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

Muscle involvement in leprosy: study of the anterior tibial muscle in 40 patients Alterações musculares na lepra: estudo do músculo tibial anterior em 40 pacientes

The involvement of skeletal striated muscle in leprosy is considered secondary due to peripheral neuropathy, but some studies point it to a primary muscle lesion. In order to investigate the muscle involvement in leprosy, we studied 40 patients (lepromatous 23, tuberculoid 13, borderline 2 and indeterminate 2). The motor nerve conduction of the peroneal nerves had a reduction of the velocity, decreased compound muscle action potential and sometimes absence of potentials. The electromyographic study of the anterior tibial muscle showed signs of recent and chronic denervation in 77.5% of the cases and no myopathic potentials. The anterior tibial muscle biopsy revealed denervation in 45% of the cases, interstitial inflammatory myopathy in 30% and mixed (myopathic and neuropathic) pattern in 12.5%. Acid fast bacillus was detected in 25% of the cases, always in the interstitial tissue. Inflammatory reaction was present in the interstitial space and in patients with the lepromatous type. The histological findings clearly defined the presence of the so-called "Leprous Interstitial Myositis" on the top of denervation signs.<br>O envolvimento do músculo estriado na lepra é considerado secundário à lesão dos nervos periféricos, mas alguns estudos relataram acometimento muscular primário. A fim de verificar esta controvérsia estudamos 40 pacientes com lepra, sendo 23 da forma lepromatosa, 13 da tuberculoide, 2 borderline e 2 indeterminada. Realizamos a neurocondução do nervo peroneiro, junto com eletromiografia e biópsia do músculo tibial anterior. Encontramos redução de velocidade de condução, da amplitude e algumas vezes ausência de potenciais no nervo peroneiro. A eletromiografia do tibial anterior mostrou sinais de desinervação recente e crônica em 77,5% dos casos e não foi encontrada evidência de padrão "miopático". A biópsia do músculo tibial anterior revelou desinervação em 45% dos casos, miopatia inflamatória intersticial em 30% e padrão misto (miopático e neuropático) em 12,5%. Bacilos alcool-ácido resistentes foram encontrados em 25% dos casos, sempre localizados no perimisio e endomisio. Na forma lepromatosa, a reação inflamatória estava presente no espaço intersticial. Os dados histológicos claramente definiram a presença de "Miosite Lepromatosa Intersticial" sobreposta às alterações histológicas encontradas em desinervação