Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Avaliação da aterosclerose carotídea por intermédio de ultra-sonografia e ressonância magnética Evaluation of carotid atherosclerosis by ultrasound and magnetic resonance imaging

OBJETIVO: Identificar ateromas carotídeos em coronariopatas com indicação de terapia cirúrgica. Avaliar o grau de estenose das artérias carótidas internas por meio de ultra-sonografia com Doppler colorido (UDC) e angiografia por ressonância magnética (ARM). Comparar a ecogenicidade das placas visualizadas pela ultra-sonografia (US), com a intensidade de sinal nos exames de ressonância magnética (RM). Avaliar a qualidade de imagens e confiabilidade interobservadores nos exames de RM. MATERIAIS E MÉTODOS: Estudo prospectivo em 50 pacientes. Utilizamos US e RM em seqüências ponderadas em T1 e T2, ambas pelas técnicas "black-blood" (BB) e "fat sat black-blood" (FSBB), e ARM 3D TOF ("time-of-flight'') com e sem contraste paramagnético. RESULTADOS: Do total de 100 segmentos, 81% apresentaram estenose pela US. Em 72 placas com ecogenicidade tipo 4 houve aumento da intensidade de sinal em 59,7% em T1-BB, 65,3% em T1-FSBB, 62,5% em T2-BB e 66,7% em T2-FSBB. Nas placas tipo 2 houve aumento da intensidade de sinal em 71,4% em T1-BB e T1-FSBB, 85,7% em T2-BB e 71,4% em T2-FSBB. Nas placas tipo 1 houve aumento da intensidade de sinal em 50,0% em T1 e T2. Em 19 segmentos a US foi considerada normal. Quando estes segmentos foram avaliados pela RM, houve aumento da intensidade de sinal em 47,4% em T1-BB, 57,9% em T1-FSBB e 52,6% em T2-BB e T2-FSBB. CONCLUSÃO: Houve alta incidência de aterosclerose carotídea. Houve reprodutibilidade marginal na associação entre o grau de estenose visualizado pela UDC e ARM. Não houve correlação entre os tipos de ecogenicidade das placas visualizadas pela US com as alterações de intensidade de sinal pela RM. A qualidade de imagens dos exames de RM foi considerada ótima em T1 e T2 e muito boa em 3D TOF (axial). A qualidade de imagem dos exames de ARM foi excelente. Notou-se ótima reprodutibilidade interobservadores, com valores de índice kappa acima de 0,71.<br>OBJECTIVE: To identify carotid plaques in patients with coronary disease and indication for surgical treatment. To evaluate the degree of stenosis of the internal carotid arteries using color Doppler ultrasound (CDU) and magnetic resonance angiography (MRA). To compare plaque ultrasound echogenicity with signal intensity in magnetic resonance imaging (MRI). To evaluate the quality of the images and inter-rater reliability of MRI analysis. MATERIALS AND METHODS: This was a prospective study of 50 patients. Imaging methods used included ultrasound, T1- and T2-weighted MRI sequences, both with black-blood (BB) and fat sat black-blood (FSBB) techniques, and 3D TOF (time-of-flight) MRA, with and without administration of paramagnetic contrast media. RESULTS: Out of a total of 100 arterial segments, 81% showed stenosis on ultrasound whereas in 72 plaques with type 4 echogenicity there was high signal intensity in MRI in 59.7% in T1-BB technique, 65.3% in T1-FSBB, 62.5% in T2-BB and 66.7% in T2-FSBB. In type 2 plaques we observed high signal intensity in 71.4% in T1-BB and T1-FSBB, 85.7% in T2-BB and 71.4% in T2-FSBB. In type 1 plaques there was high signal intensity in 50% on T1- and T2-weighted images. In 19 segments ultrasound was considered normal. The same segments showed high signal intensity in 47.4% in T1-BB, 57.9% in T1-FSBB, 52.6% in T2-BB and T2-FSBB when evaluated with MRI. CONCLUSION: A high incidence of carotid atherosclerosis was observed. There was borderline reproducibility in the association between the degree of stenosis observed by CDU and MRA. There was no correlation between the types of plaque echogenicity assessed by ultrasound and MR signal intensity changes. The quality of MR images was considered optimal on T1- and T2-weighted images, and good in 3D TOF (axial). The quality of MRA images was considered excellent. Optimal inter-rater reliability was observed, with a kappa index above 0.71