Analysis of Small Molecule Analogues of the helminth immunomodulator Dissertation

Analysis of Small Molecule Analogues of the helminth immunomodulator ES-62 for inhibitory effects on mast cell function - Dissertation ExampleHowever, particularly in countries where helminth sullyions are endemic, these diseases remain relatively rare. There is increasing evidence indicating that helminth infections and inflammatory diseases share an inverse relationship. Therefore, helminths support been the focus of new-made studies. William Harnett and his team discovered an immunomodulator ES-62 secreted by a parasitical worm that is k presentlyn to hold a well-set cure for allergic and autoimmune diseases, such as asthma and arthritis. However, there are some matter-of-f scrap 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 discount 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 f or 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 pro livenessration. 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 hirudineans disease affects millions of people throughout the developing world. These infectious diseases cause big term suffering which leads to significant economical damage. For this reason, The World Health Organization has committed to fight and destroy 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 Harnet t, 2010). population 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 image 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, 2 008a W.H.O, 2000). Over the past decade it has been hypothesised that filarial nematodes may comfort 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