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dc.contributor.advisorEhrhardt, Carsten
dc.contributor.authorAl-Shamkawy, Awfa
dc.date.accessioned2018-06-20T13:34:38Z
dc.date.available2018-06-20T13:34:38Z
dc.date.issued2016-05-26
dc.description.abstractTuberculosis (TB) is an infectious disease that represents a serious global threat, with estimations suggesting that one third of the world’s population is infected. Treating TB today requires long treatment duration and medicines must be administered orally in large doses, which leads to non-compliant patients. CPZEN-45 is a novel anti-TB drug candidate in pre-clinical development, in which pulmonary drug delivery has been proposed. As a part of the ongoing characterisation of CPZEN-45, the drug was tested for its ability to reduce the inflammation marker release in vitro on two types of immune cell lines; human monocytic cells (THP-1) and human mast cells (HMC-1). THP-1 cells were differentiated to a macrophage-like phenotypes and stimulated with lipopolysaccharide, and treated with CPZEN-45. A sandwich ELISA was performed to measure the tumour necrosis factor-α (TNF- α) release from THP-1 cells. HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, to initiate degranulation, the release of the enzyme β-hexosaminidase in particular. The cells were then compared with controls treated with only CPZEN-45, regarding their β-hexosaminidase release. Main findings showed that CPZEN-45 had an inhibitory effect on the TNF-α expression levels. THP-1 cells incubated with CPZEN-45 for 3 and 6 hours showed a decreasing trend in the TNF-α release profile with increasing CPZEN-45 concentrations. Interestingly, the findings also suggest that CPZEN-45 had an improved inhibitory effect on the TNF-α release, as the TNF-α expression level increased in the THP-1 cells. The degranulation assay showed a little increase in the release of β- hexosaminidase in cells treated with only CPZEN-45, compared to cells stimulated with PMA/ionomycin. CPZEN-45 is a promising anti-TB drug candidate, which seems to inhibit the inflammation in THP-1, while initiating a modest degranulation in HMC-1 cells. However, more repetitions are needed to ascertain the findings. Furthermore, it would be interesting to test the drug’s potential in other pulmonary cell lines, i.e. lung epithelial cells and other inflammatory cytokines, i.e. histamineen_US
dc.identifier.urihttps://hdl.handle.net/10037/12928
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2016 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)en_US
dc.subject.courseIDFAR-3911
dc.subjectPharmacyen_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728en_US
dc.titleInteraction of CPZEN-45, a novel anti-tubercular drug candidate, with immune cells in vitroen_US
dc.typeMaster thesisen_US
dc.typeMastergradsoppgaveen_US


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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
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