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We investigated the effects of incorporation of surface pre-reacted glass ionomer (S-PRG) filler in tissue conditioner (TC) on Candida albicans adhesion. We prepared specimens containing 0, 5, 10, or 20 wt% of S-PRG filler, and measured the amount of C. albicans on the surface using a colony forming unit (CFU) assay and scanning electron microscopic images. In addition, we measured the consistency, penetration depth, and surface roughness (Ra). CFU values for 10 and 20 wt% were significantly lower than that for the control (p<0.05). Hyphal density on the surface was greater in the control. The 10 and 20 wt% specimens showed significantly higher consistency and Ra, lower penetration depth ratio than control (p<0.05). These results suggest that incorporation of S-PRG filler may reduce C. albicans adhesion onto TC surface; however, the optimal amount of filler is dictated by the influence of filler incorporation on mechanical and surface characters of TC.

Healthy trabecular bone shows highly anisotropic trabecular architecture and the preferential orientation of collagen and apatite inside a trabecula, both of which are predominantly directed along the cephalocaudal axis. This makes trabecular bone stiff in the principally loaded direction (cephalocaudal axis). However, changes in these anisotropic trabecular characteristics after the insertion of implant devices remain unclear. We defined the trabecular architectural anisotropy and the preferential orientation of collagen and apatite as parameters of trabecular bone health. In the present study, we analyzed these parameters after the implantation of two types of intervertebral fusion cages, open and closed box-type cages, into sheep spines for 2 and 4months. Alteration and evolution of trabecular health around and inside the cages depended on the cage type and implantation duration. At the boundary region, the values of trabecular architectural anisotropy and apatite orientation for the closed-type cages were similar to those for isotropic conditions. In contrast, significantly larger anisotropy was found for open-type cages, indicating that the open-type cage tended to maintain trabecular anisotropy. Inside the open-type cage, trabecular architectural anisotropy and apatite orientation significantly increased with time after implantation. Assessing trabecular anisotropy might be useful for the evaluation of trabecular health and the validation and refinement of implant designs., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

The article Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain, written by Shunsuke Nakamori, Jun Takahashi, Sumiko Hyuga, Toshiko Tanaka-Kagawa, Hideto Jinno, Masashi Hyuga, Takashi Hakamatsuka, Hiroshi Odaguchi, Yukihiro Goda, Toshihiko Hanawa and Yoshinori Kobayashi, was originally published Online First without open access. After publication in volume 71, issue 1, page 105-113 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to, (© The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.)

Helicobacter pylori is a causative pathogen of chronic gastritis, gastric ulcer disease, and gastric cancer. Humans are known to be a natural host for H. pylori and tend to acquire the pathogen before the age of 5 years. The infection may then persist lifelong if eradication therapy is not applied. One of the modes of transmission of H. pylori is between family members, and therefore, the presence of infected family members is an important risk factor in children. However, other environmental factors have not been fully analyzed. The present study was performed to clarify whether and to what extent intestinal microbiota affect H. pylori intrafamilial infection. The fecal specimens from H. pylori- infected infants and H. pylori- infected and non-infected family members were collected in cohort studies conducted by Sasayama City, Hyogo Prefecture from 2010 to 2013. In total, 18 fecal DNA from 5 families were analyzed. Samples were amplified using 16S rRNA universal primers, and the amplicons were sequenced using the Ion PGM system. Principal-coordinate analysis demonstrated that there was no difference in intestinal microbiota between H. pylori- positive and H. pylori- negative groups. In intrafamilial comparison tests, the Manhattan distance of intestinal microbiota between the H. pylori- infected infant proband and H. pylori- negative mother was nearest in the family with low intestinal microbial diversity. However, in the family with the highest intestinal microbial diversity, the nearest Manhattan distance was shown between the H. pylori- infected infant proband and H. pylori- infected mother. The results in this study showed that the composition of the intestinal microbiota was very similar between members of the same family, and as such, colonization with organisms highly similar to the infected parent(s) may be a risk factor for H. pylori infection in children.

Selective laser melting (SLM) technology was recently introduced to fabricate dental prostheses. However, the fatigue strength of clasps in removable partial dentures prepared by SLM still requires improvement. In this study, we attempted to improve the fatigue strength of clasps by adding support structures for overhanging parts, which can generally be manufactured at an angle to be self-supporting. The results show that the fatigue strength of the supported specimens was more than twice that of unsupported specimens. Electron back-scattered diffraction analysis revealed that the supported specimens exhibited lower kernel average misorientation values than the unsupported specimens, which suggested that the support structure reduced the residual strain during the SLM process and helped to prevent micro-cracks led by thermal distortion. In addition, the supported specimens cooled more rapidly, thereby forming a finer grain size compared to that of the unsupported specimens, which contributed to improving the fatigue strength. The results of this study suggest that the fatigue strength of overhanging parts can be improved by intentionally adding support structures., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

As part of our continuing study of ephedrine alkaloids-free Ephedra Herb extract (EFE) in pursuit of its approval as a crude drug preparation, we identified two quantitative markers for the quality control of the manufacturing process of EFE and sought to establish cost-effective and simple methods for quantitative analyses. We analysed Ephedra Herb extracts grown in different habitats and collection years by liquid chromatography/high-resolution mass spectrometry (LC/HRMS) and detected two notable peaks common to each extract. These peaks were identified as vicenin-2 (1) and isovitexin 2″-O-rhamnoside (2). Quantitative analyses using the isocratic condition of LC/MS showed that the content percentages of 1 and 2 in EFE were 0.140-0.146% and 0.350-0.411%, respectively. We concluded that 1 and 2 were adequate quality control markers for quantitative analysis of EFE. Furthermore, we quantitatively analysed apigenin (3), an aglycon common to 1 and 2, and found that the conversion factors of 1 to 3 and 2 to 3 were 1.3 and 1.5, respectively. Therefore, we concluded that 3 was a secondary standard for quantifying the contents of 1 and 2 in EFE. A series of results obtained from this study will be valuable for the quality control of EFE.

Although titanium-zirconium (Ti-Zr) alloy has been adopted for clinical applications, the ideal proportion of Zr in the alloy has not been identified. In this study, we investigated the biocompatibility of Ti-Zr alloy by evaluating its corrosion resistance to better understand whether there is an optimal range or value of Zr proportion in the alloy. We prepared pure Ti, Ti-30Zr, Ti-50Zr, Ti-70Zr, and pure Zr (mol% of Zr) samples and subjected them to anodic polarization and immersion tests in a lactic acid + sodium chloride (NaCl) solution and artificial saliva. We observed pitting corrosion in the Ti-70Zr and Zr after exposure to both solutions. After the immersion test, we found that pure Ti exhibited the greatest degree of dissolution in the lactic acid + NaCl solution, with the addition of Zr dramatically reducing Ti ion dissolution, with the reduction ultimately exceeding 90% in the case of the Ti-30Zr. Hence, although the localized corrosion resistance under severe conditions was compromised when the Zr content was more than 70%, metal ion release reduced owing to Zr addition and the corresponding formation of a stable passive layer. The results suggest that Ti-30Zr or a Zr proportion of less than 50% would offer an ideal level of corrosion resistance for clinical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 73-79, 2018., (© 2016 Wiley Periodicals, Inc.)

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. In this study, the incidence of these adverse effects was compared between mice administered EHE and those administered EFE. Increased locomotor activity in an open-field test, reduced immobility times in a forced swim test, and reduced sleep times in a pentobarbital-induced sleep test were observed in EHE-treated mice, when compared to the corresponding values in vehicle-treated mice. In contrast, EFE had no obvious effects in these tests. In electrocardiograms, atrial fibrillation (i.e., irregular heart rhythm, absence of P waves, and appearance of f waves) was observed in the EHE-treated mice. It was suggested that this atrial fibrillation was induced by stimulation of adrenaline β 1 receptors, but not by hypokalemia. However, EFE did not affect cardiac electrophysiology. These results suggest that the abovementioned side effects are caused by ephedrine alkaloids in EHE, and that EFE is free from these adverse effects, such as excitation, insomnia, and arrhythmias. Thus, EFE is a promising new botanical drug with few adverse effects.

Anticancer drug-induced stomatitis develops in 30% to 40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan. The "hospital formulation" is a customized medicine which hospital pharmacists prepare when doctors cannot carry out the medical therapy most suitable for a patient using commercial medicines. However, as the duties of pharmacists increase, use of the "hospital fomulation" decreases. Therefore, development of "hospital fomulations" based on individual evidence has a limit. Irsogladine maleate (IM) is a drug with gastric mucosal protective properties. IM increases intracellular cAMP levels in the gastric mucosa and activates communication between cells. It has been reported that the oral administration of IM reduces the incidence of 5-FU-based chemotherapy-induced stomatitis. However, there have been no reports on the effect of the direct use of IM in treating stomatitis. Therefore, we studied the development of an IM oral spray for stomatitis treatment, and obtained evidence of a direct effect in an animal experiment using a stomatitis model. Next, rebamipide mouthwash was administered to patients who had stomatitis caused by cancer chemotherapy. The total scores were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). When comparing SES and changes in the stomatitis area in patients, gradual reductions in the extent of stomatitis were observed, even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.

To investigate the cellular response to designed topography in vitro, we studied the adhesion, proliferation, osteogenic differentiation, and calcification of mouse preosteoblasts (MC3T3-E1) cultured on titanium (Ti) surfaces with periodic micrometer scale grooves containing nanometer scale ripples in the vertical direction fabricated by single-shot, femtosecond laser irradiation (fsTi). The surface composition and chemical state of fsTi were almost the same as those of mirror-polished Ti without femtosecond laser irradiation (mTi). Cells cultured on fsTi were highly aligned, whereas the cell proliferation rate on fsTi was less than that on mTi. Higher gene expressions of Spp1 and Bglap1 were detected in cells cultured on fsTi than those on mTi, indicating that the periodic micro/nanometer scale grooves topography promoted osteogenic differentiation and calcification. This initial activation of osteoinduction on fsTi generated calcified deposits that were thicker and larger than those on mTi and hence, osteoconductivity was promoted on fsTi. Our findings indicate that femtosecond laser irradiation is a technique with potential for controlling biomaterial-cell interfaces and, in particular, the promotion of osseointegration of Ti. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3456-3464, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti-inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti-inflammatory action., Methods: The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation (IM) was carried out on the distal ileum. The anti-inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules., Key Results: Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) antagonists, such as HC-030031, significantly inhibited the amelioration of macrophage infiltration by ZSR. The inhibition of macrophage infiltration by ZSR was abolished in both α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT 4 R) knockout mice., Conclusions & Inferences: Daikenchuto-induced anti-inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI, is dependent on the effects of ZSR. Zingiberis Siccatum Rhizoma activates TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT 4 R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI., (© 2017 John Wiley & Sons Ltd.)

The adsorption of active pharmaceutical ingredients on the surface of medical devices such as polyvinl chloride, ethylene-vinyl acetate copolymer and glass often prevent the acuurate dose of drug. At dispensing of pharmaceuticals, mètre glass (MG) has been widely used for dispensing syrup. When measuring the viscous syrup, it often takes long time to dispense the accurate volume due to their adhesiveness on the glass surface. In this study, we investigate the adhesion of various syrups to MG made with uncoated glass or glass with a strongly hydrophobic silicone or fluorinated coating in terms of the following formulation parameters: viscosity, surface tension, contact angle, and surface free energy. The contact angles for syrups on the coated glass surfaces were significantly higher than those on the uncoated glass surface. In addition, the relationship between surface tension and contact angle was examined. We found that the contact angle was independent of surface tension for the uncoated glass, while it increased with increasing surface tension for the coated glasses. These results can be explained as follows: the silicone or fluorinated coatings inhibit the hydrogen bonding that usually takes place between water and silanol and siloxane groups at glass surfaces. The coatings reduced the surface free energy and increased the hydrophobicity of the glass, reduced its wettability by the syrups, and thus reduced the adhesion loss for the syrups. It was considered that as for the hydrophobic action, properties of matter of sample influence the coated device by coating in order that it is reinforced.

To add biocompatibility or biofunction to metal surface, an intelligent interface between metals and tissues must be acquired. Tremendous surface modification techniques are currently studied to create the intelligent interface. In particular, bone formation or bone bonding is major purpose of the surface modifications. Time transient of surface modification techniques are summarized and the importance of roughened or porous surface to combine materials with bone tissue is demonstrated. As an example of surface modification, electrodeposition of poly(ethylene glycol) to inhibit biofilm formation is introduced. A dual-functional surface is formed on titanium by micro arc oxidation. In addition, the effect of topography on the elongation and differentiation of human mesenchymal stem cells was confirmed on the hybrid micrometer-level and nanometer-level grooves of titanium surface. Metal surface is possibly biofunctionalized by various surface modification techniques.

Anticancer drug-induced stomatitis develops in 30% to 40% of cancer cases that undergo chemotherapy. However, medications for this condition are not commercially available in Japan. Upon obtaining approval of the ethics committee, a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash) was administered to one inpatient and four outpatients, who had developed stomatitis caused by cancer chemotherapy. Starting from 14 d after the administration of the rebamipide mouthwash, the patients scored a stomatitis survey on oral state, pain level, and diet and recorded the number of times they gargled, as well as any stomatitis observations, in a stomatitis diary. The total scores for the points for each of the three types of survey sections were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). The SES became "0" in three out of the five patients within 14 d of treatment. No change in SES was found in one patient. In the remaining patients, SES became "0" once but increased again later. Using image analysis software (ImageJ), the area at which the stomatitis was observed was measured. When comparing SES and change in the area in patients who agreed to participate, gradual reductions in the extent of stomatitis was observed even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.

Background: Kososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS., Methods: In the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1-10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1-12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13-15., Results: Oral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment., Conclusions: Our findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a "whole-body bathing method (WBBM)". In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole-body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole-body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment., (© 2016 Japanese Dermatological Association.)

To clarify the effects of micron/submicron hybrid topography on cell morphology and functionalization, we investigated the adhesion and differentiation of human mesenchymal stem cells (hMSCs) to titanium (Ti) surfaces with three different topographies: micron, submicron, and hybrid grooves created using a femtosecond laser. hMSCs cultured on Ti specimens showed high alignment on micron and hybrid surfaces after 6 h of incubation, whereas cells attached to submicron and hybrid surfaces were elongated. An examination of vinculin-positive adhesion plaques indicated that micron grooves affected cellular alignment by modifying the initial cell polarization, whereas submicron grooves affected cellular extension. A superposition effect of topography was evidenced by the highly aligned and elongated morphology of hMSCs grown on the hybrid surface, which promoted osteogenic and chondrogenic differentiation. These findings provide a basis for the design of novel biomaterial surfaces that can control specific cellular functions.

Helicobacter pylori is one of the most common causes of bacterial infection in humans, and it forms biofilms on human gastric mucosal epithelium as well as on in vitro abiotic surfaces. Bacterial biofilm is critical not only for environmental survival but also for successful infection. We previously demonstrated that strain TK1402, which was isolated from a Japanese patient with duodenal and gastric ulcers, has high biofilm-forming ability in vitro relative to other strains. In addition, we showed that outer membrane vesicles (OMV) play an important role in biofilm formation. The aim of this study was to analyze which protein(s) in the OMV contributes to biofilm formation in TK1402. We obtained a spontaneous mutant strain derived from TK1402 lacking biofilm-forming ability. The protein profiles of the OMV were compared between this mutant strain and the wild type, and it was found that AlpB, an outer membrane protein in the OMV of the mutant strain, was markedly decreased compared to that of the wild type. Restoration of TK1402 alpB to the mutant strain fully recovered the ability to form biofilm. However, restoration with alpB from other strains demonstrated incomplete recovery of biofilm-forming ability. We therefore inferred that the variable region of AlpB (amino acid positions 121 to 146) was involved in TK1402 biofilm formation. In addition, diversification of the AlpB sequence was shown to affect the ability to adhere to AGS cells. These results demonstrate a new insight into the molecular mechanisms of host colonization by H. pylori IMPORTANCE Bacterial biofilm is critical not only for environmental survival but also for successful infection. The mechanism of Helicobacter pylori adherence to host cells mediated by cell surface adhesins has been the focus of many studies, but little is known regarding factors involved in H. pylori biofilm formation. Our study demonstrated that AlpB plays an important role in biofilm formation and that this property depends upon the specific sequence of alpB This in turn was shown to be important in the ability to adhere to gastric cells. We anticipate that these results will provide new insight into the molecular mechanisms of H. pylori colonization., (Copyright © 2017 Yonezawa et al.)

Zr-Ag composites were fabricated to decrease the magnetic susceptibility by compensating for the magnetic susceptibility of their components. The Zr-Ag composites with a different Zr-Ag ratio were swaged, and their magnetic susceptibility, artifact volume, and mechanical properties were evaluated by magnetic balance, three-dimensional (3-D) artifact rendering, and a tensile test, respectively. These properties were correlated with the volume fraction of Ag using the linear rule of mixture. We successfully obtained the swaged Zr-Ag composites up to the reduction ratio of 96% for Zr-4, 16, 36, 64Ag and 86% for Zr-81Ag. However, the volume fraction of Ag after swaging tended to be lower than that before swaging, especially for Ag-rich Zr-Ag composites. The magnetic susceptibility of the composites linearly decreased with the increasing volume fraction of Ag. No artifact could be estimated with the Ag volume fraction in the range from 93.7% to 95.4% in three conditions. Young's modulus, ultimate tensile strength (UTS), and 0.2% yield strength of Zr-Ag composites showed slightly lower values compared to the estimated values using a linear rule of mixture. The decrease in magnetic susceptibility of Zr and Ag by alloying or combining would contribute to the decrease of the Ag fraction, leading to the improvement of mechanical properties., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Diamond-like carbon (DLC) material is used in blood contacting devices as the surface coating material because of the antithrombogenicity behavior which helps to inhibit platelet adhesion and activation. In this study, DLC films were doped with boron during pulsed plasma chemical vapor deposition (CVD) to improve the blood compatibility. The ratio of boron to carbon (B/C) was varied from 0 to 0.4 in the film by adjusting the flow rate of trimethylboron and acetylene. Tribological tests indicated that boron doping with a low B/C ratio of 0.03 is beneficial for reducing friction (μ = 0.1), lowering hardness and slightly increasing wear rate compared to undoped DLC films. The B/C ratio in the film of 0.03 and 0.4 exhibited highly hydrophilic surface owing to their high wettability and high surface energy. An in vitro platelet adhesion experiment was conducted to compare the blood compatibility of TiNb substrates before and after coating with undoped and boron doped DLC. Films with highly hydrophilic surface enhanced the blood compatibility of TiNb, and the best results were obtained for DLC with the B/C ratio of 0.03. Boron doped DLC films are promising surface coatings for blood contacting devices.

Kampo medicines containing Ephedra Herb (EH) such as eppikajutsubuto and makyoyokukanto are used to treat myalgia, arthralgia, and rheumatism. The analgesic effects of these Kampo medicines are attributed to the anti-inflammatory action of EH. However, the molecular mechanism of the analgesic effect of EH remains to be clarified. In this study, the effects of EH extract (EHE) on transient receptor potential vanilloid 1 (TRPV1), a nonselective ligand-gated cation channel, which plays an essential role in nociception on sensory neurons, were investigated using mTRPV1/Flp-In293 cells (stable mouse TRPV1-expressing transfectants). Administration of EHE increased the intracellular Ca 2+ concentration in these cells, which was inhibited by the TRPV1 antagonist, N-(4-tert-butylphenyl)-1,2-dihydro-4-(3-chloropyridine-2-yl) tetrahydropyrazine-1-carboxamide (BCTC), indicating that EHE activated TRPV1. Examination of EHE-induced nociceptive pain in vivo revealed that an intradermal (i.d.) injection of EHE into the hind paw of mice induced paw licking, a pain-related behavior, and that the extract increased paw licking times in a dose-dependent manner. The EHE-induced paw licking was also inhibited by BCTC. An i.d. injection of EHE 30 min before administration of capsaicin decreased capsaicin-induced paw licking times. Similarly, oral administration of the extract also suppressed capsaicin-induced paw licking, without affecting the physical performance of the mice. These results suggest that EHE suppresses capsaicin-induced paw licking by regulating TRPV1 activity. Thus, the antinociceptive effects of EHE seem to be produced by its direct action on sensory neurons through TRPV1.

The stomatitis caused by anticancer agents and radiation therapy deteriorates patient QOL, potentially causing eating disorders as a result of pain. Although gargling and ointments can be used in the treatment of stomatitis, patients must spit out mouthwash after use, while ointment application requires a finger to be inserted into the oral cavity. In contrast, sprays eliminate these potential compliance problems. Therefore, we developed a stomatitis spray that remains on the oral mucosa. It has been reported that irsogladine maleate (IM) is effective against stomatitis via oral administration. IM is water insoluble; thus, it was dissolved with various cyclodextrins (CDs). Furthermore, we examined combination with gum ghatti (GG), a mucoadhesive polymer. The interaction between mucin and GG was examined by Quartz Crystal Microbalance with Dissipation monitoring. We found that GG exhibited mucoadhesion. Furthermore, we examined the healing effects of IM on stomatitis in a stomatitis model hamster. We found that stomatitis healed after direct application of IM. However, the model used in this experiment is not based on stomatitis caused by anticancer agents. Further study is therefore necessary.

Ephedrine alkaloids (EAs) have been considered the main pharmacologically active substances in Ephedra Herb (, Mao; EH) since they were first identified by Prof. N. Nagai, and are known to induce palpitation, hypertension, insomnia, and dysuria as side effects. Therefore, the administration of drugs containing EH to patients with cardiovascular-related diseases is severely contraindicated. While our previous studies suggest that some of the effects of EH may not be due to EAs, considering their side effects would be expedient to develop a new EAs-free EH extract (EFE). Here, we established a preparation method for EFE and revealed its chemical composition, including the content of herbacetin, a flavonoid aglycon present in EH and a potential putative marker for EFE quality control. In addition, we showed the antiproliferative effects of EFE against the H1975 non-small cell lung cancer (NSCLC) cell line. EFE was prepared from EH extract using the ion exchange resin SK-1B. LC/Orbitrap MS analysis revealed the removal of EAs, 6-methoxykynurenic acid, and 6-hydroxykynurenic acid from the original extract. Quantitative analysis of herbacetin using LC/MS in acid-hydrolyzed EFE showed that its content was 0.104 %. Although several alkaloidal constituents were removed from EH extract, the antiproliferative effect of EFE against H1975 cells was comparable to that of EH extract. These results indicate that EFE retained the anticancer effect of EH and demonstrated its potential for future development as a new herbal medicine with reduced side effects.

It is generally accepted that the primary pharmacological activities and adverse effects of Ephedra Herb are caused by ephedrine alkaloids. Interestingly, our research shows that Ephedra Herb also has ephedrine alkaloid-independent pharmacological actions, such as c-MET inhibitory activity. This study describes the preparation of an ephedrine alkaloids-free Ephedra Herb extract (EFE) by ion-exchange column chromatography, as well as in vitro and in vivo evaluation of its pharmacological actions and toxicity. We confirmed that EFE suppressed hepatocyte growth factor (HGF)-induced cancer cell motility by preventing both HGF-induced phosphorylation of c-Met and its tyrosine kinase activity. We also investigated the analgesic effect of EFE. Although the analgesic effect of Ephedra Herb has traditionally been attributed to pseudoephedrine, oral administration of EFE reduced formalin-induced pain in a dose-dependent manner in mice. Furthermore, we confirmed the anti-influenza virus activity of EFE by showing inhibition of MDCK cell infection in a concentration-dependent manner. All assessments of toxicity, even after repeated oral administration, suggest that EFE would be a safer alternative to Ephedra Herb. The findings described here suggest that EFE has c-Met inhibitory action, analgesic effect, and anti-influenza activity, and that it is safer than Ephedra Herb extract itself. Therefore, EFE could be a useful pharmacological agent.

Stomatitis induced by radiation therapy or cancer chemotherapy is a factor in sleep disorders and/or eating disorders, markedly decreasing patient quality of life. In recent years, disintegrating oral films that are easy to handle have been developed; therefore, we focused on the formulation of these films. We prepared an adhesive film for the oral cavity using xyloglucan (Xylo), which is a water-soluble macromolecule. We used loperamide, which has been reported to relieve pain caused by stomatitis effectively, as a model drug in this study. Films were prepared from Xylo solutions (3% (w/w)) and hypromellose (HPMC) solutions (1% (w/w)). Xylo and HPMC solutions were mixed at ratios of 1 : 1, 2 : 1, or 3 : 1 for each film, and films 2×2 cm weighing 3 g were prepared and dried at 37°C for 24 h. Physicochemical properties such as strength, adhesiveness, disintegration behavior, and dissolution of loperamide from films were evaluated. Films prepared from Xylo solution alone had sufficient strength and mucosal adhesion. On the other hand, films prepared from a mixture of Xylo and HPMC were inferior to those made from Xylo, but showed sufficient strength and mucosal adhesion and were flexible and easy to handle. The films prepared in this study are useful as adhesion films in the oral cavity.

We aimed to investigate the fatigue strength of Co-Cr-Mo clasps for removable partial dentures prepared by selective laser melting (SLM). The Co-Cr-Mo alloy specimens for tensile tests (dumbbell specimens) and fatigue tests (clasp specimens) were prepared by SLM with varying angles between the building and longitudinal directions (i.e., 0° (TL0, FL0), 45° (TL45, FL45), and 90° (TL90, FL90)). The clasp specimens were subjected to cyclic deformations of 0.25mm and 0.50mm for 10(6) cycles. The SLM specimens showed no obvious mechanical anisotropy in tensile tests and exhibited significantly higher yield strength and ultimate tensile strength than the cast specimens under all conditions. In contrast, a high degree of anisotropy in fatigue performance associated with the build orientation was found. For specimens under the 0.50mm deflection, FL90 exhibited significantly longer fatigue life (205,418 cycles) than the cast specimens (112,770 cycles). In contrast, the fatigue lives of FL0 (28,484 cycles) and FL45 (43,465 cycles) were significantly shorter. The surface roughnesses of FL0 and FL45 were considerably higher than those of the cast specimens, whereas there were no significant differences between FL90 and the cast specimens. Electron backscatter diffraction (EBSD) analysis indicated the grains of FL0 showed preferential close to <001> orientation of the γ phase along the normal direction to the fracture surface. In contrast, the FL45 and FL90 grains showed no significant preferential orientation. Fatigue strength may therefore be affected by a number of factors, including surface roughness and crystal orientation. The SLM process is a promising candidate for preparing tough removable partial denture frameworks, as long as the appropriate build direction is adopted., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the mechanical properties and biologic response of single-phase Ti-Zr alloys cast in higher-purity casting conditions, with comprehensive compositions (from 10 to 90 mol% of Zr)., Materials and Methods: The mechanical properties and in vitro biologic response with proportional increase of Zr to Ti-Zr alloy composition were assessed. Tensile strength, surface hardness, and Young's modulus were examined. The in vitro cell response of the alloys was also tested with mouse osteoblast cells., Results: Analyses of mechanical tests demonstrated improved strength and reduced Young's modulus on this binary alloy system. In vitro cell culture studies with osteogenic MCT3T-E1 cells exhibited the highest attachment rate with the largest and more mature cells on Ti10Zr, instead of commercially pure Ti, whereas a significantly lower cell attachment rate and delayed alkaline phosphatase-specific activity (ALP) differentiation were detected on Ti50Zr., Conclusion: The results revealed that the composition did have an impact on the in vitro biologic response. Ti-Zr alloys with 50-50 mol% composition had a decreased biologic response, although the mechanical properties improved. The overall highest strength was Ti with 30 mol% Zr without significant decrease of biologic response.

The MET tyrosine kinase receptor and its ligand, hepatocyte growth factor (HGF), are known to be overexpressed in a variety of malignant tumor cells, and are implicated in the development of gefitinib-resistance in human non-small cell lung cancer (NSCLC) cells. Ephedrae herba was previously reported to prevent HGF-induced cancer cell motility by directly suppressing HGF/MET signaling through the inhibition of MET tyrosine kinase, and treatment with its extract also considerably reduced MET protein levels. To further investigate the mechanism underlying the Ephedrae herba-induced inhibition of MET phosphorylation as well as its degradation and subsequent disappearance, we examined the effect of Ephedrae herba on HGF-stimulated MET endocytosis and downregulation via early/late endocytic pathways in an NSCLC cell line. Using immunofluorescence microscopy, we found that pretreatment of cells with Ephedrae herba extract dramatically changed the intracellular distribution of plasma membrane-associated MET, and that the resultant MET staining was distributed throughout the cytoplasm. Pretreatment of the cells with Ephedrae herba extract also led to the rapid loss of MET and phosphorylated (p)-MET in HGF-stimulated cells. In contrast, inefficient endocytic delivery of MET and p-MET from early to late endosomes was observed in the absence of Ephedrae herba extract, since considerable amounts of the internalized MET accumulated in the early endosomes and were not delivered to lysosomes up to 1 h after HGF-stimulation. Furthermore, large amounts of MET and p-MET that had accumulated in late endosomes of Ephedrae herba-pretreated cells after HGF stimulation were observed along with bafilomycin A1. Therefore, we inferred that degradation of MET occurred in the late endosome/lysosome pathway. Moreover, western blot analysis revealed the accelerated degradation of MET and p-MET proceeds in cells pretreated with Ephedrae herba extract. Collectively, our results suggest that some components of Ephedrae herba have a novel role in promoting HGF-stimulated MET and p-MET endocytosis followed by its downregulation, likely mediated by the early/late endocytic pathways.

To develop metallic materials with thromboresistance, a block-type copolymer (PMbA) was immobilized onto a titanium surface with electrodeposition. The polymer was composed of a poly(2-(methacryloyloxy)ethyl phosphorylcholine (MPC)) segment and a poly(2-aminoethylmethacrylate) segment, which was designed to electronically adsorb to the surface oxide layer on the titanium surface. We confirmed that the polymer was synthesized as expected by nuclear magnetic resonance and gel permeation chromatography. In a 0.26 mmol L(-1) PMbA solution adjusted to pH 11, -3.0 V (vs. an Ag/AgCl electrode) was applied to a titanium substrate for 300 s. The immobilization of PMbA on the titanium was confirmed with X-ray photoelectron spectroscopy and an atomic force microscope. The water contact angle and amount of adsorbed protein on the PMbA-modified surface were decreased. Thrombus formation was not observed all over the surface even when the surface was contacted with human blood without an anticoagulant. Therefore, PMbA covered the surface with even density and poly(MPC) segments in PMbA inhibited platelet adsorption. Electrodeposition with PMbA improves the blood compatibility of a titanium substrate in a simple process., (© 2015 Wiley Periodicals, Inc.)

In this study, osteogenic differentiation and calcification of preosteoblast (MC3T3-E1) cultured on sputter-deposited titanium (Ti), zirconium (Zr), and gold (Au) on cover glasses were evaluated to understand the differences in bone formation ability among these three metals; these metals show the same high corrosion resistance, but Ti and Zr are covered by surface passive oxide film while Au is not covered by the oxide film. Ti and Zr promoted cellular proliferation without osteogenic differentiation. Cells cultured on Ti and Zr expressed higher levels of Runx2, Col1α1, and Akp2 at an earlier stage, which indicated faster promotion of osteogenic differentiation, as compared to those cultured on Au. Moreover, after 21 days of culture, the Bglap1 and Ifitm5 expression peaks in cells cultured on Ti and Zr were higher than those in cells cultured on Au, which indicated faster promotion of calcification. Cells cultured on Ti showed an advantage in osteogenic differentiation at an early stage, while cells on Zr showed better calcification promotion with a long-term culture. The amount of extracellular calcified deposits was in good agreement with the gene expression results. On the other hand, the intracellular calcium content of cells on Au specimens was higher than that of cells on Ti and Zr specimens. The results indicate that preosteoblasts on Ti and Zr showed faster osteogenic differentiation and calcification than those on Au, whereas Au improved the intracellular calcium content. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 639-651, 2016., (© 2015 Wiley Periodicals, Inc.)

Objectives: This study assessed the effect of surface strontium ion (Sr) modification on the osteogenic activity of an osteoconductive ceramic bone graft substitute with the hope of using the bone healing effect of Sr for potential application in periodontal and maxillofacial regenerative surgery., Materials and Methods: A simple wet chemical treatment was employed to deliver Sr to the surface of particulate porcine bone graft. The osteogenic activity of surface Sr-modified bone substitute was compared in vitro and in vivo with that of unmodified ceramic bone, other clinically available synthetic bone or osteoinductive allograft bone., Results: The resultant bone substitute showed the formation of Sr-containing microstructured surface layer along with the formation of additional nanostructures and displayed sustained Sr release. Sr modification promoted the osteogenic differentiation of bipotential ST2 stem cells. Sr-modified bone substitute increased the amount of newly formed bone at early healing period in calvarial defect of rabbits., Conclusions: These results suggest that the surface Sr modification by wet chemical treatment is a promising approach to enhance the early bone healing capacity of osteoconductive ceramic bone substitutes., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study was to investigate the bond strength of dental porcelain and the preheated Zr-14Nb alloy, and compare this strength with that of titanium. White oxide layers, which were predominantly composed of monoclinic zirconia, were formed on the preheated sample groups, and exhibited a greater roughness than the control samples. At the metal-ceramic interface, a greater Nb diffusion range was observed than in the control samples. The bond strengths of the samples subjected to 20min preheating treatment were the lowest (33.6 ± 3.2 MPa), which may be ascribed to the formation of a brittle thick oxide layer under excessive heat treatment. The samples subjected to this heat treatment for 5 min exhibited the highest mean bond strength (43.7 ± 5.9 MPa), which was significantly higher than that of titanium (35.3 ± 3.5 MPa). Thus, the Zr-14Nb alloy is a promising candidate for fixed dental prosthesis, as long as the appropriate treatment conditions are adopted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Strontium (Sr) ions were added to calcium- and phosphate-containing porous titanium oxide layers formed by micro-arc oxidation (MAO) of titanium (Ti) substrates to improve their osseointegration. An MC3T3-E1 preosteoblast was used to evaluate the effect of the incorporated Sr species on cell calcification. Similar surface microporous morphologies of the oxide layers were observed for all specimens produced by MAO, while the contents of the incorporated Sr ions increased with increasing Sr concentrations in MAO electrolytes. The calcium- and phosphate-containing porous layers promoted the cell alkaline phosphatase (ALP) activity, while cell calcification was promoted by the Sr addition. In particular, the ALP activity significantly increased after 10 days of culture, and larger areas of calcified deposits were observed for the specimens treated with MAO electrolytes containing 0.15 mol L(-1) of Sr species. The effect of Sr addition on the calcification of the MAO-treated Ti oxide layers was established in this study.

The applications of hierarchical micro/nano-structures, which possess properties of two-scale roughness, have been studied in various fields. In this study, hierarchical periodic micro/nano-structures were fabricated on nitinol, an equiatomic Ni-Ti alloy, using a femtosecond laser for the surface modification of intravascular stents. By controlling the laser fluence, two types of surfaces were developed: periodic nano- and micro/nano-structures. Evaluation of water contact angles indicated that the nano-surface was hydrophilic and the micro/nano-surface was hydrophobic. Endothelial cells aligned along the nano-structures on both surfaces, whereas platelets failed to adhere to the micro/nano-surface. Decorrelation between the responses of the two cell types and the results of water contact angle analysis were a result of the pinning effect. This is the first study to show the applicability of hierarchical periodic micro/nano-structures for surface modification of nitinol., (Copyright © 2015. Published by Elsevier B.V.)

Unlabelled: Bordetella pertussis is a bacterium that is considered to be highly adapted to humans, and it has not been isolated from the environment. As this bacterium does not utilize sugars, the abundant supply of glutamate in Stainer Scholte (SS) medium enables B. pertussis to grow efficiently in liquid culture in vitro, and as such, SS medium is a popular choice for laboratory experiments. However, the concentration of glutamate in the in vivo niche of B. pertussis is quite low. We investigated the bacterial response to low concentrations of glutamate to elucidate bacterial physiology via the expression of the type 3 secretion system (T3SS), and we discuss its relationship to the Bvg mode in which the two-component regulator of pathogenesis (BvgAS) is activated. Glutamate limitation induced the expression of both the T3SS apparatus and effector genes at the transcriptional level. (p)ppGpp, a modulator of the stringent response, was necessary for maximum expression of the T3SS genes. These observations indicate that the expression of the T3SS is managed by nutrient starvation. In addition, the autoaggregation ability was high in the absence of glutamate and no autoaggregation was observed in glutamate-replete medium. Taken together, glutamate-limited conditions in Bvg(+) mode elicit the high expression of T3SS genes in B. pertussis and promotes its sessile form., Importance: Bordetella pertussis is a highly contagious pathogen that causes respiratory infectious disease. In spite of the increasing use of vaccination, the number of patients with pertussis is increasing. The proteins produced in vivo often are different from the protein profile under laboratory conditions; therefore, the development of conditions reflecting the host environment is important to understand native bacterial behavior. In the present study, we examined the effect of glutamate limitation, as its concentration in vivo is much lower than that in the culture medium currently used for B. pertussis experiments. As predicted, the T3SS was induced by glutamate limitation. These results are suggestive of the importance of regulation by nutrient conditions and in the pathogenicity of B. pertussis., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Three cases of pulmonary actinomycosis have been postoperatively diagnosed in our hospital in the past 3 years. All the cases were preoperatively difficult to differentiate from lung cancer, and all were diagnosed in men. One of the patients was diagnosed on the basis of clinical symptoms, while the other 2 patients were diagnosed during the treatment and follow-up of other diseases. On radiological examination, 2 patients showed mass-like shadows, and the 3rd showed a cavitary lesion; fluorodeoxyglucose (FDG) -positron emission tomography showed high FDG accumulation in all the patients. One of the patients was pathologically suspected with lung cancer on transbronchial lung biopsy. Right upper lobectomy was performed in 2 patients, and right lower lobectomy in 1. One of the patients who underwent right upper lobectomy, also received chest wall resection because of the perioperative finding of chest wall invasion of lung cancer. Clinically, all the cases were preoperatively diagnosed as lung cancer.

A preliminary tensile test was performed to evaluate the mechanical properties of cobalt-chromium (Co-Cr) alloys fabricated by three new manufacturing processes: metal milling, milling for soft metal, and rapid prototyping (n=6). For comparison, the three alloy materials were also used to fabricate specimens by a casting procedure. In all groups tested, the proof strength and elongation were over 500 MPa and 2%, respectively. The milled soft alloy in particular showed a substantially greater elongation, whereas the alloy fabricated by rapid prototyping exhibited a higher proof strength.

A Velcro-like poly(ethylene glycol) (PEG) interface was prepared in order to control the friction dynamics of material surfaces. Graft- and loop-type PEGs were formed on mirror-polished Ti surfaces using an electrodeposition method with mono- and di-amine functionalized PEGs. The friction dynamics of various combinations of PEG surfaces (i.e., graft-on-graft, loop-on-loop, graft-on-loop, and loop-on-graft) were investigated by friction testing. Here, only the Velcro-like combinations (graft-on-loop and loop-on-graft) exhibited a reversible friction behavior (i.e., resetting the kinetic friction coefficient and the reappearance of the maximum static friction coefficient) during the friction tests. The same tendency was observed when the molecular weights of loop- and graft-type PEGs were tested at 1 k and 10 k, respectively. This indicates that a Velcro-like friction behavior could be induced by simply changing the conformation of PEGs, which suggests a novel concept of altering polymer surfaces for the effective control of friction dynamics.

A case of rib and pulmonary metastases of hepatocellular carcinoma (HCC) successfully treated with transcatheter arterial embolization (TAE) followed by surgery is reported. A 66-year-old male with a history of HCC treated previously with hepatectomy was admitted to our hospital for examination of a chest wall tumor. Before the admission, TAE targeting the chest wall tumor was performed. TAE followed by surgery for postresection metastases of HCC was performed and provided an excellent result with long-term survival. The combination of TAE plus salvage surgery could be an option in select patients with limited disease., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Most orthodontic equipment is fabricated from alloys such as stainless steel, Co-Cr and Ni-Ti because of their excellent elastic properties. In recent years, increasing esthetic demands, metal allergy and interference of metals with magnetic resonance imaging have driven the development of non-metallic orthodontic materials. In this study, we assessed the feasibility of using three super engineering plastics (PEEK, PES and PVDF) as orthodontic wires. PES and PVDF demonstrated excellent esthetics, although PEEK showed the highest bending strength and creep resistance. PEEK and PVDF showed quite low water absorption. Because of recent developments in coloration of PEEK, we conclude that PEEK has many advantageous properties that make it a suitable candidate for use as an esthetic metal-free orthodontic wire.

We have previously demonstrated conjugation of Escherichia coli into vacuoles of the protozoal ciliate (Tetrahymena thermophila). This indicated a possible role of ciliates in evoking bacterial quorum sensing, directly connecting bacterial survival via accumulation in the ciliate vacuoles. We therefore assessed if ciliates promoted bacterial autoinducer (AI)-2 accumulation with vacuole formation, which controls quorum sensing. E. coli AI-2 accumulation was significantly enhanced in the supernatants of a mixed culture of ciliates and bacteria, likely depending on ciliate density rather than bacterial concentration. As expected, AI-2 production was significantly correlated with vacuole formation. The experiment with E. coli luxS mutants showed that ciliates failed to enhance bacterial AI-2 accumulation, denying a nonspecific phenomenon. Fluorescence microscopy revealed accumulation of fragmented bacteria in ciliate vacuoles, and, more importantly, expulsion of the vacuoles containing disrupted bacteria into the culture supernatant. There was no increase in the expression of luxS (encoding AI-2) or ydgG (a transporter for controlling bacterial export of AI-2). We conclude that ciliates promote bacterial AI-2 accumulation in a mixed culture, via accumulation of disrupted bacteria in ciliate vacuoles followed by expulsion of the vacuoles, independently of luxS or ydgG gene induction. This is believed to be the first demonstration of a relationship between E. coli AI-2 dynamics and ciliates. In the natural environment, ciliate biotopes may provide a survival advantage to bacteria inhabiting such biotopes, via evoking quorum sensing.

To confirm similarity of hard tissue compatibility between titanium and zirconium, calcification of MC3T3-E1 cells on titanium and zirconium was evaluated in this study. Mirror-polished titanium (Ti) and zirconium (Zr) disks and zirconium-sputter deposited titanium (Zr/Ti) were employed in this study. The surface of specimens were characterized using scanning electron microscopy and X-ray diffraction. Then, the cellular proliferation, differentiation and calcification of MC3T3-E1 cells on specimens were investigated. The surface of Zr/Ti was much smoother and cleaner than those of Ti and Zr. The proliferation of the cell was the same among three specimens, while the differentiation and calcification on Zr/Ti were faster than those on Ti and Zr. Therefore, Ti and Zr showed the identical hard tissue compatibility according to the evaluation with MC3T3-E1 cells. Sputter deposition may improve cytocompatibility.

Although the reported percentage of bone-implant contact is far lower than 100%, the cause of such low levels of bone formation has rarely been investigated. This study tested the negative biological effect of hydrocarbon deposition onto titanium surfaces, which has been reported to be inevitable. Osteogenic MC3T3-E1 cells were cultured on titanium disks on which the carbon concentration was experimentally regulated to achieve carbon/titanium (C/Ti) ratios of 0.3, 0.7, and 1.0. Initial cellular activities such as cell attachment and cell spreading were concentration-dependently suppressed by the amount of carbon on the titanium surface. The osteoblastic functions of alkaline phosphatase activity and calcium mineralization were also reduced by more than 40% on the C/Ti (1.0) surface. These results indicate that osteoblast activity is influenced by the degree of hydrocarbon contamination on titanium implants and suggest that hydrocarbon decomposition before implant placement may increase the biocompatibility of titanium., (© International & American Associations for Dental Research.)

This study aimed to evaluate effects of torsional loading on the mechanical properties of endodontic instruments using the nanoindentation technique. ProFile (PF; size 30, taper 04; Dentsply Maillefer, Switzerland) and stainless steel (SS; size 30, taper 02; Mani, Japan) instruments were subjected to torsional test. Nanoindentation was then performed adjacent to the edge of fracture (edge) and at the cutting part beside the shank (shank). Hardness and elastic modulus were measured under 100-mN force on 100 locations at each region, and compared to those obtained from the same regions on new instruments. It showed that PF and SS instruments failed at 559 ± 67 and 596 ± 73 rotation degrees and mean maximum torque of 0.90 ± 0.07 and 0.99 ± 0.05 N-cm, respectively. Hardness and elastic modulus ranged 4.8-6.7 and 118-339 GPa in SS, and 2.7-3.2 and 52-81 GPa in PF. Significant differences between torsion-fractured and new instruments in hardness and elastic modulus were detected in the SS system used. While in PF system, the edge region after torsional fracture had significantly lower hardness and elastic modulus compared to new instruments. The local hardness and modulus of elasticity of endodontic instruments adjacent to the fracture edge are significantly reduced by torsional loading., (© 2014 Wiley Periodicals, Inc.)

Background: Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action., Method: Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice., Results: DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice., Conclusions: In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

In this study, surface treatment of a Co–Ni–Cr–Mo alloy (MP35N) was attempted to attain biocompatibility using an anodic oxidation technique. To determine the optimal condition of the anodic oxidation treatment for stent applications, anodic polarization of the alloy was first conducted. After anodic oxidation, the surface topology and wettability were examined, and the composition and chemical states of the surface oxide were characterized. For biocompatibility, stent surfaces must have both cell adhesion and antithrombogenic properties. Therefore, the anodically oxidized surface was assessed with an endothelial cell attachment test and an in vitro platelet adhesion test. The results indicated that the topography, wettability, and composition of the surface oxide film on the alloy were changed by anodic oxidation at a voltage near the passive and transpassive region. The surface roughness and wettability increased after anodic oxidation. The major content of the oxide layer after anodic oxidation was Cr containing a small amount of Mo, and Ni and Co were almost eliminated from the layer. Platelet activation of the alloy decreased significantly after anodic oxidation at an optimal potential, whereas the cytocompatibility remained constant. Therefore, the anodic oxidation is an effective process for treating this alloy for stent applications.

Anodic oxide nanostructures (nanopores and nanotubes) were fabricated on a biomedical β-type titanium alloy, Ti-29Nb-13Ta-4.6Zr alloy (TNTZ), by anodization in order to improve the adhesive strength of a medical polymer, segmented polyurethane (SPU), to TNTZ. TNTZ was anodized in 1.0M H3PO4 solution with 0.5 mass% NaF using a direct-current power supply at a voltage of 20V. A nanoporous structure is formed on TNTZ in the first stage of anodization, and the formation of a nanotube structure occurs subsequently beneath the nanoporous structure. The nanostructures formed on TNTZ by anodization for less than 3,600s exhibit higher adhesive strengths than those formed at longer anodization times. The adhesive strength of the SPU coating on the nanoporous structure formed on top of TNTZ by anodization for 1,200s improves by 144% compared to that of the SPU coating on as-polished TNTZ with a mirror surface. The adhesive strength of the SPU coating on the nanotube structure formed on TNTZ by anodization for 3,600s increases by 50%. These improvements in the adhesive strength of SPU are the result of an anchor effect introduced by the nanostructures formed by anodization. Fracture occurs at the interface of the nanoporous structure and the SPU coating layer. In contrast, in the case that SPU coating has been performed on the nanotube structure, fracture occurs inside the nanotubes., (Copyright © 2013 Elsevier B.V. All rights reserved.)