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Dissertations / Theses on the topic 'Chloroquine'
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1
Mahon, Gerald J. "Studies on chloroquine retinopathy." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388235.
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LAGARDE, CLAIRE. "Intoxication aigue par la chloroquine." Lille 2, 1997. http://www.theses.fr/1997LIL2P052.
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Eliot, Marc. "La chloroquine : aspect toxicologique actuel." Lyon 1, 1990. http://www.theses.fr/1990LYO1M243.
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Caliez, Catherine. "Contribution au dosage immunochimique de la chloroquine dans les milieux biologiques." Paris 5, 1988. http://www.theses.fr/1988PA05P608.
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Kendrick, Kelsie Lynn. "Mimicking Metabolism of a Reversed Chloroquine Antimalarial." PDXScholar, 2014. https://pdxscholar.library.pdx.edu/open_access_etds/2085.
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The aim of this study was to elucidate the oxidation products of a candidate antimalarial drug, PL69, using a porphyrin system and to determine the accuracy of the oxidation products produced, as compared to what is expected in metabolism. PL69 is a reversed chloroquine (RCQ) that is active against chloroquine resistant malaria. Porphyrin oxidation systems have been shown to mimic in vitro enzymatic metabolism reactions. PL69 and its known metabolite, PL16, were incubated with the porphyrin system, and then the oxidation products were collected and separated by HPLC. The oxidation products were characterized by NMR and mass spectrometry and compared to previous metabolism studies of PL69 with liver microsomes. The results of this research show that this porphyrin system is an acceptable mimic of in vitro metabolism methods for RCQs and provides a good framework for understanding the types of metabolism that will occur in vivo for RCQs.
6
Onde, Olivier. "Actualités en réanimation pré-hospitalière et hospitalière immédiate des intoxications aigues par la chloroquine." Montpellier 1, 1989. http://www.theses.fr/1989MON11325.
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Jehl, Patrick. "Mécanismes de la chloroquinorésistance chez "Plasmodium falciparum" : intérêt de l'étude de la multirésistance des cellules cancéreuses." Paris 5, 1989. http://www.theses.fr/1989PA05P070.
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Ng, Anna. "Taste-masked and controlled-release formulations of chloroquine." Thesis, University College London (University of London), 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267929.
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Saliba, Kevin John. "Chloroquine accumulation in Plasmodium falciparum isolated digestive vacuoles." Doctoral thesis, University of Cape Town, 1997. http://hdl.handle.net/11427/26631.
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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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Murphy, Kevin Vincent. "Design and Synthesis of Novel Chloroquine-based Antimalarials." PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2623.
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Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. It is imperative that a new pipeline of drugs be developed in order to combat the disease and anticipated resistance. Reversed chloroquines are a new class of multiple-ligand compounds that are active against chloroquine-sensitive and chloroquine-resistance malaria species. This thesis describes research targeted at the modification of lead reversed chloroquine molecules to discover new and effective moieties, as well as to improve pharmacokinetic-related properties. An especial emphasis of this project is the addition of a sulfonamide functional group to a reversed chloroquine. Preliminary evidence indicates that this is a promising direction for this line of research. Brief discussions of some reversed chloroquine characterization studies are included in appendices.
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Tesfaselassie, Elias Sibhatu. "Antimalarial Drug Discovery using Triazoles to Overcome Chloroquine Resistance." PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2506.
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Malaria is considered as one of the most prevalent and debilitating diseases affecting humans. Plasmodium falciparum is the most virulent form of the parasite which developed resistance to several antimalarial drugs. Chloroquine is one of the most successful antimalarials developed that is safe, effective, and cheap. However, its use has been limited due to the emergence of drug resistance. Click chemistry, particularly, the copper(I)-catalyzed reaction between azides and alkynes has shown to have a cutting-edge advantage in medicinal chemistry by its reliability, selectivity and biocompatibility.
Triazole-based antimalarials were synthesized via copper(I)-catalyzed alkyne-azide cycloaddition reaction by modifying the aliphatic chains terminal of chloroquine. The compounds synthesized contain triazole ring directly connected to an aromatic ring or via a piperazine linker. When tested for their in vitro antimalarial activity against D6, Dd2 and 7G8 strains of P. falciparum, 12 out of 28 compounds showed better activity against chloroquine resistant strains. Particularly, PL403 and PL448 exhibited potent activity than chloroquine against CQ-resistant strains Dd2 and 7G8, with IC50 values of 12.8 & 14.5 nM, and 15.2 & 11 nM respectively.
The efficiency of synthesizing several triazole-based antimalarials have proven click chemistry to be fast and efficient reaction. Generally, para-substitutions and di-substitutions with electron-withdrawing groups were found to be beneficial for having better antimalarial activity for these group of click compounds. Moreover, the incorporation of piperazine linker has brought an enhanced antimalarial activity.
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Bot, Ba Njock Simon. "Chloroquine chez l'enfant impalude : étude de la pharmacocinétique et réponses clinique et parasitologique compte tenu des conditions du terrain." Paris 5, 1991. http://www.theses.fr/1991PA05P080.
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Biarnais, Tiphaine. "Modifications de la schizogonie et de la gamétocytémie en réponse à la chloroquine chez certains Plasmodium de Muridés." Tours, 2002. http://www.theses.fr/2002TOUR3303.
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Les phénomènes de résistance des Plasmodium aux médicaments sont impliqués dans l'extension du paludisme, ainsi que les variations de production des gamétocytes (stade responsable de la transmission) en présence de chimiothérapie médicamenteuse. Afin de mieux comprendre ces mécanismes, nous avons réalisé l'étude suivante sur des Plasmodium de muridés africains transmis à la souris blanche. Dans la première partie, nous avons étudié les différences schizogoniques induites par pression de chloroquine sur deux souches de Plasmodium, P. Berghei NK 65 et P. Berghei ANKA. Les deux souches, pourtant très proches, réagissent de façon distincte à cette pression médicamenteuse et les résultats obtenus pour la synchronicité et la chimiorésistance sont très différents en raison de l'affinité propre de chaque souche pour les réticulocytes, et de l'action de la chloroquine, qui favorise une augmentation de la synchronicité en détruisant les stades parasitaires autres que les mérozoi͏̈tes. Dans le deuxième partie, nous avons étudié l'effet d'une pression infracurative de chloroquine sur la production de gamétocytes de quatre souches de Plasmodium de chloroquinosensibilité différente. Dans les quatre cas, on observe une augmentation significative de la production de gamétocytes dans le lot traité. Il n'y a pas de corrélation entre le niveau de chimiorésistance naturelle et la quantité de gamétocytes produits, que ce soit sous l'effet ou non de la chloroquine : elle modifie la quantité de gamétocytes produits par rapport au lot témoin mais le nombre de gamétocytes produits semble respecter un classement par espèce et ce classement n'est pas modifié par le médicament.
14
Maalla, Mahmalgi Jamila. "Mode d'action des antimalariques : détermination des sites de concentration des amino-4 quinoléïnes et des compartiments acides parasitaires chez des souches de Plasmodium berghei sensibles et résistantes à la chloroquine." Lille 1, 1987. http://www.theses.fr/1987LIL10159.
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How, Cheong Wen How Chan. "Paludisme chloroquinorésistant : à propos de 17 observations de chloroquinorésistance clinique observées entre 1986 et 1988." Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR1M181.
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Yvette, Mofenge Opute. "Novel adamantane-chloroquinolin conjugates to overcome plasmodium falciparum chloroquine resistance." University of the Western Cape, 2017. http://hdl.handle.net/11394/5930.
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Magister Scientiae - MSc (Pharmaceutical Chemistry)Malaria poses devastating health and socioeconomic outcomes on global health especially among pregnant women and children below the age of 5 in endemic areas. This is exacerbated by Plasmodium falciparum resistance to available antimalarial drugs, especially chloroquine (CQ), which was the drug of choice for many years against the blood stage of malaria.
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Boulter, Matthew K. "Aspects of chloroquine resistance and its reversal in Plasmodium falciparum." Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240437.
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Nweneka, Chidi Victor. "Chloroquine as a therapeutic option for mild post malaria anaemia." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2622/.
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Background: The relative importance of malaria anaemia as a cause of childhood morbidity and mortality varies between and within regions. However, malaria anaemia remains an important cause of childhood morbidity and mortality. It has been estimated that globally, severe malaria anaemia occurs 1.42 to 5.66 million times per annum and kills an estimated 190,000 to 974,000 under-5 children. Studies from different countries endemic for malaria have emphasised the importance of anaemia in malaria-associated morbidity and mortality. Most of these studies have conclusively shown that severe malaria anaemia increases the risk of death in children with malaria; and in many reports, children with severe malaria anaemia often die before blood transfusion could be commenced. In addition, blood transfusion, which is the standard management for severe malaria anaemia, apart from not being available in many rural clinics, exposes the child to transfusion related infections such as human immunodeficiency virus (HIV). Better understanding of the pathogenesis of malaria anaemia therefore will enhance its prevention and management. The pathogenesis of malaria anaemia is multifactorial and involves such mechanisms as immune and non-immune mediated haemolysis of parasitized and non-parasitized erythrocytes, bone marrow dysfunction, altered cytokine balance, nutritional deficits and interactions with common haemoglobinopathies and red cell defects such as glucose-6-phosphate dehydrogenase (G6PD) deficiency. An important component of the pathogenesis of malaria anaemia is iron delocalisation characterised by the sequestration of iron by the reticulo-endothelial tissues (the monocyte-macrophage system) as a result of malaria-induced inflammation. Iron sequestration creates a state of false iron deficiency which recovers after the inflammation has subsided. Therefore if the malaria-induced inflammation can be resolved more quickly, the degree and duration of malaria anaemia will be reduced. In addition, since the destruction of non-parasitized erythrocytes accounts for more than 90% of erythrocyte loss, use of anti-inflammatory drugs could minimize red cell loss. Chloroquine is an antimalarial with proven anti-inflammatory properties. In addition, it is cheap, safe and has been shown to reduce iron delocalisation in vitro. A proof of concept study was designed to investigate its potential use in the management of children with mild malaria anaemia. Aims and hypothesis: The goal of the study was to investigate the effect of acute and continuing administration of chloroquine on haemopoietic response after a malaria episode. My hypothesis was that the anti-inflammatory and anti-macrophageal iron-loading effects of chloroquine will enhance erythropoietic recovery after a malaria episode. Methodology: The study was designed as a randomised placebo controlled trial and was conducted over two malaria seasons. In the first year, the study consisted of four arms with a 2x2 design and only two arms in the second year. In the first year, the participants were initially randomised to receive antimalarial treatment with either chloroquine-sulphadoxine-pyrimethamine or co-artemether. All children with negative peripheral smear for malaria parasite by day three were subsequently randomised to receive either weekly chloroquine or weekly placebo until day 90. In the second year of the study, all the children were initially treated with co-artemether; subsequently, those with negative peripheral smear for malaria parasites were randomised to weekly chloroquine or weekly placebo as in the first year. Children randomised to weekly chloroquine and weekly placebo were followed up for three months. Various clinical and laboratory measurements were conducted on days 0, 3, 7, 15, 30, 45, 70 and 90. In year two of the study, no data were collected on days seven and 70. The main outcome measure was change in haemoglobin from day three to day 30 and from day three to day 90. Other outcome measures were 1. Changes in Hb in the placebo arms of the CQ-SP and ACT treatment groups 2. Changes in measures of inflammation – neopterin and cytokines 3. Changes in markers of iron status 4. Prevalence of sub-microscopic parasitaemia Results: In 2007, 1445 children were placed under malaria surveillance, of which 105 malaria cases were recorded and 61 completed the 90 days follow-up. In 2008, of 1220 children under surveillance, 49 malaria cases were recorded, and 31 completed 90 days follow-up. There was no difference in Hb change from day three to day 30 and from day three to day 90 between the weekly chloroquine and weekly placebo arms. Although not statistically significant, the Hb change in children treated CQ-SP in 2007 was nearly twice the change in children treated with ACT at both days 30 and 90. The changes in the markers of iron status – MCV, MCH and ZnPP did not differ by treatment group and by randomisation group. During the acute malaria phase, neopterin concentration was high but by day 15, the levels had fallen to near zero levels and remained at this low level until day 30. Prevalence of sub-microscopic parasitaemia in the group was 15.1% and was similar in both randomisation arms. Iron deficiency was highly prevalent among the study participants. The independent predictors of Hb change were Hb at day 0, presence of iron deficiency, age of the child and height-for-age z score. Conclusions: Giving weekly chloroquine at a dose of 5mg/kg to children with mild anaemia associated with malaria did not confer any advantage to bone marrow recovery compared to children who received placebo. The data, however, suggests that the initial therapeutic dose of chloroquine (10mg/kg/day over three days) could have some positive effects on bone marrow recovery post malaria. The Hb recovery following treatment for malaria is determined by the age of the child, the Hb at diagnosis, the presence or absence of iron deficiency, and the height-for-age z score.
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Ayoun, Anthony-Charles. "La chloroquine ex-panacée du traitement antipaludique peut-elle être remplacée par la pyronaridine ?" Paris 5, 1998. http://www.theses.fr/1998PA05P251.
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Johnson, David James. "Studies on the molecular basis of chloroquine resistance in Plasmodium falciparum." Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273985.
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Hughes, Dyfrig Arwyn. "Mechanistic studies on the effects of diazepam on chloroquine-induced cardiotoxicity." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243244.
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Abessolo, Huguette-Valérie. "Synthèse, activité antipaludique et mécanisme d'action d'analogues métallocéniques de la chloroquine." Lille 1, 2000. https://pepite-depot.univ-lille.fr/RESTREINT/Th_Num/2000/50376-2000-432.pdf.
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Le paludisme, cause par un protozoaire du genre plasmodium, demeure la premiere endemie tropicale. L'extension de la resistance de plasmodium falciparum aux antipaludeens existants et le manque de vaccin, rend necessaire et urgent le developpement de nouvelles molecules antimalariques de nouveaux composes metalloceniques inspires de la chloroquine, principal medicament antipaludique, ont ete synthetises par greffage d'un noyau ferrocenique. Deux d'entre eux, la 7-chloro-4-(n,n-dimethylaminomethyl)-n-ferrocenylmethylamino-quinoleine 1 (ferroquine) et la 7-chloro-4-(n-methyl-n-ethylaminomethyl)-n-ferrocenyl-methylaminoquinoleine 3, ont montre une activite antipaludique interessante sur p. Falciparum. La ferroquine a ete choisie pour l'etude du mecanisme d'action. Les effets ultrastructuraux et la localisation ont ete etudies dans des parasites traites par la ferroquine. L'activite inhibitrice sur la polymerisation de l'heme, principal mode d'action de la chloroquine, et l'interaction entre l'heme et la ferroquine ont ete egalement abordees.
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Nakano, Kenzo. "Chloroquine induces apoptosis in pancreatic neuroendocrine neoplasms via endoplasmic reticulum stress." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263541.
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Obua, Celestino. "Fixed-dose chloroquine and sulfadoxine/pyrimethamine treatment of malaria : outcome and pharmacokinetic aspects /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-144-9/.
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Boinet, Sylvie. "Intoxications volontaires à la chloroquine : expériences du SAMU 34 de 1982 à 1988." Montpellier 1, 1989. http://www.theses.fr/1989MON11044.
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Feng, Tzu-Shean. "Single and hybrid antimalarials based on artemisinin, chloroquine and ß-lactams : synthesis, antiplasmodial activity, cytotoxicity and effect of selected artemisinin-chloroquine hybrids on the parasitic endocytosis pathway." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/6305.
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Includes abstract.Includes bibliographical references.
Malaria remains to be one of the leading causes of morbidity and mortality throughout recorded history. It is caused by protozoan parasites of the genus Plasmodium, where P. falciparum is the most lethal. Current estimates are that over 500 million people are afflicted, while 3 million people die annually. With the emergence of resistance to antimalarial drugs in the malaria parasite, it is critical to develop new chemotherapeutic agents that can combat the disease and/or overcome resistance. This may be achieved by identifying molecules that target or interfere with unique parasitic pathways such as haemoglobin degradation or parasitic endocytosis. This thesis describes the design and synthesis of novel antimalarial agents based on the ‘Designed Multiple Ligand’ approach. Compounds were synthesized via conjugate addition or multi-component condensation reaction. 4-Aminoquinolines were hybridized with artemisinin or 1,4-naphthoquinone derivatives; selected hybrids were further investigated for their effect on the parasitic endocytosis pathway and compared to the effect of chloroquine and artemisinin on the same pathway. The effects of drug treatment on the morphology and haemoglobin levels in the parasites as well as localization of transport vesicles via immunofluorescence microscopy were determined. A series of β-lactam derivatives containing a terminal acetylene moiety were synthesized via the Staudinger and Ugi 3-component 4-centre condensation reactions. The compound with the best activity from the series was used to couple these reactions to post-condensation chemical modifications via the Mannich reaction, another multi-component reaction, to create a more diversified library. A small series of 4-aminoquinoline analogues, including amodiaquine-like compounds and bisquinoline derivatives, was also prepared in an attempt to elucidate their structure-activity relationships. The antiplasmodial and cytotoxic activities were determined for all compounds; where applicable, assays on β-haematin inhibitory activity were also carried out.
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Pundir, Sheetal. "The Characterization of the Novel Chloroquine Derivative VR23 for its Anticancer Properties." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32405.
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Since Bortezomib®, a proteasome inhibitor, was approved by US FDA for the treatment of multiple myeloma in 2003, proteasome is recognized as one of the most promising targets for cancer therapeutics. The proteasomes play a critical role in regulating the level of cellular proteins and recycling damaged and misfolded proteins. Although the activity of the proteasome is essential for normal cells, it is especially critical for the proliferation and survival of cancer cells. In an attempt to develop effective and safe proteasome inhibitor-based anticancer drugs, the Lee laboratory created a chemical library by a hybrid approach using a 4-piperazinylquinoline scaffold and a sulfonyl phamarcophore. It is known that the chloroquine scaffold possesses a weak proteasome inhibition activity, and chloroquine itself preferentially kills malignant cells over non-cancer cells, alone or in combination with other therapeutics. To identify compounds with desirable anticancer activities, I have screened the aforementioned chemical library. The screening yielded several hits with substantial efficacy and selectivity against malignant cells. In this thesis, I describe the functional mechanism of VR23, one of the most promising compounds identified from my screening, as it kills cancer cells up to 17 fold more effectively than non-cancer cells. Molecular docking and substrate competition studies revealed that VR23 binds to the β2 peptide of the 20S proteasome catalytic subunit. The IC50 value of VR23 in inhibiting trypsin-like proteasome activity is 1.0 nM. VR23 is also substantially effective in inhibiting chymotrypsin-like proteasome activity (IC50, 50-100 nM). The inhibition of proteasome activity by VR23 led to the accumulation of ubiquitinated cyclin E at centrosomes. This, in turn, induces abnormal centrosome amplification by a de novo centrosome synthesis pathway in cancer cells, but not in non-cancer cells. The presence of multiple centrosomes in single cancer cells results in cell cycle arrest at prometaphase and, eventually, cell death by apoptosis. Thus, VR23 possesses a very desirable property as a safe anticancer drug.
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Demazière, Jacques. "Intoxications aigues par la chloroquine a dakar : efficacite du diazepam, facteurs previsionnels de deces ; etude retrospective de 360 observations." Lyon 1, 1993. http://www.theses.fr/1993LYO1M042.
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Jambou, Ronan. "Evaluation des antipaludeens en zone de chloroquinoresistance recente : republique du cameroun." Nice, 1989. http://www.theses.fr/1989NICE6568.
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GAILLARD, JOELLE. "La chloroquinoresistance du paludisme en afrique : a propos d'observations recemment etudiees a toulouse." Toulouse 3, 1988. http://www.theses.fr/1988TOU31275.
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Alibert, Sandrine. "Synthèse de nouveaux dérivés 9,10-dihydro-9,10-éthano et éthénoanthracéniques : étude de leurs effets sur la résistance à la chloroquine chez Plasmodium falciparum." Aix-Marseille 2, 2002. http://theses.univ-amu.fr.lama.univ-amu.fr/2002AIX22952.pdf.
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Veignie, Étienne. "Mode d'action antimalarique de la chloroquine : rôle des propriétés acido-basiques des amino-4-quinoléines dans leur mécanisme de concentration intraparasitaire." Lille 1, 1990. http://www.theses.fr/1990LIL10108.
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Dans cette thèse, nous avons tenté de préciser quelques paramètres intervenant dans le mécanisme de concentration intraparasitaire de la chloroquine qu'ils soient d'origine parasitaire ou liés à la chloroquine des amino-4-quinoléines. Nous montrons que les vacuoles digestives des souches P. Berghei sensible et résistante à la chloroquine sont acides. D'autre part, nous démontrons que les propriétés basiques de la chloroquine, classiquement impliquées dans le mécanisme de concentration, se sont avérées insuffisantes pour rendre compte des fortes quantités de chloroquine accumulées par le parasite et nous soulignons l'importance de l'atome de chlore dans le processus d'accumulation des amino-4-quinoléines. Une analyse cinétique de l'incorporation des bases faibles chez P. Berghei N (sensible à la chloroquine) montre une accélération de la vitesse initiale de pénétration de la chloroquine sur des hématies parasitées comparée à la vitesse sur hématie saine. Enfin, nous identifions la chloroquine monoprotonée comme la forme de passage de la membrane érythrocytaire.
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Slomianny, Christian. "Action de la chloroquine sur le processus de dégradation de l'hémoglobine chez Plasmodium sp. : étude ultrastructurale morphologique et cytochimique." Lille 1, 1986. http://www.theses.fr/1986LIL10043.
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Guillet, Aurélie Chiffoleau Anne. "Atteintes oculaires induites par les antipaludéens de synthèse la rétinopathie aux APS /." [S.l.] : [s.n.], 2007. http://castore.univ-nantes.fr/castore/GetOAIRef?idDoc=25246.
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Chatain, Guillaume C. "Towards an understanding of hemozoin formation and chloroquine resistance in Plasmodium falciparum." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81609.
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Malaria is a worldwide disaster that is still killing two million lives annually. The recent rise of the epidemic is mainly attributed to the emergence of resistance to the most effective, affordable and safe antimalarial, chloroquine. Unfortunately, neither the mechanism of action of these 4-aminoquinolines nor the basis of chloroquine resistance is well understood. It has been noted that a known channel blocker, verapamil, is able to modulate chloroquine resistance.In this study, a chemical biology approach was taken to gain some light into these mechanisms. The design, synthesis and characterization of fluorescent and photoreactive probes, analogues of chloroquine and verapamil, are presented. These can be used in fluorescent microscopy and photoaffinity labeling experiments to identify a putative chloroquine export protein, Plasmodium falciparum chloroquine resistance transporter (PfCRT).
As a result of the hemoglobin degradation pathway, the liberated, toxic heme is sequestered by P. falciparum into an insoluble inert crystal, hemozoin. Hemoglobin proteases knockout parasites were generated. Their hemozoin was isolated, analyzed by synchrotron powder X-ray diffraction, and imaged using scanning electron microscopy.
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Ravichandran, Easwaran. "The fate of racemic chloroquine and its enantiomers in male F344 rats." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404566.
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Nieuwoudt, Stephnie. "Preparation, stability and in vitro evaluation of liposomes containing chloroquine / Stephnie Nieuwoudt." Thesis, North-West University, 2010. http://hdl.handle.net/10394/4740.
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Malaria is currently a huge treat worldwide, as far as infections are concerned, and is
responsible for thousands of deaths per annum. The dilemma associated with the development
of anti–malarial drug resistance over the past few decades should be addressed as a matter of
urgency. Novel drug delivery systems should be developed in order to employ new and existing
anti–malarial drugs in the treatment and management of malaria. The aim of these delivery
systems should include an improvement in the efficacy, specificity, acceptability and therapeutic
index of anti–malarial drugs.
Previous studies have suggested that liposomes have the ability to encapsulate, protect and to
promote the sustained release of anti–malarial drugs. Two liposome formulations, namely
liposomes and chloroquine entrapped in liposomes, were formulated during this thesis and
evaluated by conducting a stability study and an in vitro study with the main focus on cell
viability.
The stability study consisted of a series of stability tests regarding the stability of nine liposome
and nine chloroquine entrapped in liposome formulations over a period of twelve weeks. The in
vitro study included three assays such as a reactive oxygen species assay, a lipid peroxidation
assay and a hemolysis assay. The aims of these studies included the manufacturing of
liposomes, the incorporation of chloroquine into liposomes, the determination of the stability of
the formulations as well as the evaluation of the possible in vitro toxicity of liposomes.
Results obtained from these studies revealed that liposomes remained more stable over the
stability study period in comparison to chloroquine entrapped in liposomes. The entrapment of
chloroquine within liposomes was possible, although the initial entrapment efficiency (%) of
14.55 % was much too low. The production of reactive oxygen species occurred to a small
extent in the red blood cells and the infected red blood cells. Equal amounts of reactive oxygen
species (%) was observed within both the red blood cells and the infected red blood cells with a
maximum value of 23.27 % in the presence of the chloroquine entrapped in liposomes at
varying concentrations. Red blood cells experienced the highest degree of lipid peroxidation
(%) in the presence of chloroquine, at varying concentrations, entrapped in liposomes. The
maximum amount of lipid peroxidation (%) was 79.61 %. No significant degree of hemolysis
(%) was observed in the red blood cells neither in the presence of the liposomes nor in the
presence of the chloroquine entrapped in liposomes at varying concentrations.
It can be concluded that liposomes are a more stable formulation and have less toxic effects on
red blood cells and infected red blood cells in comparison to the chloroquine entrapped in liposome formulations. Future studies should investigate the possibility of a more stable and
less toxic chloroquine entrapped in liposome formulation.Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.
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Bray, Patrick Gerrard. "Plasmodium falciparum : studies on the mechanism of chloroquine resistance and its reversal." Thesis, University of Liverpool, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316597.
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Asamoah, Kojo Afedzie. "Effect of chloroquine on the glycaemic mechanisms in normal and diabetic rats." Thesis, University of Strathclyde, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278506.
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Carlton, Jane M. R. "The genetics of chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/13312.
Full textAbstract:
The aim of this work has been to use linkage analysis to determine the chromosomal location of genes involved in chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi. The P. chabaudi genome was found to contain 14 chromosomes. A genetic map of each chromosome was made using DNA markers. Most of the markers were known genes from other species of Plasmodium. Other markers were developed by the RAPD-PCR (random amplified polymorphic DNA-polymerase chain reaction) technique, the first time this method has been developed for use with Plasmodium parasites. In total, more than 100 markers were mapped to individual P. chabaudi chromosomes. Two important markers were cloned from P. chabaudi DNA using PCR. (i) the P. chabaudi homologue (pcmdr1) of the multiple drug resistance gene of P.falciparum (pfmdr 1); this has been implicated in the mechanism of chloroquine-resistance in P. falciparum. (ii) a possible homologue of the P. falciparum marker pS590.7, which has been claimed to be linked to a chloroquine-resistance locus in P. falciparum. 13 genetically distinct clones from the cross were phenotyped for their susceptibility to chloroquine. 8 were found to be resistant and 5 sensitive. These clones were analysed for their inheritance of 46 polymorphic markers. This revealed that neither pcmdr 1 nor the putative ps590.7 homologue were linked to chloroquine resistance in this cross. 12 of the 13 progeny showed linkage disequilibrium with a locus on chromosome 11. Statistical analysis showed the linkage to be significant, with a probability of 0.05>P>0.03. The work submitted here represents the first in-depth genetic analysis of a P. chabaudi cross and identifies a locus which may be involved in the genetic mechanism of chloroquine resistance.
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Blackie, Margaret Anne Lillias. "New mono and bimetallic chloroquine derivatives : synthesis and evaluation as antiparasitic agents." Doctoral thesis, University of Cape Town, 2002. http://hdl.handle.net/11427/6975.
Full textAbstract:
Includes bibliographical references.Several series of new ferrocenyl-quinoline antimalarial agents have been synthesised and fully characterised using standard spectroscopic and analytical techniques. The molecular structure of N-(7-Chloro-quinolin-4-yl)-N'-[2 -( N”,N""-dimethylaminomethyl)ferrocenylmethyl]-ethane-1.2-diamine has been determined by x-ray crystallography. N-(7-Chloro-quinolin-4-yl)-N'-[2-( N”, N""-dimethylaminomethyl)ferrocenylmethyl]-alkyl-1 ,n-diamine compounds were made where n = 2-6. These compounds contain a reactive secondary amine centre through which derivatisation to form aryl urea and aryl sulfonamide compounds was achieved. Complexes of the types: triphenylphosphine(L)gold(l) nitrate, pentafluorophenyl(L)gold(l) and chloro(cyclooctadiene)(L)rhodium(l) have been synthesised (where L = chloroquine, ferroquine, N-(7-chloro-quinolin-4-yl)-N'-[2-( N”, N""-dimethylaminomethyl)ferrocenyl methyl]-ethane-1 ,2-diamine, 3-benzyl-1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N"",N""-dimethylaminomethyl)-ferrocenylmethyl]urea). All compounds have been evaluated against chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum. In most cases good activity was found in both strains of the parasite. N-(7-Chloro-quinol in-4-yl)-N'-[2 -( N”, N""-dimethylaminomethyl)ferrocenyl methyl]-alkyl-1, n-diamine compounds have been made where n = 2-6. It was found that in vitro efficacy against P. falciparum diminished with increasing spacer length. The introduction of the aryl urea moiety served to influence efficacy towards P. falciparum and toxicity towards mammalian cells. In some cases the toxicity was significantly reduced accompanied by an improvement in efficacy. The coordination complexes where L = chloroquine showed improved efficacy in the chloroquine resistant K1 strain of P. falciparum. In the heterobimetallic complexes, the ligand L showed equivalent or better in vitro efficacy than the coordination complexes of L against both chloroquine sensitive D10 and chloroquine resistant K1 strains of P. falciparum. Preliminary structure-activity studies were carried out on some of the prepared compounds. Phenylene analogues of some of the ferrocenyl compounds have been synthesized and it was found that the analogues show similar in vitro efficacy to each other in both chloroquine sensitive 3D7 and chloroquine resistant K1 strains of P. falciparum. The presence of a ferrocenyl moiety in the side chain of chloroquine analogues appears to have a synergistic or additive effect on in vitro efficacy.
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Paguio, Michelle Fortaleza. "Biochemical and biophysical analysis of recombinant Plasmodium falciparum chloroquine resistance transporter (pfcrt)." Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/525210083/viewonline.
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Yanze, Maximun Frédéric. "Recherches pharmacotechnique, physico-chimique et biomédicale sur les formes pharmaceutiques solides orales d'action rapide des médicaments du paludisme à Plasmodium falciparum." Montpellier 1, 2000. http://www.theses.fr/2000MON13511.
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VIGUIER, KOURTA MARIE-JEANNE. "Perturbations biologiques au cours du paludisme a plasmodium falciparum chloroquinoresistant." Toulouse 3, 1989. http://www.theses.fr/1989TOU31703.
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Ahmadi, Pirshahid Sina. "Sensitivity and Specificity of Multifocal Electroretinography in Detecting Chloroquine and Hydroxychloroquine Retinal Toxicity." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/31997.
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To calculate the sensitivity and specificity of multifocal electroretinography (mfERG) in detection of chloroquine and hydroxychloroquine retinal toxicity, 120 eyes of 63 patients were evaluated using the currently recommended diagnostic tests. The results were compared to those of 54 eyes of 28 control subjects. The sensitivity and specificity of mfERG relative to the combination of automated visual fields and optical coherence tomography (the reference test) were calculated to be 87% and 86.5% respectively. However, analysis of the “false positive” cases proved that mfERG was more sensitive than the reference test and the actual sensitivity and specificity values were higher than the results of this study. Reduction of mfERG amplitude was a strong and reliable sign of early retinal toxicity and was correlated with the cumulative dose of hydroxychloroquine. This correlation was not observed with the reference test quantitative values.
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Salas, Fernandez Paloma. "Synthesis and biological activity of chloroquine ferrocenyl conjugates for the treatment of malaria." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43009.
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Watermeyer, Nicholas D. "Bioactive chloroquine-based ligands and their gold complexes as potential novel antimalarial agents." Master's thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/6283.
Full textAbstract:
Includes bibliographical references.Includes bibliographical references.
Chloroquine(CO)-derived 4-aminoquinolines have proven to be the most efficacious antimalarial drugs for both the treatment and prophylaxis of malaria. However, with the advent of drug resistance, their ability to treat the disease has been significantly hindered. Future research into the synthesis of new 4-aminoquinoline derivatives is warranted, since it has been found that the resistance is based on the identity of the side chain and not on the aminoquinoline ring, the functionality by which these compounds derive their activity. Consequently, the synthesis of CO derivatives with a modified side chain attached to a substituted quinoline ring is a reasonable approach in the search of novel antimalarial compounds that are active against drug-resistant parasite strains.
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Cabrera, Mynthia. "Analysis of the cellular and molecular mechanisms of Chloroquine Resistance in Plasmodium Falciparum." Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/501018382/viewonline.
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Gunsaru, Bornface. "Simplified Reversed Chloroquines to Overcome Malaria Resistance to Quinoline-based Drugs." PDXScholar, 2010. https://pdxscholar.library.pdx.edu/open_access_etds/400.
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Malaria is a major health problem, mainly in developing countries, and causes an estimated 1 million deaths per year. Plasmodium falciparum is the major type of human malaria parasite, and causes the most infections and deaths. Malaria drugs, like any other drugs, suffer from possible side effects and the potential for emergence of resistance. Chloroquine, which was a very effective drug, has been used since about 1945, but its use is severely limited by resistance, even though it has mild side effects, and is otherwise very efficacious. Research has shown that there are chloroquine reversal agents, molecules that can reinstate antimalarial activity of chloroquine and chloroquine-like drugs; many such reversal agents are composed of two aromatic groups linked to a hydrogen bond acceptor several bonds away. By linking a chloroquine-like molecule to a reversal agent-like molecule, it was hoped that a hybrid molecule could be made with both antimalarial and reversal agent properties. In the Peyton Lab, such hybrid "Reversed Chloroquine" molecules have been synthesized and shown to have better antimalarial activity than chloroquine against the P. falciparum chloroquine-sensitive strain D6, as well as the P. falciparum chloroquine-resistant strains Dd2 and 7G8. The work reported in this manuscript involves simplifying the reversal agent head group of the Reversed Chloroquine molecules, to a single aromatic ring instead of the two rings groups described by others; this modification retained, or even enhanced, the antimalarial activity of the parent Reversed Chloroquine molecules. Of note was compound PL154, which had IC50 values of 0.3 nM and 0.5 nM against chloroquine-sensitive D6 and chloroquine-resistant Dd2. Compound PL106 was made to increase water solubility (a requirement for bioavailability) of the simplified Reversed Chloroquine molecules. Molecular modifications inherent to PL106 were not very detrimental to the antimalarial activity, and PL106 was found to be orally available in mice infected with P. yoelli, with an ED50 value of about 5.5 mg/kg/d. Varying the linker length between the quinoline ring and the protonatable nitrogen, or between the head group and the protonatable nitrogen, did not have adverse effects on the antimalarial activities of the simplified Reversed Chloroquine molecules, in accord with the trends observed for the original design of Reversed Chloroquine molecules as found from previous studies in the Peyton Lab. The simplified Reversed Chloroquine molecules even tolerated aliphatic head groups (rather than the original design which specified aromatic rings), showing that major modifications could be made on the Reversed Chloroquine molecules without major loss in activity. A bisquinoline compound, PL192, was made that contained secondary nitrogens at position 4 of the quinoline ring (PL192 is a modification of piperaquine, a known antimalarial drug that contains tertiary nitrogens at position 4 of the quinoline ring); this compound was more potent than piperaquine which had an IC50 value of 0.7 nM against CQS D6 and an IC50 of 1.5 nM against CQR Dd2, PL192 had IC50 values of 0.63 nM against chloroquine sensitive D6 and 0.02 nM against chloroquine resistant Dd2. Finally, the mechanism of action of these simplified "Reversed Chloroquines" was evaluated; it was found that the simplified "Reversed Chloroquines" behaved like chloroquine in inhibiting β-hematin formation and in heme binding. However, the simplified "Reversed Chloroquines" were found to inhibit chloroquine transport for chloroquine resistant P. falciparum chloroquine resistance transporter expressed in Xenopus oocytes to a lesser extant than the classical reversal agent verapamil. From these studies it was noted that the simplified "Reversed Chloroquines" may not behave as well as classical reversal agents would in restoring chloroquine efficacy, but they are very potent, and so could be a major step in developing drug candidates against malaria.
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Makowa, Hazel Beverly. "The relationship between the insecticide dichloro-diphenyl-trichloroethane and chloroquine in Plasmodium falciparum resistance." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20310.
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Thesis (MSc)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Dichloro-diphenyl-trichloroethane (DDT) was extensively used in agriculture pest control and is still used for indoor residual spraying to control malaria. The lipophylicity of DDT and its breakdown product dichloro-diphenyl-dichloroethylene (DDE) dictates that they associate with membranes, lipids and hydrophobic proteins in the biological environment. Their poor degradable nature causes DDT and DDE to persist for decades in the environment and in individuals who are or were in contact with the pesticide. In many countries the synchronised resistance of the mosquito vector to insecticides and the malaria parasite towards antimalarial drugs led to a drastic rise in malaria cases and to malaria epidemics. This study assesses the influence of low level exposure of DDT and DDE on chloroquine (CQ) resistance of the dire human malaria parasite, Plasmodium falciparum. The in vitro activity of p,p’-DDT and p,p’-DDE towards blood stages of chloroquine sensitive (CQS) P. falciparum D10 and chloroquine resistant (CQR) P. falciparum Dd2 was determined using two complementary in vitro assays (Malstat and SYBR Green 1). The 50% inhibition concentrations (IC50s) of p,p’-DDT and p,p’-DDE were found to be ±14 to 38 μM (5-12 μg/mL) and highly similar towards CQS and CQR P. falciparum strains. This result indicated that the proteins involved in CQ resistance have no effect on the activity of the insecticide DDT and it breakdown product DDE. In order to assess the influence of DDT and DDE on CQ activity, in vitro fixed ratio drug combination assays were performed, as well as isobologram analysis. We found that CQ works in synergy with p,p’-DDT and p,p’-DDE against CQS P. falciparum D10. However, both p,p’-DDT and p,p’-DDE were antagonistic toward CQ activity in CQR P. falciparum Dd2. This indicated that p,p’-DDT and p,p’-DDE do have an effect on CQ resistance or on the action of CQ via a target other than hemozoin polymerization. The observation of reciprocal synergism of p,p’-DDT and p,p’-DDE with CQ against CQS D10 and antagonism against CQR Dd2 strain is highly significant and strongly indicates selection of CQ resistant strains in the presence of p,p’-DDT and p,p’-DDE. People who have low levels of circulating DDE and/or DDT could be at a high risk of contracting CQR malaria. However, medium term (nine days) DDE exposure of CQS P. falciparum D10 did not induce resistance, as no significant change in activity of CQ, p,p’-DDT and p,p’-DDE towards blood stages the CQS strain was observed. This exposure was, however, shorter than expected for a malaria infection and would be addressed in future studies. From our results on the interaction of CQ with p,p’-DDT and p,p’-DDE, it was important to assess the residual DDT and DDE variable and how much of residual p,p’-DDT and/or p,p’- DDE would enter into or remain in the different compartments (the RPMI media, erythrocytes and infected erythrocytes) over time. In combination with liquid-liquid extraction, we developed a sensitive GC-MS analyses method and a novel HPLC-UV analysis method for measuring DDT and DDE levels in malaria culturing blood and media. Whilst the HPLC-UV method was relatively cheaper, faster, and effective in determining high DDT and DDE concentrations, the optimised GC-MS method proved to be effective in detecting levels as low as 78 pg/mL (ppt) DDE and 7.8 ng/mL (ppb) DDT in biological media. Using both the HPLC and GC-MS methods we observed that malaria parasites influence distribution of the compounds between the erythrocytic and media fractions. P. falciparum D10 infection at ±10% parasitemia lead to must faster equilibration (less than 8 hours) between compartments. Equimolar distribution of p,p’-DDE was observed, but the parasites lead to trapping of the largest fraction of p,p’-DDT in the erythrocyte compartment. These results indicate that a substantial amount would reach the intra-erythrocytic parasite and could influence the parasite directly, possibly leading to either synergistic or antagonistic drug interactions. This study is the first to illustrate the “good and bad” of the insecticide DDT in terms of CQ resistance and sensitivity toward the human malaria parasite P. falciparum. These results will hopefully have an important influence on how future policies on malaria control and treatment particularly in endemic areas will be addressed and could also have an impact on the anti-malarial drug discovery approach.
AFRIKAANSE OPSOMMING: Dichlorodifenieltrichloroetaan (DDT) is op groot skaal in landbouplaagbeheer gebruik en word nog steeds gebruik vir binnenshuise oppervlakbespuiting om malaria te beheer. Die lipofilisiteit van DDT en sy afbraakproduk dichlorodifenieldichloroetileen (DDE) dikteer dat hulle met membrane, lipiede en hidrofobiese proteïene in die biologiese omgewing assosieer. Stadige afbraak veroorsaak dat DDT en DDE vir dekades in die omgewing agterbly, asook in individue wat in kontak is, of was met die insekdoder. In baie lande het gesinkroniseerde weerstand van die muskietvektor teenoor insekdoders en die malariaparasiet teenoor antimalariamiddels gelei tot 'n drastiese styging in malariagevalle en tot malariaepidemies. In hierdie studie word die invloed van lae vlak blootstelling van DDT en DDE op chlorokien (CQ) weerstand van die mens malariaparasiet, Plasmodium falciparum, geëvalueer. Die in vitro aktiwiteit van p,p'-DDT en p,p'-DDE teenoor die bloedstadia van chlorokiensensitiewe (CQS) P. falciparum D10 en chlorokien-weerstandbiedende (CQW) P. falciparum Dd2 is bepaal deur gebruik te maak van twee komplementêre in vitro toetse (Malstat en SYBR Groen toetse). Die 50% inhibisie konsentrasies (IC50s) van p,p'-DDT en p,p'-DDE is bepaal as ±14 to 38 μM (5-12 μg/mL) en was hoogs vergelykbaar tussen CQS en CQW P. falciparum stamme. Hierdie resultaat het aangedui dat die proteïene betrokke by CQ weerstand geen effek op die aktiwiteit van die insekdoder DDT en die afbraakproduk DDE het nie. Om die invloed van DDT en DDE op CQ aktiwiteit te evalueer, is die aktiwiteit van kombinasies van die verbindings in vaste verhoudings getoets, tesame met isobologram ontleding. Ons het gevind dat CQ sinergisties saam met p, p'-DDT en p, p'-DDE teen CQS P. falciparum D10 werk. Daarteenoor het beide p, p'-DDT en p, p'-DDE antagonistiese werking getoon teenoor CQ aktiwiteit met CQW P. falciparum Dd2 as teiken. Dit het aangedui dat p,p'-DDT en p, p'-DDE wel 'n invloed op CQ weerstand het of ‘n aktiwiteit van CQ, anders as hemozoin polimerisasie, beïnvloed. Die waarneming van resiproke sinergisme en antagonisme van p, p'-DDT en p, p'-DDE in kombinasie met CQ teenoor die CQS D10 en CQW DD2 stamme respektiewelik, is hoogs betekenisvol en dui op seleksie van CQweerstandige stamme in die teenwoordigheid van p, p'- DDT en p, p'-DDE. Mense wat lae vlakke van sirkulerende DDE/DDT het, het dus 'n hoër risiko om CQW malaria te kry. Verder is gevind dat medium termyn (nege dae) DDE blootstelling van CQS P. falciparum D10 nie weerstand nie veroorsaak nie, want geen beduidende verandering in die aktiwiteit van CQ, p,p'-DDT en p,p'-DDE teenoor die bloed stadiums van die CQS stam is waargeneem nie. Hierdie blootstelling is egter korter as in 'n malaria-infeksie en sal verder bestudeer word in toekomstige studies. Vanuit die interaksie resultate van CQ met p, p'-DDT en p, p'-DDE was dit belangrik om die residuele DDT en DDE veranderlike te evalueer, asook die distribusie van p,p'-DDT en p,p'- DDE tussen die verskillende kompartemente (die kultuurmedium, eritrosiete en geïnfekteerde rooibloedselle) oor verloop van tyd. In kombinasie met vloeistof-vloeistof ekstraksie, het ons 'n sensitiewe GC-MS en nuwe HPLC-UV analisemetode ontwikkel vir die meet van DDT en DDE-vlakke in bloed (normale en geïnfekteerde eritrosiete) en die kultuurmedium. Terwyl die HPLC-UV metode relatief goedkoper, vinniger en effektief in die bepaling van hoë DDT en DDE-konsentrasies is, was die geoptimaliseerde GC-MS metode doeltreffend in die opsporing van vlakke so laag as 78 pg/mL (dpt) DDE en 7.8 ng/mL (dpb) DDT in biologiese media. Met behulp van beide die HPLC-UV en GC-MS metodes is waargeneem dat die malariaparasiet die ekwilibrasie van die verbindings tussen die eritrosiet- en media kompartemente beïnvloed. P. falciparum D10 infeksie met ± 10% parasitemia lei tot vinniger ekwilibrasie (minder as 8 uur) tussen die kompartemente. Ekwimolêre verspreiding van p,p'- DDE is waargeneem, maar die parasiete het die grooste fraksie van p,p'-DDT in die eritrosiet kompartement vasgevang. Hierdie resultate wys dat 'n aansienlike fraksie die intraeritrositiese parasiet kan bereik en sodoende die parasiet direk kan beïnvloed en moontlik kan lei tot sinergistiese of antagonistiese middel interaksies. Hierdie studie is die eerste om die "goed en sleg" van die insekdoder DDT in terme van CQ weerstand en sensitiwiteit teenoor die menslike malariaparasiet P. falciparum te illustreer. Hierdie resultate sal hopelik 'n belangrike invloed hê op die toekomstige beleid oor die beheer van malaria en behandeling, veral in endemiese gebiede, en mag ook 'n impak hê op die antimalariamiddel navorsing.