Dissertations / Theses on the topic 'Desensitisation'
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1
Batuwangala, Madura Suharshana. "Human urotensin-II receptor desensitisation." Thesis, University of Leicester, 2009. http://hdl.handle.net/2381/7846.
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Human Urotensin-II (U-II) is a cyclic undecapeptide that binds to the U-II receptor UT. The desensitisation mechanisms of the UT receptor (G_{q/11} coupled GPCR) are not well defined and hampered by (1) lack of native (in-vitro) models; (2) paucity of ligands, especially non-peptides and (3) irreversible binding of U-II. There are some limited studies using rat aorta, where a U-II induced primary contractile response was reduced upon a secondary re-challenge after 5-hours. Studies were undertaken to characterise cell lines expressing native (SJCRH30) and recombinant human hUT (HEK293 and CHO) for their suitability in binding and functional assays (PI and Ca^2+). SAR studies were carried out to characterise novel analogues modified at Tyr^9 of the U-II(4-11) template. This led to the identification of [3,5-diiodoTyr^9]U-II(4-11) a partial agonist in aorta and Ca^2+ assays at rat UT. Full agonism was demonstrated at hUT in PI and Ca^2+ assays. Efforts were made to delineate functional and genomic desensitisation of hUT. There was no functional desensitisation in SJCRH30. In HEK293hUT functional heterologous desensitisation of hUT was observed, this was not so in CHOhUT; instead P_2YR was functionally attenuated. In SJCRH30 6-hr U-II treatments led to UT mRNA reduction. Genomic desensitisation was also studied in Peripheral blood mononuclear cells (PBMCs). U-II treatments alone did not affect UT mRNA. Lipolysaccharide treatment of PBMCs led to UT mRNA upregulation which was desensitised with U-II treatments. In recombinant systems UT mRNA was upregulated at 6-hr U-II treatments. In conclusion modification of the U-II(4-11) template at Tyr^9 is useful for reducing efficacy. There is a difference in desensitisation profiles of native and recombinant hUT, where native receptors are not prone to functional desensitisation while receptor mRNA is reduced. In recombinant systems, hUT undergoes desensitisation (HEK293hUT only) while receptor mRNA is increased in both systems.
2
Baig, Asma Hamid. "Desensitisation and downregulation of the ACTH-receptor." Thesis, Queen Mary, University of London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271428.
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De, Silva Mahappuque Anushika Sumali. "Ca²⁺ sensitisation and desensitisation mechanisms in pulmonary artery." Thesis, King's College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499978.
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Modulation of Ca²⁺sensitivity of the smooth muscle contractile apparatus plays a fundamental role in the regulation of force. Increased CA²⁺ sensitivity may contribute towards various disease conditions such as pulmonary hypertension. Ca²⁺ sensitivity is regulated by the balance between myosin light chain kinase (MLCK)-dependent phosphorylation and myosin phosphatase (MP)-dependent dephosphorylation of myosin light chain (MLC-20). Several protein kinases have been implicated in modulating this process. In particular RhoA and its effector Rho kinase (Rhok) inhibits MP activity via the MYPTl subunit; whereas protein kinase C (PKC) activates MP inhibitory protein CPI-17. Additionally the mitogen activated protein kinases (MAPK) and heat shock protein 27 (HSP27) may effectively modulate Ca²⁺ sensitivity via the cytoskeleton.
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McNicol, A. "Desensitisation and potentiation of platelet inositol phospholipid hydrolysis." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234872.
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Beaumont, Vahri. "Desensitisation of somatostatin receptors in NG108-15 cells." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246243.
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Fowler, Catherine. "Desensitisation of somatostatin receptors in NG108-15 cells." Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391197.
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Howard, Helen Clare. "The pharmacological characterisation of oxytocin receptors in the rat brain." Thesis, University of Bristol, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299594.
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Mustafa, Sanam. "Regulation and desensitisation studies on the nicotinic acid receptors." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/510/.
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The lipid-modifying qualities of nicotinic acid, a B3 vitamin, have been exploited for many years to prevent cardiovascular disease and its associated mortality. Despite its widespread availability and clinical use, the clinical target and precise molecular mechanism by which nicotinic acid acts remains elusive. In order to maximise nicotinic acid’s full potential as a lipid-modulating drug, overcome its related side effects and further develop novel and more potent drugs it is vital to understand its molecular mechanism of action. Fifty years on from its arrival on the market, receptors which this drug acts upon have recently been identified as the G protein-coupled ‘nicotinic acid receptors’. A family of three highly homologous receptors, HM74, HM74A and GPR81 are characterised by their differing affinities for nicotinic acid. Comparison of these homologues revealed a high degree of similarity between them, with the greatest similarity between HM74 and HM74A. The main structural difference between these receptors is the longer C-terminal tail of HM74. As the C-terminal tail of GPCRs is often implicated in receptor regulation it was hypothesised that the differences in this region may result in differential regulation of HM74 and HM74A. This hypothesis was tested by examining the regulation and desensitisation characteristics of each receptor in a heterologous expression system. Both HM74 and HM74A failed to interact with β-arrestin 2 or internalise in response to nicotinic acid. However, both receptors were phosphorylated in an agonist-dependent manner. HM74 but not HM74A was demonstrated to desensitise as result of prolonged nicotinic acid exposure. The importance of the C-terminal region was further analysed by the use of chimeric nicotinic acid receptors, in which the C-terminal tail of HM74 and HM74A were exchanged. It was shown that the C-terminal tail of HM74 may be implicated in the desensitisation characteristics of this receptor. Furthermore, it was shown that HM74 and HM74A display differential characteristics with respect to ERK1/2 phosphorylation.
9
Braksator, Ellen. "A Study on μ-opioid receptor desensitisation and internalisation." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520290.
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McPherson, Jamie Lorcan. "Functional selectivity and desensitisation of G protein-coupled receptors." Thesis, University of Bristol, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555868.
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The existence of functional selectivity at the mu-opioid receptor was examined by determining the efficacy of a range of opioid agonists for promoting G protein activation and arrestin-3 translocation. In general, there is a good correlation between the efficacy of an opioid agonist at promoting G protein signaling, and the efficacy at recruiting arrestin-3 to the receptor. Endomorphin 2 appears to be an example of a biased ligand with significantly higher efficacy for arrestin-3 translocation, while morphine does not appear to be biased. The kinetics of binding for DAMGO, morphine and endomorphin 2 were determined by competition kinetic assay as a potential explanation for the apparent bias of endomorphin 2. Mean occupancy times of DAMGO, endomorphin 2 and morphine at MOPr are similar to the time required for GRK2-mediated phosphorylation, indicating that kinetics of binding may be a determinant of their ability to promote arrestin-3 signaling at MOPr. The abilities of DAMGO, morphine and endomorphin 2 to induce desensitization of GIRK currents in AtT-20 cells expressing wild type mu-opioid receptor, mu-opioid receptor containing S261/363A substitutions, and mu-opioid receptor with a C terminal truncation from amino acid 354-398 were examined. From the results, it appears that agonist-induced acute desensitization in AtT-20 cells has multiple components. C terminal truncation of MOPr resulted in a slight inhibition of endomorphin 2-induced desensitization. Alanine substitution at serine 261 and 363 inhibited desensitization induced by endomorphin 2. Treatment with the GRK2 inhibitor 5-[2-(5-nitro-2- furyl)vinyl]-2-furoate slightly but significantly inhibited desensitization induced by DAMGO, and to a very small extent morphine, but not endomorph in 2, which may indicate that biased ligands trigger receptor regulation in a different manner to unbiased ligands.
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Leigh, Philippa Jane. "Desensitisation of prostacyclin receptors on neuronal somatic hybrid cells." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37758.
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Mariggio, Stefania Pasqua. "Regulation of immune receptor functional responses by G protein-coupled receptor kinases (GRKs) and arrestins." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343747.
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Hepworth, Mark Barrett. "Desensitisation of inhibitory G-protein-coupled responses in neuroblastoma cells." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336855.
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Chu, Ka Man Emily. "Desensitisation of the CGRP receptor in SK-N-MC cells." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487319.
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Calcitonin gene-related peptide (CORP) and adrenomedullin (AM) are potent vasodilators that activate the calcitonin-like receptor complexed with one of three receptor activity modifying proteins (RAMP1 for CORP, RAMP 2/3 for AM). Desensitisation of these receptors was characterised in the human neuroblastoma SK-NMC cell line. Desensitisation was dose-dependent (ICso values: CORP, 2.92 x 10-7 M; AM, 1.08 x 10-7 M) and time-dependent, being maximal with a 2-hour agonist pretreatment. Inhibitor experiments showed that CORP-induced desensitisation was independent of protein kinase A (H-89) but was partially mediated by protein kinase C (OFI09203X). Lipid raft-mediated receptor endocytosis did not seem to contribute to signal attenuation (methyl-f3-cyclodextrin and filipin), but clathrin-mediated internalisation plays a role (sucrose). Stable overexpression of dominant-negative ORK2 or dynamin had no effect on desensitisation, suggesting that ORKs and dynamin are not involved. Unlabelled CORP competed 2-[12sI]iodohistidyllO-hCORP (ICso=1.97 x 10-10 M). 15% 12SI_CORP internalised after 10 min, 47% after 120 min. Receptor endocytosis was not blocked by lipid raft inhibitors but was significantly reduced by sucrose, in line with the hypothesis that its effect on desensitisation was due to inhibition of clathrin-mediated internalisation. Overexpression of dominant-negative ORK2 or Dyn 1 did not alter internalisation, suggesting that ORKs and dynamin are not involved. CORP receptor endocytosis was confirmed by confocal immunofluorescence microscopy and biotin internalisation. f3-arrestin 2-eYFP did not redistribute following CORP stimulation. Cells stably expressing short hairpin RNA against f3-arrestinl and/or 2 were generated. Maximum silencing of f3-arrestinl mRNA was 29.8%. 48.2% f3-arrestin2 mRNA knockdown was achieved, with possible reduction of protein. CORP receptor desensitisation was unchanged compared to wild-type cells, consistent with the hypothesis that f3-arrestin2 is not required. Taken together, the data demonstrate desensitisation of the SK-N-MC CORP and AM receptors. CORP receptor desensitises through a PKC-mediated mechanism involving internalisation via clathrin-coated vesicles.
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Wills, Lauren. "SUMOylation of the B2AR influences receptor internalisation, desensitisation and downstream signalling." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8564/.
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The beta 2 adrenergic receptor (β2AR) is a GPCR that is susceptible to multiple post-translational modifications (PTMs) including phosphorylation, ubiquitination, palmitoylation and glycosylation, which can alter how the β2AR orchestrates downstream intracellular signals. Following the discovery of SUMOylation of the cardiac signalling protein SERCA2a, we hypothesised that the β2AR, which is also involved in cardiac signalling, may be a substrate for SUMOylation. This notion was supported by previous findings that five different GPCRs have been identified as susceptible to SUMOylation, including metabotropic glutamate receptors (mGluR), a cannabinoid receptor, a serotonin receptor and a receptor involved in basal cell carcinoma known as smo. For the first time, we confirm the susceptibility of the β2AR to SUMOylation by identifying SUMO accepting lysines, interaction sites between the β2AR and the enzymes of the SUMOylation cascade, and the traditional “ghost” band, which is indicative of protein SUMOylation. SUMOylation has been shown to influence receptor signalling, and we now uncover a possible role for SUMOylation in β2AR signalling. I report that SUMOylation of the β2AR (mediated via overexpression of the E3 ligase PIASγ) reduces β2AR phosphorylation by PKA altering the receptor driven phospho-ERK response, inhibits β2AR ubiquitination and degradation, and delays β2AR internalisation. These changes could be associated with steric effects of the bulky SUMO modification and ubiquitin-SUMOylation competition for available surface associated lysines. With the importance of SUMOylation in multiple disease states (including cardiovascular disease, neurodegenerative disease and cancer), we worked in conjunction with the antibody production company Badrilla ® to produce a SUMO-substrate specific antibody for a site within the third intracellular loop of the β2AR. The antibody we have produced is successful in recognising the SUMOylated form of the receptor in both cell and tissue lysate, making it the first antibody of its kind to be generated. In conjunction with the Hajjar group at Mount Sinai Cardiovascular Research Centre (New York, USA) we used the SUMO-β2AR specific antibody to assess the influence of the SUMO modification in two animal models of heart failure (HF); transverse aortic constriction (TAC) pressure overload HF model in mice and the left anterior descending (LAD) artery balloon occlusion ischemic HF model in pigs. Prior work within the Hajjar group has revealed that SUMOylation of SERCA2a is reduced in HF, and restoring this modification to SERCA2a via SUMO-1 adeno-associated viral-mediated gene delivery is beneficial in restoring cardiac function. We hypothesised that SUMOylation of the β2AR would also be reduced in HF, however unexpectedly; the SUMOylated form of the β2AR was increased in the LAD artery balloon occlusion ischemic HF model in pigs. The role of the β2AR in HF is unclear. There are studies which both report a cardio-protective and a cardio-toxic role of the receptor. To ascertain the role SUMOylation of the β2AR plays, in vivo studies promoting SUMOylation of the β2AR in the HF models described above will help to determine if enhanced SUMOylation of the receptor worsens the HF phenotype or prevents its development. To conclude, we present the first evidence that the β2AR can be modified by SUMOylation, which acts to influence the receptors downstream signalling, desensitisation and degradation. We have designed a first-in-class SUMO-β2AR antibody – which paves the way for a panel of SUMO specific antibodies – and utilised it to assess SUMOylation of the β2AR in model cellular systems and animal models of HF. Similarly, to SERCA2a, SUMOylation does influence β2AR in the HF phenotype, although not a decrease in SUMOylation as was expected, but an increase. Future work in animal models promoting SUMOylation of the receptor is vital to assess the role of this highly novel post-translational modification of the β2AR.
16
Tofighy, Azita. "N-methyl-d-aspartate receptor desensitisation and anoxia in rat olfactory cortex." Thesis, Queen's University Belfast, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361309.
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Jones, Susan Mary. "Functional beta-adrenoceptor desensitisation in isolated cardiac myocytes from animals and man." Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46850.
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Raihan, Sheikh Zahir. "Desensitisation of the human long chain fatty acid receptors FFA1 and FFA4." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8144/.
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G protein-coupled receptors (GPCRs) constitute the largest, most ubiquitous and most versatile family of membrane proteins encoded by the human genome. Due to diverse ligands and multiple physiological activities, this set of receptors has frequently been explored as potential drug targets. Deorphanisation of GPCRs successfully identified FFA1 and FFA4 (previously named GPR40 and GPR120) as long chain free fatty acid receptors. With diverse expression patterns and close association to pathophysiology of metabolic diseases, both receptors are being studied to understand both receptor pharmacology and their potential for drug development. Due to the overlap in the activation of FFA1 and FFA4 by endogenous fatty acid ligands, selective synthetic ligands have been developed for these receptors. Using a number of biochemical and biophysical assays, I have characterised TUG-770, TUG-905 and GW-1100 as FFA1 ligands and TUG-891, TUG-1197 and TUG-1275 as FFA4 ligands. TUG-905 was found to be most potent and selective FFA1 agonist and GW-1100 showed insurmountable antagonism at FFA1. At FFA4, TUG-1197 was found to be a highly potent and selective agonist. TUG-1275 showed insurmountable antagonism at FFA4 in β-arrestin2 recruitment, receptor internalisation and inositol monophosphate accumulation studies and showed complete selectivity for hFFA4. Agonist exposure rapidly phosphorylated FFA4 in an agonist-concentration-dependent fashion which was totally blocked by TUG-1275. The protein kinase C activator PMA was also noted to phosphorylate FFAA in a concentration-dependent manner. Thus both homologous and heterologous phosphorylation is involved in FFA4 regulation. The FFA4-agonist TUG-891 produced robust internalisation of FFA4 as detected by each of confocal microscopy, and both cell surface ELISA and biotinylation. PMA was able to internalise FFA4 although it was unable to recruit β-arrestin2 to FFA4 suggesting that this internalisation might not be β-arrestin2-dependent. Constitutive internalisation was seen for FFA1, where the selective FFA1 antagonist GW-1100 had no effect. Repeated agonist-exposure desensitised both FFA1 and FF4 as revealed in single-cell calcium imaging studies. Although there was a small reduction of FFA4-internalisation and a slight elevation of total calcium levels from a single-chronic exposure of agonist, elimination of β-arrestin1/2 from HEK293 cells by genome editing did not significantly change the desensitisation of FFA4 to repeated exposure of agonist and did not prevent agonist-promoted internalisation. These studies indicate that β-arrestins are not the sole factors in desensitisation of human FFA4. Gαq/11 elimination by genome editing completely blocked intracellular calcium mobilisation and accumulation of inositol monophosphates mediated by both FFA1 and FFA4 indicating that Gαq/11 coupling to agonist-activated receptors is essential for this functional signalling outcome via both receptors. FFA4 expressed in Gαq/11-null cells was found to be phosphorylated by agonist, indicating that phosphorylation-mediated desensitisation of this receptor is not dependent on Gαq/11 proteins. FRET and BRET experiments revealed for the first time homo and hetero-oligomerisation of both FFA1 and FFA4. Although ligand regulation of oligomerisation was not investigated these preliminary observations of oligomerisation may help in the future to answer many questions of regulation and desensitisation of these receptors. The selective FFA1 and FFA4 ligands characterised here in this project might be used as tool compounds to further explore the physiology and pharmacology of these therapeutically important receptors.
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Ardeman, Gabriel. "An exploratory study examining changes in traumatic memories of a single traumatic event over the course of treatment using EMDR." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246966.
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Ranu, Hardeep Kaur. "#beta#-adrenoceptor desensitisation and resensitisation in ventricular myocytes from human and animal hearts." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287381.
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Brotherton, Natalie Louise. "Eye Movement Desensitisation and Reprocessing (EMDR) for trauma : a qualitative analysis of clients' experiences." Thesis, University of Lincoln, 2009. http://eprints.lincoln.ac.uk/18975/.
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This study aimed to explore clients‟ experiences of receiving eye movement desensitisation and reprocessing (EMDR) as an intervention for trauma-related symptomatology, consistent with post traumatic stress disorder (PTSD). Seven outpatients who had experienced EMDR as an intervention for trauma-related symptomatology were interviewed using a semi-structured interview schedule, from which the verbatim transcripts provided the raw data for an interpretative phenomenological analysis (IPA). The themes that were extracted from the data were considered under five superordinate headings which were: „living with trauma‟, „doubt and apprehension; „making safe and making sense‟, „the process of „processing‟ and „change‟. Both active and passive processes were identified within participants‟ descriptions of the process of EMDR and change. Discussion focuses on the themes in relation to previous literature and further, in respect of the unique understanding of EMDR that a qualitative phenomenological study provides. Implications for future clinical and theoretical research are suggested and the limitations and theoretical underpinnings of the study are made explicit. The conclusions drawn from the study suggest that EMDR should be viewed as a holistic approach with elements such as the development of the therapeutic alliance given equal investment to the search for the active mechanism of the bi-lateral component. Additionally, it is argued that the bi-lateral element potentially involves more than a single mechanism, particularly in relation to the enhancement of positive affect and that this would benefit from further exploration.
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Finney, Paul Anthony. "Development and characterisation of an in vivo model of β₂-adrenoceptor desensitisation in the rat." Thesis, Imperial College London, 1999. http://hdl.handle.net/10044/1/7671.
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Woodward, Clare Louise. "Processing trauma : studies into post-traumatic stress disorder, eye movement desensitisation and reprocessing and post-traumatic growth." Thesis, University of Warwick, 2001. http://wrap.warwick.ac.uk/2901/.
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While PTSD results in various symptomatology, key characteristics concern a sense of being "stuck" on the trauma which keeps the person reliving it through thoughts, feelings and images and a need to avoid anything which reminds them of the trauma. Such avoidance is suggested to prevent the opportunity for processing and integrating the distressing material. One key clinical question is how to help the person work through their trauma without them becoming overwhelmed by trauma symptoms? Eye Movement Desensitisation and Reprocessing (EMDR) is a relatively new technique that has been reported to help PTSD sufferers reduce the intensity and intrusiveness of traumatic thoughts and images. Despite the growing clinical evidence of the effectiveness of EMDR, a strong debate exists within the research literature regarding its empirical and theoretical validity. One aspect of this dissertation is an experimental study looking at the role of eye movements in Eye Movement Desensitisation and Reprocessing and testing a working memory model of "distress reduction". Of course not everyone who experiences a traumatic event will go on to develop PTSD. An often neglected area of trauma investigation is how some individuals experience positive change and personal growth as a result of their traumatic experiences. This is an area that is now beginning to receive some attention and has been termed Posttraumatic Growth (PTG). The move away from looking exclusively at the impact of trauma to consider how people who have experienced trauma might construct a more positive understanding of themselves in the light of the trauma forms the main section of this dissertation. This exploratory study uses personal experience narratives of posttraumatic growth.
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Drake, W. M. "Desensitisation of calcitonin gene-related peptide of adrenomedullin receptors in vascular smooth muscle of SK-N-MC cells." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275192.
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Lilley, Steven. "Exploring the mechanisms of action underlying eye movement desensitisation and reprocessing in the treatment of posttraumatic stress disorder." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421028.
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Brown, Simon Geoffrey Archer, and simon brown@uwa edu au. "Preventing anaphylaxis to venom of the jack jumper ant (Myrmecia pilosula)." Flinders University. School of Medicine, 2003. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20050707.103356.
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Background: Myrmecia pilosula (the jack jumper ant, JJA) is the principal cause of ant venom
anaphylaxis in Australia. Whereas honeybee and wasp venom allergy can be treated by venom
immunotherapy (VIT), no such treatment is available for ant sting allergy. In addition, information on the natural history of JJA sting allergy is required to identify those most likely to benefit from immunotherapy. The main objectives of this research were to establish: (i) the prevalence, natural history and determinants of reaction severity for JJA allergy, and; (ii) the efficacy and tolerability of JJA VIT.
Methods: A search of the Royal Hobart Hospital (RHH) forensic register, a random telephone survey, and a review of emergency department (ED) presentations were performed. Three hundred eighty-eight JJA allergic volunteers were assessed, including serum venom-specific IgE
RAST, and then followed up for accidental stings over a 4-year period. Finally, a randomised
double-blind, placebo-controlled, crossover trial of JJA VIT was performed. Laboratory parameters
measured during the trial were; leukocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry.
Findings: The prevalence of JJA sting allergy was 2.7% in the Tasmanian population, compared to 1.4% for honeybee. People aged 35 or older had a greater risk of both sting allergy and hypotensive reactions. Four deaths were identified, all in adults with significant comorbidities. During follow-up, 79 (70%) of 113 accidental jack jumper stings caused systemic reactions. Only prior worst reaction severity predicted the severity of follow-up reactions, with the majority of people experiencing similar or less severe reactions when stung again. Sixty-eight otherwise healthy JJA allergic adult volunteers were enrolled in the clinical trial. Systemic reactions to therapy were recorded in 34% during VIT. Objectively defined systemic reactions to sting challenges arose in 1/35 after VIT (mild self-limiting urticaria only) versus 21/29 in the placebo group. Treatment with oxygen, intravenous adrenaline infusion and volume resuscitation was effective and well tolerated. Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. In the placebo group, only VST and HRT were predictive of sting challenge results. Although IgE RAST, leukocyte SI and IL-4 production, LRT and BAT all correlated well with VST, they did not predict sting challenge outcome. After successful VIT, venom-induced leukocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed.
Interpretation: VIT is highly effective in prevention of JJA sting anaphylaxis and is likely to be of most benefit to people with a history of severe systemic reactions, which usually occur in people aged over 35. Neurocardiogenic mechanisms &/or direct cardiac effects may be important factors in some anaphylaxis deaths. Systemic reactions to immunotherapy are common and require immediate access to resuscitation facilities. The HRT warrants further investigation as a test for selecting those most likely to benefit from VIT. None of the tests evaluated appear to be reliable markers of successful VIT.
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van, Bysterveldt Katherine. "Role of G Protein-coupled Receptor Kinase 5 in Desensitisation of the V1b Vasopressin Receptor in Response to Arginine Vasopressin." Thesis, University of Canterbury. Biological Sciences, 2011. http://hdl.handle.net/10092/6214.
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Arginine vasopressin (AVP) is a hypothalamic nonapeptide which regulates the hypothalamic-pituitary-adrenal axis response to stress by stimulating the secretion of adrenocorticotropin (ACTH) from corticotroph cells of the anterior pituitary. This effect is mediated by binding of AVP to the pituitary vasopressin receptor (V1bR). The V1bR belongs to the G protein-coupled receptor (GPCR) super family. Repeated stimulation of anterior pituitary cells with AVP has been shown to produce a loss of responsiveness to subsequent AVP stimulation. This phenomenon appears to be mediated by desensitisation of the V1bR, and may be due to phosphorylation of the receptor by G protein-coupled receptor kinase 5 (GRK5). The aim of this research was to establish and validate methods that would allow the role of GRK5 in the desensitisation of V1bR to AVP stimulation to be investigated. As no isoform specific inhibitors for GRK5 were available, HEK293 cells transiently transfected with the rat V1bR were used as a model system for this research. This allowed RNA interference (RNAi) to be used to knockdown GRK5 expression. The protocol for RNAi-mediated knockdown of GRK5 was established as part of this research. Protocols for Western blotting and qRT-PCR were also established to allow the RNAi-mediated knockdown of GRK5 protein and mRNA to be measured. Transfection of HEK293 cells with 10nM GRK5-targeting small interfering RNAs (siRNAs) reduced the expression of GRK5 protein to 53.4% ± 3.4% (mean ± SEM) of that seen in untreated control cells at 84 hours after transfection, while GRK5 mRNA levels were reduced to 28.7% ± 1.9% (mean ± SEM) of that of control cells 48 hours after transfection.
An experimental protocol was designed in this research that would coordinate the RNAi-mediated knockdown of GRK5 with transient transfection of the HEK293 cells with the rV1bR. Since, activated V1bRs couple to Gq/11 and stimulate the production of inositol phosphates (IPs), the responsiveness of the V1bR can be determined by measuring the accumulation of [H³]-IPs in cells labelled with [H³]-myo-inositol. In the protocol designed, the effect of GRK5 knockdown on V1bR desensitisation is determined by stimulating HEK293 cells expressing the rV1bR (and previously transfected with GRK5-targeting siRNA) with 0nM or 100nM AVP for 0, 5, 15, 30 or 60 minutes, and comparing the accumulation if IPs over time with that of cells that are not transfected with GRK5-targeting siRNA. This protocol can be used in future to investigate the role of GRK5 in V1bR desensitisation, and may be adapted to determine if other GRK isoforms are involved in V1bR desensitisation.
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Munton, Richard Paul. "Investigation of protein kinase-A dependant GABAb receptor desensitisation and characterisation of a novel family 3 G-protein coupled receptor." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398537.
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Gatehouse, Michelle. "Desensitisation of the pituitary vasopressin receptor : development of a model system to assess involvement of G protein-coupled receptor kinase 5." Thesis, University of Canterbury. School of Biological Sciences, 2008. http://hdl.handle.net/10092/2627.
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The hypothalamic peptide arginine vasopressin (AVP) is an important regulator of adrenocorticotropin (ACTH) release from the anterior pituitary. AVP stimulates ACTH secretion from corticotroph cells by activating the pituitary vasopressin receptor (V1b-R), a member of the G protein-coupled receptor (GPCR) family. In vitro, repeated stimulus of anterior pituitary cells with AVP results in rapid desensitisation. The aim of this research was to develop methods needed to use RNA interference (RNAi) to investigate the role of G protein-coupled receptor kinase 5 (GRK5) in this desensitisation process. This required the development of a model system using human embryonic kidney (HEK) 293 cells transfected with the pituitary vasopressin receptor, V1b-R. AVP binding to the V1bR activates the phosphoinositide signalling pathway, leading to production of inositol phosphates (IPs), which can be measured following radiolabelling of cells with myo-[³H]inositol. Stimulation of V1b-R-transfected cells for 15 min with AVP (100nM) increased IP production to 235.5 ± 23.4 % (n=3, p<0.02) of that seen in un-stimulated control cells. Following a 5 minute pre-treatment with 5nM VP, the IP response to stimulation with 100nM VP for 15 min was reduced to 62.8 ± 9.1 % (n=4, p<0.02) of that seen in control cells that were not pre-treated. These data indicate that AVP-desensitisation can be induced and measured in V1bR-transfected HEK293 cells following a brief pre-treatment with a physiological concentration of AVP. This model system will enable RNAi to be used to investigate the role of GRK5 in AVP-desensitisation. When using RNAi, it is essential to establish that the effects observed are the result of small interfering RNA (siRNA) specific degradation of the target mRNA. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of GRK5 at the mRNA level in HEK293 cells. Human GRK5 mRNA was amplified using qRT-PCR with GRK5 specific primers, providing confirmation that GRK5 is expressed endogenously in HEK293 cells. GRK5 expression studies were carried out to evaluate whether the qRT-PCR methods developed would be suitable to measure knockdown of GRK5 mRNA using RNAi. These experiments were also designed to assess the impact of HEK293 cell culture methods on expression of GRK5. Expression of GRK5 did not vary with passage number (2-26 passages). The GRK5 expression in HEK293 cells that were maintained in culture for 5 days (grown to a confluence of approximately 100%) was 7.4 ± 0.9 fold greater (n=2, p<0.05) than for cells cultured for 3 days (grown to a confluence of approximately 65%). These data indicate that GRK5 expression is affected by HEK293 culture conditions. Furthermore, the results demonstrated that a significant difference in GRK5 expression could be measured in HEK293 cells using qRT-PCR. Therefore the results reported in this thesis provide the basis for future studies utilising RNAi to investigate mechanisms underlying V1b-R desensitisation.
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Briddon, Stephen John. "Desensitisation of the human 5-HTâ†2â†A and 5-HTâ†2â†C receptors expressed in a human neuroblastoma cell line." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318968.
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Roberts, Graham Colin. "The effects of allergic desensitisation on children with seasonal allergic asthma : symptom control and inflammation as measured by exhaled nitric oxide." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408813.
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Brooker, Mary Elizabeth. "Music performance anxiety : an investigation into the efficacy of cognitive hypnotherapy and eye movement desensitisation and reprocessing when applied to grade 8 pianists." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/12130/.
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Music performance anxiety (MPA) is widespread and has a detrimental effect on performance affecting amateur and professional musicians alike (Kenny, 2011; Wilson, 2002). Previous approaches for alleviation have focused on the conscious mind; however this research targets both the conscious and unconscious mind through two psychotherapies - cognitive hypnotherapy (CH) and eye movement desensitisation and reprocessing (EMDR). The efficacy of the therapies was investigated with 52 Grade 8 pianists at the Universities of Leeds and Sheffield and at Leeds College of Music, initially a pilot study of 6 followed by 46 in a further study. A multimodal design was adopted using four different measurements: the State-Trait Anxiety Inventory (Spielberger, 1983); a self-report questionnaire (SRQ) testing subjective anxiety; assessments of performance; and subjective perceptions of therapies pre- and post-treatment. To further support the quantitative data, qualitative investigations were conducted through the SRQ and an evaluative log of performance experiences post-research. During the research period participants were randomly assigned to a therapy or control group; the therapy groups received two interventions during a two-week period between two concerts. A significant improvement in performance was found in the therapy groups post-intervention, but not in the control; subjective levels of MPA also decreased significantly in the CH and EMDR groups. Both therapy groups demonstrated a significant reduction in state anxiety which was not evident in the control group, and trait anxiety decreased significantly below baseline levels in the therapy groups. Longitudinal testing of trait levels of anxiety at four months, one year and two years post-intervention demonstrated that significant decreases from baseline were still maintained. This finding, using a large sample, has not been previously reported and has important implications for educators, performers and future research.
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Lundengård, Karin. "De- and Resensitisation of Cardiac β-Adrenergic Receptor Signaling : A Modelling Approach." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69076.
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Desensitisation is defined as a failure of a signaling pathway to respond to chronic or repeated stimulation. The β-adrenergic receptor signaling pathway of the healthy adult heart is known to desensitise, and then regain the sensitivity to stimulation if given enough time to rest between stimulations (resensitisation). The fetal heart does not desensitise, and in animal models of heart failure, a permanent desensitisation have been observed. No isolated element of the signaling pathway have yet been proven to be the sole modulator of the desensitisation behavior. Therefore a mathematical model of the signaling pathway has been constructed, minimized against theoretical desensitisation data and tested for resensitisation. The minimal models and the original model were capable of describing the theoretical de- and resensitisation of the pathway, and only one receptor type with three states was required in the minimal models, but one feedback from the kinases either to phosphorylation of the receptor or to breakdown of cAMP. The original model was also capable of describing experimental data of contraction force from chicken cardiac tissue. The cardiac tissue displays the peak behavior of the desensitisation when stimulated with ISO for ten minutes, and resensitises in less than 5 minutes.
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D'Souza, Vijay Kenneth. "Pharmacological and molecular characterisation of P2Y receptors in endothelial and epithelial cells." Thesis, University of Wolverhampton, 2007. http://hdl.handle.net/2436/20512.
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In light of the significant modulation of receptor activity previously shown by a peptide (designated L247), designed to mimic the third extracellular loop of the human P2Y2 receptor, the aim of this study was to use this peptide as an immunogen to generate and fully characterise polyclonal rabbit antibodies to the P2Y2 receptor. Other aims of this study were to characterise epithelial and endothelial cells for a thorough expression profile of P2Y receptor mRNA transcripts in order to provide a rapid screen for the molecular determinants of these receptors in these cells. These studies also aimed to confirm previously published pharmacology, thus, to set the basis for western blot studies using P2Y receptor antibodies. Bovine aortic endothelial cells that co-express P2Y1 and P2Y2 receptors; EAhy926, a human endothelial fusion cell line, that express P2Y2 receptors; and ECV304 human bladder cancer cell line, known to express P2Y2-like and P2Y11-like receptors were used in this study. The dose dependent accumulation of inositol phosphates and cAMP response to potent P2Y11 agonists and RT-PCR studies confirmed the functional expression of both P2Y2 and P2Y11 receptors in ECV304 cells. Likewise, the dose dependent accumulation of inositol phosphates in response to potent P2Y2 and P2Y6 agonists and the presence of mRNA transcripts confirmed the expression of functional P2Y2/4- like and P2Y6- like receptors in EAhy926 cells. Polyclonal antiserum raised against L247 peptide was affinity purified and the purified fractions showed strong immunoreactivity with immobilised immunogenic antigen in ELISA. In western blot analysis L247 rabbit polyclonal anti-P2Y2 antibody detected strong bands in ECV304 and EAhy926 cells. On pre-absorption with the immunogenic peptide these responses were abolished suggesting that this antibody is antigen specific. Agonist induced P2Y2 receptor desentisation studies in ECV304 cells showed that prolonged agonist incubation caused the receptor sequestration. The loss of bands caused by P2Y2 receptor desensitisation and sequestration in membrane enriched fractions of agonist incubated ECV304 cells confirmed the specificity of L247 antibody. This antibody also showed no immunoreactivity in 1321N1 human brain astrocytoma cells devoid of any P2Y receptor subtypes cells. Deglycosylation studies revealed that the P2Y2 receptors are glycosylated in ECV304 cells. The polyclonal rabbit anti-P2Y2 receptor antibodies obtained from commercial sources produced completely different immunoreactive profiles with multiple bands even in 1321N1 cells. Furthermore, in comparison to L247 anti-P2Y2 antibody the commercial antibody showed no difference between normal and agonist incubated cells suggesting that this antibody may not be recognising the P2Y2 receptors in ECV304 cells. Likewise polyclonal rabbit antibodies to other P2Y receptors either showed no response or showed strong immunoreactive profile with multiple bands even in 1321N1 cells suggesting that these antibodies may not have been extensively characterized. Furthermore, immunofluorescence studies with commercial anti-P2Y2 antibodies showed that they may be only recognising non-denatured receptors. These studies suggest that the L247 anti-P2Y2 antibody raised against peptide designed to mimic specific region in the third extracellular loop of human P2Y2 receptor is highly specific and sensitive and provides an important tool to study endogenously expressed P2Y2 receptors in both non-denatured and denatured state. These studies indicate that this strategy of generating antibodies may be used to generate highly specific antibodies to other P2Y receptor subtypes.
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Cummings, Siobhan Anne. "Desensitisation of the Pituitary Vasopressin Receptor: Development and Use of a Stably-Transfected Model Cell System to Assess the Role of G Protein-Coupled Receptor Kinases." Thesis, University of Canterbury. School of Biological Sciences, 2011. http://hdl.handle.net/10092/5351.
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Stress impacts upon all organisms and a robust stress response is required for adaptive interactions of the organism with the environment. In most higher organisms, an individual’s response to stress is mediated by the hypothalamic pituitary adrenal (HPA) axis. Inappropriate regulation of this axis can cause debilitating mental health disorders including depression and anxiety. These disorders can affect an individual’s ability to interact and respond appropriately as different situations arise.
An important component of this axis is the vasopressin V1b receptor (V1bR), which mediates adrenocorticotropin (ACTH) secretion from the anterior pituitary in response to stimulation by arginine vasopressin (AVP). AVP also potentiates the ACTH secretion mediated by corticotropin-releasing hormone type 1 receptor (CRH-R1) in response to corticotropin- releasing hormone (CRH) stimulation. Both the V1bR and CRH-R1 are G protein coupled receptors (GPCRs). A common feature of GPCR signalling is desensitisation of the response following prolonged or repeated exposure to an agonist. Phosphorylation of the receptor is one of the mechanisms of desensitisation. This directly, or indirectly, results in rapid and reversible uncoupling of the receptor from its heterotrimeric guanine nucleotide binding protein (G-protein). Previous research has shown that G protein coupled receptor kinases (GRKs) are key phosphorylators involved in the molecular mechanism of GPCR desensitisation. One of the mains goals of the research carried out in the Mason laboratory is to examine the molecular mechanisms of V1bR desensitisation. The current short term aim is to examine the potential role for GRKs in this mechanism.
It is difficult to study a single receptor type and the molecular mechanisms involved in its regulation in a system larger than a cell based assay. As the proposed method of assessing the involvement of GRKs in desensitisation of the V1bR is to use RNA interference (RNAi) to knock down the expression of the GRKs, primary cell cultures of pituitary corticotrophs are an inappropriate choice. This is due to a number of factors, including the difficulty involved in transfecting primary cells, and the difficulty involved in interpreting the results from primary cell culture experiments as these cultures are composed heterogenous population of cells. Therefore, the main aim of this research was to develop a model cell system from an immortalised cell line, stably-transfected with the V1bR, in which the involvement of GRKs in the molecular mechanism of V1bR desensitisation could be studied. Development of stably-transfected cell lines requires substantial preliminary work and planning in order to produce a successful outcome. Once developed, characterisation of the clonal cell lines is required.
The preliminary work involved determining the cell proliferation rate of the parental cell line, plasmid sub-cloning and production of a large quantity of plasmid DNA, optimisation of the antibiotic selection conditions, and optimisation of the transfection protocol, as well as modification of the inositol phosphate (IP) assay protocol. The V1bR activates the phospholipase Cβ (PLCβ) second messenger signalling pathway in response to stimulation with AVP. This results in the production of IPs and therefore, measurement of IPs in response to AVP stimulation of cells labelled with myo-[³H]inositol can be used as an indicator of functional V1bR expression.
In this research a total of nine clonal cell lines resistant to the antibiotic G418 were generated.
Initial testing of these lines indicated that four probably expressed the V1bR and these were
selected for characterisation in greater detail. All of these four lines showed significantly
increased IP production in response to AVP stimulation (P<0.05; t-test). A significant
decrease in IP production in response to AVP stimulation following an AVP pre-treatment
was also seen with all four lines (P<0.05; t-test). Current evidence therefore suggests that the
V1bR in these clonal cell lines signals and desensitises in the normal way. Although further
characterisation of the clonal cell line is desirable, the data to date indicate that these lines
should be considered to provide an appropriate model system for examining the molecular
mechanisms involved in the regulation of the V1bR. It appears that there are some minor
differences in signalling between the clonal cell lines and therefore this should be a
consideration when deciding which line is most appropriate to use for investigating a
particular question.
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Andrews, Donna Stephanie. "Therapeutic interventions in cases of post traumatic stress disorder : investigation of the psychological processes involved in eye movement desensitisation and reprocessing and cognitive behaviour therapy, using identity structure analysis." Thesis, Ulster University, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713463.
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Eye Movement Desensitisation Reprocessing (EMDR) and Cognitive Behaviour Therapy (CBT) are both trauma- focused psychological treatments that are used specifically in the treatment of Post Traumatic Stress Disorder (PTSD). Their respective aims are to alleviate sufferers’ troubling memories of the specific trauma/s and the personal meanings of the event/s and their consequences. The study involved members of the Police Service of Northern Ireland (PSNI) who had been exposed to, or involved with, either single or multiple traumatic incidents, and as a result had been diagnosed with PTSD. The research explored the nature of self and identity redefinition in the police officers that had received either EMDR or CBT intervention. Using a two phase design, in-depth analysis of each person’s identity was conducted, indicating inner psychological processes before and after intervention. Aspects of their identities had changed considerably from phase 1 (pretherapy) through to phase 2 (post therapy) evidencing the effects of therapy on ongoing psychological processes (identity redefinition). The approach used in the study involved two main elements that included case study approach (in the form of semi-structured interviews) and Identity Structure Analysis (ISA) instrument. Generic themes from all of the respondents were identified based on previous literature reviews coupled with ethnographic work, such as interviews. The results indicated that no major differences in terms of clinical outcomes were found between EMDR and CBT. Limitations of the study acknowledged more time was required to enable a further phase, and a larger sample size needed for comparative analysis. The NICE evidence update (NICE, 2013) to the guidelines for the management for PTSD (NICE, 2005) acknowledges that the evidence is still very limited with no comparison studies between CBT and EMDR. The results highlighted there is further specific research required between the two interventions in terms of specific cohorts, such as police personnel. The contribution of this study to theory, knowledge and understanding highlighted the importance and need for further research in terms of treating PTSD with comparative studies between CBT and EMDR.
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Carrat, Gaëlle. "La voie de signalisation ERK1/2 couplée au récepteur 5-HT4 et sa régulation par GRK5." Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20187/document.
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Les récepteurs couplés aux protéines G (RCPG) peuvent activer des voies de signalisation indépendantes des protéines G. Cependant, la régulation de ces voies, et en particulier leur désensibilisation, est peu connue. Le récepteur de la sérotonine de type 4 (R-5-HT4) est un RCPG exprimé dans le cerveau et les organes périphériques. Il est impliqué dans des fonctions physiologiques importantes comme la mémoire, l'apprentissage, la prise de nourriture, le contrôle respiratoire et la mobilité gastro-intestinale. Le R-5-HT4 est couplé à la protéine Gs. De plus, il active la voie Src/ERK1/2, indépendamment des protéines G et des β-arrestines.Nous avons montré que GRK5, physiquement associé à la région C-terminale (C-ter) du R-5-HT4 inhibait la voie Src/ERK1/2 couplée au récepteur, mais pas la voie Gs. Ce résultat a été observé dans la lignée de cellules HEK-293 mais aussi dans des neurones de collicules en culture. Cette inhibition nécessite deux séquences d'évènements : l'association de la β-arrestine1 à une région riche en sérines et thréonines, localisée dans le domaine C-ter du récepteur et la phosphorylation par GRK5, de la β-arrestine1 (en sérine 412) liée au récepteur. La β-arrestine1 phosphorylée empêche l'activation de Src, constitutivement liée au récepteur, nécessaire à l'activation d'ERK1/2. Ceci constitue la première démonstration que la phosphorylation d'une β-arrestine par une GRK régule la signalisation indépendante des protéines G. En plus de ces résultats, nous avons démontré que l'activation d'ERK1/2 par le R-5-HT4, indépendante des β-arrestines, implique la libération d'un ligand induite par une métalloprotéase, conduisant à la transactivation d'un autre récepteur. Par une approche protéomique, nous avons également identifiés plusieurs partenaires potentiels du R-5-HT4. L'étude de ces partenaires pourrait apporter un éclairage supplémentaire sur les voies de signalisation du récepteur et leur régulationG protein-coupled receptors (GPCRs) have been found to trigger G protein-independent signalling. However, the regulation of G protein-independent pathways, especially their desensitization, is poorly characterized.The 5-Hydroxytryptamine 4 receptor (5-HT4R) is a GPCR widely expressed in the brain and at the periphery. It is implicated in important physiological functions such as memory, cognition, feeding, respiratory control and gastrointestinal motility. 5-HT4R couples to the Gs/cAMP/PKA pathway. Moreover, this receptor can activate a Src/ERK pathway independently of both G proteins and β-arrestins.Here, we show that the G protein-independent 5-HT4R-operated Src/ERK pathway, but not the Gs pathway, is inhibited by GPCR kinase 5 (GRK5), physically associated with the proximal region of receptor C-terminus, in both HEK-293 cells and colliculi neurons. This inhibition requires two sequences of events: the association of β-arrestin1 to a phosphorylated serine/threonine cluster located within the receptor C-terminal domain and the phosphorylation by GRK5 of β-arrestin1 (at Ser 412) bound to the receptor. Phosphorylated β-arrestin1 prevents in turn activation of Src constitutively bound to 5-HT4R, a necessary step in receptor-stimulated ERK signalling. This is the first demonstration that β-arrestin phosphorylation by a GRK regulates G protein-independent signalling.In addition to these results, we also demonstrated that the β-arrestin-independent activation of ERK1/2 by the 5-HT4R involves a metalloprotease-dependant ectodomain shedding and transactivation of another receptor. By a proteomic approach, we also identified several potential partners of the 5-HT4R. Study of these proteins may provide a better understanding of 5-HT4R signalling and his regulation
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Amano, Tamaki. "The role of alternating bilateral stimulation in establishing positive cognition in EMDR therapy: a multi-channel near-infrared spectroscopy study." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225519.
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Boterman, Mark. "Heterologous amplification of homologous [beta]-adrenoceptor desensitization in airway smooth muscle implications for asthma? /." [S.l. : Groningen : s.n. ; University Library Groningen] [Host], 2006. http://irs.ub.rug.nl/ppn/292617194.
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Bodill, Brigitte. "Patterns of reduction of distress in clinical conditions using eye movement desensitisation and reprocessing (EMDR)." Thesis, 2009. http://hdl.handle.net/10413/1002.
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Almeida, Vanessa Alexandra Gomes. "Relatório de Estágio e Monografia Intitulada" Potencial da capsaicina no tratamento tópico de patologias associadas a dor neuropática"." Master's thesis, 2019. http://hdl.handle.net/10316/88262.
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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaOs produtos à base de plantas são uma alternativa ou complemento terapêutico cadavez mais procurada pela população em geral. Os principais motivos prendem-se pelo factode o conhecimento sobre esta área estar a aumentar no que respeita, principalmente, adados de eficácia e de segurança.Neste âmbito, esta monografia pretende demonstrar as potencialidades da capsaicina,um importante constituinte ativo de várias espécies do género Capsicum L., no tratamento depatologias associadas a dor neuropática, nomeadamente na nevralgia pós-herpética,neuropatia diabética e neuropatia periférica associada ao VIH. O objetivo é perceber os seusmecanismos de ação e se os efeitos da capsaicina são benéficos e seguros para o Homem.Pode concluir-se, pelos estudos realizados até ao momento, que a capsaicinaapresenta atividade no alívio de patologias associadas à dor neuropática, contribuindo para obem-estar dos doentes. Um número significativo de doentes relata um alívio relativamenterápido e duradouro da dor. Para além disso, os efeitos adversos são essencialmente no localda aplicação, sendo considerados leves a moderados e limitados no tempo. Uma dasprincipais vantagens reside no facto de não ser absorvida na corrente sanguínea. Por estemotivo, pode ser usada por doentes polimedicados, com patologias renais ou hepáticas, ouque não tolerem a medicação convencional para o tratamento destas patologias associadas àdor neuropática.Neste sentido, mais estudos são ainda necessários, nomeadamente ensaios clínicos,incluindo um maior número de doentes e um tempo de seguimento superior, de modo agarantir de forma clara a sua eficácia e segurança.
Herbal products are an alternative or therapeutic supplement that population, ingeneral, seek more and more nowadays. The main reasons are that knowledge about thisarea is increasing concerning mostly efficacy and safety data.In this context, this monograph aims to demonstrate the potentialities of capsaicin, animportant active constituent of several species of the genus Capsicum L., in the treatment ofpathologies associated with neuropathic pain, particularly post-herpetic neuralgia, diabeticneuropathy and peripheral neuropathy associated with HIV. The goal is to understand theirmechanisms of action and whether the effects of capsaicin are beneficial and safe for humans.It can be concluded from early studies that capsaicin has activity in the relief ofpathologies associated with neuropathic pain, contributing to the well-being of patients. Asignificant number of patients report relatively rapid and sustained pain relief. In addition,adverse effects are primarily at the application site and are considered mild to moderate andtime-limited. One of the main advantages is that it is not absorbed into the bloodstream. Forthis reason, it can be used by polymedicated patients, with renal or hepatic pathologies, orwho do not tolerate conventional medication for the treatment of these pathologiesassociated with neuropathic pain.In this regard, more studies are still needed, including clinical trials, with a largernumber of patients and a longer follow-up time, in order to clearly guarantee their efficacyand safety.