Serial magnetic resonance imaging based assessment of the early effects of an ACE inhibitor on postinfarction left ventricular remodeling in rats

In vivo assessment of treatment efficacy on postinfarct left ventricular (LV) remodeling is crucial for experimental studies. We examined the technical feasibility of serial magnetic resonance imaging (MRI) for monitoring early postinfarct remodeling in rats. MRI studies were performed with a 7-Tesla unit, 1, 3, 8, 15, and 30 days after myocardial infarction (MI) or sham operation, to measure LV mass, volume, and the ejection fraction (EF). Three groups of animals were analyzed: sham-operated rats (n = 6), MI rats receiving lisinopril (n = 11), and MI rats receiving placebo (n = 8). LV dilation occurred on day 3 in both MI groups. LV end-systolic and end-diastolic volumes were significantly lower in lisinopril-treated rats than in placebo-treated rats at days 15 and 30. EF was lower in both MI groups than in the sham group at all time points, and did not differ between the MI groups during follow-up. Less LV hypertrophy was observed in rats receiving lisinopril than in rats receiving placebo at days 15 and 30. We found acceptable within- and between-observer agreement and an excellent correlation between MRI and ex vivo LV mass (r = 0.96; p < 0.001). We demonstrated the ability of MRI to detect the early beneficial impact of angiotensin-converting enzyme (ACE) inhibitors on LV remodeling. Accurate and noninvasive, MRI is the tool of choice to document response to treatment targeting postinfarction LV remodeling in rats

Volumetric assessment of myocardial viability in rats using 3D double contrast enhanced T1 and T2-weighted MRI

OBJECTIVE: Volumetric evaluation of the myocardial viability post-infarction in rats using 3D in vivo MR imaging at 7 T using injection of an extracellular paramagnetic contrast agent and intravascular superparamagnetic iron oxide nanoparticles in the same imaging session. MATERIALS AND METHODS: Five hours after induction of permanent myocardial infarction in rats (n=6), 3D in vivo T1- and T2-weighted MR Imaging was performed prior to and after Gd-DOTA injection (0.2 mmol/kg) and prior to and after nanoparticle injection (5 mg Fe/kg) to assess infarct size and myocardial viability. RESULTS: 3D MR Imaging using a successive contrast agent injection showed a difference of infarct size after Gd-DOTA injection on T1-weighted images compared to the one measured on T2-weighted images after Gd-DOTA and nanoparticle injection. CONCLUSION: The use of 3D T1- and T2-weighted MR Imaging using a double contrast agents protocol made possible the accurate characterization of myocardial infarction volume and allowed the detection of myocardial viability post-infarction in rats

Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium

Structure of characteristic Lyapunov vectors in spatiotemporal chaos

We study Lyapunov vectors (LVs) corresponding to the largest Lyapunov exponents in systems with spatiotemporal chaos. We focus on characteristic LVs and compare the results with backward LVs obtained via successive Gram-Schmidt orthonormalizations. Systems of a very different nature such as coupled-map lattices and the (continuous-time) Lorenz `96 model exhibit the same features in quantitative and qualitative terms. Additionally we propose a minimal stochastic model that reproduces the results for chaotic systems. Our work supports the claims about universality of our earlier results [I. G. Szendro et al., Phys. Rev. E 76, 025202(R) (2007)] for a specific coupled-map lattice.Comment: 9 page

High throughput screening for identification of mycolactone targets : Relations between M. ulcerans and nervous system

Buruli ulcer is an infectious disease transmitted by arthropod vectors harboring Mycobacterium ulcerans, a mycobacterium which belong to the same family of bacteria causing tuberculosis and leprosy. The infection causes painless swelling and severe skin lesions. One key feature of M. ulcerans bacterium is its ability to secrete a necrotic toxin, the mycolactone within small lipophilic vesicles, which are critical for the bacterial induced cytotoxicity. The biological knowledge as well as the preventive and therapeutic means for this invalidating disease is still very limited.   Our first approach was to investigate whether the mycolactone toxin could be involved in the neutralization of pain by acting directly on the peripheral nervous system without causing destruction of nervous fibers. By use of live time fluorescence microscopy and appropriate markers, we showed that the addition of toxin at sub-toxic dose provokes modification of ionic currents of neuron cells. Based on this ability of the toxin, a molecular high throughput methodology was developed for the screening of a genome wide siRNA library and small molecules inhibitors to enable the search of the cellular targets for the toxin. The cell-based assay relies on automated confocal microscopy on macrophages coupled with dedicated image analysis. These two screening allowed us to identify a putative toxin target, and a toxin inhibitor. A binding assay confirmed that the putative target is a receptor of the toxin. Together these results allowed us to build a potential signaling pathway activated by the mycolactone and implicated in ionic channel activities.   The second approach was to confirm this model in the mouse model of M. ulcerans infection and its role in the hypoesthesia of the lesions. Toxin inhibitor, daily administered to mice, which were experimentally infected by M. ulcerans, conducted to the absence of the hypoesthesia of the lesions. Furthermore, a histological study of neuronal fibers did not show a destruction of neuronal cells. Moreover, in vitro studies have showed that M. ulcerans are able to colonize neuronal cells. Then, these results suggested that the hypoesthesia of the M. ulcerans lesions could be caused by a non-destructive process of nervous cells.

In vitro and in vivo behaviour of paclitaxel loaded lipid nanocapsules

International audienc

Dispersive stabilization of the inverse cascade for the Kolmogorov flow

It is shown by perturbation techniques and numerical simulations that the inverse cascade of kink-antikink annihilations, characteristic of the Kolmogorov flow in the slightly supercritical Reynolds number regime, is halted by the dispersive action of Rossby waves in the beta-plane approximation. For beta tending to zero, the largest excited scale is proportional to the logarithm of one over beta and differs strongly from what is predicted by standard dimensional phenomenology which ignores depletion of nonlinearity.Comment: 4 pages, LATEX, 3 figures. v3: revised version with minor correction

Response of stratospheric water vapor and ozone to the unusual timing of El Niño and the QBO disruption in 2015–2016

The stratospheric circulation determines the transport and lifetime of key trace gases in a changing climate, including water vapor and ozone, which radiatively impact surface climate. The unusually warm El Niño–Southern Oscillation (ENSO) event aligned with a disrupted Quasi-Biennial Oscillation (QBO) caused an unprecedented perturbation to this circulation in 2015–2016. Here, we quantify the impact of the alignment of these two phenomena in 2015–2016 on lower stratospheric water vapor and ozone from satellite observations. We show that the warm ENSO event substantially increased water vapor and decreased ozone in the tropical lower stratosphere. The QBO disruption significantly decreased global lower stratospheric water vapor and tropical ozone from early spring to late autumn. Thus, this QBO disruption reversed the lower stratosphere moistening triggered by the alignment of the warm ENSO event with westerly QBO in early boreal winter. Our results suggest that the interplay of ENSO events and QBO phases will be crucial for the distributions of radiatively active trace gases in a changing future climate, when increasing El Niño-like conditions and a decreasing lower stratospheric QBO amplitude are expected