Development of an in vitro model for study of the efficacy of ischemic preconditioning in human skeletal muscle against ischemia-reperfusion injury

Ischemia-reperfusion (I/R) injury causes skeletal muscle infarction and ischemic preconditioning (IPC) augments ischemic tolerance in animal models. To date, this has not been demonstrated in human skeletal muscle. This study aimed to develop an in vitro model to investigate the efficacy of simulated IPC in human skeletal muscle. Human skeletal muscle strips were equilibrated in oxygenated Krebs-Henseleit-HEPES buffer (37 degrees C). Aerobic and reperfusion phases were simulated by normoxic incubation and reoxygenation, respectively. Ischemia was simulated by hypoxic incubation. Energy store, cell viability, and cellular injury were assessed using ATP, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) assays, respectively. Morphological integrity was assessed using electron microscopy. Studies were designed to test stability of the preparation (n = 5-11) under normoxic incubation over 24 h; the effect of 1, 2, 3, 4, or 6 h hypoxia followed by 2 h of reoxygenation; and the protective effect of hypoxic preconditioning (HPC; 5 min of hypoxia/5 min of reoxygenation) before 3 h of hypoxia/2 h of reoxygenation. Over 24 h of normoxic incubation, muscle strips remained physiologically intact as assessed by MTT, ATP, and LDH assays. After 3 h of hypoxia/2 h of reoxygenation, MTT reduction levels declined to 50.1 +/- 5.5% (P <0.05). MTT reduction levels in HPC (82.3 +/- 10.8%) and normoxic control (81.3 +/- 10.2%) groups were similar and higher (P <0.05) than the 3 h of hypoxia/2 h of reoxygenation group (45.2 +/- 5.8%). Ultrastructural morphology was preserved in normoxic and HPC groups but not in the hypoxia/reoxygenation group. This is the first study to characterize a stable in vitro model of human skeletal muscle and to demonstrate a protective effect of HPC in human skeletal muscle against hypoxia/reoxygenation-induced injury.

On the application of genetic algorithms for optimising composites against impact loading

A genetic algorithm (GA) was adopted to optimise the response of a composite laminate subject to impact. Two different impact scenarios are presented: low-velocity impact of a slender laminated strip and high-velocity impact of a rectangular plate by a spherical impactor. In these cases, the GA's objective was to, respectively, minimise the peak deflection and minimise penetration by varying the ply angles.

The GA was coupled to a commercial finite-element (FE) package LS DYNA to perform the impact analyses. A comparison with a commercial optimisation package, LS OPT, was also made. The results showed that the GA was a robust, capable optimisation tool that produced near optimal designs, and performed well with respect to LS OPT for the more complex high-velocity impact scenario tested.

Canaries Coalmines Thunderstones 2010:"Suppressing the Medical Model”; “Family at War”; and “The Fallenness of Humanity"

A Poetic Annual

The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition

Innate immunity recognizes bacterial molecules bearing pathogen-associated molecular patterns to launch inflammatory responses leading to the activation of adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it has been postulated that this delays the development of immunity, creating a gap that is critical for the bacterium to reach the intracellular replicative niche. We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant induced proinflammatory responses and was attenuated. In addition, it was sensitive to killing by non-immune serum and bactericidal peptides and did not multiply in dendritic cells being targeted to lysosomal compartments. In contrast to wild type B. abortus, the wadC mutant induced dendritic cell maturation and secretion of pro-inflammatory cytokines. All these properties were reproduced by the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core-mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading to subsequent increase in intracellular signaling. Here we show that Brucella escapes recognition in early stages of infection by expressing a shield against recognition by innate immunity in its LPS core and identify a novel virulence mechanism in intracellular pathogenic gram-negative bacteria. These results also encourage for an improvement in the generation of novel bacterial vaccines.

Whole grains and health:attitudes to whole grains against a prevailing background of increased marketing and promotion

To explore current awareness and perceptions of whole grain foods and perceived barriers and facilitators of whole grain consumption.

A Case for Humanity in the Law of Rape.

One of Irigaray’s most insistent criticisms of the operation of patriarchal law is its overwhelming focus on the protection of property at the expense of law that regulates relations between and amongst persons. This paper argues, with reference to Irigaray’s work, that the conceptual change involved in such a reorientation of law’s focus has important implications for the legal perception of the harm of rape and woman’s sexuality. The possessive paradigm operates in the law of rape by disassociating the harm of rape from its psychic and subjective impact and encouraging the ‘simple’rape/ ‘real’ rape dichotomy. In returning subjectivity to woman herself we can begin to see perhaps how the crime of rape involves a harm to woman that affects the whole of her being, and to be. Such a reading allows the law to perhaps move away from understanding rape as a violation of undifferentiated bodies to a violation of the innate ‘virginity’ of woman.

Serological correlate of protection against norovirus-induced gastroenteritis

Norovirus infection is the leading cause of acute nonbacterial gastroenteritis. Histoblood group antigens (HBGAs) are host susceptibility determinants for Norwalk virus (NV) infection. We hypothesized that antibodies that block NV-HBGA binding are associated with protection from clinical illness following NV exposure.