Saleem, Hamad (1999) Magnesium Transport In Mammalian Erythrocytes And Its Effect On Platelet Aggregation. Masters thesis, University of Central Lancashire.
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Renal failure is a decrease or cessation of Glomerular filtration. In acute renal failure (ARE) the kidneys abruptly stop working entirely or almost entirely. The main feature of ARF is suppression of urine flow, where the daily urine output is less than 250 ml or even less than 50 ml daily. Causes include low blood volume, decreased cardiac output and damaged renal tubules. Both the acute and chronic renal failure conditions show disturbances of ion transport systems in erythrocytes. In acute renal failure an elevation of intracellular free magnesium [Mg 2+ has been reported.
The main aim of this study was to investigate and characterise magnesium (Mg2+) transport in mammalian erythrocytes in the presence of various drugs. Healthy human controls and patients suffering from acute renal failure who are undergoing treatment via haemodialysis (Pre- and Post-dialysis) were employed for the study. The effects of varying extracellular Mg 2+ on platelet aggregation was also investigated employing different concentrations of adenosine diphosphate (ADP) on the plasma from both pre- and post-dialysis patients. Healthy human controls were used as a comparison. The Mg 2+ level in plasma from both Pre- and post-dialysis patients was slightly lower than in human control. In the erythrocytes normal Mg 2+ was lower in human control than in both the pre- and post-dialysis patients Upon Mg 2+ -loading, the human control Mg 2+ was still lower than loaded erythrocytes from both pre - and post-dialysis patients. After a period of 50 min efflux, the human control Mg 2+ level was higher than the efflux in both the pre- and post-dialysis patients, but both the pre- and post-dialysis patients had released smaller amounts of Mg 2+ than human control, indicating acute renal failure is associated with large fluxes of Mg 2+ Amiloride (a sodium channel blocker) and N-methyl-D-glucamine (NMDG) a substitute for sodium were used to test the mechanism of Mg 2+ transport.
Following Mg 2+ loading, in pre-dialysis patients the Mg 2+ efflux in the presence of (10 -3 M) amiloride was greatly elevated compared to untreated erythrocytes. When extracellular sodium chloride was replaced with NIMDG there was a large and significant decrease in Mg 2+ efflux compared to control. In post-dialysis patients a larger Mg 2+ efflux was observed in the presence of amiloride (10 M), but in NMDG there was an initial reduction in Mg 2+ efflux (lower than control) which increased and remained the same as control.
Mg 2+ showed a time-dependent manner of uptake and release in erythrocytes, which suggested it would affect platelet aggregation. The plasma from healthy human controls as well as both pre- and post-dialysis patients was employed in the presence of ADP (10 -3 - 10 -7 M) and a varying range of extracellular Mg 2+ (1-7 mM). In human control, ADP can aggregate platelets in a dose dependent manner. A perturbation of extracellular Mg 2+ caused a decrease in the ADP induced platelet aggregation. However, during acute renal failure a perturbation of extracellular Mg 2+ had no significant effect on platelet aggregation in plasma from acute renal failure patients compared to healthy human controls.
In conclusion, the results of this study employing blood (erythrocytes and plasma) from both pig and human (healthy control and acute renal failure patients) indicate that erythrocytes can take up Mg 2+ and release it in a time-dependent manner. In some cases, the efflux was sensitive to either amiloride or extracellular sodium: In addition, ADP can induce a dose dependent increase in platelet aggregation, which was attenuated by a perturbation of extracellular Mg 2+ Further experiments are required to characterise precisely the transport of Mg 2+ and its role in platelet aggregation during diseased states.
|Item Type:||Thesis (Masters)|
|Uncontrolled Keywords (separate with ;):||renal failure; glomerular filtration; acute renal failure; amiloride;|
|Schools:||Faculty of Clinical & Biomedical Sciences > School of Pharmacy and Biomedical Sciences|
|Deposited By:||Hayley Gayle Moran|
|Deposited On:||02 May 2013 14:26|
|Last Modified:||10 Feb 2017 12:43|
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