serviços policiais e de segurança. Concluiu-se com esta investigação que o sítio da Guarda Nacional Republicana é uma ferramenta de divulgação de conteúdos de cariz policial que fomenta a cidadania digital como forma de chegar até ao cidadão.<br>Abstract The Internet is a cultural brand of contemporary society, known as Information Society, where information and services available are subject to an increasing use, to wit sites. Institutions rely on this communication tool at the service of public relations, to ensure a more efficient communication which will bring citizens together. In this context, the aim of this investigation was to see how the site of the National Republican Guard on the Internet provides institutional information and online services, taking into account the needs and expectations of citizens in the area of security. The first part of this work presents the conceptual framework used as research support, and the second part is centered on the case study of the National Republican Guard site. In a qualitative approach, we made a comparative analysis of the Ministry of Internal Affairs central services sites of operational nature. To this end, we developed an Analysis Table with five evaluation indicators, the level of content, accessibility, usability and navigability, and privacy and authentication services, which also include the police and security services. This analysis was carried out by five experts in the fields of communication, communication design, marketing, information technology and journalism. With the results of this procedure, we discovered that, regarding the architectural quality of information, the site of Public Security Police was rated Very Good, distinguishing itself from other sites analyzed, which were rated only as Good. The National Republican Guard stood out with the highest score at police and security services. With this investigation, we concluded that the National Republican Guard site is a dissemination tool of police-oriented contents that fosters digital citizenship as a way to reach citizens.
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Arruda, Jalsi Tacon. "Comparação entre dois protocolos para estimulação ovariana com agonista/antagonista do hormônio liberador de gonadotrofinas (GnRH) em mulheres submetidas ao primeiro ciclo de reprodução assistida." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3814.

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Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2014-12-19T18:38:39Z No. of bitstreams: 2 Tese - Jalsi Tacon Arruda - 2013.pdf: 4216712 bytes, checksum: ec49a9884c1f4b73b53a9b224c7c4aa1 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)<br>Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-22T11:01:46Z (GMT) No. of bitstreams: 2 Tese - Jalsi Tacon Arruda - 2013.pdf: 4216712 bytes, checksum: ec49a9884c1f4b73b53a9b224c7c4aa1 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)<br>Made available in DSpace on 2014-12-22T11:01:46Z (GMT). No. of bitstreams: 2 Tese - Jalsi Tacon Arruda - 2013.pdf: 4216712 bytes, checksum: ec49a9884c1f4b73b53a9b224c7c4aa1 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-07-01<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES<br>Infertility affects more couples and assisted reproduction techniques offer a possibility of treatment and the chance of having a child. Thus, the first attempt to ovulation induction is critical to the success of the cycle or even for future attempts is successful. Objective: To compare the protocols using GnRH agonist or antagonist for ovarian stimulation in normo-responders undergoing the first cycle of IVF/ICSI. Methods: we conducted a literature review on the history of ovulation induction controlled by medications. From the data available in the database of electronic medical records SISFERT used in the Laboratory of Human Reproduction (LabRep-HC-FM-UFG) a comparative retrospective observational study was conducted with 50 patients divided into two groups according to protocol: GnRH-agonist (leuprolide acetate 1 mg/day short protocol) or GnRHantagonist (Cetrorelix 0.25 mg/day), which received 150 IU/day of rFSH (follitropin alpha) and 250 µg of rhCG (alpha-coriogonadotrofina) in both groups. Results: Statistically significant differences were observed in the days of stimulation with rFSH, total dose of gonadotropin, days of use of GnRH, GnRH dose and total number of follicles (≥ 16 mm) on the day of the group rhCG GnRH agonist. There was no significant difference in other parameters, however, the number of oocytes retrieved was slightly higher in the GnRH agonist, but fertilization rate was higher in the GnRH-antagonist. Pregnancy rates and clinical chemistry were similar in both groups. Conclusions: although no significant differences in the results analyzed, the use of flexible antagonist protocol facilitates the handling and enables the patient using much lower doses of gonadotropins itself as the antagonist, reducing the cost of treatment when compared to the protocol with GnRH agonist.<br>A infertilidade afeta cada vez mais casais e as técnicas de reprodução assistida oferecem uma possibilidade de tratamento e a chance de ter um filho. Assim, a primeira tentativa de indução da ovulação é fundamental para o sucesso do ciclo ou, até mesmo, para que tentativas futuras sejam bem sucedidas. Objetivo: comparar os protocolos utilizando agonista ou antagonista do GnRH para estimulação ovariana em pacientes normo-respondedoras submetidas ao primeiro ciclo de FIV/ICSI. Métodos: foi realizada uma revisão da literatura sobre a história da indução da ovulação controlada por medicamentos. A partir dos dados disponíveis no banco de prontuários eletrônicos SISFERT utilizado pelo Laboratório de Reprodução Humana (LabRep–HC–FM–UFG), um estudo observacional retrospectivo comparativo foi conduzido com 50 pacientes distribuídas em dois grupos de acordo com o protocolo: GnRH-agonista (acetato de leuprolide 1 mg/dia protocolo curto) ou GnRH-antagonista (cetrorelix 0,25 mg/dia); e que receberam 150 UI/dia de rFSH (alfa-folitropina) e 250 µg de rhCG (alfa-coriogonadotrofina) em ambos os grupos. Resultados: foram observadas diferenças estatisticamente significativas nos dias de estimulação com rFSH, dose total de gonadotrofina, dias de uso do GnRH, dose total de GnRH e o número de folículos (≥ 16 mm) no dia do rhCG no grupo GnRH-agonista. Não houve diferença significativa nos outros parâmetros, no entanto, o número de oócitos recuperados foi ligeiramente maior no grupo GnRH-agonista, mas a taxa de fertilização foi maior no grupo GnRH-antagonista. As taxas de gravidez química e clínica foram similares nos dois grupos. Conclusões: embora não tenha havido diferenças significativas nos resultados analisados, o uso do protocolo flexível com antagonista facilita a manipulação pela paciente usuária e possibilita doses menores tanto de gonadotrofinas quanto do próprio antagonista, reduzindo o custo do tratamento quando comparado ao protocolo com agonista do GnRH
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26

Hussein, Hassan. "Untersuchungen zur ovariellen Reaktion im Rahmen der Zyklussynchronisation mittels GnRH-PGF2[alpha] [GnRH-PGF2-alpha] und deren Graviditätsresultat bei Milchrindern." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=967778794.

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27

Periasamy, Vinod Babu [Verfasser]. "Development of kisspeptin-GnRH neural circuit in utero and mapping of GnRH receptor neurons in mice brain / Vinod Babu Periasamy." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2017. http://d-nb.info/1200408500/34.

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28

Junqueira, Flávia Raquel Rosa. "Uso do análogo do GnRH para diagnóstico de puberdade precoce." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/17/17145/tde-21062008-112920/.

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Introdução - A puberdade precoce verdadeira ou dependente de GnRH apresenta importante morbidade: a baixa estatura, conseqüência da rápida progressão da idade óssea, além das seqüelas psico-emocionais do desenvolvimento sexual secundário precoce. Daí a importância da realização de um diagnóstico precoce e preciso, a fim de que a terapêutica adequada seja instituída o quanto antes. O uso do análogo do GnRH (aGnRH) em teste diagnóstico vem sendo utilizado com este objetivo. Neste estudo avaliou-se os valores de corte para o diagnóstico de puberdade precoce verdadeira, usando-se o teste do aGnRH. Material e métodos - Estudo prospectivo, com 44 meninas, com desenvolvimento dos caracteres sexuais secundários antes dos 8 anos de idade, atendidas no Ambulatório de Ginecologia Infanto-Puberal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Realizou-se, em todos os casos, o teste do aGnRH, que consistiu na coleta de amostra sanguínea basal para dosagem de FSH e LH, seguida da aplicação subcutânea de 500µg de acetato de leuprolida (Lupron®). Novas amostras sanguíneas foram realizadas após 3 horas, para dosagem de FSH e LH, e após 24 horas da aplicação, para dosagem de estradiol Compararam-se os níveis de LH e FSH basais, de 3 horas e a relação LH/FSH obtida, além do estradiol de 24h, com a evolução clínica das pacientes. Este foi o padrão ouro utilizado para análise do teste, sendo que, após 6 meses, as pacientes foram divididas em 2 grupos: puberdade progressiva (puberdade precoce verdadeira) e não-progressiva. Para análise estatística, utilizou-se curvas ROC, estabelecendo-se sensibilidade, especificidade e melhor nível de corte para o diagnóstico de puberdade precoce verdadeira, para os diferentes critérios analisados. Além disso, avaliou-se a concordância entre os diversos tipos de análise do teste, através do coeficiente kappa. Resultados - O LH de 3 horas apresentou valor de corte > 4,5 mUI/mL, sensibilidade 59,1% e especificidade 86,4%, com área sobre a curva de 0,723. O valor de kappa foi de 0,45, com concordância de 0,73. O estradiol de 24 horas apresentou valor de corte > 40,6 pg/mL, sensibilidade 70% e especificidade 73,7%, com área sobre a curva de 0,703. O valor de kappa foi de 0,436, com concordância de 0,718. Dentre todos os critérios analisados, o melhor deles foi a relação LH/FSH de 3 horas, com valor de corte > 0,14, sensibilidade 72,7% e especificidade 77,3%, com área sobre a curva de 0,771. O valor de kappa foi de 0,5, com concordância de 0,75. Conclusões - Em nossa avaliação, a relação LH/FSH de 3 horas foi superior ao valor de LH de 3 horas ou estradiol de 24 horas, que haviam sidos os melhores critérios diagnósticos no trabalho pioneiro na utilização deste teste.<br>Introduction - True or GnRH-dependent precocious puberty involves important morbidity such as short stature due to the rapid progression of bone age, as well as psycho-emotional sequels of precocious secondary sexual development. Thus, it is important to make an early and precise diagnosis so that appropriate treatment can be instituted as early as possible. The GnRH analogue (aGnRH) in the diagnostic test has been used for this purpose. In the present study, the sensitivity and specificity of different laboratory criteria for the diagnosis of true precocious puberty were compared using the aGnRH test. Material and methods - This was a prospective study conducted on 44 girls with the development of secondary sexual traits before 8 years of age attended at the Childhood-Pubertal Gynecology Outpatient Clinic of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. The aGnRH test was performed in all cases, consisting of collection of a basal blood sample for the determination of FSH and LH, followed by subcutaneous application of 500 µg leuprolide acetate (Lupron®). New blood samples were obtained after 3 hours, for the determination of FSH and LH, and after 24hours of application, for determination of estradiol. Basal LH and FSH levels and levels after 3 hours, the LH/FSH ratio obtained 3 hours after the administration of 500 µg Lupron®, and 24 hour estradiol levels were compared with the clinical course of the patients. This was the gold standard used for the analysis of the test and after 6 months the patients were divided into 2 groups: progressive puberty (true precocious puberty) and non-progressive puberty. ROC curves were used for statistical analysis, with the determination of the sensitivity, specificity and best cut-off value for the diagnosis of true precocious puberty of the different criteria analyzed. In addition, the agreement of the various types of test analysis was evaluated using the kappa coefficient. Results - Three hour LH presented a cut-off value of > 4.5 mIU/mL, 59.1% sensitivity and 86.4% specificity, with an area under the curve of 0.723. The kappa value was 0.45, with 0.73 agreement. Twenty-four hour estradiol presented a cut-off value of > 40.6 pg/mL, 70% sensitivity and 73.7% specificity, with an area under the curve of 0.703. The kappa value was 0.436, with 0.718 agreement. The best of all criteria used was the 3 hour LH/FSH ratio, with a cut-off value of > 0.14, 72.7% sensitivity and 77.3% specificity, with an area under the curve of 0.771. The kappa value was 0.5, with 0.75 agreement. Conclusions - In the present evaluation, the 3 hour LH/FSH ratio was superior to the 3 hour LH value and the 24 hour estradiol value, which had been the best diagnostic criteria in the pioneering study using this test.
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Montenegro, Ivan Sereno. "Avaliação da estimulação ovariana com uso de análogos do gnrh." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/56618.

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Introdução: Novos medicamentos trouxeram um considerável aumento na chance de gravidez no momento em que a estimulação ovariana controlada permitiu aumentar o número de oócitos a serem recuperados e, consequentemente, um maior número de embriões para serem transferidos. Os análogos de hormônio liberador de gonadotrofina, em associação com gonadotrofinas, trouxeram a solução para um dos problemas da estimulação ovariana controlada: o pico precoce de hormônio luteinizante, que prejudicava a coleta de oócitos em torno de 20% dos casos. Rotineiramente, usamos o protocolo com agonista, mas a possibilidade do uso de antagonistas resulta em maior facilidade de manuseio pelo usuário, envolve um único menstrual ciclo e dispensa orientação para uso de drogas, no final do ciclo anterior. Assim, buscamos avaliar o uso dos dois protocolos e analisar seus resultados. Objetivos: Análise e comparação de dados entre dois protocolos de indução (longo com agonista e flexível com antagonista) em pacientes submetidas a técnicas de reprodução assistida na SEGIR – Serviço de Ecografica, Genética e Reprodução Assistida – Porto Alegre. Métodos: Estudo transversal comparando os resultados intermediários com o uso de dois diferentes protocolos de estimulação ovariana com de agonista versus antagonista do hormônio liberador de gonadotrofina para técnicas de reprodução assistida. A análise estatística dos dados recuperados (idade, índice de massa corpórea, número de oócitos recuperados, número de oócitos fertilizados, número de oócitos clivados, dose total de FSH utilizada e ocorrência de síndrome do hiperestímulo ovariano) foi realizada através de teste t de Student para dados paramétricos e análise de covariância para as variáveis dependentes, calculados com o programa SPSS 16.0. Resultados: Um total de 50 pacientes preencheram os critérios para inclusão no estudo entre janeiro e março no ano de 2010, sendo 25 em cada grupo. Houve diferença estatística apenas na idade média entre os grupos (p=0,031). Não houve diferença estatística para os demais dados analizados (índice de massa corpórea, número de oócitos recuperados, número de oócitos fertilizados, número de oócitos clivados e dose de FSH utilizada) entre os grupos. Não houve casos de síndrome do hiperestímulo ovariano. Conclusão: Ambos protocolos os são iguais em termos de resultados. O agonista tem vantagens sobre o agendamento do procedimento, mas leva muito tempo para começar a estimulação e tem a possibilidade de iniciar a medicação em uma paciente grávida. Somado a isso, temos a possibilidade de ter síndrome do hiperestímulo ovariano como complicação. No grupo antagonista, está claro a maior facilidade de uso da medicação e o início mais rápido da estimulação ovariana.<br>Background: New medications have brought a considerable increase in the chance of pregnancy at the time that controlled ovarian stimulation allowed an increase in the number of oocytes to be recruited and, consequently, a greater number of embryos to be transferred. The gonadotropin-releasing hormone analogues, in association with gonadotropins, brought the solution to one of the controlled ovarian stimulation's problems: the early peak of luteinizing hormone, which harmed the oocytes collection around 20% of the cases. We, routinely, used the agonist protocol, but the possibility of antagonists usage results in greater ease of handling by the user, involves a single menstrual cycle and dispensation guidance for drug use, at the end of the previous cycle. Thus we seek to evaluate the use of the two protocols and analyze their results. Objective: Analysis and compare data between two induction protocols (long agonist and flexible antagonist) in patients submitted an assisted reproduction technique in SEGIR – Serviço de Ecografia Genética e Reprodução assistida – Porto Alegre. Methods: Cross-sectional study comparing the intermediate results with the use of two different ovarian stimulation protocols with gonadotropin-releasing hormone agonist versus antagonist to assisted reproductive techniques. The statistical analysis of the retrieved data (age, body mass index, number of oocytes recovered, number of fertilized oocytes, number of oocytes cleaved, total dose of FSH used and occurrence of ovarian hyperstimulation syndrome) was performed by Student t test for parametric data and analysis of covariance for the dependent variables, calculated with the program SPSS 16.0. Results: A total of 50 patients, 25 in each group, met the criteria for inclusion in the study between January and March in the year 2010. There was statistically significant difference only in the middle ages between the groups (p = 0 .031). There was no statistical difference for the remaining data analyzed (body mass index, number of oocytes recovered, number of fertilized oocytes, number of oocytes cleaved and dose of FSH utilized) between the groups. There were no cases of ovarian hyperstimulation syndrome. Conclusion: Both protocols are equal in terms of results. The agonist has advantages about scheduling of the procedure, but it takes too long to start the stimulation and have possibility to start medication in a pregnant patient. Added to this, we have the possibility of getting the ovarian hyperstimulation syndrome as complication. In the antagonist group, is clear the ease-of-use of the medication and the fastest start of the ovarian stimulation.
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Hempelt, Daniela. "Analytische Untersuchungen zur Aggregation von Cetrorelix und weiteren GnRH-Antagonisten." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-99807.

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In der vorliegenden Arbeit werden Beiträge zur Entwicklung neuer qualitativer und quantitativer analytischer Methoden für die Untersuchung von Cetrorelix und anderen GnRH-Antagonisten während des Aggregationsprozesses vorgestellt. Für die qualitative Untersuchung von GnRH-Antagonisten wurden am Modellpeptid Cetrorelix massenspektrometrische Methoden entwickelt und auf weitere GnRH-Antagonisten übertragen. Eingesetzt wurde sowohl die ESI-TOF-MS als auch die MALDI-TOF-MS. Beide massenspektrometrische Verfahren zeigten für die untersuchten GnRH-Antagonisten polydisperse Verteilungen oberhalb der fluoreszenzspektroskopisch bestimmten kritischen Aggregatbildungskonzentration (cac). Bei den ESI-TOF-MS-Messungen konnte ein stark von Cetrorelix abweichendes Aggregationsverhalten für Ozarelix beobachtet werden. Für die Quantifizierung des Aggregatanteils in Cetrorelix- bzw. Ozarelixproben wurde eine Methode mit der MALDI-TOF-MS etabliert, die Untersuchungen an pharmazeutisch relevanten Peptidhormon-Formulierungen ermöglicht. Systematische Untersuchungen zum Einfluss verschiedener An- und Kationen sowie deren Konzentrationen auf die Cetrorelixaggregation erfolgten mit der Fluoreszenzspektroskopie. Die erhaltenen Ergebnisse ermöglichen eine bessere Charakterisierung der Aggregation und lassen Abschätzungen über das Aggregationsverhalten von Cetrorelix in verschiedenen Medien mit unterschiedlichen Elektrolyten zu. Mit dem Einsatz der Transmissionselektronenmikroskopie war es erstmals möglich, Aggregate von GnRH-Antagonisten visuell darzustellen.
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31

Borges, João. "As Operações Especiais na GNR." Master's thesis, Academia Militar. Direção de Ensino, 2010. http://hdl.handle.net/10400.26/8239.

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As Operações Especiais são uma área muito sensível devido à perigosidade e complexidade da sua missão. É a esse tema que este trabalho está subordinado, mais especificamente “As Operações Especiais na GNR”. Com a aprovação da lei nº 63/2007 de 6 de Novembro que aprovou a Lei Orgânica da GNR, deu-se uma reestruturação na Guarda em geral, sendo que neste trabalho irão ser referidas as alterações que deram origem ao Grupo de Intervenção de Operações Especiais assim como a anterior estrutura do GIOE. Definir a actual estrutura para perceber quais as valências que o GIOE deve ter no seu interior por forma a maximizar as suas intervenções do ponto de vista da segurança e da eficácia. O trabalho foi dividido em duas partes: a primeira que gira em torno da pesquisa bibliográfica sobre o tema, onde é abordada uma muito breve história da Guarda Nacional Republicana e onde se explora o Grupo de Intervenção de Operações Especiais assim como outras forças de Operações Especiais; a segunda parte que é destinada à parte prática, onde se apresentam a metodologia, onde se fazem as análises às entrevistas que foram realizadas e de onde se retiram as conclusões. Metodologicamente foram realizadas entrevistas semi-directivas, na generalidade a oficiais especializados em Operações Especiais, pelos vastos conhecimentos que têm nessa área, assentando ainda o trabalho na análise bibliográfica e na legislação disponível. Com a investigação elaborada conclui-se que a passagem de Companhia para Grupo se justifica, sendo que este precisa de absorver algumas competências formais tais como um núcleo de negociação, um núcleo de Operações e informações e uma Secção de Combate ao Crime Violento. Na área da Doutrina e Formação impõe-se a devida reestruturação.<br>Abstract Special Operations are a sensitive area, due to the danger and complexity of his mission. The theme of this work is specifically, “The Special Operations in GNR”. With the approval of the Law Nºº 63/2007 of 6 November, begins a restructuration in the GNR. In this work it will be referred the modifications that origin «Intervention Group of Special Forces», as well as the last and the actual structure of GIOE. The objectives of this investigation are defining the actual structure of GIOE and understanding what should be the valences that it should have, so that could maximize their interventions by a safer and effective way. The work has been divided in two: the first part talks about the bibliographic research, about the theme, where a short story about the GNR is made and where the «Intervention Group of Special Forces» is explored. The second part is the practical one, where the methodology is presented, the analyses to the interviews are made as well as the conclusions. Methodologically were realized semi-directive interviews, generally to officers with specialization in Special Operations, because of the vast knowledge they have in that area, and also settling the work on some of the bibliographic analyses and some legislation. After the investigation ended, it has been concluded that the passage from Company to Group justify, despite needing to absorb some formal competences, formally, such as: a cell of negotiation, a cell of Operations and Information, a Section of Combat to Violent Crimes, and structuring correctly the area of doctrine and formation.
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Sauer, Franziska. "Untersuchungen zu Schlachtkörperqualität und Ebergeruchsstoffen bei mit einem GnRH-Analogon geimpften, chirurgisch kastrierten und intakten männlichen Mastschweinen." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-167957.

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Untersuchungen zu Schlachtkörperqualität und Ebergeruchsstoffen bei mit einem GnRH-Analogon geimpften, chirurgisch kastrierten und intakten männlichen Mastschweinen Franziska Sauer Universität Leipzig, Medizinische Tierklinik, Leipzig, Deutschland Zielstellung Ziel der vorliegenden Studie war, Auswirkungen der Impfung gegen Ebergeruch bei männlichen Mastschweinen in konventioneller Haltung zu untersuchen und mit intakten Mastebern und Kastraten zu vergleichen. Tiere und Methode Insgesamt 348 männliche Mastschweine wurden in vier Gruppen wie folgt unterteilt: Zwei Gruppen enthielten mit Improvac® geimpfte Schweine (1. Impfung 11. Lebenswoche (LW)): Gruppe 1: n=84, 2. Impfung 18. LW, Gruppe 2: n=83, 2. Impfung 21. LW. Gruppe 3 bestand aus 90 Kastraten und Gruppe 4 aus 91 unkastrierten männlichen Mastschweinen. Die Schweine wurden im Alter von 26 bzw. 27 Wochen geschlachtet. Mast- und Schlachtleistung, das Fettsäuremuster im Rückenfett sowie Hodengewicht, Hodenhistologie und Ebergeruchsstoffe im Rückenfett wurden untersucht. Ergebnisse GnRH-geimpfte Schweine wiesen eine bessere Futterverwertung als chirurgisch kastrierte auf. Die Schlachtkörper der Geimpften hatten einen signifikant höheren Magerfleischanteil und weniger Rückenfett als die der Kastraten und erzielten dadurch einen höheren Schlachterlös. Das Fettsäuremuster der geimpften Schweine gleicht im Hinblick auf die Menge an PUFA eher den intakten als den chirurgisch kastrierten. In früherem Alter geimpfte Schweine zeigen histologisch eher eine Hodenhypoplasie, später geimpfte eher eine Hodenatrophie. Ebergeruchsstoffe im Rückenfett waren in beiden Impfgruppen und bei den Kastraten signifikant niedriger als bei intakten Mastebern. Schlussfolgerung Die Impfung männlicher Schweine mit Improvac® ist eine tierschutzgerechte, praktikable und wirtschaftliche Alternative zur Vermeidung von Ebergeruch. Literatur Sattler et al: BMTW 2014; 127:10-16 Sauer et al: WTM 2014;101:103-109 franziska.sauer@vetmed.uni-leipzig.de
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33

Silveira, Marina Augusto. "Controle neuroendócrino da reprodução: fatores que modulam a atividade de neurônios GNRH e kisspetina." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-16112017-175827/.

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Neurônios GnRH e kisspeptina representam as populações neuronais de maior importância no controle da reprodução. Estradiol liga-se ao seu receptor expresso pelos neurônios kisspeptina para regular a libertação de GnRH. No modelo animal OVX+E a atividade do neurônio GnRH e pico de LH é depende do estradiol e hora do dia. Nesse estudo, embora a taxa de disparo dos neurônios GnRH seja similar entre os grupos, o padrão dos potenciais revelou uma mudança para maior duração do estouro em camundongos no proestrous, além do fato de uma maior resposta da hipófise. A prolactina tem grande impacto na modulação do eixo HPG e kisspeptina são mediadores dos efeitos da prolactina sobre a reprodução. Uma pequena porcentagem de neurônios de kisspeptina do AVPV foi indiretamente despolarizada pela prolactina. Este efeito requeria a via de sinalização PI3K. Camundongos portadores de inativação de Stat5a/b em células kisspeptina exibiram um início precoce de ciclicidade estro, indicando que os fatores de transcrição STAT5 exercem um efeito inibitório sobre o momento da puberdade.<br>GnRH and kisspeptina neurons represent the most important neuronal populations in the control of reproduction. Estradiol binds to its receptor expressed by the kisspeptina neurons to regulate the release of GnRH. In the animal model OVX+E the activity of the GnRH neuron and LH surge is dependent of estradiol and time of day. In this study, although the firing rate of GnRH neurons was similar between groups, the pattern of potentials revealed a change to longer burst duration in mice in proestrous, and the pituitary response was greater in this group. Prolactin has impact on HPG axis modulation and kisspeptin is a mediator of the effects of prolactin on reproduction. A small percentage of AVPV kisspeptin neurons were indirectly depolarized by prolactin. This effect required the PI3K signaling pathway. Mice bearing Stat5a/b inactivation on kisspeptin cells exhibited an early onset of estrus cyclicity, indicating that STAT5 transcription factors exert an inhibitory effect on the time of puberty.
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34

Vosges, Mélanie. "Effets neuroendocrines des perturbateurs endocriniens chez le poisson zèbre (Danio rerio) : étude du système à GnRH." Thesis, Tours, 2010. http://www.theses.fr/2010TOUR4035/document.

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A ce jour, les effets des perturbateurs endocriniens (PE) sur les circuits neuroendocrines contrôlant la fonction de reproduction ont fait l’objet de très peu de travaux. Chez les vertébrés, l’élément majeur du contrôle central de la fonction de reproduction est la GnRH (Gonadotropin-Releasing Hormone). Le développement et l’activité des neurones à GnRH sont finement régulés, notamment par les hormones stéroïdes, ce qui les rend potentiellement sensibles aux PE. L’objectif de ce travail était d'étudier les effets neuroendocrines des xéno-œstrogènes chez le poisson zèbre (Danio rerio). Nous montrons que le 17α-éthinylestradiol (EE2) et le nonylphénol (NP) perturbent l'ontogenèse du système à GnRH au cours du développement précoce. De plus, nous démontrons que ces effets impliquent des récepteurs des œstrogènes. Parallèlement, nous mettons en évidence l’effet inducteur de l’EE2 et du NP sur l'expression de l’aromatase cérébrale, l’enzyme de synthèse des œstrogènes. L’ensemble de ces données souligne la nécessité de considérer les réseaux neuroendocrines comme des variables critiques et sensibles dans le domaine de la perturbation endocrinienne<br>Until now, studies dedicated to the actions of endocrine disrupting chemicals (EDCs) on the reproductive axis have focused on the gonads and peripheral organs leaving virtually unexplored their actions on neuroendocrine circuits controlling reproduction. In vertebrates, gonadotropin-releasing hormone (GnRH) is the key factor controlling the activity of the reproductive axis. The development and functioning of GnRH neurons are finely tuned, notably by sex steroids, making these neurons potential targets of EDCs. The aim of this work was to explore the neuroendocrine effects of xenoestrogens in the zebrafish (Danio rerio). We show that 17α-ethinylestradiol (EE2) and nonylphenol (NP) disrupts the ontogeny of GnRH system during zebrafish early life stage. Moreover, we demonstrate that these effects involve functional estrogens receptors. In parallel, we report the inducing effects of EE2 and NP on the expression of brain aromatase protein, the enzyme responsible for estrogen biosynthesis. Altogether, these results highlight the need to consider neuroendocrine networks as critical and sensitive endpoints in the field of endocrine disruption
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35

Dorling, A. A. V. "Sex steroid regulation of gonadotrophin-releasing hormone (GnRH) neurons." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598603.

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Prior studies in the laboratory using quantitative <i>in situ</i> hybridisation and transgenic methodologies have shown that estrogen suppresses GnRH gene transcription and GnRH mRNA expression at times of negative feedback. Using the same approaches, I demonstrated that the positive feedback actions of estrogen were not coupled to alterations of GnRH gene expression. Recent RT-PCR studies identified estrogen receptor (ER)b transcripts in subpopulations of GnRH neurons in the mouse. To assess the presence of functional ERs in GnRH neurons, I undertook various gonadectomy-steroid replacement paradigms in several new transgenic reporter mouse line in which multiple estrogen response elements (EREs) drive the expression of LacZ (EREZ mice). Others have shown that this construct provides a functional reporter of ER-regulated gene transcription <i>in vitro</i> and I demonstrated its functionality in the uterus of EREZ mice. However, LacZ expression in the brain did not change in response to estrogen treatment and did not, therefore, enable us to evaluate the GnRH neurons. One possible reason for this failure is the recent discovery that the orphan nuclear receptors, termed estrogen receptor-related receptors (ERRs), constitutively transactivate EREs. To evaluate this further, I used <i>in situ</i> hybridisation to examine the topography of ERRa and ERRg expression in the mouse brain. I further demonstrated an estradiol-dependent decrease in ERRg expression in specific brain regions, suggesting a novel mechanism through which estradiol may regulate gene expression in the brain. Finally, I examined the negative feedback actions of estrogen upon GnRH neurons by evaluating LH levels and GnRH mRNA expression in knockout mice lacking either ERa or ERb.
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Li, Wenqin. "Novel intranasal GNRs-DNA vaccines against human papillomavirus infection." Thesis, University of Strathclyde, 2015. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=28807.

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37

Intriago, Rachel Elizabeth. "Role and regulation of DUSP-1 in GnRH signaling." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1465076.

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Thesis (M.S.)--University of California, San Diego, 2009.<br>Title from first page of PDF file (viewed June 19, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 55-57).
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38

Castillo, Farfán Juan Carlos. "Ciclos de fecundación in vitro y maduración final con agonista GNRH: Explorando dosis bajas de HCG para soporte de fase lutea." Doctoral thesis, Universitat de València, 2010. http://hdl.handle.net/10803/52180.

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La hormona gonadotropina coriónica humana (hCG) se emplea de forma rutinaria para inducir la maduración final ovocitaria en ciclos de fecundación in vitro (FIV). Sin embargo, su utilización está relacionada con la aparición del Síndrome de Hiperestimulación Ovárica (SHO), especialmente cuando ciertos factores de riesgo están presentes, principalmente la presencia de un número elevado de folículos. Este riesgo puede ser drásticamente disminuido sustituyendo la hCG por un agonista GnRH como inductor de la maduración final en ciclos FIV con antagonistas GnRH. Aunque, este uso se asocia a una alta tasa de aborto temprano ocasionada por una fase lútea deficiente. La función del cuerpo lúteo se ve seriamente comprometida con el empleo del agonista GnRH (luteólisis), sin embargo, la potente acción luteotrópica de la hCG puede ser beneficiosa empleando dosis pequeñas como suplemento en la fase lútea y sin incrementar el riesgo de SHO. En un esfuerzo por reducir la tasa de abortos clínicos asociada al empleo de agonista GnRH, la presente tesis estudia la utilización de pequeñas dosis de hCG como suplemento de la fase lútea con el objetivo de rescatar el cuerpo lúteo, normalizar las tasas de embarazo y gestación evolutiva; además de reducir la presentación del SHO en la paciente con alta respuesta a la estimulación ovárica en ciclos FIV.<br>Human gonadotropin chorionic hormone (hCG) is widely used to induce final follicular maturation in in vitro fertilization cycles (IVF). However, its use is closely related to Ovarian Hyperstimulation Syndrome (OHSS) genesis, especially when certain risk factors are present, mainly a high number of recruited follicles. This risk may be drastically reduced, substituting hCG by a GnRH agonist for triggering in GnRH antagonist cycles. Nonetheless, this protocol is linked to high rates of early pregnancy loss due to a deficient luteal phase. Corpus luteum function is seriously compromised when a GnRH agonist is used for triggering (luteolysis), however, the potent luteotrophic action of hCG may be of benefit if low doses are employed for supplementing luteal phase, without increasing OHSS risk. In an effort to reduce early pregnancy losses associated to the use of GnRH agonist for triggering, this PhD. Thesis focuses on the use of low doses of hCG as luteal phase support with the aim of rescue corpus luteum function, normalizing pregnancy and on-going pregnancy rates; and at the same time reducing the frequency of OHSS in high responders to ovarian stimulation in IVF cycles.
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39

Silva, Guilherme Costa de Oliveira e. "Análise ultrassonográfica, comportamental e produtiva dos efeitos do tratamento com análogo de GnRH em fêmeas de avestruz (Struthio camelus)." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-08102012-161442/.

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A falta de conhecimento sobre a reprodução do avestruz dificulta o desenvolvimento da sua criação comercial devido a uma baixa eficiência reprodutiva. O objetivo deste estudo foi avaliar a ação da aplicação de um análogo de GnRH (lecirelina - Gestran Plus®) na indução da ovulação em fêmeas adultas de avestruz. Primeiramente, um grupo de 10 fêmeas foi avaliado para determinação de seu status reprodutivo, por meio da mensuração das concentrações séricas de estradiol e progesterona (coletas de sangue 3x/semana); da observação do comportamento reprodutivo; da determinação do desenvolvimento ovariano por exame ultrassonográfico (a cada 21 dias); e pela postura de ovos. Após o término desta primeira fase, as fêmeas foram separadas em grupo controle (n = 3) e grupo tratado (n = 6). A cada semana, 2 fêmeas do grupo tratado eram selecionadas para a aplicação intramuscular de 1ml (25&#956;l) de lecirelina, e os seus efeitos avaliados pela análise das concentrações séricas de estradiol, progesterona e corticosterona (0h, 6h, 24h, 48h e 96h pós-aplicação); pela verificação do desenvolvimento ovariano e ocorrência de ovulação através de exames ultrassonográficos (24h, 48h e 96h); pela observação de comportamento reprodutivo (0h, 48h e 96h) e pela postura de ovos. O tratamento foi repetido no mesmo animal a cada 21 dias e em cada tratamento realizado, 2 fêmeas do grupo controle eram submetidas às mesmas análises. Os resultados indicam que a aplicação de lecirelina foi capaz de induzir a ovulação em 77% dos tratamentos realizados, com postura de ovos normais em 50% das induções. Assim, o tratamento proposto foi considerado eficiente na indução da ovulação em fêmeas de avestruz desde que seja aplicado em fêmeas que apresentem ovário bem desenvolvido.<br>The lack of knowledge about the ostrich reproduction delays the development of the ostrich commercial breeding due to a low reproductive performance. The aim of this study was to evaluate the effect of the application of an analog of GnRH (Lecirelin - Gestran Plus®) for induction of ovulation in adult female ostriches. Initially, a group of 10 adult female ostriches were evaluated in order to determine their reproductive status, by measuring serum levels of estradiol and progesterone (blood sampling - 3 times a week), by the observation of reproductive behavior, by the evaluation of the ovarian development through ultrasound examination (repeated every 21 days) and by the egg laying data. After the end of the first phase, female ostriches were separated into a control group (n = 3) and a treated group (n = 6). Every week, two females from the treated group were selected to receive the treatment: an intramuscular application of 1 ml (25&#956;l) of Lecirelin. The effect of the application was evaluated by the analysis of serum concentrations of estradiol, progesterone and corticosterone (0h, 6h, 24h, 48h and 96h post-application), by the verification of the ovarian development and the occurrence of ovulation through ultrasound examinations (24h, 48h and 96h), by the observation of reproductive behavior (0h, 48h and 96h) and by the egg laying data. The intramuscular application was repeated in the same animal every 21 days and two females from the control group were subjected to the same analysis during each treatment. The results indicate that the application of Lecirelin was able to induce ovulation in 77% of the treatments with normal egg laying in 50% of inductions. Thus, the treatment was found effective in inducing ovulation in female ostrich provided that it is applied in females who exhibit well developed ovary.
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Godinho, Cláudio. "A aplicação do SIADAP à GNR." Master's thesis, Academia Militar. Direção de Ensino, 2009. http://hdl.handle.net/10400.26/8070.

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O presente trabalho está subordinado ao tema: “Aplicação do SIADAP à GNR.” A avaliação do desempenho constitui uma ferramenta indispensável à sobrevivência de qualquer organização pois permite, por um lado, gerir as competências e carreiras dos trabalhadores e, por outro, aumentar a sua motivação. Os trabalhadores motivados desempenham a sua função com um nível muito superior de eficiência e qualidade do que trabalhadores desmotivados e insensíveis às causas da organização a que pertencem. Na tentativa de prestar serviços de qualidade ao cidadão, a Administração Pública Portuguesa tem vindo a realizar um número de reformas introduzindo novas práticas de gestão. Fruto dessas reformas, surge um sistema de avaliação do desempenho designado de Sistema Integrado de Avaliação do Desempenho da Administração Pública (SIADAP). Este Sistema de avaliação tem como base a gestão por objectivos, o qual se tem revelado como sendo um dos métodos mais eficazes na avaliação dos trabalhadores e das organizações. Por imposição governamental, todos os Serviços Públicos obrigam-se a colocar em prática este sistema de avaliação do desempenho, com as necessárias adaptações a cada Instituição. Nesse sentido a Guarda Nacional Republicana (GNR), como Instituição Pública, terá impreterivelmente de adoptar e adaptar o SIADAP à sua natureza organizacional. Neste âmbito desenvolveu-se o presente estudo a partir da pergunta: “Será importante para a GNR a implementação do SIADAP?” A metodologia utilizada para realizar este trabalho compôs-se numa pesquisa bibliográfica e ainda na interpretação dos resultados obtidos através de inquéritos. Através da pesquisa bibliográfica e da análise aos dados obtidos pelos questionários, concluiu-se que a implementação do SIADAP na GNR é fundamental. O SIADAP implica que o efectivo total da GNR passe a ser avaliado e, portanto, deverá permitir, por um lado, reconhecer e distinguir o desempenho de todos os militares e, por outro, criar um clima de maior motivação e de maior justiça dentro da Instituição.O presente trabalho foi realizado entre Janeiro e Março 2009.<br>Abstract The present work focuses on the theme: "SIADAP Application on GNR." The performance evaluation is an indispensable tool for the survival of any organization as it allows to manage the skills and careers of other workers as well as to increase their motivation. Motivated employees play their role with a much higher level of efficiency and quality than workers who are discouraged and insensitive to the causes of the organization to which they belong. In an attempt to provide quality services to citizens, the Portuguese Government has made a number of reforms introducing new management practices. Due to these reforms, there is a performance assessment system called Integrated System for Performance Evaluation of Public Administration (SIADAP). This evaluation system is based on management by objectives, which have proved to be one of the most effective concerning workers’ and organizations’ evaluation. Due to government imposing, all public services are obliged to put into practice this system of performance evaluation with the necessary adjustments to each institution. In this sense, the Guarda Nacional Republicana (GNR), as a public institution, is liable to adopt and adapt the SIADAP in its organizational nature. In this context this study was developed having as its primary question: "Is the implementation of SIADAP important to the GNR?" The methodology used to carry out this work consisted of literature research and interpretation of results obtained through surveys. Through literature research and analysis of data obtained through questionnaires, it was concluded that the implementation of SIADAP in the GNR is essential. Through this method, not only the total military forces of the GNR will be evaluated recognizing and distinguishing the performance of all soldiers involved, but also a climate of motivation and greater justice within the institution will be created. This work was carried out between January and March 2009.
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Passeira, Carla. "A GNR e as redes sociais." Master's thesis, Academia Militar. Direção de Ensino, 2011. http://hdl.handle.net/10400.26/8328.

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Vivemos numa época em que a livre circulação de informação no âmbito das novas Dinâmicas Tecnológicas, características da designada Web 2.0, e o fácil acesso à comunicação influencia os comportamentos individuais e institucionais, neste caso específico da Guarda Nacional Republicana enquanto veículo comunicacional. Partindo desta premissa, o presente Trabalho de Investigação Aplicada que se subordina ao tema “A GNR e as Redes Sociais” tem como objectivo perceber em que medida a adesão da GNR às novas dinâmicas da nova geração da internet, pode contribuir para aumentar a proximidade bem como a qualidade do serviço policial prestado ao cidadão, enquanto sujeito cada vez mais activo na Era Digital. O trabalho foi dividido em duas partes distintas: a primeira destinada a uma revisão literária, levantamento de perguntas e hipóteses, aborda a Sociedade da Informação, seu quadro legal e os novos paradigmas da comunicação de colaboração em rede. A segunda fase está relacionada com o trabalho de campo realizado com entrevistas, à análise e discussão dos resultados obtidos, resposta às perguntas de investigação e verificação das hipóteses terminando com conclusões e recomendações futuras. Com o presente estudo chegou-se à conclusão que as Redes Sociais funcionam como veículo comunicacional fulcral no espectro de intervenção da GNR bem como plataforma moderna de proximidade e qualidade de serviços prestados às novas gerações. Sugere-se uma aposta de intervenção da GNR como potenciadora de Cidadania Digital, designadamente porque os jovens de hoje que serão os adultos de amanha.<br>Abstract We live in an era in which the free circulation of information under the New Technologies, typical of the well known Web 2.0, and the easy access to communication influences the individual and institutional behaviors, in this specific case, those of the Guarda Nacional Republicana as a communication vehicle. Bearing this in mind, this Work of Applied Research under the theme “The GNR and the Social Networks” aims to understand to what extent the adherence of GNR to the new dynamics of the new internet generation can contribute to improve the proximity and the quality of the police service provided to citizens, as individuals that are more and more active in the Digital Era. The work was divided into two distinct parts: the first one aims a literature review, the raise of questions and hypotheses and it addresses the Information Society, its legal framework and the new paradigms of Collaborative Network Communication. The second phase is related to the fieldwork accomplished through interviews, analysis and discussion of the obtained results, answers to the investigation’s questions, verification of the hypotheses, conclusions and future recommendations. With this study, we can conclude that Social Networks can work as a vehicle of communication and play a key role in the GNR´s investigation, as well as a modern platform for quality and proximity in services given to new generations. It is recommended that we invest in the interference of the GNR as a means of enhancing a Digital Citizenship towards, in particular because, young people of today who will be the adults of tomorrow.
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Perera, Uswatteliyanaralalage Felicia Ruwanie. "Investigation of the presence of GnRH and GnRH-R system in bovine oocytes, sperm and early embryos and their functional role in reproduction." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/23318.

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The objectives of this study were to investigate: 1) the effect of GnRH agonist on oocyte maturation, sperm function and fertilization, 2) the presence of GnRH-R in bovine oocytes, sperm and early embryos. To examine the effect of GnRH agonist on sperm function, sperm were incubated in modified Tyrode’s medium with 0, 0.2, 0.4, 0.8 and 1.2 µgmL⁻¹ of buserelin and with1 µgmL⁻¹ P₄ for 3 h. Acrosome status in each group was assessed at 0 h and 3 h. For zona-binding assay, in vitro matured oocytes were co-incubated with sperm in different concentrations of buserelin and P₄ for 4 h and the zona-bound sperm in each treatment group was determined. Acrosome reacted percentage were higher in sperm treated with 0.4, 0.8 µgmL⁻¹ buserelin than the control group (p<0.001). The number of zona-bound sperm were higher in 0.8 µgmL⁻¹ buserelin compared to negative control (p<0.01). Effect of buserelin was blocked by antide. To investigate the effect of GnRHa on maturation of bovine oocytes 0.8 µgmL⁻¹ buserelin was added to the in vitro maturation media and maturation rate was obtained after 24 h against control groups with FSH and without FSH. To assess the effect on fertilization rate one group of oocytes undergoing in vitro fertilization was treated with 0.8 µgmL⁻¹ buserelin, while in vitro fertilization without buserelin served as control. Maturation rate was not different among the groups and were 55.14 ± 0.39, 50.69 ± 0.42 and 43.5 ± 0.46 % for oocytes treated with FSH, buserelin and negative control, respectively. No difference was observed on fertilization rates, with fertilization rates being 55.25 ± 0.89 and 51.25 ± 0. 51% for buserelin treated and the control group, respectively. Presence of GnRH-R protein and mRNA on bovine sperm, oocytes, cumulus cells and early embryos were studied using immunostaining technique and RT-PCR. No receptors for GnRH were detected in bovine sperm, oocytes or early embryos studied and expression of GnRH-R mRNA was also not evident. GnRH-R mRNA was expressed by cumulus cells, immature and mature COC. GnRH receptor mRNA expression by mature COC was higher than immature COC (2.01±0.12 and 0.89±0.2).
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43

Orlauskaitė, Ieva. "GnRH agonisto, metų laiko bei kalės veislės dydžio ir amžiaus įtaka ovuliacijos pasireiškimo laikui." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140305_134057-38642.

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Šio darbo tikslas buvo nustatyti ovuliacijos pasireiškimo laiko priklausomybę nuo kalės veislės dydžio ir amžiaus bei metų laiko, bei palyginti GnRH agonisto Suprelorin implanto sukeltos ovuliacijos pasireiškimo laiką su natūraliai pasireiškusios rujos ovuliacijos laiku. Šiam tikslui pasiekti pirmiausiai buvo ištirta 194 kalių (51 skirtingos veislės) progesterono koncentracija kraujo serume. Iš šių kalių buvo atrinktos tos kalės, kurioms pagal progesterono koncentraciją pasireiškė ovuliacija (53 kalės). Nustatyta, kad progesterono koncentracija kraujo serume siekė 20-30 nmol/l. Kalės buvo suskirstytos į grupes: pagal amžių (2 grupės – iki 5 metų (n=41); 5 metų ir vyresnės (n=12) ), pagal veislės dydį (3 grupės – mažos (n=22), vidutinės (n=14) ir didelės (n=17) veislės), pagal sezoną (4 grupės – žiema (n=3), pavasaris (n=16), ruduo (n=11), vasara (n=23) ). Pagal kiekvieną požymį statistiškai buvo įvertinti ovuliacijos pasireiškimo laiko skirtumai tarp grupių, bei įvertinta ovuliacijos priklausomybė nuo kalės amžiaus, dydžio, metų laiko. Statistiškai patikimų skirtumų tarp grupių ir koreliacinių ryšių tarp ovuliacijos pasireiškimo laiko ir kalės amžiaus ir dydžio, bei metų laiko nebuvo nustatyta. Panašių tyrimų iki šiol buvo atlikta labai mažai, todėl informacija yra vertinga. Paskutiniame tyrimųetape4 kalėms buvo panaudoti GnRH agonisto Suprelorin implatai rujai sukelti. Implantas buvo įvedamas po oda, bambos srityje. Po įvedimo buvo imamas kraujas kelis kartus kas 3-5 dienas... [toliau žr. visą tekstą]<br>The main goal of this paper was to determine whether or not there is a significant influence of GnRH agonist, seasonality, age and size of the bitch on ovulation time, and to compare ovulation time induced by GnRH agonist Suprelorin implant and the ovulation time that occured naturally. To achieve this goal we tested the blood of 194 bitches (51 breeds) for progesterone levels in blood serum. Out of these 194 bitches we selected the ones (53 bitches) that ovulated. Meaning, the progesterone levels for these 53 bitches varied between 20-30 nmol/l. These 53 bitches were divided into groups: by age (2 groups – younger than 5 years (n=41); 5 years old and older (n=12),, by size (3 groups – small (n=22), medium (n=14), large (n=17), and by season (4 groups – winter (n=3), spring (n=16), summer (n=11), autumn (n=23). All the groups were statistically analyzed to determine whether or not there is a significant difference between the groups, and to determine if there are correlations between the ovulation time and the size and age of the bitch and time of year (season). No significant difference or correlations were determined. We have found a little information about influence of seasonality, and age and size of the bitch on ovulation time, so the information in this paper is valuable. For the last step to achieving the goal of the paper, GnRH agonist Suprelorin implant was used on 4 bitches. The agonist was implanted subcutaneously around the navel area. After the implantation... [to full text]
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44

Poluparthi, Aparna Kranthi. "Large Gold Nanorods Cytotoxicity in Human Red Blood Cells." Wright State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1547590006416218.

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45

Cooper, Dee A. "Reproductive neuroendocrine function in the mare as reflected in the intercavernous sinus during ovulatory, anovulatory, and transitional seasons." Thesis, Texas A&M University, 2003. http://hdl.handle.net/1969.1/3910.

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We hypothesized that marked reductions in secretion of luteinizing hormone (LH) during transitional and anovulatory periods can be accounted for by similar reductions in hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Catheters were inserted surgically into the intercavernous sinus (ICS) of seven non-pregnant mares via the superficial facial vein during the ovulatory season (August 12-23), fall transition (November 15-30), the anovulatory season (January 19 - February 1) and spring transition (March 24 - May 12). Catheter placement was confirmed and standardized in each mare by lateral radiography. Ovarian status was monitored throughout the study by transrectal ultrasonography and serum concentrations of progesterone. During the breeding season, ICS blood samples were collected at 5-min intervals for 8 h when the dominant follicle reached approximately 35 mm and estrous behavior was observed. All mares ovulated within 5 d after sampling, except one mare who ovulated < 24 h before sampling. During the fall, mares were anovulatory (n = 5) or had a final ovulation within 5 d following intensive sampling (n = 2). Winter anovulation sampling was performed when all mares were anovulatory. During spring transition, each mare was sampled just before the second ovulation of the season. Similar to the ovulatory season, mares were sampled when the dominant, preovulatory follicle reached approximately 35 mm and estrous behavior was observed. Mean concentrations of LH were markedly higher (P < 0.01) during the breeding season than during all other seasons. Lower mean concentrations of LH in the fall transition, winter anovulation and spring transition sampling periods occurred coincident with a similar reduction (P < 0.01) in amplitude of LH pulses. Unexpectedly, neither the frequency (pulse/8 h) of LH pulses, frequency and amplitude of GnRH pulses, nor mean concentrations of GnRH differed among seasons. In addition, there were no differences observed due to season in mean concentrations of FSH or amplitude of FSH pulses. However, a small but significant (P < 0.05) reduction in the frequency of FSH pulses was observed during fall transition compared to all other seasons. In summary, contrary to accepted dogma, these results indicate that the photoperiodic initiation of seasonal anovulation in the mare is mediated at the level of the anterior pituitary, and appears to occur through a dampening of gonadotroph responsiveness to an unchanging pattern and magnitude of GnRH secretion.
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46

Rometo, Adonna Marie. "Ovarian Steroid Modulation of Neuropeptide Gene Expression and Neuronal Morphology in the Primate Hypothalamus." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/194500.

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In the United States, there are currently more than 40 million postmenopausal women. These women are faced with a variety of physiological changes including ovarian steroid withdrawal and alterations in hypothalamic neurons. Within the hypothalamic infundibular nucleus of postmenopausal women, there is neuronal hypertrophy and an increase in neurokinin B gene expression. Recent studies identified the kisspeptins and dynorphins as major regulators of reproduction. In our first experiment, we examined the location and alterations of KiSS-1 mRNA-expressing neurons in the hypothalami of pre and postmenopausal women. KiSS-1 neurons were largely confined to the infundibular nucleus, and in postmenopausal women, exhibited neuronal hypertrophy and increased gene expression. To determine if these changes could result from alterations in ovarian steroids, we investigated KiSS-1 gene expression in the hypothalamic infundibular nucleus of non-human primates. Similar to the findings in postmenopausal women, ovariectomy of monkeys resulted in neuronal hypertrophy and increased KiSS-1 gene expression within the infundibular nucleus. Further, estrogen treatment of ovariectomized monkeys yielded a dramatic decrease in KiSS-1 gene expression. Together, these findings suggest that the postmenopausal alterations in KiSS-1 neurons are secondary to ovarian failure.In a second study, we examined alterations in dynorphin gene expression in the hypothalami of pre and postmenopausal women. Dynorphin mRNA-expressing neurons were identified in multiple nuclei. Numbers of dynorphin neurons were decreased within the mPOA and infundibular nucleus of postmenopausal women. In the infundibular nucleus of postmenopausal women, dynorphin neurons were hypertrophied. To determine the contribution of ovarian steroids on dynorphin gene expression, we examined dynorphin mRNA in a monkey model of menopause. Young ovariectomized monkeys exhibited hypertrophy of dynorphin neurons, with no changes in dynorphin gene expression. Estrogen replacement yielded a decrease in neuronal size and an increase in dynorphin neuron number.In future studies, we will use Quantum Dot FISH to determine if NKB, KiSS-1, and dynorphin are colocalized in the hypertrophied neurons. These neuropeptides are involved in the regulation of GnRH and changes in their gene expression likely contribute to postmenopausal alterations in reproductive hormones. Our findings provide greater understanding of the postmenopausal condition and offer opportunities for pharmaceutical investigation and treatment.
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47

Francou, Bruno. "Contribution à la caractérisation de nouveaux gènes impliqués dans les hypogonadismes hypogonadotropes : caractérisation des mécanismes moléculaires et cellulaires." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS101/document.

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Les hypogonadismes hypogonadotropes congénitaux (CHH) sont des maladies héréditaires caractérisées par un déficit de sécrétion des gonadotrophines par l’hypophyse, à l’origine d’une infertilité ou d’une absence complète de puberté. On distingue les formes isolées avec olfaction normale (nCHH) et les formes syndromiques associant au déficit gonadotrope d’autres signes, tel qu’un défaut d’olfaction dans le cas du syndrome de Kallmann (SK), la forme plus fréquente de CHH. Les gènes identifiés dans le SK participent au développement embryonnaire et les gènes des nCHH sont impliqués dans la régulation de la sécrétion de la GnRH ou de son action. A ce stade, deux populations de neurones hypothalamiques gonadotropes sont connues, le neurone à GnRH et le neurone KNDy, sécrétant les Kisspeptines et la Neurokinine B. On estimait que l’ensemble des gènes identifiés couvraient moins de 20% des étiologies génétiques. L’objectif de ce doctorat était d’étudier prévalences et mécanismes physiopathologiques des gènes connus et d’identifier de nouvelles étiologies génétiques de CHH. Dans la première partie, nous avons caractérisé la fonctionnalité de tous les variants identifiés sur les gènes KISS1R, TACR3 et TAC3. Cela a permis de préciser les prévalences chez 600 patients, d’identifier un profil neuroendocrinien propre à l’altération de la signalisation Neurokinine B et de démontrer l’implication des Kisspeptines au cours de la vie embryonnaire. Enfin, nous proposons un modèle d’interaction entre le neurone à GnRH et le neurone KNDy. Dans la seconde partie, nous avons identifié deux nouveaux gènes, SEMA3A dans une forme familiale de SK et PNPLA6 dans une forme familiale rare de CHH syndromique. En conclusion, notre connaissance accrue des formes génétiques de CHH, a permis de développer un panel d’exome ciblé dédié au diagnostic par séquençage nouvelle génération permettant l’analyse simultanée de gènes candidats et de gènes connus<br>Congenital hypogonadotropic hypogonadism (CHH) is characterized by deficient or absent pubertal development due to deficient or absent secretion of the pituitary gonadotropins. The many known genetic causes are generally classified into distinct nosological groups. One comprises abnormalities that affect the pre-natal development or migration of GnRH neurons, the paradigm of which is Kallmann syndrome. The other encompasses molecular abnormalities that only affect hypothalamic GnRH synthesis, GnRH release or GnRH signaling at pituitary level. At this stage, two populations of hypothalamic neurons implicated in a gonadotrop function are identified, GnRH neurons and KNDy neurons secreting kisspeptins and neurokinin B. All of the identified genes would represent less than 20% of genetic etiologies.The aim of this PhD was to study the prevalence and pathophysiology mechanisms of known genes and to identify new genetic etiologies of CHH.In the first part, we characterized the function of all molecular events identified on KISS1R, TACR3 and TAC3 genes. Prevalences were estimated in 600 patients. A particular neuroendocrine profile was identified in patients presenting an alteration of neurokinin B signaling. Importance of Kisspeptins during embryonic life was validated. According to these data, a model of interaction between GnRH and KNDy neurons was proposed.In the second part, we identified two new CHH genes using various molecular genetics approaches. SEMA3A was identified in a familial form of Kallmann syndrome and PNPLA6 in a rare familial form of CHH.Finally, our increased knowledge of the various genetic forms of CHH allows proposing a new genetic approach based on next generation sequencing to test together all known and several candidate genes
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48

Gault, Paula Marie. "GnRH-II receptor and the regulation of reproduction in mammals." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/24605.

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The GnRH-II system is thought to regulate sexual behaviour through an action in the brain, and/or control gonadotrophin secretion in association with the classical GnRH-I system at the level of the gonadotroph. The aim of this study described in this thesis was to comprehensively investigate the GnRH-II receptor system in a well characterised sheep model. Four types of studies were performed. The first study sequenced the ovine GnRH-II receptor gene by long-distance PCR. The second study investigated GnRH-II receptor gene expression in ovine tissues. The third study investigated evidence for GnRH-II receptor on gonadotrophs. A fourth study used two selective GnRH-I receptor antagonists to test whether administered GnRH-II acts through the GnRH-I receptor to elicit gonadotrophin secretion. In conclusion the presence of a premature stop codon in the ovine GnRH-II receptor, and a major deletion mean it is unlikely that a full 7 transmembrane domain G-protein coupled receptor is expressed in the sheep. RNA transcripts for part of the receptor were detected in testis, ovary and hindbrain, indicating that a partial GnRH-II receptor protein may be produced in a tissue-specific manner. The lack of a Pit-1 binding site in the 5’ flanking sequence of the ovine GnRH-II gene, the lack of RNA transcripts specifically in gonadotrophs and the <i>in vivo</i> evidence collectively suggest that GnRH-II does not function to regulate gonadotrophin secretion in the sheep. Overall these data complement recent published data for the marmoset, African green monkey, rhesus macaque and man, and are consistent with the generalised hypothesis that there has been redundancy in the multiple GnRH receptor systems during vertebrate evolution.
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49

Hamed, Hisham Hilal Ahmed. "A study of GnRH analogue in the treatment of mastalgia." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338894.

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50

Chang, Lynda. "Molecular characterisation of GnRH regulated factors isolated from gonadotroph cells." Thesis, University of Edinburgh, 2002. http://hdl.handle.net/1842/30448.

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The aim of this thesis was to isolate the factors regulated by GnRH. To identify these, the LβT2 gonadotroph cell line was used as a model system for differential display RT-PCR analysis (DD-RT-PCR) of GnRH regulated transcripts. DD-RT-PCR showed that varying the GnRH pulse regime both differentially regulated and induced rapid changes in mRNA transcript levels. Myosin light chain and a putative tyrosine phosphatase were up regulated by GnRH, as were two expressed sequence tags (ESTs); one expressed in the thesis, the other in the mammary glands of pregnant or lactating mice. In addition, GnRH also down-regulated Fanconi’s anaemia complementation group A (FAA) mRNA expression levels. Fanconi’s anaemia (FA) is a autosomal recessive human disease, characterised by aplastic anaemia, short stature, developmental abnormalities, microcephaly, and infertility. Most FA genetic abnormalities map to the <i>FAA</i> gene, which may have a role in DNA repair, and cell cycle checkpoint control. A role for FAA in controlling gonadotrophin gene expression was tested by transient transfection assay in gonadotroph cell-lines. Transfection of a FAA expression construct specifically repressed the GnRH response of the αGSU promoter, but not the LHβ gene promoter, in LβT2 cells. The regulatory region of the FAA protein, responsible for repression of αGSU, was mapped between amino acid (aa) residues 322aa and 800aa, by serial transfection of successive C-terminal deletion constructs. Furthermore, results also suggested that FAA might mediate its effects through a paired homeodomain binding site on the αGSU promoter. Therefore, using DD-RT-PCR to isolate transcripts from GnRH treated LβT2 cells has identified novel transcripts, transcripts encoding secretion and second messenger signalling pathway proteins and FAA. Furthermore, a novel role for FAA in specifically repressing GnRH-regulated αGSU transcription was discovered.
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