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dc.contributor.authorINYANG, A. L.
dc.date.accessioned2018-10-17T10:38:27Z
dc.date.accessioned2019-10-04T10:01:00Z
dc.date.available2018-10-17T10:38:27Z
dc.date.available2019-10-04T10:01:00Z
dc.date.issued1985-08
dc.identifier.urihttps://library.adhl.africa/handle/123456789/12271
dc.descriptionA THESIS IN THE DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS SUBMITTED TO THE FACULTY OF BASIC MEDICAL SCIENCES IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF IBADAN.en_US
dc.description.abstractIn this thesis the problem of haemostatic disorders with particular reference to platelet dysfunction in experimental malaria models has been examined. In the Swiss albino mouse model infected with Plasmodium berghei (P. berghei), regular thrombocytopaenia was associated with the parasitaemia. Mild leucocytosis due to the presence of red cells in the peritoneal space and partly due to the infection was also observed. It was found that treatment of the infection with standard dose of chloroquine sulphate for the standard 4 days was not adequate to eradicate the parasites completely, and the platelet count did not return to preinfection levels in up to 27 days. On the other hand, treatment of the infection with the same dose of chloroquine for 7 days completely cleared the paramitaemia by the end of the treatment period and platelet counts returned to baseline values by the 27th post-infection day. Coagulation parameters, such as PT and APTT were significantly prolonged in the infected animals while clottable fibrinogen was reduced when compared to control animals. A negative correlation existed between clottable fibrinogen and percentage parasitaemia. It was concluded that disseminated intravascular coagulation (DIC) complicated acute malaria in Swiss albino mice. Platelet hypersensitivity to only low concentrations of ADP (0.5uM) but not collagen, was manifested in the infected mice PRP, although this was not accompanied by any dense granule secretory defect when stimulated with either agonist. In the suckling rat model infected with P. berghei, platelet survival studies using 51Cr-labelled homologous platelets revealed a 52% reduction in mean survival time. There was also a significant reduction in total platelet sialic acid content in the infected animals. The decrease in platelet survival in the infected rat was attributed to a drop in total platelet sialic acid content. The latter, was shown to have a negative correlation with rise in parasitaemia. It was concluded from this study that the drop in total platelet sialic acid content was probably as a result of loss of membrane rather than granule sialic acid. In the in vitro system designed in this study, washed human platelet suspension was allowed to interact with washed cultured P. falciparum infected human rbcs, and the post-interaction platelet rich suspensions (PRSi) tested for changes in platelet function. The control system comprised similarly treated sham cultured erythrocytes (PRSc). Platelet hypersensitivity to low ADP concentrations (0.25uM) was observed only in the PRSi samples. This result was attributed to synergism between ADP, TxA2 and serotonin secreted from the stimulated platelet as well as an unidentified protein "factor" demonstrated in significant amount on SDS-PAGE gel. The latter factor was heat stable at 560C for 1 hour and was still present after thrombin inactivation. It was concluded that the in vitro model is a suitable system to use in investigating different aspects of platelet/malaria interactions. It was also concluded from these studies that platelet dysfunction is common in acute malaria infections. Some of the mechanisms involved have been identified and the direction of further investigations identified.en_US
dc.language.isoenen_US
dc.subjectPlateleten_US
dc.subjectMalariaen_US
dc.subjectChanges in platelet functionsen_US
dc.titleINVESTIGATIONS INTO CHANGES IN PLATELET FUNCTION IN EXPERIMENTAL MALARIAen_US
dc.typeThesisen_US


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