Protective effects of idebenone against alterations in dynamic microstructure induced by lipid peroxidation in rat cardiac mitochondria

The antioxidative effect of idebenone was studied in isolated mitochondria from the rat heart. Variables for dynamic microstructure, membrane viscosity and wobbling angle of phospholipids, were measured by means of a nanosecond time-resolved fluorometer. Exposure of isolated cardiac mitochondria to oxidative conditions in vitro caused significant alterations in lipid peroxidation, wobbling angle of phospholipids and membrane viscosity. Exposure of mitochondria to oxidative conditions after idebenone pretreatment resulted in no significant alterations in membrane viscosity and wobbling angle of phospholipids. Alterations in these variables seemed to be related to the amount of peroxidized lipid. Protection of phospholipids against peroxidation by antioxidative substances is effective in maintaining nearly normal physical properties in the dynamic microstructure of cardiac mitochondrial membranes.     

Myocardial perfusion imaging using adenosine triphosphate stress multi-slice spiral computed tomography: alternative to stress myocardial perfusion scintigraphy.

BACKGROUND: The present study was designed to: (i) detect myocardial ischemia in contrast enhanced multi-slice spiral computed tomography (CE-MSCT) using adenosine triphosphate (ATP) pharmacological stress test; and (ii) evaluate the potential of ATP stress CE-MSCT in a clinical setting. METHODS AND RESULTS: Twelve patients underwent ATP stress CE-MSCT and stress thallium-201 myocardial perfusion scintigraphy (MPS) and 9 of the patients received conventional coronary angiography (CAG). Dual CE-MSCT scans were performed for stress and rest images, with and without intravenous infusion of ATP (0.16 mg.kg-1.min-1) at intervals of 20 min. Myocardial perfusion and coronary artery were visually evaluated using MSCT and compared the results obtained from MPS and CAG. Of 36 territories, stress images of CE-MSCT described 26 hypo-perfusion areas and MPS described 22 redistributions. The agreement between MSCT and MPS was 83% (30/36, p<0.05). In 141 coronary artery segments of 9 patients undergoing CAG, rest images of CE-MSCT, which had significantly higher assessability than stress images (89% vs 48%, p<0.05), described 76% (13/17) of culprit coronary stenoses. CONCLUSIONS: Although CT-angiography should be currently assessed using rest images, ATP stress CE-MSCT can describe both ATP-induced myocardial ischemia and coronary artery stenoses in patients with coronary artery disease.     

The activation of supraspinal GPR40/FFA1 receptor signalling regulates the descending pain control system

Background and Purpose

The ω-3 polyunsaturated fatty acids exert antinociceptive effects in inflammatory and neuropathic pain; however, the underlying mechanisms remain unclear. Docosahexaenoic acid-induced antinociception may be mediated by the orphan GPR40, now identified as the free fatty acid receptor 1 (FFA1 receptor). Here, we examined the involvement of supraspinal FFA1 receptor signalling in the regulation of inhibitory pain control systems consisting of serotonergic and noradrenergic neurons.

Experimental Approach

Formalin-induced pain behaviours were measured in mice. Antinociception induced by FFA1 receptor agonists was examined by intrathecal injections of a catecholaminergic toxin, 5-HT lowering drug or these antagonists. The expression of FFA1 receptor protein and c-Fos was estimated by immunohistochemistry, and the levels of noradrenaline and 5-HT in the spinal cord were measured by LC-MS/MS.

Key Results

FFA1 receptors colocalized with NeuN (a neuron marker) in the medulla oblongata and with tryptophan hydroxylase (TPH; a serotonergic neuron marker) and dopamine β-hydroxylase (DBH; a noradrenergic neuron marker). A single i.c.v. injection of GW9508, a FFA1 receptor agonist, increased the number of c-Fos-positive cells and the number of neurons double-labelled for c-Fos and TPH and/or DBH. It decreased formalin-induced pain behaviour. This effect was inhibited by pretreatment with 6-hydroxydopamine, DL-p-chlorophenylalanine, yohimbine or WAY100635. Furthermore, GW9508 facilitated the release of noradrenaline and 5-HT in the spinal cord. In addition, GW1100, a FFA1 receptor antagonist, significantly increased formalin-induced pain-related behaviour.

Conclusion and Implications

Activation of the FFA1 receptor signalling pathway may play an important role in the regulation of the descending pain control system.     

Endoscopic treatment for appendiceal intussusception due to barium stool impaction that mimics a submucosal tumor

Techniques in Coloproctology -