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Title: Antimalarial properties of rabbit tumour necrosis serum : in vitro and in vivo studies
Author: Rockett, Kirk Allan
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1990
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Plasmodium falciparum multiplication in culture, as measured by tritiated hypoxanthine incorporation, was inhibited in a dose dependent manner by rabbit tumour necrosis serum. The regimen by which tumour necrosis serum is produced caused significant increases in triglycerides and lipid peroxides, with the latter being indicated by the level of malondialdehyde in the serum. Tumour necrosis serum depleted of lipoproteins by aerosil (fumed silica), had no parasiticidal activity. This activity was recovered in the lipoproteins after preparative ultracentrifugation. This suggests that the in vitro activity of TNS was principally mediated by lipid peroxides. This was further confirmed by the parasiticidal activities of oxidised artificial lipoproteins made with unsaturated fats. The multiplication of lethal P.yoelii parasites in mice was inhibited by i/p injection of rabbit tumour necrosis serum every other day from the day of infection. This activity was solely present in the non-lipid fraction of tumour necrosis serum, unlike the in vitro activity. Ion-exchange chromatography demonstrated that there were at least three different active factors in the serum whose combined activity is either additive or synergistic. Further separation of these factors was not achieved. In vivo activity of tumour necrosis serum was almost totally reversed by vitamin C, vitamin E or superoxide dismutase, suggesting that the serum acts in vivo via oxygen radicals. Antioxidants had little or no effect on parasite growth in primary infections, whereas they increased parasite growth in vaccinated animals, but did not prevent parasite clearance, therefore suggesting that oxygen radicals are not the main element responsible for controlling normal infections. The control of parasite growth by tumour necrosis serum via oxygen radicals may be achieved by some or all of the following; increasing the quantity of radicals made, reducing the time for peak release to occur or increasing the length of time of the peak activity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available