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Analysis of Small Molecule Analogues of the helminth immunomodulator ES-62 for inhibitory effects on mast cell function - Dissertation Example

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Contents Summary Acknowledgements Contents page 1, Introduction 1.1, Filarial nematode 1.2, ES-62 and its structure 1.3, Immunomodulatory Properties of ES-62 1.4, Mast Cells 1.5, Function of ES-62 on mast cells 1.6, Evidence of ES-62 mechanism of action 1.7, Small Molecule Analogues 1.8, Aim 2, Materials and Methods 2.1, Reagents 2.2, Buffers 2.3, Methods 3, Results 3.1, Mast cells Degranulation Assay 3.2, ELISA to measure cytokines (IL-6 and TNF-?…
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Analysis of Small Molecule Analogues of the helminth immunomodulator ES-62 for inhibitory effects on mast cell function
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Download file to see previous pages However, particularly in countries where helminth infections are endemic, these diseases remain comparatively rare. There is increasing evidence indicating that helminth infections and inflammatory diseases share an inverse relationship. Therefore, helminths have been the focus of recent studies. William Harnett and his team discovered an immunomodulator ES-62 secreted by a parasitic worm that is known to hold a strong cure for allergic and autoimmune diseases, such as asthma and arthritis. However, there are some practical implications associated with a high level of ES-62 production that renders it unable to be used as a drug. Hence, it is hypothesized that synthesis of ES-62 derived SMAs based around its Phosphorylcholine moiety can mimic the effect of the parent molecule and have a potential to be used as a drug for clinical trials. This project investigated the effect of SMAs on mast cells by implementing the Rat Basophilic leukaemia degranulation assay in which SMA 53 and SMA S3 were found to inhibit Fc?RI-mediated mast cell proliferation. Also, a substantial decrease was observed in IL-6 and TNF-? cytokines production. The data presented here established that some SMAs certainly have potential to induce the same effects as ES-62 and thus to be used as a therapeutic agent. Introduction Tropical parasites disease affects millions of people throughout the developing world. These infectious diseases cause long term suffering which leads to significant economical damage. For this reason, The World Health Organization has committed to fight and extirpate many of the most costly diseases (W.H.O, 1990). 1.1 Filarial nematode Filarial nematodes are thread like worms that infect up to 1/3 of the human population and cause diseases such as river blindness and elephantiasis (Harnett and Harnett, 2010). People infected by these worms appear to be comparatively asymptomatic, even when they are carrying a noticeable parasite burden (Harnett et al., 2010). According to a number of reviews, infected individuals can harbour more than one type of parasite, but major tissue habitants of humans are the filarial nematodes which usually live in the lymphatic system or the subcutaneous tissue (Harnett and Harnett, 2008a; Schmidt and Roberts, 1989). Infection with such worms is transmitted to humans by blood-sucking insects that act as an intermediate host; they do this by transferring L3 stage larvae to humans (Harnett and Harnett, 2008a). Fig. 1: This diagram illustrates the life cycle of filarial nematode and how the worm is transmitted into the human body [6]. The duration of these infections are very long as an individual worm can survive for up to 10 years, which indicates the importance of this parasitic worm in the medical field (Harnett et al., 2010; Harnett and Harnett, 2008a; W.H.O, 2000). Over the past decade it has been hypothesised that filarial nematodes may protect against autoimmune and allergic inflammations. For this reason, parasitic nematodes have been involved in many recent studies and there is now enough evidence to prove that nematode-derived immunomodulators play a fundamental role in preventing inflammatory diseases in the human populat ...Download file to see next pagesRead More
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