Diesel Engine Exhaust Initiates a Sequence of Pulmonary and Cardiovascular Effects in Rats

This study was designed to determine the sequence of events leading to cardiopulmonary effects following acute inhalation of diesel engine exhaust in rats. Rats were exposed for 2 h to diesel engine exhaust (1.9 mg/m3), and biological parameters related to antioxidant defense, inflammation, and procoagulation were examined after 4, 18, 24, 48, and 72 h. This in vivo inhalation study showed a pulmonary anti-oxidant response (an increased activity of the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase and an increase in heme oxygenase-1 protein, heme oxygenase activity, and uric acid) which precedes the inflammatory response (an increase in IL-6 and TNF-α). In addition, increased plasma thrombogenicity and immediate anti-oxidant defense gene expression in aorta tissue shortly after the exposure might suggest direct translocation of diesel engine exhaust components to the vasculature but mediation by other pathways cannot be ruled out. This study therefore shows that different stages in oxidative stress are not only affected by dose increments but are also time dependent

Acute left ventricular dysfunction secondary to right ventricular septal pacing in a woman with initial preserved contractility: a case report

<p>Abstract</p> <p>Introduction</p> <p>Right ventricular apical pacing-related heart failure is reported in some patients after long-term pacing. The exact mechanism is not yet clear but may be related to left ventricular dyssynchrony induced by right ventricular apical pacing. Right ventricular septal pacing is thought to deteriorate left ventricular function less frequently because of a more normal left ventricular activation pattern.</p> <p>Case presentation</p> <p>We report the case of a 55-year-old Tunisian woman with preserved ventricular function, implanted with a dual-chamber pacemaker for complete atrioventricular block. Right ventricular septal pacing induced a major ventricular dyssynchrony, severe left ventricular ejection fraction deterioration and symptoms of congestive heart failure. Upgrading to a biventricular device was associated with a decrease in the symptoms and the ventricular dyssynchrony, and an increase of left ventricular ejection fraction.</p> <p>Conclusion</p> <p>Right ventricular septal pacing can induce reversible left ventricular dysfunction and heart failure secondary to left ventricular dyssynchrony. This complication remains an unpredictable complication of right ventricular septal pacing.</p

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Assessment of normal tricuspid valve anatomy in adults by real-time three-dimensional echocardiography

Background: The tricuspid valve (TV) is a complex structure. Unlike the aortic and mitral valve it is not possible to visualize all TV leaflets simultaneously in one cross-sectional view by standard two-dimensional echocardiography (2DE) either transthoracic or transesophageal due to the position of TV in the far field. Aim: Quantitative and qualitative assessment of the normal TV using real-time 3-dimensional echocardiography (RT3DE). Methods: RT3DE was performed for 100 normal adults (mean age 30 ± 9 years, 65% males). RT3DE visualization was evaluated by 4-point score (1: not visualized, 2: inadequate, 3: sufficient, and 4: excellent). Measurements included TV annulus diameters (TAD), TV area (TVA), and commissural width. Results: In 90% of patients with good 2DE image quality, it was possible to analyse TV anatomy by RT3DE. A detailed anatomical structure including unique description and measurement of tricuspid annulus shape and size, TV leaflets shape, and mobility, and TV commissural width were obtained in majority of patients. Identification of each TV leaflet as seen in the routine 2DE views was obtained. Conclusion: RT3DE of the TVis feasible in a large number of patients. RT3DE may add to functional 2DE data in description of TV anatomy and providing highly reproducible and actual reality (anatomical and functional) measurements

Does heart rate influence CMR image quality of the coronary vessel wall?

Cardiolog

Renal clearable catalytic gold nanoclusters for in vivo disease monitoring

Ultra-small gold nanoclusters (AuNCs) have emerged as agile probes for in vivo imaging, as they exhibit exceptional tumour accumulation and efficient renal clearance properties. However, their intrinsic catalytic activity, which can enable increased detection sensitivity, has yet to be explored for in vivo sensing. By exploiting the peroxidase-mimicking activity of AuNCs and the precise nanometer size filtration of the kidney, we designed multifunctional protease nanosensors that respond to disease microenvironments to produce a direct colorimetric urinary readout of disease state in less than 1 h. We monitored the catalytic activity of AuNCs in collected urine of a mouse model of colorectal cancer where tumour-bearing mice showed a 13-fold increase in colorimetric signal compared to healthy mice. Nanosensors were eliminated completely through hepatic and renal excretion within 4 weeks after injection with no evidence of toxicity. We envision that this modular approach will enable rapid detection of a diverse range of diseases by exploiting their specific enzymatic signatures

Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication via Interaction with DDX3X

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16–36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent protein (GFP) fusions to HCV core protein residues 16–36, but not by GFP fusions to core protein residues 16–35 or 16–34. Notably, the inhibition of HCV replication due to expression of the GFP fusion to HCV core protein residues 16–36 can be reversed by overexpression of DDX3X. These results suggest that the protein interface on DDX3X that binds the HCV core protein is important for replicon maintenance. However, infection of HuH-7 cells by HCV viruses of genotype 2a (JFH1) was not affected by expression of the GFP fusion protein. These results suggest that the role of DDX3X in HCV infection involves aspects of the viral life cycle that vary in importance between HCV genotypes