Combining Nitrous Oxide with Carbon Dioxide Decreases the Time to Loss of Consciousness during Euthanasia in Mice — Refinement of Animal Welfare?

Carbon dioxide (CO2) is the most commonly used euthanasia agent for rodents despite potentially causing pain and distress. Nitrous oxide is used in man to speed induction of anaesthesia with volatile anaesthetics, via a mechanism referred to as the “second gas” effect. We therefore evaluated the addition of Nitrous Oxide (N2O) to a rising CO2 concentration could be used as a welfare refinement of the euthanasia process in mice, by shortening the duration of conscious exposure to CO2. Firstly, to assess the effect of N2O on the induction of anaesthesia in mice, 12 female C57Bl/6 mice were anaesthetized in a crossover protocol with the following combinations: Isoflurane (5%)+O2 (95%); Isoflurane (5%)+N2O (75%)+O2 (25%) and N2O (75%)+O2 (25%) with a total flow rate of 3l/min (into a 7l induction chamber). The addition of N2O to isoflurane reduced the time to loss of the righting reflex by 17.6%. Secondly, 18 C57Bl/6 and 18 CD1 mice were individually euthanized by gradually filling the induction chamber with either: CO2 (20% of the chamber volume.min−1); CO2+N2O (20 and 60% of the chamber volume.min−1 respectively); or CO2+Nitrogen (N2) (20 and 60% of the chamber volume.min−1). Arterial partial pressure (Pa) of O2 and CO2 were measured as well as blood pH and lactate. When compared to the gradually rising CO2 euthanasia, addition of a high concentration of N2O to CO2 lowered the time to loss of righting reflex by 10.3% (P<0.001), lead to a lower PaO2 (12.55±3.67 mmHg, P<0.001), a higher lactataemia (4.64±1.04 mmol.l−1, P = 0.026), without any behaviour indicative of distress. Nitrous oxide reduces the time of conscious exposure to gradually rising CO2 during euthanasia and hence may reduce the duration of any stress or distress to which mice are exposed during euthanasia

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

Obesity and Type 2 Diabetes in Children: Epidemiology and Treatment

The incidence of overweight and obesity among children has increased dramatically in recent decades, with about one-third of children in the U.S. currently being either overweight or obese. Being overweight in early childhood increases risk for later obesity. There is evidence for the efficacy of family-based behavioral treatment to control weight and improve health outcomes. Obesity-related health risks have been documented, including metabolic syndrome. There is also increasing incidence of type 2 diabetes (T2D) among youth in recent years, with obesity and family history of T2D generally present. Lower income and ethnic minority status are associated with both obesity and T2D in youth. Most youth with T2D do not achieve optimal glycemic control, and are at high risk for later health complications. Obesity and T2D represent significant public health issues with potentially great personal and societal cost. Research addressing the prevention of obesity and T2D among youth is urgently needed