MRI plaque imaging and its role in population-based studies

Noninvasive direct vessel wall (plaque) imaging may provide a good opportunity to study unique aspects of atherosclerotic lesions in different populations. The article published by Esposito et al. provides new insights into our understanding of diabetic atherosclerotic vascular disease by using direct plaque imaging techniques. The findings from this article call for attention to more in vivo imaging to understand the nature of high-risk atherosclerosis, especially in prospective studies in diabetic patients

Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

<p>Abstract</p> <p>Background</p> <p>Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients.</p> <p>Methods</p> <p>The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed.</p> <p>Results</p> <p>In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline F_ENOand the increase in F_ENOor BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed.</p> <p>Conclusion</p> <p>The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients.</p

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy

Axons Amplify Somatic Incomplete Spikes into Uniform Amplitudes in Mouse Cortical Pyramidal Neurons

BACKGROUND: Action potentials are the essential unit of neuronal encoding. Somatic sequential spikes in the central nervous system appear various in amplitudes. To be effective neuronal codes, these spikes should be propagated to axonal terminals where they activate the synapses and drive postsynaptic neurons. It remains unclear whether these effective neuronal codes are based on spike timing orders and/or amplitudes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated this fundamental issue by simultaneously recording the axon versus soma of identical neurons and presynaptic vs. postsynaptic neurons in the cortical slices. The axons enable somatic spikes in low amplitude be enlarged, which activate synaptic transmission in consistent patterns. This facilitation in the propagation of sequential spikes through the axons is mechanistically founded by the short refractory periods, large currents and high opening probability of axonal voltage-gated sodium channels. CONCLUSION/SIGNIFICANCE: An amplification of somatic incomplete spikes into axonal complete ones makes sequential spikes to activate consistent synaptic transmission. Therefore, neuronal encoding is likely based on spike timing order, instead of graded analogues

Sex differences in mood disorders: Perspectives from humans and rodent models

Mood disorders are devastating, often chronic illnesses characterized by low mood, poor affect, and anhedonia. Notably, mood disorders are approximately twice as prevalent in women compared to men. If sex differences in mood are due to underlying biological sex differences, a better understanding of the biology is warranted to develop better treatment or even prevention of these debilitating disorders. In this review, our goals are to: 1) summarize the literature related to mood disorders with respect to sex differences in prevalence, 2) introduce the corticolimbic brain network of mood regulation, 3) discuss strategies and challenges of modeling mood disorders in mice, 4) discuss mechanisms underlying sex differences and how these can be tested in mice, and 5) discuss how our group and others have used a translational approach to investigate mechanisms underlying sex differences in mood disorders in humans and mice

Coronary and peripheral artery remodeling in patients undergoing PTCA: an intracoronary and transcutaneous ultrasound study.

The aim of this study was to assess the relationship between the plaque burden of nonstenotic coronary artery segments and the wall thickness of peripheral arteries using intracoronary and transcutaneous ultrasound imaging, respectively. Intracoronary ultrasound (CVIS, 3.5 Fr) was performed in 27 patients undergoing percutaneous transluminal coronary angioplasty. Carotid arteries were imaged by B-mode ultrasound with semiautomatic edge detection and radial arteries by high resolution A-mode echotracking (NIUS 2). Quantitative measurements included coronary artery intima-media cross-sectional area (IM(CSA)) and cross-sectional narrowing (CSN), as well as intima-media thickness (IMT) and lumen radius (r) of the common carotid and the radial arteries. Intima-media thickness was increased in coronary, carotid, and radial arteries. Coronary arteries had an IM(CSA) of 7.7 +/- 2.5 mm(2) and a CSN of 24% +/- 8%. Despite this moderate plaque burden, lumen area was preserved (12.3 +/- 4.2 mm(2)) because of compensatory enlargement of coronary arteries. Right and left carotid and right radial arteries had an IMT of 575 +/- 78 microm, 570 +/- 129 microm, and 328 +/- 61 microm, respectively. There was no correlation between coronary IM(CSA) and carotid IMT (r = 0.07) or radial IMT (r = 0.02), and there was no correlation between coronary CSN and carotid IMT/r (r = 0.12), or radial IMT/r (r = 0.25). In conclusion, in these patients with symptomatic ischemic disease no relationship between IMT of the coronary arteries and IMT of carotid or radial arteries was found. Although increasingly popular, IMT of peripheral arteries may be of limited value as surrogate marker for the severity of coronary artery disease. Cathet. Cardiovasc. Intervent. 48:12-17, 1999