Overexpression of mitochondrial Hsp70/Hsp75 protects astrocytes against ischemic injury in vitro.

Mitochondrial heat shock protein 70 (mtHsp70/Hsp75/Grp75/mortalin/TRAP-1/PBP74) is an essential mitochondrial chaperone and a member of the heat shock protein 70 (HSP70) family. Although many studies have shown the protective properties of overexpression of the cytosolic inducible member of the HSP70 family, Hsp72, few studies have investigated the protective potential of Hsp75 against ischemic injury. Mitochondria are one of the primary targets of ischemic injury in astrocytes. In this study, we analyzed the effects of Hsp75 overexpression on cellular levels of reactive oxygen species (ROS), mitochondrial membrane potential, ATP levels, and viability during the ischemia-like conditions of oxygen-glucose deprivation (OGD) or glucose deprivation (GD) in primary astrocytic cultures. We show that Hsp75 overexpression decreases ROS production and preserves mitochondrial membrane potential during GD, and preserves ATP levels and cell viability during OGD. These findings indicate that Hsp75 can provide protection against ischemia-like in vitro injury and suggest that it should be further studied as a potential candidate for protection against ischemic injury.     

Designing a statewide agenda for nursing research

This article describes the background, development, and beginning implementation of a nursing research action plan for New York state. Working together over the past two years and building on past collaborative efforts, the New York State Nurses Association (NYSNA) and the Foundation of the NYSNA created an agenda for nursing research in New York state. The agenda contains five major goals, subgoals, an action plan for achieving these goals, and desired outcomes. Several implementation activities, including initiation of Web-based activities, strategies to bring research to the clinical nurse, and the development of a proposal to create evidence-based practice teams, are under way. The process of agenda development may serve as a model for other associations or organizations.     

What makes a good head positioner for preventing occipital pressure ulcers

Patients who are stationary endure prolonged soft tissue distortions and deformations at contact areas between their body and the support surface, which may lead to the onset of pressure ulcers (PUs) over time. A novel technology for patient positioning employs innovation in materials science, specifically viscoelastic materials with shape memory properties that compose the Z‐Flo™ head positioner (Mölnlycke Health Care, Gothenburg, Sweden). Head positioners are generally known to reduce the occurrence of PUs in scalp tissues and the ears, but quantitative assessments of their biomechanical efficacy are missing in the literature. To determine potential differences in mechanical loads formed in the soft tissues of the back of the head while in contact with 2 head positioner types, Z‐Flo vs flat medical foam, we developed 2 comparable finite element model configurations, both including the same 3‐dimensional adult head. For both model variants, stresses in skin and fat peaked at the occiput. The skin at the back of the resting head is subjected to greater stress values with respect to fat; however, the Z‐Flo positioner reduced the exposure of both skin and fat tissues to elevated stresses considerably (by a factor of 3) compared to the medical foam support. We found the Z‐Flo device effective in reducing tissue loads at the surface of the head as well as internally in scalp tissues, with a particular strength in reducing internal tissue shear. The Z‐Flo device achieves this protective quality through highly effective immersion and envelopment of the back of the head, generated in the process of manual moulding of the device in preparation for use. Additional protection is achieved through the viscoelastic response of the filling material of this positioner, which relaxes promptly and considerably under the weight of the head (by more than 2‐fold within approximately 1 s) as opposed to the elastic recoil of the foam that pushes back on scalp tissues.     

Using bladder instillations to manage indwelling catheters

Indwelling urinary catheters are commonly used in both acute and primary care settings but patients often experience problems with blockage of the catheter as a result of encrustation. Bladder instillations of differing solutions are used in an attempt to prevent and treat this problem of encrustation. This article looks at some of the issues surrounding the use and methods of these solutions. Based on an audit performed by a group of continence clinical nurse specialists in five areas of the UK, results of a questionnaire sent to acute and primary care nursing staff in 2003 are presented and discussed. The questionnaire covered a variety of clinical issues involved in performing bladder instillations and the results show that there is a wide variation of practice across the UK. The authors conclude that there are issues pertaining to bladder instillations which warrant further work.     

Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes

OBJECTIVE: Since apoptosis is an important contributor to heart diseases in which ischemia and hypoxia are key elements, we tested the hypothesis that hypoxia predisposes neonatal rat ventricular myocytes (NRVM) to Fas-mediated apoptosis, by shifting the balance between antiapoptotic and proapoptotic proteins towards the latter. METHODS: Normoxic or hypoxic (22 h, 1% O(2)) cultured NRVM were exposed to recombinant Fas L (rFasL) for 7 h, and apoptosis measured thereafter. RESULTS: Whereas in normoxic NRVM, rFasL did not cause apoptosis measured by the TUNEL assay (4.8+/-0.5% in control versus 4.5+/-0.9% in rFasL), in hypoxic cultures rFasL increased the background apoptosis level by 100%. That Fas was functional in normoxic NRVM, despite its inability to mediate apoptosis, was evidenced by the finding that Fas activation increased the diastolic [Ca(2+)](i) levels measured by Fura 2 fluorescence, and caused arrhythmias. In support of our working hypothesis, hypoxia increased Fas expression by 200% (measured by quantitative Western blot), and the expression of the proapoptotic proteins ARTS and FADD by 323 and 250%, respectively, and decreased the expression of the antiapoptotic proteins ARC and FLIP by 90 and 60%, respectively. CONCLUSION: By upregulating Fas expression and key proapoptotic proteins, and by downregulating antiapoptotic proteins, hypoxia predisposes ventricular myocytes to Fas-induced apoptosis.     

Application of scientific criteria to food allergens of public health importance

Scientific criteria for identifying allergenic foods of public health importance (Björkstén, B., Crevel, R., Hischenhuber, C., Løvik, M., Samuels, F., Strobel, S., Taylor, S.L., Wal, J.-M., Ward, R., 2008. Criteria for identifying allergenic foods of public health importance. Regulatory Toxicology and Pharmacology 51(1), 42–52) have been further refined to incorporate an assessment of the strength of available scientific evidence (van Bilsen, J.H., Ronsmans, S., Crevel, R.W., Rona, R.J., Przyrembel, H., Penninks, A.H., Contor, L., Houben, G.F., 2011. Evaluation of scientific criteria for identifying allergenic food of public health importance. Regulatory Toxicology and Pharmacology 60, 281–289). A multi-disciplinary group was invited to critically test the refined approach. They independently evaluated selected publications on coconut, soy and/or peanut allergy, scored them using the newly developed level of evidence criteria, and debated proposed approaches for combining and utilising the scores to measure the overall impact of an allergen in public health impact assessments. The evaluation of selected publications using the modified criteria produced a relatively consistent result across the experts. These refined criteria were judged to be a way forward for the identification of allergenic foods of public health importance, and for prioritisation of allergen risk management and future data gathering. The debate to combine available evidence when assessing whether an allergenic food is of sufficient public health importance to warrant active management led to proposals on how to weight and combine evidence on allergen severity, potency and prevalence. The refined criteria facilitate a debate to find a meaningful sequence of steps to summarise the available information in relation to a food allergen.     

Accumulation of prion protein in the brain that is not associated with transmissible disease

Prion diseases or transmissible spongiform encephalopathies are characterized histopathologically by the accumulation of prion protein (PrP) ranging from diffuse deposits to amyloid plaques. Moreover, pathologic PrP isoforms (PrP(Sc)) are detected by immunoblot analysis and used both as diagnostic markers of disease and as indicators of the presence of infectivity in tissues. It is not known which forms of PrP are associated with infectivity. To address this question, we performed bioassays using human brain extracts from two cases with phenotypically distinct forms of familial prion disease (Gerstmann-Str?ussler-Scheinker P102L). Both cases had PrP accumulations in the brain, but each had different PrP(Sc) isoforms. Only one of the brains had spongiform degeneration. Tissue from this case transmitted disease efficiently to transgenic mice (Tg PrP101LL), resulting in spongiform encephalopathy. In contrast, inoculation of tissue from the case with no spongiform degeneration resulted in almost complete absence of disease transmission but elicited striking PrP-amyloid deposition in several recipient mouse brains. Brains of these mice failed to transmit any neurological disease on passage, but PrP-amyloid deposition was again observed in the brains of recipient mice. These data suggest the possible isolation of an infectious agent that promotes PrP amyloidogenesis in the absence of a spongiform encephalopathy. Alternatively, the infectious agent may be rendered nonpathogenic by sequestration in amyloid plaques, or PrP amyloid can seed amyloid accumulation in the brain, causing a proteinopathy that is unrelated to prion disease. Formation of PrP amyloid may therefore not necessarily be a reliable marker of transmissible spongiform encephalopathy infectivity.