Nociceptors: a phylogenetic view

The ability to react to environmental change is crucial for the survival of an organism and an essential prerequisite is the capacity to detect and respond to aversive stimuli. The importance of having an inbuilt “detect and protect” system is illustrated by the fact that most animals have dedicated sensory afferents which respond to noxious stimuli called nociceptors. Should injury occur there is often sensitization, whereby increased nociceptor sensitivity and/or plasticity of nociceptor-related neural circuits acts as a protection mechanism for the afflicted body part. Studying nociception and nociceptors in different model organisms has demonstrated that there are similarities from invertebrates right through to humans. The development of technology to genetically manipulate organisms, especially mice, has led to an understanding of some of the key molecular players in nociceptor function. This review will focus on what is known about nociceptors throughout the Animalia kingdom and what similarities exist across phyla; especially at the molecular level of ion channels

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

A meta-analysis of the Gamma nail and dynamic hip screw in treating peritrochanteric fractures

The objective of this meta-analysis was to compare the fixation outcome of the Gamma nail and dynamic hip screw (DHS) in treating peritrochanteric fractures. Relevant randomised controlled studies were included, and the search strategy followed the requirements of the Cochrane Library Handbook. Methodological quality was assessed and data were extracted independently. Seven studies involving 1,257 fractures were included which compared the effect of the Gamma nail and DHS. The results showed a higher rate of postoperative femoral shaft fracture with the Gamma nail compared to the DHS [relative risk (RR): 7.27, 95% confidence interval (CI): 2.83–18.70, P < 0.0001] but no statistical differences in wound infection (RR: 1.02, 95% CI: 0.56–1.86), mortality (RR: 1.00, 95% CI: 0.81–1.24), re-operation (RR: 1.64, 95% CI: 0.91–2.95) and walking independently after rehabilitation (RR: 0.89, 95% CI: 0.60–1.33). It seemed that there were no obvious advantages of the Gamma nail over the DHS in treating peritrochanteric fractures