Transient receptor potential canonical type 3 channels control the vascular contractility of mouse mesenteric arteries

Transient receptor potential canonical type 3 (TRPC3) channels are non-selective cation channels and regulate intracellular Ca2+ concentration. We examined the role of TRPC3 channels in agonist-, membrane depolarization (high K+)-, and mechanical (pressure)-induced vasoconstriction and vasorelaxation in mouse mesenteric arteries. Vasoconstriction and vasorelaxation of endothelial cells intact mesenteric arteries were measured in TRPC3 wild-type (WT) and knockout (KO) mice. Calcium concentration ([Ca2+]) was measured in isolated arteries from TRPC3 WT and KO mice as well as in the mouse endothelial cell line bEnd.3. Nitric oxide (NO) production and nitrate/nitrite concentrations were also measured in TRPC3 WT and KO mice. Phenylephrine-induced vasoconstriction was reduced in TRPC3 KO mice when compared to that of WT mice, but neither high K+- nor pressure-induced vasoconstriction was altered in TRPC3 KO mice. Acetylcholine-induced vasorelaxation was inhibited in TRPC3 KO mice and by the selective TRPC3 blocker pyrazole-3. Acetylcholine blocked the phenylephrine-induced increase in Ca2+ ratio and then relaxation in TRPC3 WT mice but had little effect on those outcomes in KO mice. Acetylcholine evoked a Ca2+ increase in endothelial cells, which was inhibited by pyrazole-3. Acetylcholine induced increased NO release in TRPC3 WT mice, but not in KO mice. Acetylcholine also increased the nitrate/nitrite concentration in TRPC3 WT mice, but not in KO mice. The present study directly demonstrated that the TRPC3 channel is involved in agonist-induced vasoconstriction and plays important role in NO-mediated vasorelaxation of intact mesenteric arteries.Fil: Yeon, Soo-In. Yonsei University College of Medicine; Corea del SurFil: Kim, Joo Young. Yonsei University College Of Medicine; . Yonsei University College of Medicine; Corea del SurFil: Yeon, Dong-Soo. Kwandong University College of Medicine; Corea del SurFil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados UnidosFil: Muallem, Shmuel. National Institutes of Health; Estados UnidosFil: Lee, Young-Ho. Yonsei University College of Medicine; Corea del Su

Crack-Resistance Behavior of an Encapsulated, Healing Agent Embedded Buffer Layer on Self-Healing Thermal Barrier Coatings

In this work, a novel thermal barrier coating (TBC) system is proposed that embeds silicon particles in coating as a crack-healing agent. The healing agent is encapsulated to avoid unintended reactions and premature oxidation. Thermal durability of the developed TBCs is evaluated through cyclic thermal fatigue and jet engine thermal shock tests. Moreover, artificial cracks are introduced into the buffer layer’s cross section using a microhardness indentation method. Then, the indented TBC specimens are subject to heat treatment to investigate their crack-resisting behavior in detail. The TBC specimens with the embedded healing agents exhibit a relatively better thermal fatigue resistance than the conventional TBCs. The encapsulated healing agent protects rapid large crack openings under thermal shock conditions. Different crack-resisting behaviors and mechanisms are proposed depending on the embedding healing agents

Crack-Growth Behavior in Thermal Barrier Coatings with Cyclic Thermal Exposure

Crack-growth behavior in yttria-stabilized zirconia-based thermal barrier coatings (TBCs) is investigated through a cyclic thermal fatigue (CTF) test to understand TBCs’ failure mechanisms. Initial cracks were introduced on the coatings’ top surface and cross section using the micro-indentation technique. The results show that crack length in the surface-cracked TBCs grew parabolically with the number of cycles in the CTF test. Failure in the surface-cracked TBC was dependent on the initial crack length formed with different loading levels, suggesting the existence of a threshold surface crack length. For the cross section, the horizontal crack length increased in a similar manner as observed in the surface. By contrast, in the vertical direction, the crack did not grow very much with CTF testing. An analytical model is proposed to explain the experimentally-observed crack-growth behavior

The limited immunomodulatory effects of escharectomy on the kinetics of endotoxin, cytokines, and adhesion molecules in major burns.

Escharectomy has been shown to improve the survival rates and the outcomes in burns. This observational study was conducted to assess the role of escharectomy on the inflammatory mediators in major burns. Seventeen ASA physical status II or status III adult surviving major burn patients were recruited. When the escharectomy was scheduled, a series of blood samples was obtained at -3 and -1 days preoperation, and +1 and +3 postoperation. The changing levels of endotoxin, cytokines, and adhesion molecules were measured with a quantitative sandwich immunoassay. Extensive escharectomy did not appear to have any significant impact on the levels of tumor necrosis factor alpha, interleukin-10, soluble intracellular adhesion molecule-1 and soluble vascular adhesion molecule-1. Meanwhile, endotoxin and E-selectin were significantly decreased after escharectomy. Escharectomy appeared to have a limited immunomodulatory effect on the inflammatory mediators in systemic inflammatory responses induced by major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn-related inflammation

The Role of Sphingosine Kinase 1/Sphingosine-1-Phosphate Pathway in the Myogenic Tone of Posterior Cerebral Arteries

AIMS: The goal of the current study was to determine whether the sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) pathway is involved in myogenic vasoconstriction under normal physiological conditions. In the present study, we assessed whether endogenous S1P generated by pressure participates in myogenic vasoconstriction and which signaling pathways are involved in SK1/S1P-induced myogenic response under normal physiological conditions. METHODS AND RESULTS: We measured pressure-induced myogenic response, Ca(2+) concentration, and 20 kDa myosin light chain phosphorylation (MLC(20)) in rabbit posterior cerebral arteries (PCAs). SK1 was expressed and activated by elevated transmural pressure in rabbit PCAs. Translocation of SK1 by pressure elevation was blocked in the absence of external Ca(2+) and in the presence of mechanosensitive ion channel and voltage-sensitive Ca(2+) channel blockers. Pressure-induced myogenic tone was inhibited in rabbit PCAs treated with sphingosine kinase inhibitor (SKI), but was augmented by treatment with NaF, which is an inhibitor of sphingosine-1-phosphate phosphohydrolase. Exogenous S1P further augmented pressure-induced myogenic responses. Pressure induced an increase in Ca(2+) concentration leading to the development of myogenic tone, which was inhibited by SKI. Exogenous S1P further increased the pressure-induced increased Ca(2+) concentration and myogenic tone, but SKI had no effect. Pressure- and exogenous S1P-induced myogenic tone was inhibited by pre-treatment with the Rho kinase inhibitor and NADPH oxidase inhibitors. Pressure- and exogenous S1P-induced myogenic tone were inhibited by pre-treatment with S1P receptor blockers, W146 (S1P1), JTE013 (S1P2), and CAY10444 (S1P3). MLC(20) phosphorylation was increased when the transmural pressure was raised from 40 to 80 mmHg and exogenous S1P further increased MLC(20) phosphorylation. The pressure-induced increase of MLC(20) phosphorylation was inhibited by pre-treatment of arteries with SKI. CONCLUSIONS: Our results suggest that the SK1/S1P pathway may play an important role in pressure-induced myogenic responses in rabbit PCAs under normal physiological conditions

A KINEMATIC ANALYSIS OF ELDERLY GAIT WHILE STEPPING OVER OBSTACLES OF VARYING HEIGHT

The purpose of this study was to investigate the kinematics of elderly people who had experienced a fall stepping over obstacles of varying height. Six elderly non-fallers and six elderly fallers stepped over obstacles of height 0, 2.5, 5.1, 15.2cm. The longest stance duration was found in the highest obstacle 15.2cm, which might reflect relatively fast degrading gait function of the faller group. It was found that fallers took a longer time to cross the obstacles, which resulted in slower crossing speeds than when non-fallers stepped over the obstacles. We concluded that elderly persons who had experienced falling tend to step over obstacles conservatively as characterized

Fracture behavior and thermal durability of lanthanum zirconate-based thermal barrier coatings with buffer layer in thermally graded mechanical fatigue environments

The effects of buffer layer on the fracture behavior and lifetime performance of lanthanum zirconate (La2Zr2O7; LZO)-based thermal barrier coatings (TBCs) were investigated through thermally graded mechanical fatigue (TGMF) tests, which are designed to simulate the operating conditions of rotating parts in gas turbines. To improve the thermal durability of LZO-based TBCs, composite coats consisting of two feedstock powders of LZO and 8 wt% yttria-doped stabilized zirconia (8YSZ) were prepared by mixing different volume ratios (50:50 and 25:75, respectively). The composite coat of 50:50 volume ratio was employed as the top coat, and two types of buffer layers were introduced (25:75 volume ratio in LZO and 8YSZ, and 8YSZ only). These TBC systems were compared with a reference TBC system of 8YSZ. The TGMF tests with a tensile load of 60 MPa were performed for 1000 cycles, at a surface temperature of 1100 °C and a dwell time of 10 min, and then the samples were cooled at room temperature for 10 min in each cycle. For the single-layer TBCs, the composite top coat showed similar results as for the reference TBC system. The triple-layer coating (TLC) showed the best thermal cycle performance among all samples, suggesting that the buffer layer was efficient in improving lifetime performance. Failure modes were different for the TBC systems. Delamination and/or cracks were created at the interface between the bond and top coats or above the interface in the single-layer TBCs, but the TBCs with the buffer layer were delaminated and/or cracked at the interface between the buffer layer and the top coat, independent of buffer layer species. This study allows further understanding of the LZO-based TBC failure mechanisms in operating conditions, especially in combined thermal and mechanical environments, in order to design reliable TBC systems

Activation of Protein Kinase G After Repeated Cocaine Administration Is Necessary for the Phosphorylation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor GluA1 at Serine 831 in the Rat Nucleus Accumbens

Phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the striatum plays a crucial role in regulating the receptor-coupled signaling cascades leading to behavioral changes associated with psychostimulant exposure. The present study determined if activation of protein kinase G (PKG) contributes to the phosphorylation of AMPA receptor GluA1 subunit at the position of serine 831 (GluA1-S831) in the rat nucleus accumbens (NAc) after repeated cocaine administration. The results demonstrated that repeated intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once a day for seven consecutive days significantly increased the level of phosphorylated (p)GluA1-S831. This increase was decreased by the intra-NAc infusion of either the cyclic guanosine monophosphate (cGMP) analog, Rp-8-Br-PET-cGMPS (5 nmol/1 μL), or the PKG inhibitor, KT5823 (2 nmol/1 μL). Repeated cocaine administration increased PKG binding activity to GluA1. This increase in GluA1-S831 phosphorylation after repeated cocaine administration was decreased by the intra-NAc infusion of the synthetic peptide (Tat-tagged interfering peptide (Tat-GluA1-i)), that interferes with the binding of PKG to GluA1. Intra-NAc infusion of the interfering peptide also reduced the repeated cocaine-induced increase in locomotor activity. These findings suggest that activated PKG, after repeated exposure to cocaine, binds to AMPA receptor GluA1 and is required for the phosphorylation of S831, contributing to behavioral changes

SYNGAS PRODUCTION WITH A DUAL FLUIDIZED BED GASIFIER FOR POLYGENERATION

A pilot scale dual fluidized bed gasification system was developed for polygeneration with biomass. The gasification system is designed for supplying syngas for Fischer Tropsch (F-T) synthesis of bio-diesel and power generation with a syngas engine. Characteristics of biomass steam gasification were investigated in a lab scale bubbling fluidized bed, and hydrodynamics of a dual fluidized bed were investigated in a cold flow model. Based on the results from the lab scale test and cold flow model, a pilot scale dual fluidized bed gasifier was designed. In this paper, the developing process of the gasifier and preliminary results of system operation will be presented