The effectiveness of a self-reported questionnaire on masticatory function in health examinations.

Periodontal diseases have been reported to be lifestyle-related and associated with metabolic syndrome (MetS). The introduction of dental checkups in a health checkup program may create a synergistic effect and aid the prevention of MetS. In Japan, a chewing function questionnaire has now been introduced into the national health checkup program. The purpose of this study was to investigate whether the questionnaire reflects dental and oral conditions and whether it helps improve general and oral health. A total of 6599 subjects who underwent health checkups or guidance specified by the National Health Insurance of Japan for two consecutive years were included. A single comprehensive question to evaluate masticatory function was asked. Medical and dental examinations and insurance data were collected and used for analysis. In terms of masticatory function during chewing, 82.3% of subjects experienced no problems, 17.3% experienced some difficulty, and 0.4% experienced severe problems. There was a significant relationship between the questionnaire response and dental examinations results for several items of examination. The overall dental consultation rate after health screening was 42.3%. Improvement in periodontal disease was achieved in those who reported some problems with chewing function. Improvement in blood pressure was also observed in those who reported some problem with chewing function and subsequently had a dental consultation. The results of this study indicate that questionnaires on masticatory function reflect the status of dental and oral health. In addition, the results suggested that questionnaire results are potentially linked to improvement in dental and oral health status, and improvement in MetS.

Sibutramine provokes apoptosis of aortic endothelial cells through altered production of reactive oxygen and nitrogen species.

Overdose administration of sibutramine, a serotonin-noradrenalin reuptake inhibitor, is considered to elicit severe side effects including hypertension, whose pathogenic mechanism remains unclear. Here, we found that 48-h incubation with >10µM sibutramine provokes apoptosis of human aortic endothelial (HAE) cells. Treatment with the lethal concentration of sibutramine facilitated production of reactive oxygen species (ROS), altered expression of endoplasmic reticulum stress response genes (heat shock protein 70 and C/EBP homologous protein), and inactivated 26S proteasome-based proteolysis. The treatment also decreased cellular level of nitric oxide (NO) through lowering of expression and activity of endothelial NO synthase. These results suggest that ROS production and depletion of NO are crucial events in the apoptotic mechanism and may be linked to the pathogenesis of vasoconstriction elicited by the drug. Compared to sibutramine, its metabolites (N-desmethylsibutramine and N-didesmethylsibutramine) were much less cytotoxic to HAE cells, which hardly metabolized sibutramine. In contrast, both the drug and metabolites showed low cytotoxicity to hepatic HepG2 cells with high metabolic potency and expression of cytochrome P450 (CYP) 3A4. The cytotoxicity of sibutramine to HepG2 and Chang Liver cells was remarkably augmented by inhibition and knockdown of CYP3A4. This study also suggests an inverse relationship between sibutramine cytotoxicity and CYP3A4-mediated metabolism into the N-desmethyl metabolites.

Novel -75°C SEM cooling stage: application for martensitic transformation in steel.

Microstructural changes during the martensitic transformation from face-centred cubic (FCC) to body-centred cubic (BCC) in an Fe-31Ni alloy were observed by scanning electron microscopy (SEM) with a newly developed Peltier stage available at temperatures to -75°C. Electron channelling contrast imaging (ECCI) was utilized for the in situ observation during cooling. Electron backscatter diffraction analysis at ambient temperature (20°C) after the transformation was performed for the crystallographic characterization. A uniform dislocation slip in the FCC matrix associated with the transformation was detected at -57°C. Gradual growth of a BCC martensite was recognized upon cooling from -57°C to -63°C.

Unique transition of yielding mechanism and unexpected activation of deformation twinning in ultrafine grained Fe-31Mn-3Al-3Si alloy.

Tensile mechanical properties of fully recrystallized TWIP steel specimens having various grain sizes (d) ranging from 0.79 µm to 85.6 µm were investigated. It was confirmed that the UFG specimens having the mean grain sizes of 1.5 µm or smaller abnormally showed discontinuous yielding characterized by a clear yield-drop while the specimens having grain sizes larger than 2.4 µm showed normal continuous yielding. In-situ synchrotron radiation XRD showed dislocation density around yield-drop in the UFG specimen quickly increased. ECCI observations revealed the nucleation of deformation twins and stacking faults from grain boundaries in the UFG specimen around yielding. Although it had been conventionally reported that the grain refinement suppresses deformation twinning in FCC metals and alloys, the number density of deformation twins in the 0.79 µm grain-sized specimen was much higher than that in the specimens with grain sizes of 4.5 µm and 15.4 µm. The unusual change of yielding behavior from continuous to discontinuous manner by grain refinement could be understood on the basis of limited number of free dislocations in each ultrafine grain. The results indicated that the scarcity of free dislocations in the recrystallized UFG specimens changed the deformation and twinning mechanisms in the TWIP steel.

Change of Deformation Mechanisms Leading to High Strength and Large Ductility in Mg-Zn-Zr-Ca Alloy with Fully Recrystallized Ultrafine Grained Microstructures.

Recently, we have found that fully recrystallized ultrafine-grained (UFG) microstructures could be realized in a commercial precipitation-hardened Magnesium (Mg) alloy. The UFG specimens exhibited high strength and large ductility under tensile test, but underlying mechanisms for good mechanical properties remained unclear. In this study, we have carried out systematic observations of deformation microstructures for revealing the influence of grain size on the change of dominant deformation modes. We found that plastic deformation of conventionally coarse-grained specimen was predominated by {0001} <11-20> slip and {10-12} <10-11> twinning, and the quick decrease of work-hardening rate was mainly due to the early saturation of deformation twins. For the UFG specimens, {10-12} <10-11> twinning was dramatically suppressed, while non-basal slip systems containing component of Burgers vector were activated, which contributed significantly to the enhanced work-hardening rate leading to high strength and large ductility. It was clarified by this study that limited ductility of hexagonal Mg alloys could be overcome by activating unusual slip systems ( dislocations) in fully recrystallized UFG microstructures.

Sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species.

Sibutramine had been prescribed as an oral anorexiant that reduces dietary intake, but was withdrawn from the market due to frequent occurrence of severe cardiovascular events including hypertension. To elucidate the pathogenic mechanism of hypertension, we here investigated whether sibutramine facilitates damage and contraction of human aortic smooth muscle (HASM) cells or not. Treatment with sibutramine provoked HASM cell apoptosis, which was attributed to production of reactive oxygen species and mitochondria dysfunction. In addition, the drug treatment of the cell promoted calcium influx, phosphorylation of myosin light chain and contraction, which were abrogated by pretreating the cells with antioxidant and nitric oxide (NO) donor. Thus, the drug-evoked contraction is likely due to a preceding disturbance of balance between the drug-elicited reactive oxygen species production and exogenous NO supply. Compared to sibutramine, its N-desmethyl and N-didesmethyl metabolites exhibited much less toxicity and contraction against HASM cells, in which sibutramine was hardly demethylated. The low metabolic capacity of the cells may also be pertinent to the damage and contraction elicited by sibutramine. Taken together, our data suggest that sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species and decreasing exogenous NO supply, leading to pathogenesis of hypertension.

α-Pyrrolidinononanophenone provokes apoptosis of neuronal cells through alterations in antioxidant properties.

In this study, we found that exposure to α-pyrrolidinononanophenone (α-PNP), a highly lipophilic synthetic cathinone, provokes apoptosis of human neuronal SK-N-SH cells. The drug sensitivity of the cells (50% lethal concentration of 12µM) was similar to those of aortic endothelial and smooth muscle cells, and was higher than those of cells derived from colon, liver, lung and kidney, suggesting that α-PNP overdose and abuse cause serious damage in central nervous and vascular systems. SK-N-SH cell treatment with lethal concentrations (20 and 50µM) of α-PNP facilitated the reactive oxygen species (ROS) production. The treatment also prompted elevation of Bax/Bcl-2 ratio, lowering of mitochondrial membrane potential, release of cytochrome-c into cytosol, and resultant activation of caspase-9 and caspase-3. The apoptotic events (caspase-3 activation and DNA fragmentation) were abolished by pretreatment with antioxidants, N-acetyl-l-cysteine and polyethyleneglycol-conjugated catalase. These results suggest that ROS production, mitochondrial dysfunction and caspase activation are potential events in the mechanism underlying the α-PNP-triggered neuronal cell apoptosis. Intriguingly, the α-PNP treatment of SK-N-SH cells was found to promote formation of 4-hydroxynonenal, a reactive aldehyde generated from lipid peroxidation. The α-PNP treatment also decreased cellular levels of total and reduced glutathiones, expression of γ-glutamylcysteine synthetase mRNA and glutathione reductase activity. Furthermore, the α-PNP treatment resulted in both decrease in proteasomal activities and increase in expression of autophagy-related factors, which were significantly prevented by pretreating with N-acetyl-l-cysteine. Therefore, the ROS formation by α-PNP treatment may be ascribable to the decrease in glutathione level through its consumption during 4-hydroxynonenal detoxification and dysfunction of both de novo synthesis and regeneration of glutathione, in addition to impairments in proteasomal and autophagic systems that degrade cellular oxidized components.

Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties.

Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application.