Concept for a gas operated actuator

Palladium valve, permeable to hydrogen gas, is used to fill a bellows mechanism from a source of hydrogen to power an actuator. A similar valve provides retraction. The valves have no moving parts and are heat operated. One limitation on the use of this actuator is discussed

Phthalate esters used as plasticizers in packed red blood cell storage bags may lead to progressive toxin exposure and the release of pro-inflammatory cytokines

Phthalate esters (PE's) are plasticizers used to soften PVC-based medical devices. PE's are the most abundant man-made pollutants and increase the risk of developing an allergic respiratory disease or a malignancy. The leaching of PE's in donated packed red blood cells (PRBC) during storage was assessed. PRBC transfusion bags containing CPD/AS-1 (ADSOL) buffer were analyzed. Samples were collected on storage day 1 and day 42. Two PE's, di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP), were measured by liquid chromatography coupled to mass spectrometry (LCMS). Interleukin-8 (IL-8) was measured by standard ELISA techniques. DEHP significantly increased from 34.3 µM (±20.0 SD) on day 1 to 433.2 µM (±131.2 SD) on day 42, a 12.6-fold increase. Similarly, MEHP significantly increased from 3.7 µM (±2.8 SD) on day 1 to 74.0 µM (±19.1 SD) on day 42, a 20.2-fold increase. Also, DEHP and MEHP increased the release of IL-8 from human umbilical vein endothelial cells (HUVEC). The transfusion of older units of PRBC could lead to an accumulation of PE's possibly resulting in inflammation and other effects. This accumulation could be exacerbated due to the decreased metabolism of PE's since trauma patients have a lower esterase activity, the enzymes responsible for metabolizing PE's. The effect of oxidative stress caused by PE's is discussed as a potential mechanism for increases in inflammation caused by older units of PRBC

Implications for oxidative stress and astrocytes following 26S proteasomal depletion in mouse forebrain neurones

Neurodegenerative diseases are characterized by progressive degeneration of selective neurones in the nervous system, but the underlying mechanisms involved in neuroprotection and neurodegeneration remain unclear. Dysfunction of the ubiquitin proteasome system is one of the proposed hypotheses for the cause and progression of neuronal loss. We have performed quantitative two-dimensional fluorescence difference in-gel electrophoresis combined with peptide mass fingerprinting to reveal proteome changes associated with neurodegeneration following 26S proteasomal depletion in mouse forebrain neurones. Differentially expressed proteins were validated by Western blotting, biochemical assays and immunohistochemistry. Of significance was increased expression of the antioxidant enzyme peroxiredoxin 6 (PRDX6) in astrocytes, associated with oxidative stress. Interestingly, PRDX6 is a bifunctional enzyme with antioxidant peroxidase and phospholipase A2 (PLA2) activities. The PLA2 activity of PRDX6 was also increased following 26S proteasomal depletion and may be involved in neuroprotective or neurodegenerative mechanisms. This is the first in vivo report of oxidative stress caused directly by neuronal proteasome dysfunction in the mammalian brain. The results contribute to understanding neuronal–glial interactions in disease pathogenesis, provide an in vivo link between prominent disease hypotheses and importantly, are of relevance to a heterogeneous spectrum of neurodegenerative diseases

Use of hydroxyethyl starch in leukocytapheresis procedures does not increase renal toxicity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134412/1/trf13795.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134412/2/trf13795_am.pd

Educational paper: Defects in number and function of neutrophilic granulocytes causing primary immunodeficiency

The neutrophilic granulocyte (neutrophil) is the most important cellular component of the innate immune system. A total absence of neutrophils or a significant decrease in their number leads to severe immunodeficiency. A mature neutrophil, released from the bone marrow, should be able to migrate from the blood towards the tissues, following a chemotactic gradient to a pathogen. In order to be neutralized, this pathogen has to be recognized, phagocytosed, and destroyed by lytic enzymes contained in the neutrophil's granules and reactive oxygen species formed by the enzyme complex NADPH oxidase. Rare genetic defects leading to the loss of each one of these biological properties of the neutrophil have been described and are associated with immunodeficiency. This review provides a summary of the normal development and biological functions of neutrophils and describes the diseases caused by defects in neutrophil number and function

Role of Rac GTPase activating proteins in regulation of NADPH oxidase in human neutrophils

Precise spatiotemporal regulation of O2 --generating NADPH oxidases (Nox) is a vital requirement. In the case of Nox1-3, which depend on the small GTPase Rac, acceleration of GTP hydrolysis by GTPase activating protein (GAP) could represent a feasible temporal control mechanism. Our goal was to investigate the molecular interactions between RacGAPs and phagocytic Nox2 in neutrophilic granulocytes. In structural studies we revealed that simultaneous interaction of Rac with its effector protein p67phox and regulatory protein RacGAP was sterically possible. The effect of RacGAPs was experimentally investigated in a cell-free O2 --generating system consisting of isolated membranes and recombinant p47phox and p67phox proteins. Addition of soluble RacGAPs decreased O 2 - production and there was no difference in the effect of four RacGAPs previously identified in neutrophils. Depletion of membrane-associated RacGAPs had a selective effect: a decrease in ARHGAP1 or ARHGAP25 level increased O2 - production but a depletion of ARHGAP35 had no effect. Only membrane-localized RacGAPs seem to be able to interact with Rac when it is assembled in the Nox2 complex. Thus, in neutrophils multiple RacGAPs are involved in the control of O2 - production by Nox2, allowing selective regulation via different signaling pathways. © 2013 Elsevier Inc