Granular flow analysis considering soil strength using moving particle simulation method

In recent years, many sediment-related disasters have occurred in Japan. To predict the sediment flow, granular flow analysis was conducted with the moving particle simulation method, using the viscosity term formulated by the Drucker-Prager model. The program code used is Particleworks Ver. 6, developed by Prometech Software. Plastic viscosity is described as a function of (cohesion) c and Φ (the shear resistance angle). Simple problems, such as freestanding height and dam breakage of the simulations were analyzed to assess the accuracy of the particle simulation method with the model

Cardioprotection by regular ethanol consumption: potential mechanisms and clinical application.

Epidemiological studies demonstrate that excessive drinking is associated with hypertension, cerebral bleeding and loss of cardiac contractility. Conversely, studies have shown that mortality rates for people who regularly drink ethanol in moderation are lower than in abstainers, primarily due to decreased fatal ischemic heart disease. Further, moderate ethanol consumers have lower rates of myocardial infarction compared with abstainers. These beneficial cardiac effects may be due to pleiotropic effects of ethanol on lipids, platelets, and fibrinolytic activity. During the past decade, studies conducted in several animal models have revealed that light to moderate regular ethanol consumption renders hearts more tolerant to myocardial ischemia-reperfusion injury; to a degree similar to cardiac ischemic preconditioning (brief episodes of ischemia dramatically limit infarct size following prolonged ischemia). Recent clinical evidence suggests that light to moderate ethanol consumption in the year prior to myocardial infarction is associated with reduced mortality following myocardial infarction. These findings suggest that light to moderate ethanol consumption not only prevents myocardial infarction but also improves survival after myocardial infarction. Proposed mechanisms of cardioprotection by regular ethanol consumption include activation of adenosine A1 receptors, alpha(1)-adrenoceptors, protein kinase C-delta and epsilon, adenosine triphosphate-dependent potassium (K(ATP)) channels, nitric oxide synthase and reduced leukocyte-endothelial cell adhesive interactions. In this review, we focus on the recent progress in elucidating the endogenous myocyte signaling mediating cardioprotection by light to moderate ethanol consumption

Direct evidence for inhibition of mitochondrial permeability transition pore opening by sevoflurane preconditioning in cardiomyocytes: comparison with cyclosporine A.

To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 μM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed and end-diastolic pressures, coronary flow and infarct size were measured. Expressions of Akt and glycogen synthase kinase 3β (GSK3β), known mediators of inhibition of MPTP opening, were determined by Western blot analysis. GSK3β inhibition was achieved with LY294002. The effects of sevoflurane and cyclosporine A on calcium-induced MPTP opening in isolated calcein-loaded mitochondria were assessed. After ischemia-reperfusion, sevoflurane and cyclosporine A had higher left ventricular developed pressure. Infarct size was significantly reduced in sevoflurane and cyclosporine A vs. control. This was abolished by LY294002 in sevoflurane, but not in cyclosporine A. Akt and GSK3β phosphorylation after reperfusion were significantly increased in sevoflurane and cyclosporine A. Ca²⁺-induced reduction in calcein fluorescence was significantly attenuated in sevoflurane and cyclosporine A. Preconditioning agents, sevoflurane and cyclosporine A increase the threshold of calcium-induced MPTP opening to a similar extent. This effect by sevoflurane, but not cyclosporine A is at least partially mediated by GSK3β inactivation

Regular dipyridamole therapy produces sustained protection against cardiac ischemia-reperfusion injury: is it time to revisit PARIS?

BACKGROUND: Increased activated Akt and eNOS expression coincide with this persistent cardioprotection. Emergent coronary reperfusion therapies are rarely carried out before considerable myocardial injury has occurred. Moreover, reperfusion after prolonged ischemia produces paradoxical ischemia-reperfusion injury, attenuating the efficacy of reperfusion therapies. This has provided impetus for identifying chronic therapies to protect against ischemia-reperfusion injury in those at risk. We previously found that regular dipyridamole therapy produces a chronic preconditioning-like effect mediated through adenosine A1 receptors. METHODS: To determine how long this chronic preconditioning effect of dipyridamole remains present after discontinuing therapy, guinea pigs received 4 mg/kg/day in their water for 6 weeks. Ischemia-reperfusion was performed at 0, 2, 3, and 4 days after dipyridamole discontinuation (0 day, 2 days, 3 days and 4 days; n=8 per group). Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), coronary flow (CF), infarct size, and western blot analyses for Akt and endothelial nitric oxide synthase (eNOS) were studied. RESULTS: After ischemia-reperfusion, 0 day, 2 days and 3 days, but not 4 days, had significantly higher LVDP and lower LVEDP compared to control. Myocardial infarct size was significantly reduced at 0 day, 2 days and 3 days, but not 4 days, compared to control. Western blot analyses demonstrated upregulation of phospho-Akt and phospho-eNOS expression at 0 day, 2 days, and 3 days, but not 4 days. CONCLUSIONS: A chronic preconditioning-like cardioprotection by regular dipyridamole treatment persists for 3 days after discontinuing therapy. Increased activated Akt and eNOS expression may play a role in this persistent cardioprotection

Sevoflurane enhances ethanol-induced cardiac preconditioning through modulation of protein kinase C, mitochondrial KATP channels, and nitric oxide synthase, in guinea pig hearts.

BACKGROUND: Volatile anesthetics and regular ethanol consumption induce cardioprotection mimicking ischemic preconditioning. We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial K(ATP) channels attenuated this enhanced cardioprotection. The effects of regular ethanol consumption on expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase were determined. METHODS: Isolated perfused guinea pig hearts underwent 30-min global ischemia and 120-min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 wk. Anesthetic preconditioning was elicited by 10-min exposure to sevoflurane (1 minimum alveolar anesthetic concentration; 2%) in ethanol (EtOH + SEVO) or nonethanol (SEVO) hearts. PKC and mitochondrial K(ATP) channels were inhibited with chelerythrine and 5-hydroxydecanoate pretreatment, respectively. Contractile recovery was assessed by monitoring of left ventricular developed and end-diastolic pressures. Infarct size was determined by triphenyltetrazolium chloride staining. Expression of iNOS and eNOS were determined by Western blot analysis. RESULTS: After ischemia-reperfusion, hearts from the EtOH, sevoflurane (SEVO), and EtOH + SEVO groups had higher left ventricular developed pressure and lower left ventricular end-diastolic pressure compared with CTL. Infarct size was reduced in EtOH and SEVO hearts compared with CTL (27% and 23% vs 45%, respectively, P \u3c 0.001). Sevoflurane further reduced infarct size in EtOH hearts (27% vs 15%, P \u3c 0.001). Chelerythrine and 5-hydroxydecanoate abolished cardioprotection in both SEVO and EtOH cardioprotected hearts. iNOS expression was reduced and eNOS expression was increased in EtOH hearts. CONCLUSIONS: Sevoflurane enhances cardiac preconditioning induced by regular EtOH consumption. This effect is mediated in part by modulation of PKC and mitochondrial K(ATP) channels, and possibly by altered modulation of NOS expression

Acute memory phase of sevoflurane preconditioning is associated with sustained translocation of protein kinase C-alpha and epsilon, but not delta, in isolated guinea pig hearts.

BACKGROUND AND OBJECTIVE: Anaesthetic preconditioning (APC) exerts cardioprotective effects by reducing infarct size and improving recovery of contractile function after ischaemia-reperfusion. The interval between brief exposure to volatile anaesthetic and sustained ischaemia, the acute memory phase, is dependent on intracellular signalling mediating this cardioprotection. Intramyocyte translocation of protein kinase C (PKC) is known to be a key mediator in APC. We examined the relationship between the time frame of the acute memory phase of sevoflurane preconditioning and intramyocyte translocation of PKC-alpha, delta and epsilon to the particulate fraction. METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischaemia and 120 min reperfusion. APC was elicited with one minimum alveolar concentration sevoflurane for 10 min. Washout times of 10, 30, 60 and 90 min were studied. Contractile recovery was assessed by monitoring left ventricular developed pressures. Infarct size was determined by triphenyltetrazolium chloride staining. Translocation of PKC was examined by western blot analysis. RESULTS: After ischaemia-reperfusion, left ventricular developed pressure recovered to a greater degree with APC compared with control for washout times of 10 and 30 min, but not 60 and 90 min. Similarly, infarct size was reduced for washout times of 10 and 30 min, but not 60 and 90 min. Sustained translocation of PKC-alpha and epsilon, but not delta, was associated with the time frame of the acute memory phase. CONCLUSION: The acute memory phase of sevoflurane preconditioning is limited to less than 60 min. Sustained translocation of PKC-alpha and epsilon, but not delta, correlates with this acute memory phase of sevoflurane preconditioning

Combination of necroptosis and apoptosis inhibition enhances cardioprotection against myocardial ischemia-reperfusion injury.

PURPOSE: Necroptosis has been proposed as a mode of cell death that is a caspase-independent programmed necrosis. We investigated whether necroptosis is involved in myocardial ischemia-reperfusion injury in isolated guinea pig hearts and, if so, whether simultaneous inhibition of necroptosis and apoptosis confers enhanced cardioprotection. METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischemia and 4 h reperfusion (control = CTL, n = 8). Necrostatin-1 (necroptosis inhibitor, 10 μM), Z-VAD (apoptosis inhibitor, 0.1 μM) and both inhibitors were administered starting 5 min before ischemia and during the initial 30 min of reperfusion (Nec, Z-VAD, Nec + Z-VAD; n = 8 each). Contractile recovery was monitored by left ventricular developed (LVDP) and end-diastolic (LVEDP) pressure. Infarct size was determined by triphenyltetrazolium chloride staining. Tissue samples were obtained after 4 h reperfusion to determine expression of receptor-interacting protein 1 (RIP1) and activated caspase 3 by Western blot analysis. RESULTS: After reperfusion, Nec + Z-VAD had higher LVDP and lower LVEDP compared with CTL. Infarct size was reduced in Nec and Z-VAD compared with CTL. Combination of necroptosis and apoptosis inhibition further reduced infarct size. Expression of activated caspase 3 was not increased in Z-VAD and Nec + Z-VAD compared with Nec and CTL. Expression of RIP1 was preserved in Z-VAD and Nec + Z-VAD compared with CTL, suggesting RIP1-mediated necrosis is involved in myocardial ischemia-reperfusion injury. CONCLUSION: Necroptosis is involved in myocardial ischemia-reperfusion injury, and simultaneous inhibition of necroptosis and apoptosis enhances the cardioprotective effect. These findings may provide a novel, additive strategy for cardioprotection in acute myocardial infarction

Sevoflurane induces cardioprotection through reactive oxygen species-mediated upregulation of autophagy in isolated guinea pig hearts.

PURPOSE: Sevoflurane increases reactive oxygen species (ROS), which mediate cardioprotection against myocardial ischemia-reperfusion injury. Emerging evidence suggests that autophagy is involved in cardioprotection. We examined whether reactive oxygen species mediate sevoflurane preconditioning through autophagy. METHODS: Isolated guinea pigs hearts were subjected to 30 min ischemia followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2 % sevoflurane for 10 min before ischemia (SEVO). The ROS-scavenger, N-(2-mercaptopropionyl) glycine (MPG, 1 mmol/l), was administered starting 30 min before ischemia to sevoflurane-treated (SEVO + MPG) or non-sevoflurane-treated (MPG) hearts. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained after reperfusion to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, -II) and 5\u27 AMP-activated protein kinase (AMPK) expression using Western blot analysis. Electron microscopy was used to detect autophagosomes. RESULTS: Infarct size was significantly reduced and there were more abundant autophagosomes in SEVO compared with control. Western blot analysis revealed that the ratio of LC3-II/I and phosphorylation of AMPK were significantly increased in SEVO. These effects were abolished by MPG. CONCLUSIONS: Sevoflurane induces cardioprotection through ROS-mediated upregulation of autophagy

Suzaku observation of the giant radio galaxy 3C 326

A Suzaku observation of a giant radio galaxy, 3C 326, which has a physical size of about 2 Mpc, was conducted on 2008 January 19 -- 21. In addition to several X-ray sources, diffuse emission was significantly detected associated with its west lobe, but the east lobe was contaminated by an unidentified X-ray source WARP J1552.4+2007. After careful evaluation of the X-ray and Non X-ray background, the 0.4 -- 7 keV X-ray spectrum of the west lobe is described by a power-law model. The photon index and 1 keV flux density was derived as $1.82_{-0.24}^{+0.26}\pm0.04$ and $19.4_{-3.2}^{+3.3}\pm 3.0$ nJy, respectively, where the first and second errors represent the statistical and systematic ones. The diffuse X-rays were attributed to be inverse Compton radiation by the synchrotron radio electrons scattering off the cosmic microwave background photons. This radio galaxy is the largest among those with lobes detected through inverse Compton X-ray emission. A comparison of the radio to X-ray fluxes yields the energy densities of electron and magnetic field as $u_e = (2.3 \pm 0.3 \pm 0.3) \times 10^{-13}$ ergs/cm3 and $u_m = (1.2_{-0.1}^{+0.2}\pm 0.2) \times 10^{-14}$ ergs/cm3, respectively. The galaxy is suggested to host a low luminosity nucleus with an absorption-corrected 2 -- 10 keV luminosity of $<2 \times 10^{42}$ ergs/s, together with a relatively weak radio core. The energetics in the west lobe of 3C 326 were compared with those of moderate radio galaxies with a size of $\sim 100$ kpc. The west lobe of 3C 326 is confirmed to agree with the correlations for the moderate radio galaxies, $u_e \propto D^{-2.2\pm0.4}$ and $u_m \propto D^{-2.4\pm0.4}$, where $D$ is their total physical size. This implies that the lobes of 3C 326 are still being energized by the jet, despite the current weakness of the nucleus.Comment: 11 pages, 10 figures, 6 tables, Accepted for ApJ (v706 issue