Astrocyte Mitochondria in In Vitro Models of Ischemia

There is growing evidence that preservation of mitochondrial respiratory function during cerebral ischemia-reperfusion predicts the ultimate extent of tissue injury. Because neurons are selectively vulnerable to ischemic injury, many studies have focused on neuronal mitochondrial dysfunction in ischemia. However, positron emission tomography (PET) studies in animals and humans suggest that non-neuronal cells such as astrocytes may also experience mitochondrial metabolic compromise that contributes to ischemic necrosis. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support of neurons. Mitochondria are important for many of these actions. We have used a cell culture model of stroke, oxygen-glucose deprivation (OGD), to study the response of astrocyte mitochondria to ischemia, and to evaluate how changes in astrocyte mitochondrial function might affect neuronal survival and recovery after ischemia.     

The dielectric properties of cancerous tissues in a nude mouse xenograft model

The dielectric properties of various cancers, namely brain tumor, breast cancer, gastric carcinoma, and colon cancer, were measured in the frequency range of 500 MHz to 5 GHz. Cancers were cultivated applying the xenograft model of growing human cancerous tissues using the specific pathogen free, homo inbred mouse (a nude mouse). The complex permittivity was measured using an open-ended coaxial probe (HP85070B) and a computer controlled network analyzer (HP8510C). For the measurement of the dielectric properties, a total of 58 xenografted specimens was used. The results showed that measured values of complex permittivity for all four cancerous tissues were similar, with little variations over the frequency range used. It might be agreed that components and characteristics of different cancerous tissues would be similar despite their different occurrences in the human body. It is necessary to investigate this result further.     

Influence of 50 Hz frequency sinusoidal magnetic field on the blood-brain barrier permeability of diabetic rats

The combined effects of diabetes and a 50 Hz, 5 mT RMS flux density sinusoidal magnetic field for 8 h a day, for 21 consecutive days on the permeation of Evans-blue dye through the blood-brain barrier were studied in male Wistar albino rats. Our results suggest that magnetic field has no effect on the blood-brain barrier permeability in normoglycemic animals, but that diabetic rats are vulnerable to magnetic fields.     

Group Training with Healthy Computing Practices to Prevent Repetitive Strain Injury (RSI): A Preliminary Study

This pilot study investigated whether group training, in which participants become role models and coaches, would reduce discomfort as compared to a nontreatment Control Group. Sixteen experimental participants participated in 6 weekly 2-hr group sessions of a Healthy Computing program whereas 12 control participants received no training. None of the participants reported symptoms to their supervisors nor were they receiving medical treatment for repetitive strain injury prior to the program. The program included training in ergonomic principles, psychophysiological awareness and control, sEMG practice at the workstation, and coaching coworkers. Using two-tailed t tests to analyze the data, the Experimental Group reported (1) a significant overall reduction in most body symptoms as compared to the Control Group and (2) a significant increase in positive work-style habits, such as taking breaks at the computer, as compared to the Control Group. This study suggests that employees could possibly improve health and work style patterns based on a holistic training program delivered in a group format followed by individual practice.     

Oxidative stress induced by corticosterone administration in broiler chickens (Gallus gallus domesticus) 1. Chronic exposure

Two trials were conducted to evaluate the effects of short-term administration of corticosterone (CORT) on the induction of oxidative injury in broiler chickens (Gallus gallus domesticus). Twelve broiler chickens of 30 and of 40 days of age were respectively employed in Trial 1 and 2. Half of the chickens were administered subcutaneously with CORT (4 mg/kg body weight [BW] in corn oil), while another half served as controls (corn oil) in each trail. In Trial 1, a blood sample was obtained from each chicken immediately before administration and at 1 and 3 h after injection. In Trial 2, the liver and heart were obtained after 3 h of CORT exposure. Short-term administration of CORT resulted in enhanced proteolysis and gluconeogenesis. There were no obvious changes in lipid peroxidation status of the heart and liver, whereas a decrease in lipid peroxidation in the plasma was observed after acute CORT exposure. The significantly increased plasma nonenzymatic antioxidants (uric acid [UA] and total antioxidant capacity) in concert with the enhanced enzymatic antioxidant activity (SOD in heart) during short-term CORT administration indicate preventive changes to counteract the oxidative injury, and these may be tissue specific.     

Organ-specific expression of the lacZ gene controlled by the opsin promoter after intravenous gene administration in adult mice

BACKGROUND: The tissue-specific expression of an exogenous gene, under the influence of a tissue-specific promoter, has been examined in the past with pro-nuclear injections of the transgene and the development of transgenic mouse models. 'Adult transgenics' is possible with the acute expression of an exogenous gene that is administered to adult animals, providing the transgene can be effectively delivered to distant sites following an intravenous administration. METHODS: The organ specificity of exogenous gene expression in adult mice was examined with a bacterial beta-galactosidase (LacZ) expression plasmid under the influence of the bovine rhodopsin gene promoter. The 8-kb plasmid DNA was delivered to organs following an intravenous administration with the pegylated immunoliposome (PIL) non-viral gene transfer technology. The PIL carrying the gene was targeted to organs with the rat 8D3 monoclonal antibody (MAb) to the mouse transferrin receptor (TfR). RESULTS: The rhodopsin/beta-galactosidase gene was expressed widely in both the eye and the brain of adult mice, but was not expressed in peripheral tissues, including liver, spleen, lung, or heart. Ocular expression included the retinal-pigmented epithelium, the iris, and ciliary body, and brain expression was observed in neuronal structures throughout the cerebrum and cerebellum. CONCLUSIONS: The expression of trans-genes in adult animals is possible with the PIL non-viral gene transfer method. The opsin promoter enables tissue-specific gene expression in the eye, as well as the brain of adult mice, whereas gene expression in peripheral tissues, such as liver or spleen, is not observed.     

Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury

Tumor necrosis factor (TNF)-alpha-induced hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure. TNF-alpha exerts a variety of effects that are mediated mainly by TNF-receptor 1 (TNF-R1) in cell death. The activation of TNF-R1 leads to the activation of multiple apoptotic pathways involving the activation of the pro-death Bcl-2 family proteins, reactive oxygen species, C-Jun NH2-terminal kinase, cathepsin B, acidic sphingomyelinase and neutral sphingomyelinase. These pathways are closely interlinked and mainly act on mitochondria, which release the apoptogenic factors and other events, resulting in apoptosis. This article reviews the recent progress in the molecular mechanisms of TNF-alpha-induced apoptosis in hepatocytes, and discusses how these molecular findings are shaping our understanding of the pathogenesis of liver diseases and our strategy to develop novel therapeutics.     

Regulation of recombinant human brain tandem P domain K+ channels by hypoxia: a role for O2 in the control of neuronal excitability?

The tandem P domain potassium channels, TREK1 and TASK1, are expressed throughout the brain but expression patterns do not significantly overlap. Since normal pO₂ in central nervous tissue is as low as 20 mmHg and can decrease even further in ischemic disease, it is important that the behaviour of human brain ion channels is studied under conditions of acute and chronic hypoxia. This is especially true for brain-expressed tandem P-domain channels principally because they are important contributors to neuronal resting membrane potential and excitability. Here, we discuss some recent data derived from two recombinant tandem P-domain potassium channels, hTREK1 and hTASK1. Hypoxia represents a potent inhibitory influence on both channel types and occludes the activation by arachidonic acid, intracellular acidosis and membrane deformation of TREK1. This casts doubt on the idea that TREK1 activation during brain ischemia might facilitate neuroprotection via hyperpolarising neurons in which it is expressed. Interestingly, hypoxia is unable to regulate alkalotic inhibition of TREK1 suggesting that this channel may be more intimately involved in control of excitability during physiological or pathological alkalosis.     

Optimization of the first dimension for separation by two-dimensional gel electrophoresis of basic proteins from human brain tissue

A major cause of poor resolution in the alkaline pH range of two-dimensional electrophoresis (2-DE) gels is unsatisfactory separation of basic proteins in the first dimension. We have compared methods for the separation of basic proteins in the isoelectric focusing dimension of human brain proteins. The combined use of anodic cup-loading and the hydroxyethyldisulphide containing solution (DeStreak) produced better resolution in both analytical and micropreparative protein loaded 2-DE gels than the other methods investigated.