Ultrastructural changes of erythrocytes in whole blood after exposure to prospective in silico-designed anticancer agents: a qualitative case study.

BACKGROUND: Novel, in silico-designed anticancer compounds were synthesized in our laboratory namely, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). These compounds were designed to have improved bioavailability when compared to their source compound, 2-methoxyestradiol. This theoretically would be due to their increased binding affinity to carbonic anhydrase II, present in erythrocytes. Since the novel compounds under investigation are proposed to be transported within erythrocytes bound to carbonic anhydrase II, the morphological effect which they may exert on whole blood and erythrocytes is of great significance. A secondary outcome included revision of previously reported procedures for the handling of the whole blood sample. The purpose of this study was twofold. Firstly, the ultrastructural morphology of a healthy female's erythrocytes was examined via scanning electron microscopy (SEM) after exposure to the newly in silico-designed compounds. Morphology of erythrocytes following exposure to ESE-15-ol and ESE-16 for 3 minutes and 24 hours at 22°C were described with the use of SEM. The haemolytic activity of the compounds after 24 hours exposure were also determined with the ex vivo haemolysis assay. Secondly, storage conditions of the whole blood sample were investigated by determining morphological changes after a 24 hour storage period at 22°C and 37°C. RESULTS: No significant morphological changes were observed in the erythrocyte morphology after exposure to the novel anticancer compounds. Storage of the whole blood samples at 37°C for 24 hours resulted in visible morphological stress in the erythrocytes. Erythrocytes incubated at 22°C for 24 hours showed no structural deformity or distress. CONCLUSIONS: From this research the optimal temperature for ex vivo exposure of whole blood samples to ESE-15-ol and ESE-16 for 24 hours was determined to be 22°C. Data from this study revealed the potential of these compounds to be applied to ex vivo study techniques, since no damage occurred to erythrocytes ultrastructure under these conditions. As no structural changes were observed in erythrocytes exposed to ESE-15-ol and ESE-16, further ex vivo experiments will be conducted into the potential effects of these compounds on whole blood. Optimal incubation conditions up to 24 hours for whole blood were established as a secondary outcome.

Migraine-Associated Vertigo and Dizziness as Presenting Complaint in a Private General Medical Practice

Migraine-associated vertigo (MV) remains a developing entity because accepted diagnostic criteria are unavailable. Patients present with debilitating dizziness without experiencing headache; and are often misdiagnosed as anxious. The condition is manageable in primary care without the need for neurological referral. The aim of this study was to investigate the prevalence of MV and migraine-associated dizziness (MD) as presenting complaints. Methods: Patients presented with dizziness probably or definitely associated with migraine history based on the criteria of the International Headache Society. Patients with other vestibulopathies and medical conditions were excluded. Patients were evaluated over a period of nine months. Seven hundred and seventeen patients were examined. The numbers of patients were recorded as a percentage of the population visiting a general practitioner. Response to migraine prophylactic medications was regarded as supporting evidence of the diagnosis. Response was regarded as a complete resolution of symptoms. Results: Of the 717 patients seen; 12 were identified as having probable or definite MV. Five patients were treated with migraine prophylactic medications; namely amitriptyline 25 mg nocte and/or sodium valproate CR 300 mg bd; and all showed a response to the treatment. Conclusions: We conclude that the prevalence of MV as presenting complaint may be as high as 1.67. This figure does however not reflect the total patient population that suffers from the condition - this figure may be much higher. Of those patients treated for MV the response was 100; further supporting the diagnosis. MV is a relevant complaint that is often misdiagnosed as psychogenic in origin