Educational Effect of Externalization of Know-how Information for Care Planning Processes

Non

Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level

Equilibrium-point control of human elbow-joint movement under isometric environment by using multichannel functional electrical stimulation

Functional electrical stimulation (FES) is considered an effective technique for aiding quadriplegic persons. However, the human musculoskeletal system has highly nonlinearity and redundancy. It is thus difficult to stably and accurately control limbs using FES. In this paper, we propose a simple FES method that is consistent with the motion-control mechanism observed in humans. We focus on joint motion by a pair of agonist-antagonist muscles of the musculoskeletal system, and define theelectrical agonist-antagonist muscle ratio (EAA ratio) and electrical agonist-antagonist muscle activity (EAA activity) in light of the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, respectively, to extract the equilibrium point and joint stiffness from electromyography (EMG) signals. These notions, the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, are based on the hypothesis that the equilibrium point and stiffness of the agonist-antagonist motion system are controlled by the central nervous system. We derived the transfer function between the input EAA ratio and force output of the end-point. We performed some experiments in an isometric environment using six subjects. This transfer-function model is expressed as a cascade-coupled dead time element and a second-order system. High-speed, high-precision, smooth control of the hand force were achieved through the agonist-antagonist muscle stimulation pattern determined by this transfer function model

ヒト白血病K562細胞でクロトリマゾールにより誘発される細胞死に対するマイクロモル濃度の亜鉛の影響

Our recent study showed that the simultaneous application of clotrimazole with CdCI2 or PbCI2 exerted potent cytotoxic action in rat thymocytes although respective agents were ineffective. It was also the case of ZnCl2 and clotrimazole in preliminary study using rat thymocytes. Since clotrimazole is supposed to be a candidate for anticancer drug, we examined the effects of clotrimazole, ZnCI2, and their combination on human leukemia K562 cells. The combination of clotrimazole and ZnCl2 exerted potent cytotoxic effects on the growth and lethality of K562 cells by presumably modifying the process of cell death. The result suggests the possibility that endogenous Zn2+ may modify the action of clotrimazole

ヒト白血病K562細胞におけるアドリアマイシン作用のクレモフォールELによる修飾

Adriamycin and paclitaxel are simultaneously used for cancer treatment in some cases. The formula of paclitaxel contains cremophor EL as a solvent. Since this solvent exerts diverse biological actions, the modification of adriamycin action by cremophor EL has been studied on human leukemia K562 cells. Cremophor EL did not significantly affect the concentration-response relation for antiproliferative action of adriamycin and the cell cycle changed by adriamycin. However, the induction of morphological change by adriamycin was significantly augmented by cremophor EL. The simultaneous application of cremophor EL increased the intensity of fluorescence from adriamycin trapped inside the cells in a concentration-dependent manner, suggesting an increase in intracellular concentration of adriamycin by cremophor EL. Adriamycin alone at concentrations higher than those to completely inhibit the growth induced morphological change in K562 cells. Therefore, cremophor EL may potentiate some of actions induced by adriamycin when adriamycin and paclitaxel are simultaneously applied

Glutathione adducts induced by ischemia and deletion of glutaredoxin-1 stabilize HIF-1α and improve limb revascularization

Reactive oxygen species (ROS) are increased in ischemic tissues and necessary for revascularization; however, the mechanism remains unclear. Exposure of cysteine residues to ROS in the presence of glutathione (GSH) generates GSH-protein adducts that are specifically reversed by the cytosolic thioltransferase, glutaredoxin-1 (Glrx). Here, we show that a key angiogenic transcriptional factor hypoxia-inducible factor (HIF)-1α is stabilized by GSH adducts, and the genetic deletion of Glrx improves ischemic revascularization. In mouse muscle C2C12 cells, HIF-1α protein levels are increased by increasing GSH adducts with cell-permeable oxidized GSH (GSSG-ethyl ester) or 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanyl thiocarbonylamino) phenylthiocarbamoylsulfanyl] propionic acid (2-AAPA), an inhibitor of glutathione reductase. A biotin switch assay shows that GSSG-ester-induced HIF-1α contains reversibly modified thiols, and MS confirms GSH adducts on Cys520 (mouse Cys533). In addition, an HIF-1α Cys520 serine mutant is resistant to 2-AAPA–induced HIF-1α stabilization. Furthermore, Glrx overexpression prevents HIF-1α stabilization, whereas Glrx ablation by siRNA increases HIF-1α protein and expression of downstream angiogenic genes. Blood flow recovery after femoral artery ligation is significantly improved in Glrx KO mice, associated with increased levels of GSH-protein adducts, capillary density, vascular endothelial growth factor (VEGF)-A, and HIF-1α in the ischemic muscles. Therefore, Glrx ablation stabilizes HIF-1α by increasing GSH adducts on Cys520 promoting in vivo HIF-1α stabilization, VEGF-A production, and revascularization in the ischemic muscle

Relevance of Some Damage Factors to Structures Damage in the 1995 Kobe Earthquake

The 1995 Kobe Earthquake (Hyogoken-nanbu Earthquake) caused a severe damage to various kinds of structures. As damage factors of these structures, the characteristics of seismic motion, distance from the earthquake source fault, ground conditions, liquefaction, and strength of structures can be considered. In this paper, paying attention to the distance from the earthquake source fault and ground conditions among them, the relevance to structures damage in wooden houses (on-ground structure) and water supply pipelines (under-ground structure) in Nishinomiya-City area was examined. As the results, the relationship between wooden houses damage and the distance from the fault can be approximately represented as a unique exponential function. In liquefied areas, however, the rate of completely collapsed wooden houses decreases 5 to 20% from the average value. This might be because the damping of earthquake motion brought the decrease of the damage rate. While, the relationship between water supply pipelines damage and the distance from the fault completely differs from the above-mentioned for wooden houses. A characteristic value Tg estimated from the distribution of N value at each location can be used for the ground classification in earthquake-proof design. The damage rate of water supply pipelines increases as increasing Tg , while that of wooden houses decreases as increasing Tg

Regulation of energy metabolism by interleukin-1 β, but not by interleukin-6, is mediated by nitric oxide in primary cultured rat hepatocytes

AbstractThe effects of inflammatory cytokines (interleukin-1 β, interleukin-6, and tumor necrosis factor-α) on energy metabolism were studied in primary cultured rat hepatocytes. Adenine nucleotide (ATP, ADP, and AMP) content, lactate production, the ketone body ratio (acetoacetate/β-hydroxybutyrate) reflecting the liver mitochondrial redox state (NAD+/NADH), and nitric oxide formation were measured. Insulin increased ATP content in hepatocytes and had a maximal effect after 8–12 h of culture. Both interleukin-1β and interleukin-6, but not tumor necrosis factor-α, significantly inhibited the ATP increase time- and dose-dependently. Interleukin-1β and interleukin-6 also stimulated lactate production. During the same period, interleukin-1 β but not interleukin-6 decreased the ketone body ratio. Furthermore, interleukin-1 β markedly stimulated nitric oxide formation in hepatocytes, and this increase was blocked by NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor) and by interleukin-1 receptor antagonist. NG-monomethyl-l-arginine reversed inhibition of the ATP increase, decrease in the ketone body ratio, and increase in lactate production, which were induced by interleukin-lβ. Interleukin-1 receptor antagonist completely abolished all of the effects induced by interleukin-1 β. These results demonstrated that interleukin-1 β and interleukin-6 affect the insulin-induced energy metabolism in rat hepatocytes by different mechanisms. Specifically, interleukin-1 β inhibits ATP synthesis by causing the mitochondrial dysfunction, a process which may be mediated by nitric oxide

Effects of Zn2+ chelators, DTPA and TPEN, and ZnCl2 on the cells treated with hydrogen peroxide: a flow-cytometric study using rat thymocytes

Recently, we have revealed that trace Zn2+ partly attenuates Ca2+-dependent cell death induced by A23187, a calcium ionophore, in rat thymocytes. In this study, to see if Zn2+ attenuates the H2O2-induced cell death that is also Ca2+-dependent, the effects of ZnCl2 and chelators for Zn2+ have been examined by using a flowcytometer with propidium iodide. The incubation with H2O2 increased the cell lethality. Simultaneous application of ZnCl2 greatly augmented the H2O2-induced increase in lethality. DTPA, a chelator for extracellular Zn2+, did not affect the increase in cell lethality by H2O2. However, the H2O2-induced increase in cell lethality was greatly attenuated by TPEN, a chelator for extracellular and intracellular Zn2+. Taken together, it may be likely that intracellular Zn2+ modifies the H2O2-induced cytotoxicity. However, it cannot be ruled out the possibility that TPEN chelates intracellular Fe2+, resulting in inhibiting the formation of hydroxyl radical from H2O2 that leads to an attenuation of H2O2 cytotoxicity