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Characterisation of Mefloquine accumulation in Plasmodium falciparum
Includes bibliographical references (leaves 165-180).
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Division of Clinical Pharmacology
2014
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| _version_ | 1867613157734744064 |
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| access_status_str | Open Access |
| author | Walden, Jason C |
| author2 | Smith, Peter |
| author_browse | Smith, Peter Walden, Jason C |
| author_facet | Smith, Peter Walden, Jason C |
| author_sort | Walden, Jason C |
| collection | Thesis |
| description | Includes bibliographical references (leaves 165-180). |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/8601 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:31:41.113Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Division of Clinical Pharmacology |
| publisherStr | Division of Clinical Pharmacology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/8601 Characterisation of Mefloquine accumulation in Plasmodium falciparum Walden, Jason C Smith, Peter Folb, Peter I Pharmacology Includes bibliographical references (leaves 165-180). Mefloquine has been in use for over twenty years and still very little is known about its interaction with Plasmodium falciparum. In 1979, Fitch er al carried out the only other published extensive investigation of mefloquine accumulation, but were not able to demonstrate energy dependent uptake. They later indicated that an energy requirement may be being masked by mefloquine’s ability to bind membrane phospholipids to a large extent (Chevli & Fitch, 1982).Until now no energy requirement for mefloquine accumulation has been uncovered. This thesis investigates the relationship between chloroquine and mefloquine resistance, and characterizes the mechanism of mefloquine accumulation in Plasmodium falciparum. Conditions were established that enabled the amplification of the parasites' contribution to overall mefloquine accumulation in the parasitised erythrocyte. It was found that mefloquine accumulation is stimulated by glucose and is inhibited by the glycolysis inhibitor, iodoacetate, and also by incubation at low temperature. Mefloquine accumulation was also found to be partly dependent on the pH gradient between the acidic food vacuole and the external medium. It has also been determined that mefloquine-resistant Plasmodium falciparum accumulate approximately half the amount of mefloquine than do mefloquine-sensitive parasites. It has been shown that the accumulation of both chloroquine and mefloquine have two components, a high affinity saturable component and a low affinity non-saturable component (Fitch et aI., 1979; Fitch et al., 1974; Bray et al., 1998). The saturable component has been well characterized, but until now the non-saturable component has not been identified. This thesis shows that chloroquine and mefloquine adsorption to synthetic β-haematin and pure isolated haemozoin is non-saturable. It is proposed that the malaria pigment is responsible for the low affinity, non-saturable component of chloroquine and mefloquine accumulation. The effect of chloroquine, mefloquine and artemisinin on haemoglobin levels in parasitised erythrocytes was also measured. Chloroquine caused a buildup in haemoglobin and mefloquine caused a decrease in haemoglobin levels. This adds weight to previously published work (Famin & Ginsburg, 2002) suggesting that chloroquine prevents the degradation of haemoglobin, while mefloquine inhibits the endocytosis of haemoglobin. 2014-10-18T06:00:02Z 2014-10-18T06:00:02Z 2003 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/8601 eng application/pdf Division of Clinical Pharmacology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Pharmacology Walden, Jason C Characterisation of Mefloquine accumulation in Plasmodium falciparum |
| thesis_degree_str | Doctoral |
| title | Characterisation of Mefloquine accumulation in Plasmodium falciparum |
| title_full | Characterisation of Mefloquine accumulation in Plasmodium falciparum |
| title_fullStr | Characterisation of Mefloquine accumulation in Plasmodium falciparum |
| title_full_unstemmed | Characterisation of Mefloquine accumulation in Plasmodium falciparum |
| title_short | Characterisation of Mefloquine accumulation in Plasmodium falciparum |
| title_sort | characterisation of mefloquine accumulation in plasmodium falciparum |
| topic | Pharmacology |
| url | http://hdl.handle.net/11427/8601 |
| work_keys_str_mv | AT waldenjasonc characterisationofmefloquineaccumulationinplasmodiumfalciparum |