Amyloid deposits derived from the amylin peptide accumulate within pancreatic islet b-cells in most cases of type-2 diabetes mellitus (T2Dm). Human amylin 'oligomers' are toxic to these cells. Using two different experimental techniques, we found that H 2 O 2 was generated during the aggregation of human amylin into amyloid fibrils. This process was greatly stimulated by Cu(II) ions, and human amylin was retained on a copper affinity column. In contrast, rodent amylin, which is not toxic, failed to generate any H 2 O 2 and did not interact with copper. We conclude that the formation of H 2 O 2 from amylin could contribute to the progressive degeneration of islet cells in T2Dm.

Using a method based on ESR spectroscopy and spin-trapping, we have shown that Abeta (amyloid beta-peptide) (implicated in Alzheimer's disease), alpha-synuclein (implicated in Parkinson's disease), ABri (British dementia peptide) (responsible for familial British dementia), certain toxic fragments of the prion protein (implicated in the transmissible spongiform encephalopathies) and the amylin peptide (found in the pancreas in Type 2 diabetes mellitus) all have the common ability to generate H(2)O(2) in vitro. Numerous controls (reverse, scrambled and non-toxic peptides) lacked this property. We have also noted a positive correlation between the ability of the various proteins tested to generate H(2)O(2) and their toxic effects on cultured cells. In the case of Abeta and ABri, we have shown that H(2)O(2) is generated as a short burst during the early stages of aggregation and is associated with the presence of protofibrils or oligomers, rather than mature fibrils. H(2)O(2) is readily converted into the aggressive hydroxyl radical by Fenton chemistry, and this extremely reactive radical could be responsible for much of the oxidative damage seen in all of the above disorders. We suggest that the formation of a redox-active complex involving the relevant amyloidogenic protein and certain transition-metal ions could play an important role in the pathogenesis of several different protein misfolding disorders.

No abstract

Coronary Heart Disease (CHD) is a highly prevalent disease all over the world. Magnesium (Mg) plays a role in CHD but it is still unclear. C-Reactive Protein (CRP) is an inflammatory marker which may rise in CHD. Aim of study: To assess the impact of dietary Mg intake and its level in relation to CRP among newly diagnosed CHD at middle zone of Gaza Strip. Methodology: Patients (n = 140) with confirmed CHD, 50 ± 10 years, presented in the cardiac care unit at Aqsa Martyr's Hospital between 1 April 2012 and 30 December 2012, were enrolled in this cross-sectional study after taking consent. ECG, clinical status, and cardiac markers were used to confirm diagnosis by cardiologist. Food frequency questionnaire was used to assess Mg intake and calcium intake in addition to measurement of its level in serum. CRP latex slide was used for measurement of CRP. Results: Mg intake and serum Mg were inversely associated with risk of CHD. Mean of serum Mg among cases (1.80) was lower than controls (2.41) (P = 0.001). Percent of positive CRP was higher in cases (32.9%) than controls (12.9%) (P = 0.005). Mean of serum Mg was (1.96 ± 0.47) for positive CRP which was lower than the mean of serum Mg (2.15 ± 0.44) for negative CRP. Conclusion: Newly diagnosed patients with CHD have a positive CRP, low serum and low Mg intake, and low serum Mg was associated with elevated CRP.