The macrophage in the pathogenesis of severe acute respiratory syndrome coronavirus infection

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Gas-filled microbubbles: a novel susceptibility contrast agent for brain and liver MRI

Theme: Engineering the Future of BiomedicineGas-filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility and localized manipulation via ultrasound cavitation. However, in vivo demonstration of microbubble susceptibility effect is limited so far and microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, two types of microbubbles, custom-made albumin-coated microbubbles (AMBs) and a commercially available lipid-based clinical ultrasound contrast agent (SonoVue® ), were investigated with in vivo dynamic brain and liver MRI in Sprague-Dawley rats at 7 Tesla. Transverse relaxation rate enhancements (ΔR2*) maps were computed for brain and liver, yielding results similar to those obtained with a common MR blood pool contrast agent. These results indicate that gas-filled microbubbles can serve as an intravascular MR contrast agent at high field. Enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into microbubbles was also investigated at 7 T in vitro. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas-filled microbubble susceptibility effect can be substantially increased using iron oxides nanoparticles. With such approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Such capability has the potential to lead to real-time MRI guidance in various microbubble-based drug delivery and therapeutic applications. ©2009 IEEE.published_or_final_versionThe 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2009), Minneapolis, MN., 3-6 September 2009. In Proceedings of the 31st EMBC, 2009, p. 4049-405

Service load analysis of unbonded partially prestressed concrete members

In the design of unbonded partially prestressed concrete (UPPC) members, it is necessary to estimate the stresses in steel and concrete in order to satisfy the requirements of the serviceability limit state. A numerical method has been developed to predict the response of UPPC beams under service load, and the results agree well with experimental results reported in the technical literature. A parametric study has been undertaken to evaluate the variation of stress in prestressed steel under service load as well as the ratio of length of equivalent deformation region to the neutral axis depth at critical section. Results show that this ratio is not sensitive to the variation of the combined reinforcement index. From the moment of application of load to the cracking of the beam, and until the yielding of non-prestressed steel, this ratio is fairly stable and it can be taken as a constant. With the determination of this ratio, an approximate cubic equation similar to that used for cracked section analysis of bonded partially prestressed members is established. Predictions of stresses under service load are in good agreement with available test data. © 2005 Thomas Telford Ltd.published_or_final_versio

Contexts Paired with Junk Food Impair Goal-Directed Behavior in Rats: Implications for Decision Making in Obesogenic Environments.

The high prevalence of obesity and related metabolic diseases calls for greater understanding of the factors that drive excess energy intake. Calorie-dense palatable foods are readily available and often are paired with highly salient environmental cues. These cues can trigger food-seeking and consumption in the absence of hunger. Here we examined the effects of palatable food-paired environmental cues on control of instrumental food-seeking behavior. In Experiment 1, adult male rats received exposures to one context containing three "junk" foods (JFs context) and another containing chow (Chow context). Next, rats were food-deprived and trained to perform instrumental responses (lever-press) for two novel food rewards in a third, distinct context. Contextual influences on flexible control of food-seeking behavior were then assessed by outcome devaluation tests held in the JF, chow and training contexts. Devaluation was achieved using specific satiety and test order was counterbalanced. Rats exhibited goal-directed control over behavior when tested in the training and chow-paired contexts. Notably, performance was habitual (insensitive to devaluation) when tested in the JF context. In Experiment 2 we tested whether the impairment found in the JF context could be ameliorated by the presentation of a discrete auditory cue paired with the chow context, relative to a second cue paired with the JF context. Consistent with the results of Experiment 1, the devaluation effect was not significant when rats were tested in the JF context with the JF cue. However, presenting the chow cue increased the impact of the devaluation treatment leading to a robust devaluation effect. Further tests confirmed that performance in the chow context was goal-directed and that sensory-specific satiety in the JF context was intact. These results show that environments paired with palatable foods can impair goal-directed control over food-seeking behavior, but that this deficit was improved by a cue paired with chow. This has promising implications for assisting individuals in controlling their eating behavior in environments designed to dysregulate it

MRI detection of peritoneal adhesion with dialysate enhancement

This study investigated the use of clinical peritoneal dialysis fluid (dialysate) as a peritoneal contrast agent to visualize peritoneal adhesions in rats at 7 Tesla. Intraperitoneal injection of dialysate (~0.1 mL/g) allowed the MR detection of peritoneal adhesions that were surgically induced in all rats studied (N = 6). MR measurements of adhesion surface areas correlated well with the postmortem estimations (R = 0.99). T1 and T2 values of undiluted dialysate were found to be 3017.5¡Ó35.3 ms and 108.4¡Ó2.0 ms, respectively. These findings demonstrated dialysate-enhanced MRI as a potentially valuable technique in clinical detection and evaluation of post-surgical peritoneal adhesion and to monitor therapeutic interventions (i.e., against peritoneal adhesion) in future preclinical research.published_or_final_versio

Noninvasive fMRI investigation of interaural level difference processing the rat auditory subcortex

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Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model

Background: Postoperative intra-abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesion was investigated. Methods: Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound-microbubble-mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF-β, fibrogenic factors, α-SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF-β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound-microbubble-mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.postprin

Cell number quantification of USPIO-labeled stem cells by MRI: An in vitro study

MRI plays an expanding role in stem cell therapies. The non-invasive nature and high spatial resolution of MR imaging make MR imaging a powerful tool to investigate biologic processes at the molecular and cellular level in vivo longitudinally. Quantitative detection of stem cells after transplantation may allow assessment of stem cell localization and migration, and monitoring of the therapeutic effectiveness of stem cell therapy. In this study, we present a technique for MR quantification of magnetically labeled mouse embryonic stem cells distributed or injected in agarose gel phantoms. Apparent transverse relaxation rate enhancements (ΔR2*) were measured by gradient echo sequences. The linear relationship between ΔR2* and the concentration of USPIO-labeled mouse embryonic stem cells was observed and used for quantifying cell density and cell number after injection or transplantation. The MRI acquisition and analysis protocol were validated by good agreement between actual cell numbers and MRI-estimated cell numbers over a wide range of cell numbers. This MR technique for cell number and cell density quantification is applicable to future in vivo studies. © 2006 IEEE.published_or_final_versio

Lipoteichoic acid from an Enterococcus faecalis clinical strain promotes TNF-α expression through the NF-κB and p38 MAPK signaling pathways in differentiated THP-1 macrophages

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Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells

<p>Abstract</p> <p>Background</p> <p>The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS.</p> <p>Results</p> <p>Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs.</p> <p>Conclusion</p> <p>The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.</p