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Haemolysis by Sendal virus, -toxin, and activated complement is inhibited by high concentrations of divalent cations. In Daudi cells, sublytic amounts of these agents induce the following changes: collapse of surface membrane potential, uptake of Na+ and loss of K+ from cells, and leakage of phosphorylated metabo-tites from cells. The changes induced by Sendal virus and complement are sensitive to physiological concentrations of extracellular Ca2+. It is concluded that fluctuations in plasma Ca2+ concentration may affect the damaging action of certain pore-forming agents on susceptible cells. 相似文献
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Environmental context and magnitude of disturbance influence trait‐mediated community responses to wastewater in streams 下载免费PDF全文
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Janet Alder Wendy Fujioka Jonathan Lifshitz David P. Crockett Smita Thakker-Varia 《Journal of visualized experiments : JoVE》2011,(54)
Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair.Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20.We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP. 相似文献
5.
Michael Eddleston Peter Eyer Franz Worek Edmund Juszczak Nicola Alder Fahim Mohamed Lalith Senarathna Ariyasena Hittarage Shifa Azher K. Jeganathan Shaluka Jayamanne Ludwig von Meyer Andrew H. Dawson Mohamed Hussain Rezvi Sheriff Nick A. Buckley 《PLoS medicine》2009,6(6)
Background
Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote''s effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.Methods and Findings
We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88–3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71–2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.Conclusions
Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.Trial Registration
Controlled-trials.com ISRCTN55264358 Please see later in the article for Editors'' Summary 相似文献6.
7.
Davis DR McAlpine JB Pazoles CJ Talbot MK Alder EA White C Jonas BM Murray BE Weinstock GM Rogers BL 《Journal of molecular microbiology and biotechnology》2001,3(2):179-184
Using bioinformatics approaches, 34 potential multidrug resistance (MDR) transporter sequences representing 4 different transporter families were identified in the unannotated Enterococcus faecalis database (TIGR). A functional genomics campaign generating single-gene insertional disruptions revealed several genes whose absence confers significant hypersensitivities to known antimicrobials. We constructed specific strains, disrupted in a variety of previously unpublished, putative MDR transporter genes, as tools to improve the success of whole-cell antimicrobial screening and discovery. Each of the potential transporters was inactivated at the gene level and then phenotypically characterized, both with single disruption mutants and with 2-gene mutants built upon a delta norA deleted strain background. 相似文献
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9.
Pauly D Watson R Alder J 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2005,360(1453):5-12
This contribution, which reviews some broad trends in human history and in the history of fishing, argues that sustainability, however defined, rarely if ever occurred as a result of an explicit policy, but as result of our inability to access a major part of exploited stocks. With the development of industrial fishing, and the resulting invasion of the refuges previously provided by distance and depth, our interactions with fisheries resources have come to resemble the wars of extermination that newly arrived hunters conducted 40,000-50,000 years ago in Australia, and 11,000-13,000 years ago against large terrestrial mammals arrived in North America. These broad trends are documented here through a map of change in fish sizes, which displays characteristic declines, first in the nearshore waters of industrialized countries of the Northern Hemisphere, then spread offshore and to the Southern Hemisphere. This geographical extension met its natural limit in the late 1980s, when the catches from newly accessed stocks ceased to compensate for the collapse in areas accessed earlier, hence leading to a gradual decline of global landing. These trends affect developing countries more than the developed world, which have been able to meet the shortfall by increasing imports from developing countries. These trends, however, together with the rapid growth of farming of carnivorous fishes, which consumes other fishes suited for human consumption, have led to serious food security issues. This promotes urgency to the implementation of the remedies traditionally proposed to alleviate overfishing (reduction of overcapacity, enforcement of conservative total allowable catches, etc.), and to the implementation of non-conventional approaches, notably the re-establishment of the refuges (also known as marine reserves), which made possible the apparent sustainability of pre-industrial fisheries. 相似文献
10.
Respiratory Complex II of the mitochondrial inner membrane serves as a link between the tricarboxylic acid cycle and the electron transport chain. Complex II dysfunction has been implicated in a wide range of heritable mitochondrial diseases, including cancer, by a mechanism that likely involves the production of reactive oxygen species (ROS). Using Complex II enzymes reconstituted into nanoscale lipid bilayers (nanodiscs) with varying lipid composition, we demonstrate for the first time that the phospholipid environment, specifically the presence of cardiolipin, is critical for the assembly and enzymatic activity of the complex, as well as in the curtailment of ROS production. 相似文献