Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its ...metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C ₂C ₁₂ myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of K ᵥ7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and K ᵥ7.4-bound PIP2 levels in C ₂C ₁₂ cells and inhibits K ᵥ7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of K ᵥ7.4 channels.
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Objectives
We sought to evaluate the effectiveness of post-mortem cardiac magnetic resonance (PM-CMR) for the identification of myocardial ischemia as cause of sudden cardiac death (SCD) when the ...time interval between the onset of ischemia and SCD is ≤ 90 min.
Methods
PM-CMR was performed in 8 hearts explanted from pigs with spontaneous death caused by occlusion of the left anterior descending coronary artery: 4 with SCD after ≤ 40 min of coronary occlusion and 4 between 40 and 90 min. PM-CMR included conventional T1 and T2-weighted image and T1, T2, and T2* mapping techniques. Imaging data were compared and validated with immunohistochemical evaluation of the altered proportion and redistribution of phosphorylated versus non-phosphorylated connexin 43 (CX43 and npCX43, respectively), an established molecular marker of myocardial ischemia.
Results
At T2-weighted images, the ischemic core was hypointense (core/remote ratio 0.67 ± 0.11) and surrounded by and hyperintense border zone. Compared to remote myocardium, the ischemic core had higher T1 (
p
= 0.0008), and lower T2 (
p
= 0.007) and T2* (
p
= 0.002). Cytoplasmatic npX43 and the npCX43/CX43 ratio were significantly higher in animals deceased > 40 min than in others.
Conclusion
PM-CMR can reliably detect early signs of myocardial damage induced by ischemia, based on conventional pulse sequences complemented by a novel ad hoc application of quantitative mapping techniques.
Key Points
• Post-mortem MRI may help to understand cause of sudden cardiac death.
• Post-mortem MRI allows detection of signs of myocardial ischemia as cause of sudden cardiac death within 90 and 40 min following coronary occlusion as demonstrated in a pig model of myocardial ischemia.
• Signs of myocardial ischemia using conventional and mapping MRI technique are associated with the immunohistochemical changes of phosphorylated and dephosphorylated connexin-43 which is an established molecular marker of myocardial ischemia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Treatment of lesions located in saphenous vein grafts (SVGs) is associated with increased procedural risk and a high rate of restenosis.
We conducted a randomized, multicenter trial to evaluate the ...usefulness of a polytetrafluoroethylene (PTFE)-covered stent compared with a bare stainless steel (SS) stent for prevention of restenosis and major adverse cardiac events (MACE) in patients undergoing SVG treatment. The primary end point was angiographic restenosis at 6 months. Secondary end points were 30-day and 6-month MACE rates, defined as the cumulative of death, myocardial infarction (MI), and target lesion revascularization. Between September 1999 and January 2002, 301 patients with SVG lesions were randomized to either the PTFE-covered JoStent coronary stent graft (PTFE group, n=156) or the SS JoFlex stent (control group, n=145). Angiographic and procedural success rates were similar between the 2 groups (97.4% versus 97.9% and 87.3% versus 93.8%, respectively). The incidence of 30-day MACE was higher in the PTFE group (10.9% versus 4.1%, P=0.047) and was mainly attributed to MI (10.3% versus 3.4%, P=0.037). The primary end point, the restenosis rate at 6-month follow-up, was similar between the 2 groups (24.2% versus 24.8%, P=0.237). Although the 6-month non-Q-wave MI rate was higher in the PTFE group (12.8% versus 4.1%, P=0.013), the cumulative MACE rate was not different (23.1% versus 15.9%, P=0.153).
The study did not demonstrate a difference in restenosis rate and 6-month clinical outcome between the PTFE-covered stent and the SS stent for treatment of SVG lesions. However, a higher incidence of nonfatal myocardial infarctions was found in patients treated with the PTFE-covered stent.
Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its ...metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C...C... myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of K...7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and K...7.4-bound PIP2 levels in C...C... cells and inhibits K...7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of K...7.4 channels. (ProQuest: ... denotes formulae/symbols omitted.)
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Significance
Although CB1 cannabinoid receptors control skeletal muscle insulin signaling, little is known of their role in muscle formation during differentiation from myoblasts to myotubes. The ...voltage-dependent K
v
7 K
+
channels, which are tonically activated by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), instead activate myotube formation. We found that the levels of the endogenous CB1 agonist 2-arachidonoylglycerol are decreased during murine myoblast differentiation into myotubes, whereas CB1 expression is up-regulated. CB1 activation inhibits myotube formation. This effect is exerted by reducing PIP2 binding to K
v
7.4, which represents the K
v
7 subunit responsible for the pro-myogenic effects. Accordingly, CB1 activation inhibits K
v
7.4-mediated currents in transfected CHO cells. The endocannabinoid system might thus play a role in skeletal muscle dystrophies.
Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C
2
C
12
myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of K
v
7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and K
v
7.4-bound PIP2 levels in C
2
C
12
cells and inhibits K
v
7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of K
v
7.4 channels.
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Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract The mitochondrial permeability transition (PT) – an abrupt increase permeability of the inner membrane to solutes – is a causative event in ischemia–reperfusion injury of the heart, and the ...focus of intense research in cardioprotection. The PT is due to opening of the PT pore (PTP), a high conductance channel that is critically regulated by a variety of pathophysiological effectors. Very recent work indicates that the PTP forms from the F-ATP synthase, which would switch from an energy-conserving to an energy-dissipating device. This review provides an update on the current debate on how this transition is achieved, and on the PTP as a target for therapeutic intervention. This article is part of a Special Issue entitled "Mitochondria: from basic mitochondrial biology to cardiovascular disease".
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
While X-ray spectroscopy, timing, and imaging have improved much since 1962 when the first astronomical nonsolar source was discovered, especially wi the launch of the Newton/X-ray ...Multi-Mirror Mission, Rossi/X-ray Timing Explorer, and Chandra/Advanced X-ray Astrophysics Facility, the progress of X-ray polarimetry has been meager. This is in part due to the lack of sensitive polarization detectors, which in turn is a result of the fate of approved missions and because celestial X-ray sources appear less polarized than expected. Only one positive measurement has been available until now: the Orbiting Solar Observatory measured the polarization of the Crab Nebula in the 1970s. The advent of microelectronics techniques has allowed for designing a detector based on the photoelectric effect of gas in an energy range where the optics are efficient at focusing in X-rays. Here we describe the instrument, which is the major contribution of the Italian collaboration to the Small Explorer mission called IXPE, the Imaging X-ray Polarimetry Explorer, which will launch in late 2021. The instrument is composed of three detector units based on this technique and a detector service unit. Three mirror modules provided by Marshall Space Flight Center focus X-rays onto the detectors. We show the technological choices, their scientific motivation, and results from the calibration of the instrument. IXPE will perform imaging, timing, and energy-resolved polarimetry in the 2–8 keV energy band opening this window of X-ray astronomy to tens of celestial sources of almost all classes.
Abstract
The Gas Pixel Detector (GPD) is an X-ray polarimeter to fly onboard IXPE and other missions. To correctly measure the source polarization, the response of IXPE’s GPDs to unpolarized ...radiation has to be calibrated and corrected. In this paper, we describe the way such response is measured with laboratory sources and the algorithm to apply such correction to the observations of celestial sources. The latter allows to correct the response to polarization of single photons, therefore allowing great flexibility in all the subsequent analysis. Our correction approach is tested against both monochromatic and nonmonochromatic laboratory sources and with simulations, finding that it correctly retrieves the polarization up to the statistical limits of the planned IXPE observations.
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