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The role of haem in the mechanism of action of antimalarials in Plasmodium falciparumCombrinck, Jill Michelle January 2016 (has links)
The malaria parasite detoxifies host red blood cell derived haem by conversion into the inert biocrystal haemozoin. Inhibiting this critical pathway is proposed to be the mechanism of action of chloroquine and related antimalarials and several studies have linked inhibition of the formation of synthetic haemozoin, β-haematin, to parasite survival. However, haemozoin inhibition with a dose related increase in "free" haem correlated to decreased survival has not been demonstrated in the parasite. This project investigated the role of haem in the mechanism of action of several clinically relevant and novel antimalarials in the malaria parasite, Plasmodium falciparum.
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A study of the antiherpes simplex virus type 1 properties of barringtonia racemosaPefile, Sibongile C January 2001 (has links)
Bibliography: leaves 198-216. / The study of the aqueous extract of Barringtonia racemosa has produced strong indication of antiviral effect against herpes simplex virus type 1 in vitro.
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Isolation and characterization of antiplasmodial compounds from Siphonochilus aethiopicus and Aloe ferox and bioavailability of a novel furanoterpenoidLategan, Carmen January 2008 (has links)
Includes abstract.
Includes bibliographical references (leaves 138-162).
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The role of the pharmacokinetics, host folate levels and parasite mutations in the in vivo efficacy of pyrimethamine-sulfadoxine against Plasmodium falciparumDzinjalamala, Fraction Kunseu January 2003 (has links)
Includes bibliographical references.
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A study of the antimalarial action of Pyronaridine and its accumulation into Plasmodium falciparumMtegha, Chikumbusko J January 2004 (has links)
Includes abstract. / Includes bibliographical references. / Pyronaridine (PND), a hydroxyanilino-benzonaphthyridine derivative and also a structural analogue of chloroquine, was synthesized in China in the 1970s as a result of a search for alternative drugs to treat chloroquine-resistant (CQR) Plasmodium falciparum malaria.
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Characterisation of Mefloquine accumulation in Plasmodium falciparumWalden, Jason C January 2003 (has links)
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.
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Chloroquine accumulation in Plasmodium falciparum isolated digestive vacuolesSaliba, Kevin John January 1997 (has links)
Due to the development of drug-resistance by Plasmodium falciparum, the utilisation of chloroquine, a cheap and effective antimalarial has become limited. The mechanism of chloroquine-resistance is, at best, unresolved. This thesis describes an investigation of chloroquine accumulation in pure and intact Plasmodium falciparum isolated digestive vacuoles, the site of chloroquine accumulation and action. Marker enzymes and gel electrophoresis were used to demonstrate purity, and electron microscopy to verify integrity of isolated vacuoles. Using this method, vacuoles were isolated in a yield high enough to enable characterisation of chloroquine accumulation in this organelle in terms of time-, temperature-, Mg²⁺-, pH-, ATP- and other nucleotide-dependence. The chloroquine accumulating capabilities of vacuoles isolated from chloroquine-resistant and chloroquine-sensitive parasites were compared. At an external chloroquine concentration of 100 and 250nM vacuoles isolated from two chloroquine-sensitive strains accumulated significantly more chloroquine (± 3 x) than those isolated from three of the four chloroquine-resistant strains of Plasmodium falciparum tested. Although it is often suggested that the parasite digestive vacuole is involved in the mechanism of chloroquine-resistance, this is the first direct evidence to suggest this. Vacuolar proton pump inhibitors, proton gradient dissipaters, P-glycoprotein ATPase- and drug transport-inhibitors, weak bases, and structural analogues of chloroquine were used to examine the driving force of chloroquine accumulation in the isolated food vacuole. A pH gradient between the vacuole and cytoplasm is necessary to retain chloroquine in this organelle, but a chloroquine transport mechanism appears to be the main driving force in chloroquine accumulation. A polyclonal antibody directed at Pgh1, a Plasmodium falciparum homologue of P-glycoprotein, confirmed its presence on the vacuole, but was unable to inhibit chloroquine accumulation in isolated vacuoles. This thesis also shows that agents, such as verapamil, which are able to reverse chloroquine-resistance by increasing chloroquine accumulation in parasitised erythrocytes, are unable to increase chloroquine accumulation in the isolated vacuole, suggesting the involvement of an alternate site for the reversal of chloroquine-resistance.
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Determinants and consequences of the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol in a cohort of tuberculosis patientsMcIlleron, Helen January 2004 (has links)
Includes bibliographical references (leaves 190-203). / A prospectlve pharmacokinetic study was conducted amongst a cohort of 142 patients with tuberculosis (TB) susceptible to rifampicin and isoniazid at Brewelsleloof Hospital, Worcester, in the Western Cape.
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Isolation and characterisation of antiplasmodial compounds from Xerophyta species and the bioavailability, metabolic and efficacy evaluation of 9-0-acetylhydnocarpin in a mouse modelWiesner, Lubbe January 2008 (has links)
Includes abstract.
Includes bibliographical references (leaves 237-265).
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Antimalarial activity and pharmacokinetic properties of new chemical entitiesDambuza, Ntokozo Shirley January 2013 (has links)
Includes abstract.
Includes bibliographical references.
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